Search

The objective of this study is to explore whether sodium valproate (VPA) alleviates epileptic seizures via suppressing lysyl oxidase (Lox)-mediated ferroptosis. Epileptic seizure mouse model was prepared via intrahippocampal injection of kainic acid (250 ng/μl). After treatment with kainic acid, VPA was injected intraperitoneally by the dose of 250 mg/kg twice daily for 4 days. Ferroptosis-associated indices including lipid peroxides (LPO) level and Ptgs2 mRNA in hippocampal tissue samples were detected. Additionally, effects of VPA on Lox mRNA and enzymatic activity were assessed by quantitative real-time PCR and a commercial kit, respectively. Neuronal survival was assessed by Nissl staining. In kainic acid-induced epileptic seizure mouse model, VPA significantly suppressed LPO level and Ptgs2 mRNA and the suppression of ferroptosis was positively correlated with its anti-seizure effect. Lox mRNA and enzymatic activity were also found to decrease in hippocampus of epileptic seizure mice after VPA treatment. Furthermore, overexpression of Lox via adeno-associated virus infection remarkably abrogated the inhibitory effect of VPA on ferroptosis and neuronal impairment together with its anti-seizure effect. VPA suppresses Lox-mediated ferroptosis process, which can provide the explanation for its anti-seizure property., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Epilepsy remains a prevalent chronic neurological disease that is featured by aberrant, recurrent and hypersynchronous discharge of neurons and poses a great challenge to healthcare systems. Although several therapeutic interventions are successfully utilized for treating epilepsy, they can merely provide symptom relief but cannot exert disease-modifying effect. Therefore, it is of urgent need to explore other potential mechanism to develop a novel approach to delay the epileptic progression. Since approximately 30 years ago, histone deacetylases (HDACs), the versatile epigenetic regulators responsible for gene transcription via binding histones or non-histone substrates, have grabbed considerable attention in drug discovery. There are also substantial evidences supporting that aberrant expressions and/activities of HDAC isoforms are reported in epilepsy and HDAC inhibitors (HDACi) have been successfully utilized for therapeutic purposes in this condition. However, the specific mechanisms underlying the role of HDACs in epileptic progression have not been fully understood. Herein, we reviewed the basic information of HDACs, summarized the recent findings associated with the roles of diverse HDAC subunits in epilepsy and discussed the potential regulatory mechanisms by which HDACs affected the development of epilepsy. Additionally, we also provided a brief discussion on the potential of HDACs as promising therapeutic targets for epilepsy treatment, serving as a valuable reference for basic study and clinical translation in epilepsy field., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is a common neurosurgical disorder with high morbidity and poor prognosis, and the associated delayed cerebral ischemia (DCI) is a key factor contributing to poor prognosis. Despite extensive research on the risk factors associated with DCI development, the evidence remains conflicting. Therefore, this meta-analysis of case-control studies aimed to investigate the risk factors for DCI occurrence during hospitalization in patients with aSAH., Methods: We systematically searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials for eligible studies published before November 20, 2023. Two independent reviewers extracted relevant data from the included studies using a pre-established data extraction form. The primary outcome was DCI occurrence during hospitalization in patients with aSAH., Results: A total of 42 studies involving 21,726 patients with aSAH were included. The pooled meta-analysis showed that female sex; Hunt-Hess, modified Fisher, and World Federation of Neurosurgical Societies scale scores of 4-5, 3-4, and 4-5, respectively; vasospasm; combined intraventricular hemorrhage; pre-existing hypertension; hydrocephalus; intracranial infections; and high white blood cell count on admission were independent risk factors for the development of postoperative DCIs in patients with aSAH., Conclusions: Patients with aSAH who have a Hunt-Hess scale score ≥4, a modified Fisher scale score ≥3, a WFNS scale score ≥4, intraventricular hemorrhage, pre-existing hypertension, cerebral vasospasm, a high white blood cell count on admission, intracranial infection, and female sex are at high risk of DCI and hence should be carefully monitored in the intensive care unit., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Minimally invasive surgery (MIS) and craniotomy (CI) are the current treatments for spontaneous supratentorial cerebral haemorrhage (SSTICH)., Aim: To compare the efficacy and safety of MIS and CI for the treatment of SSTICH., Methods: Clinical and imaging data of 557 consecutive patients with SSTICH who underwent MIS or CI between January 2017 and December 2022 were retrospectively analysed. The patients were divided into two subgroups: The MIS group and CI group. Propensity score matching was performed to minimise case selection bias. The primary outcome was a dichotomous prognostic (favourable or unfavourable) outcome based on the modified Rankin Scale (mRS) score at 3 months; an mRS score of 0-2 was considered favourable., Results: In both conventional statistical and binary logistic regression analyses, the MIS group had a better outcome. The outcome of propensity score matching was unexpected (odds ratio: 0.582; 95%CI: 0.281-1.204; P = 0.144), which indicated that, after excluding the interference of each confounder, different surgical modalities were more effective, and there was no significant difference in their prognosis., Conclusion: Deciding between MIS and CI should be made based on the individual patient, considering the hematoma size, degree of midline shift, cerebral swelling, and preoperative Glasgow Coma Scale score., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Epilepsy is a widespread central nervous system disorder with an estimated 50 million people affected globally. It is characterized by a bimodal incidence peak among infants and the elderly and is influenced by a variety of risk factors, including a significant genetic component. Despite the use of anti-epileptic drugs (AEDs), drug-refractory epilepsy develops in about one-third of patients, highlighting the need for alternative therapeutic approaches., Aims: The primary aim of this study was to evaluate the neuroprotective effects of troglitazone (TGZ) in epilepsy and to explore the potential mechanisms underlying its action., Methods: We employed both in vitro and in vivo models to assess TGZ's effects. The in vitro model involved glutamate-induced toxicity in HT22 mouse hippocampal neurons, while the in vivo model used kainic acid (KA) to induce epilepsy in mice. A range of methods, including Hoechst/PI staining, CCK-8 assay, flow cytometry, RT-PCR analysis, Nissl staining, scanning electron microscopy, and RNA sequencing, were utilized to assess various parameters such as cellular damage, viability, lipid-ROS levels, mitochondrial membrane potential, mRNA expression, seizure grade, and mitochondrial morphology., Results: Our results indicate that TGZ, at doses of 5 or 20 mg/kg/day, significantly reduces KA-induced seizures and neuronal damage in mice by inhibiting the process of ferroptosis. Furthermore, TGZ was found to prevent changes in mitochondrial morphology. In the glutamate-induced HT22 cell damage model, 2.5 μM TGZ effectively suppressed neuronal ferroptosis, as shown by a reduction in lipid-ROS accumulation, a decrease in mitochondrial membrane potential, and an increase in PTGS2 expression. The anti-ferroptotic effect of TGZ was confirmed in an erastin-induced HT22 cell damage model as well. Additionally, TGZ reversed the upregulation of Plaur expression in HT22 cells treated with glutamate or erastin. The downregulation of Plaur expression was found to alleviate seizures and reduce neuronal damage in the mouse hippocampus., Conclusion: This study demonstrates that troglitazone has significant therapeutic potential in the treatment of epilepsy by reducing epileptic seizures and the associated brain damage through the inhibition of neuronal ferroptosis. The downregulation of Plaur expression plays a crucial role in TGZ's anti-ferroptotic effect, offering a promising avenue for the development of new epilepsy treatments., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

The association between cooking fuel and hearing loss still needs more research to clarify, and two longitudinal cohort studies were explored to find if solid fuel use for cooking affected hearing in Chinese adults. The data from Chinese Health and Retirement Longitudinal Survey (CHARLS) and Chinese Longitudinal Healthy Longevity Survey (CLHLS) were analyzed. Participants (older than 18) without hearing loss at baseline and follow-up visits were included, which were divided into clean fuel and solid fuel groups. Hearing loss rate was from follow-up visits (both in year 2011) until the recent one (year 2018 in CHARLS and 2019 in CLHLS). Cox regressions were applied to examine the associations with adjustment for potential confounders. Fixed-effect meta-analysis was used to pool the results. A total of 9049 participants (average age 8.34 ± 9.12 [mean ± SD] years; 4247 [46.93%] males) were included in CHARLS cohort study and 2265 participants (average age, 78.75 ± 9.23 [mean ± SD] years; 1148 [49.32%] males) in CLHLS cohort study. There were 1518 (16.78%) participants in CHARLS cohort and 451 (19.91%) participants in CLHLS cohort who developed hearing loss. The group of using solid fuel for cooking had a higher risk of hearing loss (CHARLS: HR, 1.16; 95% CI 1.03-1.30; CLHLS: HR, 1.43; 95% CI 1.11-1.84) compared with the one of using clean fuel. Pooled hazard ratio showed the incidence of hearing loss in the solid fuel users was 1.17 (1.03, 1.29) times higher than that of clean fuel users. Hearing loss was associated with solid fuel use and older people were at higher risk. It is advised to replace solid fuel by clean fuel that may promote health equity., (© 2024. The Author(s).)

