Function of proprotein convertase subtilisin/kexin type 9 and its role in central nervous system diseases: An update on clinical evidence.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has attracted lots of attention in preventing the clearance of plasma low-density lipoprotein cholesterol (LDL-C). PCSK9 inhibitors are developed to primarily reduce the cardiovascular risk by lowering LDL-C level. Recently, a number of pleiotropic extrahepatic functions of PCSK9 beyond the regulation of cholesterol metabolism, particularly its effects on central nervous system (CNS) diseases have been increasingly identified. Emerging clinical evidence have revealed that PCSK9 may play a significant role in neurocognition, depression, Alzheimer's disease, and stroke. The focus of this review is to elucidate the functions of PCSK9 and highlight the effects of PCSK9 in CNS diseases, with the aim of identifying the potential risks that may arise from low PCSK9 level (variant or inhibitor) in the clinical practice.

Model-based dosing optimization and therapeutic drug monitoring practices of teicoplanin in patients with complicated or non-complicated methicillin-resistant staphylococcus aureus infection.

AIMS: This study aims to establish a population pharmacokinetic (PK) model of teicoplanin in Chinese adult patients to evaluate the dosing regimen in the label sheet and optimize it. METHODS: Nonlinear mixed-effects modelling was used to estimate PK parameters. Monte Carlo simulations were used to evaluate the attainment of various dosing regimens in achieving the target trough concentrations in patients with normal or decreased renal function. RESULTS: A total of 115 patients were enrolled in this retrospective study. Creatinine clearance (CrCL) and albumin (ALB) were identified as covariates on the clearance of teicoplanin. For the treatment of non-complicated methicillin-resistant Staphylococcus aureus (MRSA) infections in patients with normal renal function and serum ALB concentration, the recommended dosing regimen was 600 mg q12h with five administrations as the loading dose followed by 600 mg qd as the maintenance dose; for the treatment of serious and/or complicated MRSA infections, the recommended dosing regimen was 800 mg q12h with five administrations as the loading dose followed by 800 mg qd as the maintenance dose. It is worth noting that both the loading and maintenance doses ought to be modified based on the patient's renal function and serum ALB concentration. In addition, trough concentrations of teicoplanin were significantly increased every other week. CONCLUSIONS: Both loading dosing and maintenance dosing regimens were recommended to be adjusted according to patient's renal function and serum ALB concentration. In addition, it is necessary to perform follow-up therapeutic drug monitoring of teicoplanin at least once every week.

The influence of spousal support on the outcomes and willingness of work from home for female knowledge workers.

This study identified the key factors of spousal support that influence the outcomes and willingness of female knowledge workers to work from home (WFH). A questionnaire of 59 items was developed, covering basic personal information, spousal support, work perception, work-life balance, and willingness to WFH: 139 valid responses from female participants were collected and analysed. Exploratory factor analysis revealed six distinct factors of spousal support. Regression analysis found that personal-related emotional support, personal-related instrumental support, work-related emotional support, and work-related instrumental support demonstrated positive correlations with work perception and work-life balance, while family-related instrumental support positively correlated with work-life balance. Personal-related emotional support and personal-related instrumental support positively correlated with the willingness to WFH. Notably, personal-related emotional support exhibited the strongest correlation coefficients for willingness and outcomes. The findings could provide information on how a husband could improve his wife's well-being when WFH.Practitioner summary: A survey was conducted among female knowledge workers to examine the influence of different factors of spousal support on the outcomes and willingness of WFH. The results shed light on how husbands can improve their wives' well-being during WFH, offering practical guidance for supporting spouses in this context.

Creutzfeldt-Jakob disease presenting as Korsakoff syndrome caused by E196A mutation in PRNP gene: A case report.

BACKGROUND: Prion diseases are a group of degenerative nerve diseases that are caused by infectious prion proteins or gene mutations. In humans, prion diseases result from mutations in the prion protein gene (PRNP). Only a limited number of cases involving a specific PRNP mutation at codon 196 (E196A) have been reported. The coexistence of Korsakoff syndrome in patients with Creutzfeldt-Jakob disease (CJD) caused by E196A mutation has not been documented in the existing literature. CASE SUMMARY: A 61-year-old Chinese man initially presented with Korsakoff syndrome, followed by rapid-onset dementia, visual hallucinations, akinetic mutism, myoclonus, and hyperthermia. The patient had no significant personal or familial medical history. Magnetic resonance imaging of the brain revealed extensive hyperintense signals in the cortex, while positron emission tomography/computed tomography showed a diffuse reduction in cerebral cortex metabolism. Routine biochemical and microorganism testing of the cerebrospinal fluid (CSF) yielded normal results. Tests for thyroid function, human immunodeficiency virus, syphilis, vitamin B1 and B12 levels, and autoimmune rheumatic disorders were normal. Blood and CSF tests for autoimmune encephalitis and autoantibody-associated paraneoplastic syndrome yielded negative results. A test for 14-3-3 protein in the CSF yielded negative results. Whole-genome sequencing revealed a disease-causing mutation in PRNP. The patient succumbed to the illness 11 months after the initial symptom onset. CONCLUSION: Korsakoff syndrome, typically associated with alcohol intoxication, also manifests in CJD patients. Individuals with CJD along with PRNP E196A mutation may present with Korsakoff syndrome.