Objective: To explore the effects of pelvic-abdominal mechanics exercises during pregnancy on improving pelvic floor function in primiparous women during the perinatal period. Methods: A single-center prospective study selected 200 primipara of singleton pregnancies with prenatal care and delivery established at Shanghai Tongren hospital from June 2022 to June 2023 as the study subjects. Participants were divided into two groups: the exercise group (100 cases) and the control group (100 cases) by using a random number table method, five participants dropped out of the study due to reasons such as follow-up failure. Ultimately, the exercise group consisted of 97 cases, while the control group consisted of 98 cases. Participants who engaged in pelvic-abdominal mechanics exercises for at least 3 months, exercising once a week, were included in the exercise group. Those who did not engage in exercise were included in control group. Comparing the two groups in terms of pregnancy discomfort symptoms, delivery outcomes, postpartum pelvic floor electromyography results, postpartum quality of life, and pelvic floor disease incidence. The statistical methods utilized included independent t -test, Pearson chi-square test, Fisher's exact test, and Mann-Whitney U test. Results: In the late stage of pregnancy, the VAS score for low back pain was 5.05±1.22 in the exercise group and 5.47±1.55 in the control group, with a statistically significant difference ( t =2.090, P <0.05). The PFDI-20 score was 23.33±8.41 in the exercise group and 25.76±8.34 in the control group, with a statistically significant difference ( t =2.026, P <0.05). The PFIQ-7 score was 19.21±7.69 in the exercise group and 26.66±6.19 in the control group, with a statistically significant difference ( t =6.851, P <0.05). There was no statistically significant difference in sleep quality and incidence of urinary incontinence between the two groups in late pregnancy ( t =1.252, P =0.396, P >0.05). In terms of childbirth outcomes, the exercise group had a vaginal delivery rate of 81.44% (79 cases), while the control group had a rate of 64.28% (63 cases), with a statistically significant difference (χ 2 =9.022, P <0.05). The duration of the second stage of labor was (42.68±21.38) minutes in the exercise group and (50.54±21.33) minutes in the control group, with a statistically significant difference ( t =2.178, P <0.05). At 42 days postpartum, the evaluation of pelvic floor function showed that the vaginal pressure in the exercise group was 62.19±10.04, while in the control group it was 52.68±15.55, with a statistically significant difference ( t =-5.074, P <0.05). The MOS grading in the exercise group was 3.82±1.26, whereas in the control group it was 2.34±1.55, with a statistically significant difference ( t =-7.355, P <0.05). In terms of the incidence of postpartum pelvic floor disorders, the occurrence of pelvic organ prolapse was 7.22% in the exercise group and 12.24% in the control group, with no statistically significant difference (χ 2 =1.402, P >0.05). The occurrence rate of stress urinary incontinence was 13.4% in the exercise group and 30.61% in the control group, with a statistically significant difference ( P =0.015, P <0.05). Conclusion: Pelvic-abdominal mechanics exercises may have some advantages in reducing symptoms related to perinatal pelvic floor dysfunction, enhancing pelvic floor function, and preventing the occurrence of pelvic floor disease.

Epilepsy-associated cognitive disorder (ECD), a prevalent comorbidity in epilepsy patients, has so far uncharacterized etiological origins. Our prior work revealed that lysyl oxidase (Lox) acted as a novel contributor of ferroptosis, a recently discovered cell death mode in the regulation of brain function. However, the role of Lox-mediated ferroptosis in ECD remains unknown. ECD mouse model was established 2 months later following a single injection of kainic acid (KA) for. After chronic treatment with KA, mice were treated with different doses (30 mg/kg, 100 mg/kg and 300 mg/kg) of Lox inhibitor BAPN. Additionally, hippocampal-specific Lox knockout mice was also constructed and employed to validate the role of Lox in ECD. Cognitive functions were assessed using novel object recognition test (NOR) and Morris water maze test (MWM). Protein expression of phosphorylated cAMP-response element binding (CREB), a well-known molecular marker for evaluation of cognitive performance, was also detected by Western blot. The protein distribution of Lox was analyzed by immunofluorescence. In KA-induced ECD mouse model, ferroptosis process was activated according to upregulation of 4-HNE protein and a previously discovered ferroptosis in our group, namely, Lox was remarkably increased. Pharmacological inhibition of Lox by BAPN at the dose of 100 mg/kg significantly increased the discrimination index following NOR test and decreased escape latency as well as augmented passing times within 60 s following MWM test in ECD mouse model. Additionally, deficiency of Lox in hippocampus also led to pronounced improvement of deficits in ECD model. These findings indicate that the ferroptosis regulatory factor, Lox, is activated in ECD. Ablation of Lox by either pharmacological intervention or genetic manipulation ameliorates the impairment in ECD mouse model, which suggest that Lox serves as a promising therapeutic target for treating ECD in clinic., Competing Interests: Declaration of Competing Interest I represent all the authors declare that there is no potential conflict of interest to declare in this study., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Ulcer colitis (UC) is a chronic, nonspecific, and noninfectious inflammatory bowel disease. Recently, Toll-like receptors (TLRs) have been found to be closely associated with clinical inflammatory diseases. Achieving complete remission in patients with intermittent periods of activity followed by dormancy is challenging. Moreover, no study has explored the mechanism by which Kuicolong-yu enema decoction retains traditional Chinese medicine enemas to attenuate the inflammatory response in UC., Aim: To explore the mechanism by which Kuicolong-yu enema decoction retains traditional Chinese medicine enemas to attenuate the inflammatory response in UC., Methods: This prospective clinical study included patients who met the exclusion criteria in 2020 and 2021. The patients with UC were divided into two groups (control and experimental). The peripheral blood of the experimental and control groups were collected under aseptic conditions. The expression of TLR4 protein, NF-κB, IL-6, and IL-17 was detected in the peripheral blood of patients in the experimental group and control group before and 1 month after taking the drug. Linear correlation analysis was used to analyze the relationship between the expression level of TLR4 protein and the expression levels of downstream signal NF-κB and inflammatory factors IL-6 and IL-17, and P < 0.05 was considered statistically significant., Results: There were no significant differences in the patient characteristics between the control and experimental groups. The results showed that the expression levels of TLR4 and NF-κB in the experimental group were significantly lower than those in the control group ( P < 0.05). The levels of IL-6 and IL-17 in the experimental group were significantly lower than those in the control group ( P < 0.05). The TLR4 protein expression in the experimental group was positively correlated with the expression level of downstream signal NF-κB and was positively correlated with the levels of downstream inflammatory cytokines IL-6 and IL-17 ( r = 0.823, P < 0.05)., Conclusion: Kuicolong-yu enema decoction retains traditional Chinese medicine enema attenuates the inflammatory response of UC through the TLR4/NF-κB signaling pathway., Competing Interests: Conflict-of-interest statement: Dr. Li has nothing to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objectives: To investigate the age-related changes of the mandibular third molar root pulp visibility in individuals in East China, and to explore the feasibility of applying this method to determine whether an individual is 18 years or older., Methods: A total of 1 280 oral panoramic images were collected from the 15-30 years old East China population, and the mandibular third molar root pulp visibility in all oral panoramic images was evaluated using OLZE 0-3 four-stage method, and the age distribution of the samples at each stage was analyzed using descriptive statistics., Results: Stages 0, 1, 2 and 3 first appeared in 16.88, 19.18, 21.91 and 25.44 years for males and in 17.47, 20.91, 22.01 and 26.01 years for females. In all samples, individuals at stages 1 to 3 were over 18 years old., Conclusions: It is feasible to determine whether an individual in East China is 18 years or older based on the mandibular third molar root pulp visibility on oral panoramic images.

Background: The nasal tip plays a crucial role both esthetically and functionally. The application of nasal tip grafts is an effective method for improving nasal tip form. Ear cartilage is a common choice for nasal tip grafts, but it still presents several challenges in clinical application that need to be addressed. This study aims to address the issues associated with the use of ear cartilage in clinical rhinoplasty applications through the development of a novel septal extension graft using ear cartilage for nasal tip reconstruction., Methods: From May 2018 to April 2022, a total of 132 cases of nasal tip reconstruction surgeries were performed using a seagull-shaped nasal septum extension graft, constructed with bilateral cavum concha cartilage. Among these cases, 25 patients had previously undergone rhinoplasty using silicone implant, 7 patients had undergone augmentation rhinoplasty using expanded polytetrafluoroethylene, whereas the rest were primary rhinoplasty cases. All patients were followed up for a period ranging from 3 months to 4 years postoperatively, with photographs taken to assess the nasal tip morphology., Results: In this study, all patients exhibited good healing of the incisions made at the posterior aspect of the auricular concha, with no occurrences of hematoma and inconspicuous scarring. In 116 cases, significant improvement in nasal appearance and a realistic nasal tip form were achieved postoperatively, yielding satisfactory outcomes. Only 16 patients experienced minor issues with nasal tip morphology, which were subsequently improved through further surgical procedures., Conclusion: This study reports a surgical technique for nasal tip refinement using bilaterally harvested cavum concha cartilage to construct a seagull-shaped nasal septal extension graft. The procedure has achieved satisfactory outcomes, and its application is worth extending to clinical practice., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Soil microorganisms are important components of terrestrial ecosystems, affecting soil formation and fertility, plant growth and stress tolerance, nutrient turnover and carbon storage. In this study, we collected soil samples (humus layer, 0-10 cm, 10-20 cm, 20-40 cm, and 40-80 cm) from Caragana jubata shrubland in Shanxi subalpine to explore the composition, diversity, and assembly of soil bacterial communities at different depths across the soil profile. The results showed that Actinomycota (19%-28%), Chloromycota (10%-36%) and Acidobacteria (15%-24%), and Proteobacteria (9%-25%) were the dominant bacterial phyla. α-diversity of soil bacterial community significantly decreased with the increases of soil depth. Soil bacterial β-diversity varied across different soil depths. Soil pH, water content, and enzyme activity were the main ecological factors affecting the distribution of soil bacterial communities. Soil bacterial communities had more complex interactions in humus layer and 0-10 cm layer. On the whole, soil bacterial communities were dominated by coexistence in C. jubata shrubland, and the soil bacterial community assembly was driven by random process.

Purpose: To elucidate incidence rates of vascular lake phenomenon (VLP) in hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), hepatic metastasis (HMT) on transarterial angiography before chemoembolization, and to identity CT features predictive for it., Materials and Methods: A comprehensive evaluation involved 665 subjects for incidence analysis, comprising 527 of HCC, 33 of ICC and 105 of HMT. VLP was characterized as intratumoral contrast material pool persisting late into venous phase. Incidences were cataloged on both super-selective and common hepatic artery angiography. For CT features analysis, a subset of 182 cases were analyzed. Enhancement ratio served as an index for comparative analysis of nodule enhancement degrees., Results: In HCC, incidence of VLP ascertained via super-selective angiography was 13.5%, whereas it as 7.8% on common hepatic artery angiography. Remarkably, no incidences of VLP were recorded in either ICC or HMT cases. On pre-interventional CT, the prevalence of pseudocapsule was statistically greater in VLP group than Non-VLP group (66.6% vs. 37.6%, P = 0.015). The Houndsfield units (HU) of tumors in plain scan (P = 0.007), arterial phase (P = 0.001), venous phase (P = 0.041), arterial phase enhancement ratio (P < 0.001) were statistically higher in VLP group compared to Non-VLP group. Arterial phase enhancement ratio (P = 0.025), presence of pseudocapsule (P = 0.001), HU of tumor in plain scan (P = 0.035) serve as independent risk factors for VLP manifestation., Conclusion: VLP is a distinct angiography phenomenon uniquely associated with HCC. High arterial phase enhancement ratio, presence of pseudocapsule, high HU of tumor in plain scan are independent risk factors for VLP., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

To investigate the effects of biochar(BC) addition on soil organic carbon(SOC) contents and its fractions under different biochar applications, Eucalyptus waste twigs in Northern Guangxi were used to produce BC at 500℃. Additionally, we sought to clarify and define the carbon sequestration potential of soil and provide a basis for the preparation of biochar from Eucalyptus forest wastes and soil improvement. In a long-term positioning test of biochar application from 1997, six different treatments were selected:0(CK), 0.5%(T1), 1%(T2), 2%(T3), 4%(T4), and 6%(T5). The contents of SOC, light fraction organic carbon(LFOC), heavy fraction organic carbon(HFOC), easily oxidized organic carbon(EOC), dissolved organic carbon(DOC), particulate organic carbon(POC), microbial biomass carbon(MBC), and carbon stock(CS) following the different treatments were measured. The results showed that:① compared to that in the control, biochar application induced an increase in each soil organic carbon fraction with increasing application rate and reached a maximum under the T4 or T5 treatments; with the increase in biochar application, the contents of SOC, DOC, EOC, POC, MBC, and CS increased significantly by 101.62%, 67.46%, 143.03%, 164.78%, 110.88%, and 41.73%, respectively. ② The contents of LFOC and HFOC in the 0-10, 10-20, and 20-30 cm soil layers increased significantly by 41.41%-140.63%, 9.26%-87.04%, and -19.54%-106.90% and 15.32%-78.99%, 15.72%-75.25%, and 89.49%-148.64%, respectively, with the increase in biochar application. The average contents of LFOC and HFOC in the 0-30 cm soil layer also increased gradually. The soil carbon pool of the Eucalyptus forest was dominated by a relatively stable heavy fraction organic carbon. ③ The contents of carbon stock, soil organic carbon, and its fractions decreased with the increase in soil depth. In conclusion, the application of forestry waste biochar for five years could significantly increase the content of SOC and its components, thereby increasing soil organic carbon activity. Therefore, increasing the amount of biochar was an effective measure to enhance the carbon storage, soil stable carbon pool, and soil quality of the Eucalyptus plantation field. This study provides a reference for the resource utilization of forestry waste and improvements in soil fertility of Eucalyptus plantations.

The gut microbiota may have an effect on the therapeutic resistance and toxicity of immune checkpoint inhibitors (ICIs). However, the associations between the highly variable genomes of gut bacteria and the effectiveness of ICIs remain unclear, despite the fact that merely a few gene mutations between similar bacterial strains may cause significant phenotypic variations. Here, using datasets from the gut microbiome of 996 patients from seven clinical trials, we systematically identify microbial genomic structural variants (SVs) using SGV-Finder. The associations between SVs and response, progression-free survival, overall survival, and immune-related adverse events are systematically explored by metagenome-wide association analysis and replicated in different cohorts. Associated SVs are located in multiple species, including Akkermansia muciniphila, Dorea formicigenerans, and Bacteroides caccae. We find genes that encode enzymes that participate in glucose metabolism be harbored in these associated regions. This work uncovers a nascent layer of gut microbiome heterogeneity that is correlated with hosts' prognosis following ICI treatment and represents an advance in our knowledge of the intricate relationships between microbiota and tumor immunotherapy., (© 2023. The Author(s).)

The objective of this study was to research the characteristics of fractions of organic nitrogen and active nitrogen and their relationship under different biochar applications and to provide a basis for the preparation and practical application of biochar from Eucalyptus forest wastes. In a long-term positioning test of biochar application from 2017, six different treatments were selected:0(CK), 0.5%(T1), 1%(T2), 2%(T3), 4%(T4), and 6%(T5). The contents of soil organic nitrogen components, total nitrogen(TN), dissolved organic nitrogen(DON), and microbial biomass nitrogen(MBN) following the different treatments were measured. The results showed that:① compared with that of the control, with the increase in biochar application, the contents of soil TN, acidolysis of total organic nitrogen(AHON), ammonia nitrogen(AN), amino acid nitrogen(AAN), MBN, DON, and nitrogen storage(NS) increased significantly by 45.48%-156.32%, 44.31%-171.31%, 38.06%-223.37%, 39.42%-163.32%, 36.72%-109%, 23.27%-113.51%, and 29.45%-62.37%, respectively. The contents of soil hydrolyzable unknown nitrogen(HUN) and non-hydrolyzable nitrogen(NHN) also increased significantly by 88.41%-158.71% and 50.24%-139.01%, respectively. The contents of soil amino sugar nitrogen(ASN) decreased by 7.72%-32.73%. The contents of different forms of organic nitrogen fractions in all treatments displayed an order of AN > AAN > NHN > HUN > ASN. Compared with the no biochar treatment, each biochar treatment increased the contents and proportion of AHON in the TN. ② With the exception of HUN, the contents of other soil organic nitrogen components and active nitrogen content decreased with the increase in soil depth. ③ There were significantly positive correlations between TN, MBN, and DON and AHON, NHN, and NS contents. The principal component analysis showed that bulk density and ASN and TN and HUN, AAN, DON, and AHON were closely related, respectively. In conclusion, the application of forestry waste biochar for five years could significantly increase the content of soil organic nitrogen component and active nitrogen, thereby improving the capacity of the soil to supply nitrogen. AHON, AN, and AAN were the main factors contributing to soil active nitrogen content.