Real-World Prescribing Patterns for Hypertensive Children in China from 2018 to 2021: A Cross-Sectional Multicenter Study.

Background: Pediatric hypertension become an early marker of cardiovascular diseases, but their antihypertensive drug use patterns are rarely known. Purpose: To investigate the epidemiological characteristics of pediatric hypertension and the use of antihypertensive drugs in the real world in China. Methods: In this study, the demographic, diagnosis, and medication prescription data including the antihypertensive drug types and comorbidities, were analyzed. The antihypertensive drugs use were evaluated according to the Chinese guidelines for hypertension. Results: 1301 prescriptions (number of visits) containing 1880 antihypertensive medical orders were collected. The average number of antihypertensive drugs per prescription was 1.45 (±0.75). The patients aged 16 to 18 (70.18%) accounted for the highest proportion. Kidney diseases (33.28%) were the most common comorbidities. Calcium channel blocker (CCB), angiotensin II receptor blocker (ARB), and ß receptor blocker (BB) were the most used antihypertensive drugs. The most frequent monotherapy was CCB, while that of two and three drugs combination were ARB+CCB and ARB+BB+CCB, respectively. Metoprolol (11.44%), nifedipine (10.64%), amlodipine (10.59%), valsartan (6.12%) were the most commonly used antihypertensive drugs. The utilization rate of fixed compound preparations was 7.34%. However, the percentage of recommended antihypertensive drugs was just 14.20%, while the recommended drug combination was 84.93% according to the guidelines. Conclusion: For the first time ever we reported the antihypertensive prescription analysis in children in a large area of China. Our data provided new insights into the epidemiological characteristics and drug use in hypertensive children. We found that the guidelines for medication management in hypertensive children were not routinely followed. The wide use of antihypertensive drugs in children and those with weak clinical evidence raised concerns regarding its rational use. The findings could lead to more effective management of hypertension in children.

Treatment strategies and pharmacist-led medication management for Helicobacter pylori infection.

Half of the world's population is Helicobacter pylori carrier. Updated guidelines and consensus have been issued across regions with the main aim of reducing social transmission and increasing H. pylori eradication rate. Although alternative therapies including traditional Chinese medicine and probiotics have also been used to improve H. pylori eradication rate in clinical practice, current mainstream treatment is still dependent on triple and quadruple therapies that includes antibacterial agents (e.g., amoxicillin and furazolidone) and proton pump inhibitor. Researches also assessed the eradication rate of optimized high-dose dual therapy in treating H. pylori infection. With the increase of antibiotic resistance rate, the treatment strategies for H. pylori infection are constantly adjusted and improved. Besides, low medication compliance is another key influencing factor for H. pylori treatment failure. Emerging studies indicate that pharmacists' intervention and new pharmaceutical care methods can enhance patient medication compliance, reduce adverse drug reactions, and improve H. pylori eradication rate. The purpose of this review is to summarize the advances in treating H. pylori infection and highlight the necessity of developing novel strategies to cope with the increasing challenges and to achieve personalized medication. Also, this review attaches great importance to pharmacists in optimizing H. pylori treatment outcomes as a routine part of therapy.

Modification of Vancomycin Dosing in Cardiac Surgery With Cardiopulmonary Bypass.

This study aims to assess the risk factors for insufficient vancomycin concentrations for its prophylactic use in adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) and to modify the dosing regimen to achieve appropriate plasma concentrations. A total of 27 patients with vancomycin dosing of 1 to 1.5 g based on a weight cutoff of 67 kg were included, of which only 13 (48.15%) had vancomycin plasma concentration >15 mg/L at surgical closure. Risk factors of vancomycin concentration <15 mg/L at surgical-site closure were confirmed by multivariate logistic regression analysis, which showed that CPB duration was an independent predictor. Patients with CPB duration >4 hours had significantly lower vancomycin concentrations and lower proportion in achieving target vancomycin concentration at the end of CPB and surgical closure. For patients with CPB >4 hours, the modified dosing regimen that a second dose of 0.5 to 0.75 g added at 4 hours since the onset of CPB improved the target achievement of vancomycin concentration at surgical closure. Taken together, CPB duration >4 hours was the risk factor for insufficient vancomycin concentration at surgical closure, while our modified dosing could improve the vancomycin concentrations for its prophylactic use in patients undergoing cardiac surgery with CPB.