Background: The optimal dosage and method of esketamine for postpartum depressive symptoms (PDS) are unclear. We conducted a randomized controlled trial (RCT) to investigate the effect of different doses of esketamine on PDS in women undergoing cesarean section, with evidence of prenatal depression., Methods: The three groups were high- (2 mg kg -1 ) and low-dose (1 mg kg -1 ) esketamine via patient controlled intravenous analgesia (PCIA), following an initial intravenous infusion of 0.25 mg kg -1 esketamine, compared to placebo (0.9 % saline infusion). All groups also received the sufentanil (2.2 μg kg -1 ). The primary outcome was the incidence of PDS at 7 and 42 days postpartum. The secondary outcomes were: the remission from depression and total EPDS scores at 7 days and 42 days postpartum; mean change from baseline in the EPDS score; postoperative analgesia., Results: i). 0.25 mg kg -1 of esketamine intravenous infusion combined with 1 mg kg -1 (n = 99) or 2 mg kg -1 (n = 99) esketamine PCIA reduces PDS incidence at 7 days postpartum (p < 0.05), with high-dose esketamine PCIA also reduces PDS incidence 42 days postpartum (p < 0.05), compared to placebo (n = 97). ii). Low- and high-dose esketamine PCIA lowers NRS scores at rest within 48 h postoperatively (p < 0.01), with high-dose esketamine also reducing the NRS score during movement at 48 h postoperatively (p = 0.018). iii). Neither high- nor low-dose esketamine PCIA increased postoperative adverse reactions (p > 0.05)., Conclusions: Esketamine (0.25 mg kg -1 ) intravenous infusion combined with 1 mg kg -1 or 2 mg kg -1 esketamine PCIA seems safe and with few adverse effects in the management of PDS and pain in women undergoing cesarean section., Limitations: The tolerability and safety of esketamine requires further investigation based on more specific scales; the transient side effects of esketamine could have biased the staff and patients., Trial Registration: ChiCTR-ROC-2000039069., Competing Interests: Declaration of competing interest All authors report no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Accumulating evidence shows that Schwann cells' (SCs) death caused by high glucose (HG) is involved in the pathological process of diabetic peripheral neuropathy (DPN). Ferroptosis is a novel form of regulatory cell death driven by iron-dependent lipid peroxidation. However, it is not clear whether ferroptosis is involved in the death process of SCs induced by HG. The expression of ferroptosis-related indicators in the serum of DPN patients was detected by ELISA. Subsequently, using cell counting kit‑8, western blot, real-time PCR, and Ki-67 staining, we investigated the effects of HG on the ferroptosis of SCs and initially explored the underlying mechanism. The results showed that the serum levels of glutathione peroxidase 4 (GPX4) and glutathione in patients with DPN decreased, while malondialdehyde levels increased significantly. Then, we observed that erastin and HG induced ferroptosis in SCs, resulting in the decrease in cell activity and the expression level of GPX4 and SLC7A11, which could be effectively reversed by the ferroptosis inhibitor Fer-1. Mechanistically, HG induced ferroptosis in SCs by inhibiting the NRF2 signaling pathway. Our results showed that ferroptosis was involved in the death process of SCs induced by HG. Inhibition of ferroptosis in SCs might create a new avenue for the treatment of DPN., Competing Interests: Conflict of interest: The authors declare that they have no competing interest., (© 2023 the author(s), published by De Gruyter.)

Recently, 3D dental intraoral scanning technology has been developed rapidly and applied widely in everyday dental practice. Since 3D dental scanning could provide valuable personal information, it enabled researchers to develop novel procedures for individual identification through 3 D- 3 D dentition superimposition. This study aimed to test the applicability of this method in an Eastern Chinese population and propose a threshold for personal identification. For this purpose, 40 volunteers were recruited, and the initial 80 (upper and lower) 3D intraoral scans (IOS) were collected. After one year, 80 IOS of these volunteers were repeatedly collected. In addition, the other 120 IOS of 60 patients were extracted from the database. The 3D models were trimmed, aligned, and superimposed via Geomagic Control X software, and then the root mean square (RMS) value of point-to-point distance between the two models was calculated. The superimposition of two IOS belonging to the same individual was considered as a match, and superimposition of two IOS belonging to different individuals was considered as a mismatch. Totally, superimpositions of 80 matches and 3120 mismatches were obtained. Intra- and inter-observer errors were assessed through the calculation of relative technical error of measurement (rTEM). Mann-Whitney U test verified possible statistically significant differences between matches and mismatches (P < 0.05). The rTEM of intra- and inter-observer repeatability analyses was lower than 4.7 %. The range of RMS value was 0.05-0.18 mm in matches and 0.72-2.28 mm in mismatches without overlapping. The percentage of accurate identification reached 100 % in blind test through an arbitrary RMS threshold of 0.45 mm. The results indicated that individual identification through the 3 D- 3 D dentition superimposition was effective in Eastern Chinese population. Successful identification could be achieved with high probability when the RMS value of the point-to-point distance of two dentitions is <0.45 mm., Competing Interests: Declaration of Competing Interest The authors declare that they have no potential conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Cancer stem cells (CSCs) are the leading cause of recurrence and poor prognosis in non-small cell lung cancer (NSCLC). Eukaryotic translation initiation factor 3a (eIF3a) participates in many tumor development processes, such as metastasis, therapy resistance, and glycolysis, all of which are closely associated with the presence of CSCs. However, whether eIF3a maintains NSCLC-CSC-like properties remains to be elucidated. In this study, eIF3a was highly expressed in lung cancer tissues and was linked to poor prognosis. eIF3a was also highly expressed in CSC-enriched spheres compared with adherent monolayer cells. Moreover, eIF3a is required for NSCLC stem cell-like traits maintenance in vitro and in vivo. Mechanistically, eIF3a activates the Wnt/β-catenin signaling pathway, promoting the transcription of cancer stem cell markers. Specifically, eIF3a promotes the transcriptional activation of β-catenin and mediates its nuclear accumulation to form a complex with T cell factor 4 (TCF4). However, eIF3a has no significant effect on protein stability and translation. Proteomics analysis revealed that the candidate transcription factor, Yin Yang 1 (YY1), mediates the activated effect of eIF3a on β-catenin. Overall, the findings of this study implied that eIF3a contributes to the maintenance of NSCLC stem cell-like characteristics through the Wnt/β-catenin pathway. eIF3a is a potential target for the treatment and prognosis of NSCLC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Paired pigeons only lay 2 eggs in a laying period, which is closely related to ovarian follicle development, but this process is not well understood. In this study, 60 pairs of 12-mo-old White King pigeons were selected and serum and follicles were collected at 4 stages of laying interval (LI), including the first (LI1), the third (LI3), the fifth (LI5), and the seventh day (LI7). Morphological results showed that paired pigeons normally had 2 preovulatory follicles and the second-largest follicle (F2) developed from LI3 and had been selected in LI5. Prehierarchical follicles were coupled and hierarchical, which was in accordance with its clutch size. The P 4 concentration increased gradually from LI1 to LI5, reaching a maximum of 30.67 ng/mL in LI5 and decreasing to 27.83 ng/mL in LI7 (P < 0.05). The levels of T in LI1 and LI5 were higher than LI3 and LI7 (P < 0.05), although there was no significant difference in E 2 in LI (P > 0.05), but it stayed at high levels. In the TCs of the largest follicle (F1), HSD3B1 mRNA and HSD17B1 mRNA levels peaked in LI7. The expression pattern of CYP17A1 and CYP19A1 was similar, increasing from LI3 to LI5 and then decreasing. In the TCs of F2, the expressions of HSD3B1 and CYP17A1 had no significant difference between LI5 and LI7 (P > 0.05), while the expression pattern of HSD17B1 and CYP19A1 was the opposite. In TCs of SF1, HSD3B1 mRNA level peaked in LI3 while CYP19A1 mRNA levels peaked in LI7. The expression of CYP17A1 had a minor change (P > 0.05) and the expression pattern of HSD17B1 was similar to F1. It was concluded that the morphological characteristics of follicles during the LI for the first time, including the number and diameter of small follicles (SFs) and hierarchical follicles in pigeon and the concentrations of steroid hormones and expressions of steroidogenic genes in TCs of different follicles could explain the growth and selection of 2 preovulatory follicles. This study facilitates further research into the regulation of ovulation and egg production in pigeons., (Copyright © 2023. Published by Elsevier Inc.)

Cortical interneurons can be categorized into distinct populations based on multiple modalities, including molecular signatures and morpho-electrical (M/E) properties. Recently, many transcriptomic signatures based on single-cell RNA-seq have been identified in cortical interneurons. However, whether different interneuron populations defined by transcriptomic signature expressions correspond to distinct M/E subtypes is still unknown. Here, we applied the Patch-PCR approach to simultaneously obtain the M/E properties and messenger RNA (mRNA) expression of >600 interneurons in layer V of the mouse somatosensory cortex (S1). Subsequently, we identified 11 M/E subtypes, 9 neurochemical cell populations (NCs), and 20 transcriptomic cell populations (TCs) in this cortical lamina. Further analysis revealed that cells in many NCs and TCs comprised several M/E types and were difficult to clearly distinguish morpho-electrically. A similar analysis of layer V interneurons of mouse primary visual cortex (V1) and motor cortex (M1) gave results largely comparable to S1. Comparison between S1, V1, and M1 suggested that, compared to V1, S1 interneurons were morpho-electrically more similar to M1. Our study reveals the presence of substantial M/E variations in cortical interneuron populations defined by molecular expression., (© 2022. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences.)

Microbial communities are the key component to maintaining the structure and function of forest soil ecosystems. The vertical distribution of bacterial communities on the soil profile has an important impact on forest soil carbon pools and soil nutrient cycling. Using Illumina MiSeq high-throughput sequencing technology, we analyzed the characteristics of bacterial communities in the humus layer and 0-80 cm soil layer of Larix principis-rupprechtii in Luya Mountain, China, to explore the driving mechanisms affecting the structure of bacterial communities in soil profiles. The results showed that the α diversity of bacterial communities decreased significantly with increasing soil depth, and community structure differed significantly across soil profiles. The relative abundance of Actinobacteria and Proteobacteria decreased with increased soil depth, whereas the relative abundance of Acidobacteria and Chloroflexi increased with the increase in soil depth. The results of RDA analysis showed that soil NH + 4 , TC, TS, WCS, pH, NO - 3 , and TP were important factors determining the bacterial community structure of the soil profile, among which soil pH had the most significant effect. Molecular ecological network analysis showed that the complexity of bacterial communities in the litter layer and subsurface soil (10-20 cm) was relatively high, whereas the complexity of bacterial communities in deep soil (40-80 cm) was relatively low. Proteobacteria, Acidobacteria, Chloroflexi, and Actinobacteria played important roles in the structure and stability of soil bacterial communities in Larch. The species function prediction of Tax4Fun showed a gradual decline in microbial metabolic capacity along the soil profile. In conclusion, soil bacterial community structure showed a certain distribution pattern along the vertical profile of soil, the community complexity gradually decreased, and the unique bacterial groups of deep soil and surface soil were significantly different.

To reveal the assembly mechanisms of soil protozoan community in subalpine forest ecosystems, we analyzed the composition and diversity of protozoan communities and their drivers at the six strata (the litter profile, humus profile, 0-10 cm, 10-20 cm, 20-40 cm and 40-80 cm) of soil profiles in subalpine Larix principis-rupprechtii forest in Luya Mountain using Illumina Miseq high-throughput sequencing technology. The results showed that protozoa in the soil profiles belonged to 335 genera, 206 families, 114 orders, 57 classes, 21 phyla, and 8 kingdoms. There were five dominant phyla (relative abundance >1%) and 10 dominant families (relative abundance >5%). The α diversity decreased significantly with increasing soil depth. Results of PCoA analysis showed that the spatial composition and structure of protozoan community differed significantly across soil depths. The results of RDA analysis showed that soil pH and soil water content were important factors driving protozoan community structure across soil profile. Null model analysis suggested that the heterogeneous selection dominated the processes of protozoan community assemblage. Molecular ecological network analysis revealed that the complexity of soil proto-zoan communities decreased continuously with increasing depth. These results elucidate the assembly mechanism of soil microbial community in subalpine forest ecosystem.

Objective: To analyze whole brain structural volume asymmetry in temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) using automated brain segmentation technology, and to investigate the application value of this technology in the diagnosis of TLE-HS and the performance in determining the location the lateralization of epileptogenic focus. Methods: Twenty-eight patients with TLE-HS were enrolled in the First Affiliated Hospital of Zhengzhou University from April 2019 to October 2020, including 13 females and 15 males, aged ranged from 18 to 63 (30±12) years, and these patients were divided two group according to the epilepsy lateralization, left TLE-HS(LTLE-HS) group ( n =11), right TLE-HS(RTLE-HS) group ( n =17) and 28 normal controls [aged ranged from 18 to 49 (29±10) years]. All of these subjects underwent three-dimensional T 1 weighted image (3D T 1 WI). The differences of brain structure and volumes in LTLE-HS, RTLE-HS and normal controls group were retrospectively analyzed, and Pearson's correlation coefficient was used to evaluate the left and right volume correlations, and effect size was used for evaluating the differences in left and right volume averages. The asymmetry index (AI) of the left and right lateral volumes in each group was also calculated and compared among the three groups. Results: Standard volumes of all structures within the brain were asymmetric in the normal controls, LTLE-HS, and RTLE-HS groups, with smaller volumes of ipsilateral hippocampus than contralateral hippocampus in both the LTLE-HS and RTLE-HS groups(0.20%±0.03% vs 0.24%±0.02%,0.21%±0.03% vs 0.25%±0.02% respectively;both P <0.001), and smaller volumes of gray and white matter of the ipsilateral temporal lobe than contralateral in the LTLE-HS group(4.41%±0.38% vs 5.01%±0.43%,1.83%±0.22 % vs 2.22%±0.14%;both P <0.001). There was a moderate to strong linear correlation (0.553< r <0. 964,all P <0.05) between left and right lateral volumes in the normal controls, LTLE-HS, and RTLE-HS groups. All three groups showed the largest effect sizes in the cingulate gyrus (The effect sizes were 3.07, 4.85 and 4.22 in control, LTLE-HS and RTLE-HS, respectively.). The AI values of the hippocampus, temporal lobe gray matter, and temporal lobe white matter were statistically different among the three groups (-1.48±8.64 vs 15.91±10.15 vs -17.59±10.00, 7.46±2.67 vs 12.67±6.67 vs 3.67±6.15, 6.53±3.71 vs 19.91±9.85 vs 1.57±8.38;all P <0.001). Conclusion: Volumetric measurements by automated brain segmentation techniques can play an important role in preoperative assessment of TLE, and the asymmetry of brain volume may be of value in determining the localization and extent of the epileptogenic focus.

The functional properties of endogenous Schwann cells (SCs) during nerve repair are dynamic. Optimizing the functional properties of SCs at different stages of nerve repair may have therapeutic benefit in improving the repair of damaged nerves. Previous studies showed that miR-221-3p promotes the proliferation and migration of SCs, and miR-338-3p promotes the myelination of SCs. In this study, we established rat models of sciatic nerve injury by bridging the transected sciatic nerve with a silicone tube. We injected a miR-221 lentiviral vector system together with a doxycycline-inducible Tet-On miR-338 lentiviral vector system into the cavity of nerve conduits of nerve stumps to sequentially regulate the biological function of endogenous SCs at different stages of nerve regeneration. We found that the biological function of SCs was sequentially regulated, the diameter and density of myelinated axons were increased, the expression levels of NF200 and myelin basic protein were increased, and the function of injured peripheral nerve was improved using this system. miRNA Target Prediction Database prediction, Nanopore whole transcriptome sequencing, quantitative PCR, and dual luciferase reporter gene assay results predicted and verified Cdkn1b and Nrp1 as target genes of miR-221-3p and miR-338-3p, respectively, and their regulatory effects on SCs were confirmed in vitro. In conclusion, here we established a new method to enhance nerve regeneration through sequential regulation of biological functions of endogenous SCs, which establishes a new concept and model for the treatment of peripheral nerve injury. The findings from this study will provide direct guiding significance for clinical treatment of sciatic nerve injury., Competing Interests: None

An ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of a mosaic-type recombinant vaccine candidate, named NVSI-06-09, as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had administered two or three doses of inactivated vaccine BBIBP-CorV at least 6 months prior to enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. Between May 25 and 30, 2022, 516 adults received booster vaccination with 260 in NVSI-06-09 group and 256 in BBIBP-CorV group. Interim results showed a similar safety profile between two booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 post-booster, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those by BBIBP-CorV. Our findings indicated that a booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against divergent SARS-CoV-2 variants, including Omicron and its sub-lineages., (© 2022. The Author(s).)

Background/purpose: The effect of roxadustat on iron homeostasis in patients with chronic kidney disease (CKD) is unclear. This study aimed to evaluate the efficacy of roxadustat for the treatment of iron metabolism disorders in dialysis-dependent (DD) and non-dialysis-dependent (NDD) CKD patients., Methods: We searched the PubMed, Embase, China National Knowledge Internet and Web of Science databases for randomized controlled trials (RCTs). The primary outcomes were changes in serum iron, total iron binding capacity (TIBC), transferrin saturation (TSAT), ferritin, transferrin, and hepcidin. The secondary outcomes included the changes in hemoglobin (Hb) and the incidences of adverse events (AEs) and severe adverse events (SAEs)., Results: Twelve RCTs comprising 4976 participants were included. Compared to the control group, increases in the serum iron (SMD = 0.21, 95% CI: 0.15 to 0.27, P < 0.00001), TIBC (SMD = 1.02, 95% CI: 0.82 to 1.22, P < 0.00001) and transferrin levels (WMD = 0.55, 95% CI: 0.41 to 0.69, P < 0.00001) were found in the roxadustat group. Compared to the control group, decreases in the ferritin levels (WMD = -37.82, 95% CI: -59.89 to -15.74, P = 0.0008) and hepcidin levels (WMD = -24.04, 95% CI: -36.28 to -11.79, P = 0.0001) were observed in the roxadustat group. The meta-analysis showed that roxadustat significantly increases Hb levels (WMD = 0.77, 95% CI: 0.42 to 1.12, P < 0.0001). The incidences of AEs and SAEs in the roxadustat group was significantly higher than that in the control group (RR = 1.03, 95% CI: 1.00 to 1.07, P = 0.04; RR = 1.08, 95% CI: 1.00 to 1.15, P = 0.04)., Conclusion: Our findings suggest that roxadustat could effectively improve iron metabolism in patients with CKD., Competing Interests: Declaration of competing interest The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this article., (Copyright © 2022. Published by Elsevier B.V.)

Background: Colorectal peritoneal carcinomatosis (CRPC) is a primary cause of death in colorectal cancer (CRC) patients. In the past, computed tomography (CT) has been the primary method used to evaluate the distribution of CRPC. This study uses 18 F-FDG positron emission tomography/computed tomography (PET/CT) to investigate the distribution characteristics of CRPC. Materials and Methods: The distribution characteristics of 46 patients with CRC who were treated in the authors' hospital were retrospectively analyzed using the peritoneal cancer index (PCI). Results: The 46 patients in the study showed CRPC involvement in 203 of the 598 abdominal and pelvic regions studied (33.9%, 203/598). The regional proportions of CRPC involvement, from high to low, were as follows: region 6 (13.8%), region 0 (10.3%), region 1 (9.9%), region 5 (8.9%), region 7 (8.4%), region 3 (8.4%), region 2 (7.4%), region 4 (7.4%), region 11 (6.9%), region 8 (6.4%), region 12 (5.4%), region 9 (3.4%), and region 10 (3.4%). Thirty-three patients had a PCI of <20, and 13 patients had a PCI of ≥20. Those 13 were among the 17 (37% 17/46) who had CRPC involvement in all three regions. According to the location of the primary CRC focus, the 46 patients were divided into three groups: right hemicolon, left hemicolon, and rectum. The frequency of CRPC was greater in the rectum group than in the left hemicolon group, and the SUV max of CRPC was greater in the right hemicolon group than in the left hemicolon group; these differences were statistically significant ( p  < 0.05). Conclusions: The distribution of CRPC has certain characteristics in the abdominal and pelvic cavities. The PET-PCI scores can provide a basis for the diagnosis and clinical treatment strategies in patients with CRC.

Background : Previous investigations have illustrated that lysyl oxidase family enzymes (LOXs) are contributing factors for tumor progression and remodeling immunomicroenvironment. However, it is scarce regarding comprehensive analysis of LOXs in the predictions of prognosis, chemotherapy and immunotherapy in glioma, the highly invasive brain tumor. Our present work aimed to explore the prognostic value, chemotherapeutic drug sensitivity and immunotherapy according to distinct LOXs expressions in glioma through bioinformatics analysis and experimental verification. Methods: We collected gene expression data and clinical characteristics from the public databases including Chinese Glioma Genome Atlas (CGGA)-325, CGGA-693, the Cancer Genome Atlas (TCGA), IMvigor210 and Van Allen 2015 cohorts. The correlations between the clinicopathological factors and differential LOXs expressions were analyzed. The ROC curve and Kaplan-Meier analysis were conducted to evaluate the prediction ability of prognosis. Chemotherapeutic drug sensitivity via distinct LOXs expression levels was predicted using the pRRophetic package. Immune score, immune cell infiltration and immune checkpoint expression levels were also analyzed through diverse algorithms in R software. Finally, mRNA and protein expressions of LOXs were validated in glioma cells (T98G and A172) by real-time quantitative PCR and Western blot, respectively. Results: Our results demonstrated that high levels of LOXs expressions were positively associated with glioma grades, older age and MGMT unmethylated status while elevations of LOXs were negatively correlated with IDH mutation or 1p/19q co-deletion. Furthermore, the glioma patients with low levels of LOXs also exhibited better prognosis. Also, differential LOXs expressions were associated with at least 12 chemotherapeutic drug sensitivity. Besides, it was also found that glioma patients with high LOXs expressions showed higher enrichment scores for immune cell infiltration and increased levels of immune checkpoints, suggesting the critical role of distinct LOXs expression levels for glioma immunotherapy. The predictive roles of LOXs expression in tumor immunotherapy were also validated in two immunotherapy cohorts including IMvigor 210 and Van Allen 2015. Experimental results revealed that expressions of LOX, LOXL1, LOXL2, and LOXL3 were higher in glioma cell lines at mRNA and protein levels. Conclusion: Our findings altogether indicate that LOXs have potent predictive value for prognosis, chemotherapy and immunotherapy in glioma patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xia, Yu, Wang, Guan and Mao.)

Repetitive seizures, a common phenomenon in diverse neurologic conditions such as epilepsy, can undoubtedly cause neuronal injury and our prior work reveals that ferroptosis is a contributing factor of neuronal damage post seizure. However, there is no drug available in clinical practice for ameliorating seizure-induced neuronal impairment via targeting ferroptosis. Our present work aimed to explore whether D-penicillamine (DPA), an originally approved drug for treating Wilson's disease, inhibited neuronal ferroptosis and alleviated seizure-associated brain damage. Our findings revealed that DPA remarkably improved neuronal survival in kainic acid (KA)-treated mouse model. Furthermore, ferroptosis-associated indices including acyl-coA synthetase long chain family member 4 (ACSL4), prostaglandin-endoperoxide synthase 2 ( Ptgs2 ) gene and lipid peroxide (LPO) level were significantly decreased in KA mouse model after DPA treatment. In a ferroptotic cell death model induced by glutamate or erastin, DPA was also validated to evidently suppress neuronal ferroptosis. The results from RNA-seq analysis indicated that Aqp11 , a gene coding previously reported channel protein responsible for transporting water and small solutes, was identified as a molecular target by which DPA exerted anti-ferroptotic potential in neurons. The experimental results from in vivo Aqp11 siRNA transfer into the brain also confirmed that knockdown of Aqp11 abrogated the inhibitory effect of seizure-induced ferroptosis after DPA treatment, suggesting that the effects of DPA on ferroptosis process are dependent upon Aqp11 . In conclusion, DPA can be repurposed to cure seizure disorders such as epilepsy.

Background: The development of precision medicine is essential for personalized treatment and improved clinical outcome, whereas biomarkers are critical for the success of precision therapies., Aim: To investigate whether iCEMIGE (integration of CEll-morphometrics, MIcro biome, and GEne biomarker signatures) improves risk stratification of breast cancer (BC) patients., Methods: We used our recently developed machine learning technique to identify cellular morphometric biomarkers (CMBs) from the whole histological slide images in The Cancer Genome Atlas (TCGA) breast cancer (TCGA-BRCA) cohort. Multivariate Cox regression was used to assess whether cell-morphometrics prognosis score (CMPS) and our previously reported 12-gene expression prognosis score (GEPS) and 15-microbe abundance prognosis score (MAPS) were independent prognostic factors. iCEMIGE was built upon the sparse representation learning technique. The iCEMIGE scoring model performance was measured by the area under the receiver operating characteristic curve compared to CMPS, GEPS, or MAPS alone. Nomogram models were created to predict overall survival (OS) and progress-free survival (PFS) rates at 5- and 10-year in the TCGA-BRCA cohort., Results: We identified 39 CMBs that were used to create a CMPS system in BCs. CMPS, GEPS, and MAPS were found to be significantly independently associated with OS. We then established an iCEMIGE scoring system for risk stratification of BC patients. The iGEMIGE score has a significant prognostic value for OS and PFS independent of clinical factors (age, stage, and estrogen and progesterone receptor status) and PAM50-based molecular subtype. Importantly, the iCEMIGE score significantly increased the power to predict OS and PFS compared to CMPS, GEPS, or MAPS alone., Conclusion: Our study demonstrates a novel and generic artificial intelligence framework for multimodal data integration toward improving prognosis risk stratification of BC patients, which can be extended to other types of cancer., Competing Interests: Conflict-of-interest statement: All the authors declare no conflicts of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) is a common and deadly malignancy worldwide. Current treatment methods for hepatocellular carcinoma have many disadvantages; thus, it is urgent to improve the efficacy of these therapies. Glycolysis is critical in the occurrence and development of tumors. However, survival and prognosis biomarkers related to glycolysis in HCC patients remain to be fully identified. Methods: Glycolysis-related genes (GRGs) were downloaded from "The Molecular Signatures Database" (MSigDB), and the mRNA expression profiles and clinical information of HCC patients were obtained from TCGA. Consensus clustering was performed to classify the HCC patients into two subgroups. We used the least absolute shrinkage and selection operator (LASSO) regression analysis to construct the risk signature model. Kaplan-Meier (K-M) survival analysis was performed to evaluate the prognostic significance of the risk model, and the receiver operating characteristic (ROC) curve analysis was used to evaluate the prediction accuracy. The independent prediction ability of the risk model was validated by univariate and multivariate Cox regression analyses. The differences of immune infiltrates and relevant oncogenic signaling between different risk groups were compared. Finally, biological experiments were performed to explore the functions of screened genes. Results: HCC patients were classified into two subgroups, according to the expression of prognostic-related GRGs. Almost all GRGs categorized in cluster 2 showed upregulated expressions, whereas GRGs in cluster 1 conferred survival advantages. GSEA identified a positive correlation between cluster 2 and the glycolysis process. Ten genes were selected for risk signature construction. Patients were assigned to high-risk and low-risk groups based on the median risk score, and K-M survival analysis indicated that the high-risk group had a shorter survival time. Additionally, the risk gene signature can partially affect immune infiltrates within the HCC microenvironment, and many oncogenic pathways were enriched in the high-risk group, including glycolysis, hypoxia, and DNA repair. Finally, in vitro knockdown of ME1 suppressed proliferation, migration, and invasion of hepatocellular carcinoma cells. Conclusion: In our study, we successfully constructed and verified a novel glycolysis-related risk signature for HCC prognosis prediction, which is meaningful for classifying HCC patients and offers potential targets for the treatment of hepatocellular carcinoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zheng, Liu, Zhu, Liu, Gao, Dai, Zhuo, Mao, He and Liu.)

NVSI-06-08 is a potential broad-spectrum recombinant COVID-19 vaccine that integrates the antigens from multiple SARS-CoV-2 strains into a single immunogen. Here, we evaluate the safety and immunogenicity of NVSI-06-08 as a heterologous booster dose in BBIBP-CorV recipients in a randomized, double-blind, controlled, phase 2 trial conducted in the United Arab Emirates (NCT05069129). Three groups of healthy adults over 18 years of age (600 participants per group) who have administered two doses of BBIBP-CorV 4-6-month, 7-9-month and >9-month earlier, respectively, are randomized 1:1 to receive either a homologous booster of BBIBP-CorV or a heterologous booster of NVSI-06-08. The incidence of adverse reactions is low, and the overall safety profile is quite similar between two booster regimens. Both Neutralizing and IgG antibodies elicited by NVSI-06-08 booster are significantly higher than those by BBIBP-CorV booster against not only SARS-CoV-2 prototype strain but also multiple variants of concerns (VOCs). Especially, the neutralizing antibody GMT against Omicron variant induced by heterologous NVSI-06-08 booster reaches 367.67, which is substantially greater than that boosted by BBIBP-CorV (GMT: 45.03). In summary, NVSI-06-08 is safe and immunogenic as a booster dose following two doses of BBIBP-CorV, which is immunogenically superior to the homologous boost with another dose of BBIBP-CorV., (© 2022. The Author(s).)

Objective: To investigate the potential pathogenic mechanism of temporal lobe epilepsy with hippocampal sclerosis (TLE+HS) by analyzing the expression profiles of microRNA/ mRNA/ lncRNA/ DNA methylation in brain tissues., Methods: Brain tissues of six patients with TLE+HS and nine of normal temporal or parietal cortices (NTP) of patients undergoing internal decompression for traumatic brain injury (TBI) were collected. The total RNA was dephosphorylated, labeled, and hybridized to the Agilent Human miRNA Microarray, Release 19.0, 8 × 60K. The cDNA was labeled and hybridized to the Agilent LncRNA+mRNA Human Gene Expression Microarray V3.0,4 × 180K. For methylation detection, the DNA was labeled and hybridized to the Illumina 450K Infinium Methylation BeadChip. The raw data was extracted from hybridized images using Agilent Feature Extraction, and quantile normalization was performed using the Agilent GeneSpring. P -value < 0.05 and absolute fold change >2 were considered the threshold of differential expression data. Data analyses were performed using R and Bioconductor. BrainSpan database was used to screen for signatures that were not differentially expressed in normal human hippocampus and cortex (data from BrainSpan), but differentially expressed in TLE+HS' hippocampus and NTP' cortex (data from our cohort). The strategy "Guilt by association" was used to predict the prospective roles of each important hub mRNA, miRNA, or lncRNA., Results: A significantly negative correlation ( r < -0.5) was found between 116 pairs of microRNA/mRNA, differentially expressed in six patients with TLE+HS and nine of NTP. We examined this regulation network's intersection with target gene prediction results and built a lncRNA-microRNA-Gene regulatory network with structural, and functional significance. Meanwhile, we found that the disorder of FGFR3, hsa-miR-486-5p, and lnc-KCNH5-1 plays a key vital role in developing TLE+HS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Qu, Yang, Liu, Jiang, Zhang, Yang, Mao and Liu.)

Background: Seizures are a common symptom in glioma patients, and they can cause brain dysfunction. However, the mechanism by which glioma-related epilepsy (GRE) causes alterations in brain networks remains elusive., Objective: To investigate the potential pathogenic mechanism of GRE by analyzing the dynamic expression profiles of microRNA/ mRNA/ lncRNA in brain tissues of glioma patients., Methods: Brain tissues of 16 patients with GRE and 9 patients with glioma without epilepsy (GNE) were collected. The total RNA was dephosphorylated, labeled, and hybridized to the Agilent Human miRNA Microarray, Release 19.0, 8 × 60 K. The cDNA was labeled and hybridized to the Agilent LncRNA + mRNA Human Gene Expression Microarray V3.0, 4 × 180 K. The raw data was extracted from hybridized images using Agilent Feature Extraction, and quantile normalization was performed using the Agilent GeneSpring. P-value < 0.05 and absolute fold change > 2 were considered the threshold of differential expression data. Data analyses were performed using R and Bioconductor., Results: We found that 3 differentially expressed miRNAs (miR-10a-5p, miR-10b-5p, miR-629-3p), 6 differentially expressed lncRNAs (TTN-AS1, LINC00641, SNHG14, LINC00894, SNHG1, OIP5-AS1), and 49 differentially expressed mRNAs play a vitally critical role in developing GRE. The expression of GABARAPL1, GRAMD1B, and IQSEC3 were validated more than twofold higher in the GRE group than in the GNE group in the validation cohort. Pathways including ECM receptor interaction and long-term potentiation (LTP) may contribute to the disease's progression. Meanwhile, We built a lncRNA-microRNA-Gene regulatory network with structural and functional significance., Conclusion: These findings can offer a fresh perspective on GRE-induced brain network changes., (© 2022. The Author(s).)

The increased coronavirus disease 2019 (COVID-19) breakthrough cases pose the need of booster vaccination. We conducted a randomised, double-blinded, controlled, phase 2 trial to assess the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated COVID-19 vaccine (BBIBP-CorV) followed by a recombinant protein-based vaccine (NVSI-06-07), using homologous boost with BBIBP-CorV as control. Three groups of healthy adults (600 individuals per group) who had completed two-dose BBIBP-CorV vaccinations 1-3 months, 4-6 months and ≥6 months earlier, respectively, were randomly assigned in a 1:1 ratio to receive either NVSI-06-07 or BBIBP-CorV boost. Immunogenicity assays showed that in NVSI-06-07 groups, neutralizing antibody geometric mean titers (GMTs) against the prototype SARS-CoV-2 increased by 21.01-63.85 folds on day 28 after vaccination, whereas only 4.20-16.78 folds of increases were observed in control groups. For Omicron variant, the neutralizing antibody GMT elicited by homologous boost was 37.91 on day 14, however, a significantly higher neutralizing GMT of 292.53 was induced by heterologous booster. Similar results were obtained for other SARS-CoV-2 variants of concerns (VOCs), including Alpha, Beta and Delta. Both heterologous and homologous boosters have a good safety profile. Local and systemic adverse reactions were absent, mild or moderate in most participants, and the overall safety was quite similar between two booster schemes. Our findings indicated that NVSI-06-07 is safe and immunogenic as a heterologous booster in BBIBP-CorV recipients and was immunogenically superior to the homologous booster against not only SARS-CoV-2 prototype strain but also VOCs, including Omicron., (© 2022. The Author(s).)

Promoting adaptive repair in acute kidney injury (AKI) is an effective strategy to prevent the progression from AKI to chronic kidney disease. However, the mechanisms involved in renal repair after AKI remain unclear. In this study, we investigated the role of hypoxia-inducible factor (HIF), an important regulator of ischemic and hypoxic injury, in AKI during the repair phase. We established mouse models of ischemia-reperfusion injury-induced AKI with adaptive repair or maladaptive repair. We found that after injury, activation of HIF in the adaptive repair group was rapid, whereas in the maladaptive repair group HIF activation was relatively delayed, and its expression was significantly lower than that in the adaptive repair group during the early repair phase. To further investigate the mechanism of HIF, we regulated the expression of HIF-1α and HIF-2α in HK-2 cells and EA.hy926 cells, respectively. Silencing HIF expression reduced proliferation and increased apoptosis in cells injured by hypoxia/reoxygenation. Self-healing ability was further reduced due to the downregulation of HIF. Moreover, HIF overexpression had the opposite effect. HIF increased the expression of β-catenin and its downstream target genes. Activation of Wnt/β-catenin by the small-molecule activator SKL2001 mitigated the damaging effect of HIF knockdown, whereas blockade of β-catenin with the inhibitor IWR-1-endo reduced the protective effects of HIF. In conclusion, HIF, which is highly expressed in the early stage after AKI, promotes renal repair by interacting with the Wnt/β-catenin signaling pathway. NEW & NOTEWORTHY We investigated the role of hypoxia-inducible factor (HIF) in acute kidney injury in vivo and in vitro. Expression of HIF in the adaptive repair group was more rapid and sufficient than that in the maladaptive repair group during the early repair phase. HK-2 and EA.hy926 cells treated with hypoxia/reoxygenation were used to elucidate the cross talk between HIF and the Wnt/β-catenin signaling pathway by which HIF played a renoprotective role in acute kidney injury.

Objective: The imaging features of peritoneal carcinomatosis (PC) with different locations and pathological types of colorectal cancer (CRC) on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) were analyzed and discussed., Methods: The PET/CT data of 132 patients with colorectal peritoneal carcinomatosis (CRPC) who met the inclusion and exclusion criteria between May 30, 2016, and December 31, 2019, were collected and analyzed. Observations included the location and pathological type of CRC, the peritoneal cancer index (PCI), standardized uptake maximum value (SUV max ), and retention index (RI) of the CRPC. Statistical analysis was performed using SPSS 20.0 software, and P < 0.05 was considered statistically significant., Results: (1) The range of the PCI in the 132 patients studied was 2-30, with a mean value of 7.40 ± 8.14. The maximum long diameter of the CRPC lesions ranged from 0.6 to 12.1 cm, with an average of 3.23 ± 1.94 cm. The SUV max ranged from 1.2 to 31.0, with a mean value of 9.65 ± 6.01. The SUV max and size correlation coefficient for maximal CRPC lesions was r = 0.47 ( P < 0.001). The RI range of the 72 patients who underwent time-lapse scanning was -10.0-112.2%, with RI quartiles of 13.5-48.9%; RI was ≥5% in 65 cases and <5% in seven cases. (2) The patients were grouped by the location of their CRC: the right-sided colon cancer (RCC, n = 37), left-sided colon cancer (LCC, n = 44), and rectal cancer groups (RC, n = 51). There were significant differences in the CRC pathological types ( P = 0.009) and PCI scores ( P = 0.02) between the RCC and RC groups and the RI between the RCC group and the other two groups ( P < 0.001). (3) There were 88 patients organized into three groups by the pathology of their CRC: the moderately well-differentiated adenocarcinoma (group A, n = 57), poorly differentiated adenocarcinoma (group B, n = 16), and mucinous adenocarcinoma groups (group C, n = 15 cases, including one case of signet-ring cell carcinoma). There were significant differences in the CRC position ( P = 0.003) and SUV max ( P = 0.03) between groups A and C., Conclusion: The PCI, SUV max , and RI of peritoneal metastatic carcinoma caused by CRC in different locations and pathological types vary. Mucinous adenocarcinoma and poorly differentiated adenocarcinoma are relatively common in the right colon, and the PCI of peritoneal metastatic carcinoma is fairly high, but the SUV max and RI are somewhat low., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sun, Zhang, Gao, Mao, Tan, Bao and Shen.)

Vascular remodeling and angiogenesis are two key processes in the maintenance of vascular homeostasis and involved in a wide array of vascular pathologies. Following these processes, extracellular matrix (ECM) provides the mechanical foundation for vascular walls. Lysyl oxidase (LOX), the key matrix-modifying enzyme, has been demonstrated to significantly affect structural abnormality and dysfunction in the blood vessels. The role of LOX in vascular remodeling and angiogenesis has always been the subject in the current medical research. Therefore, we presently make a summarization of the biosynthesis of LOX and the mechanisms involved in vascular remodeling and angiogenesis, as well as the role of LOX in diseases associated with vascular abnormalities and the therapeutic potential via targeting LOX. In particular, we give a proposal that LOX likely reshapes matrisome-associated genes expressions in the regulation of vascular remodeling and angiogenesis, which serves as a mechanistic insight into the critical role of LOX in these two aspects. Additionally, LOX has also dual effects on the vascular dysfunction, namely, inhibition of LOX for improving hypertension, restenosis and malignant tumor while activation of LOX for curing arterial aneurysm and dissection. LOX-targeted therapy may provide a promising therapeutic strategy for the treatment of various vascular pathologies associated with vascular remodeling and angiogenesis., (© 2022 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

Background: The Stevens-Johnson syndrome (SJS) is a severe skin reaction to non-steroidal anti-inflammatory drugs (NSAIDs), and can even be life-threatening. However, there are still few real-world studies to compare the specific differences in the adverse effects of skin and mucosal invasion., Methods: Disproportionality analysis and Bayesian analysis were devoted to data-mining of the suspected SJS after using NSAIDs based on the FDA's Adverse Event Reporting System (FAERS) from January 2004 to March 2021. The times to onset, fatality, and hospitalization rates of antipyretic analgesic-associated SJS were also investigated., Results: A total of 1,868 reports of SJS adverse events were identified with NSAIDs. Among 5 NSAIDs monotherapies we studied (acetaminophen, ibuprofen, aspirin, diclofenac and celecoxib), ibuprofen had the highest association with SJS based on the highest reporting odds ratio (ROR = 7.06, 95% two-sided CI = 6.59-7.56), proportional reporting ratio (PRR = 6.98, χ 2 = 4201.14) and empirical Bayes geometric mean (EBGM = 6.78, 95% one-sided CI = 6.40). However, ibuprofen-associated SJS had the lowest fatality rate (6.87%, p < 0.0001) and the highest hospitalization rate (79.27%, p < 0.0001). Celecoxib-associated SJS had the latest time to onset (317.56 days, p < 0.0001). Diclofenac-associated SJS cases appeared to be associated with the highest risk of death (25.00%, p < 0.0001)., Conclusions: The analysis of FAERS data provides a more accurate profile of the incidence and prognosis of SJS after NSAIDs treatment, enabling continued surveillance and timely intervention in patients at risk of SJS following these NSAIDs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shao, Yin, Zeng, Zhou, Mao, Zhu, Zhao and Li.)

The renal medulla is a key site for the regulation of renal sodium excretion. However, the molecular mechanism remains unclear. Cyclooxygenase 2 (COX2) is specifically expressed in the renal medulla and contributes to the maintenance of the electrolyte/water balance in the body. Hypoxia-inducible factors (HIFs) have also been found to be expressed in the renal medulla, probably owing to the hypoxic conditions in the renal medulla. This study was designed to test the effects of HIF activation on renal sodium handling and renal medullary COX2 expression. Our data showed that HIF activation by the prolyl hydroxylase inhibitor (PHI) FG4592 enhanced natriuresis in mice challenged with a high-salt diet. In addition, FG4592 upregulated the expression of COX2 in the renal medulla. An in vitro study further supported the finding that HIF can induce the expression of COX2 and that this induction is mediated through direct binding to the promoter region of the Cox2 gene, facilitating its transcription. In addition, the COX2 inhibitor celecoxib diminished the natriuretic effect of FG4592. Together, these results suggest that HIF activation promotes sodium excretion through upregulation of COX2 in the renal medulla and therefore maintains sodium homeostasis in the body., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Aims: We aimed to estimate the risk of drug-induced liver injury (DILI) from various antifungal treatments with azoles and echinocandins causing in real-world practice. Methods: We performed disproportionality and Bayesian analyses based on data from the first quarter in 2004 to the third quarter in 2021 in the Food and Drug Administration Adverse Event Reporting System to characterize the signal differences of antifungal drugs-related DILI. We also compared the onset time and mortality differences of different antifungal agents. Results: A total of 2943 antifungal drugs-related DILI were identified. Affected patients tended to be aged >45 years (51.38%), with more males than females (49.03% vs. 38.09%). Antifungal drug-induced liver injury is most commonly reported with voriconazole (32.45%), fluconazole (19.37%), and itraconazole (14.51%). Almost all antifungal drugs were shown to be associated with DILI under disproportionality and Bayesian analyses. The intraclass analysis of correlation between different antifungal agents and DILI showed the following ranking: caspofungin (ROR = 6.12; 95%CI: 5.36-6.98) > anidulafungin (5.15; 3.69-7.18) > itraconazole (5.06; 4.58-5.60) > voriconazole (4.58; 4.29-4.90) > micafungin (4.53; 3.89-5.27) > posaconazole (3.99; 3.47-4.59) > fluconazole (3.19; 2.93-3.47) > ketoconazole (2.28; 1.96-2.64). The onset time of DILI was significantly different among different antifungal drugs ( p < 0.0001), and anidulafungin result in the highest mortality rate (50.00%), while ketoconazole has the lowest mortality rate (9.60%). Conclusion: Based on the Food and Drug Administration Adverse Event Reporting System database, antifungal drugs are significantly associated with DILI, and itraconazole and voriconazole had the greatest risk of liver injury. Due to indication bias, more clinical studies are needed to confirm the safety of echinocandins., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Yin, Zhang, Shao, Mao, Hu, Shen, Zhao and Li.)

Background/purpose: Roxadustat, a first-in-class hypoxia-inducible factor prolyl hydroxylase inhibitor, promotes erythropoiesis and regulates iron metabolism. This study investigated the efficacy and safety of roxadustat in Chinese patients with anemia on peritoneal dialysis (PD)., Methods: One hundred and twenty-nine patients were randomized and treated with roxadustat (n = 86) or erythropoiesis-stimulating agents (ESAs) (n = 43) for 24 weeks. The primary end points were the mean hemoglobin (Hb) level at week 24, the change in average Hb levels from baseline to week 24, and the cumulative response rate throughout the treatment period. The secondary end points included changes in hepcidin and iron indices and serum lipid levels. Subgroup analysis examined the effect of inflammatory status on the efficacy of Hb. Safety was assessed as the occurrence of emergent adverse events after treatment., Results: The mean average Hb levels at week 24 and average change in Hb levels from baseline to week 24 were 11.5 g/dL and 2.5 g/dL in the roxadustat group and 11.2 g/dL and 2.2 g/dL in the ESAs group, respectively. The cumulative response rate was 96% in the roxadustat group and 92% in the ESAs group at week 24. Roxadustat decreased hepcidin levels and increased total iron-binding capacity. The decreases in total cholesterol and low-density lipoprotein cholesterol were greater with roxadustat than with ESAs. Roxadustat-induced Hb increases were independent of baseline C-reactive protein levels. Common adverse events included hyperkalemia, hypertension, and insomnia., Conclusion: Roxadustat effectively corrected and maintained target Hb levels in Chinese PD patients. This trial was registered in the Chinese Clinical Trial Register (ChiCTR2000035054)., Competing Interests: Declaration of competing interest None., (Copyright © 2021 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)