Population pharmacokinetic analysis, renal safety, and dosing optimization of polymyxin B in lung transplant recipients with pneumonia: A prospective study.

Objectives: This study aims to characterize the population pharmacokinetics of polymyxin B in lung transplant recipients and optimize its dosage regimens. Patients and methods: This prospective study involved carbapenem-resistant organisms-infected patients treated with polymyxin B. The population pharmacokinetic model was developed using the NONMEM program. The clinical outcomes including clinical treatment efficacy, microbiological efficacy, nephrotoxicity, and hyperpigmentation were assessed. Monte Carlo simulation was performed to calculate the probability of target attainment in patients with normal or decreased renal function. Results: A total of 34 hospitalized adult patients were included. 29 (85.29%) patients were considered of clinical cure or improvement; 14 (41.18%) patients had successful bacteria elimination at the end of the treatment. Meanwhile, 5 (14.71%) patients developed polymyxin B-induced nephrotoxicity; 19 (55.88%) patients developed skin hyperpigmentation. A total of 164 concentrations with a range of 0.56-11.66 mg/L were obtained for pharmacokinetic modeling. The pharmacokinetic characteristic of polymyxin B was well described by a 1-compartment model with linear elimination, and only creatinine clearance was identified as a covariate on the clearance of polymyxin B. Monte Carlo simulations indicated an adjusted dosage regimen might be needed in patients with renal insufficiency and the currently recommended dose regimens by the label sheet of polymyxin B may likely generate a subtherapeutic exposure for MIC = 2 mg/L. Conclusion: Renal function has a significant effect on the clearance of polymyxin B in lung transplant recipients, and an adjustment of dosage was needed in patients with renal impairments.

Population Pharmacokinetics of Colistin Sulfate in Critically Ill Patients: Exposure and Clinical Efficacy.

Background: Presently, colistin is commercially available in two different forms, namely, colistin sulfate and its sulphomethylated derivative, colistimethate sodium (CMS). However, in the currently reported studies, most of the clinical studies on colistin for parenteral use are referred to as CMS. Data on the pharmacokinetics (PK), clinical efficacy, and side effects of colistin sulfate in clinical use have not been reported. Methods: This retrospective study was performed on carbapenem-resistant organism (CRO)-infected patients treated with colistin sulfate for more than 72 h. The population pharmacokinetic model was developed using the NONMEM program. The clinical outcomes including clinical treatment efficacy, microbiological eradication, and nephrotoxicity were assessed. Monte Carlo simulation was utilized to calculate the probability of target attainment (PTA) in patients with normal or decreased renal function. Results: A total of 42 patients were enrolled, of which 25 (59.52%) patients were considered clinical treatment success and 29 (69.06%) patients had successful bacteria elimination at the end of treatment. Remarkably, no patient developed colistin sulfate-related nephrotoxicity. A total of 112 colistin concentrations with a range of 0.28-6.20 mg/L were included for PK modeling. The PK characteristic of colistin was well illustrated by a one-compartment model with linear elimination, and creatinine clearance (CrCL) was identified as a covariate on the clearance of colistin sulfate that significantly explained inter-individual variability. Monte Carlo simulations showed that the recommended dose regimen of colistin sulfate, according to the label sheet, of a daily dose of 1-1.5 million IU/day, given in 2-3 doses, could attain PTA > 90% for MICs ≤ 0.5 µg/mL, and that a daily dose of 1 million IU/day could pose a risk of subtherapeutic exposure for MIC ≥1 µg/ml in renal healthy patients. Conclusion: Renal function significantly affects the clearance of colistin sulfate. A dose of 750,000 U every 12 h was recommended for pathogens with MIC ≤1 µg/ml. The dosage recommended by the label inserts had a risk of subtherapeutic exposure for pathogens with MIC ≥2 µg/ml. Despite higher exposure to colistin in patients with acute renal insufficiency, dose reduction was not recommended.

Efficacy and Pharmacodynamic Target Attainment for Ceftazidime-Avibactam Off-Label Dose Regimens in Patients with Continuous or Intermittent Venovenous Hemodialysis: Two Case Reports.

Limited data are available for ceftazidime-avibactam (CZA) dosing in patients receiving renal replacement therapy, especially the data on the dosing in patients receiving intermittent hemodialysis (IHD). In this report, we firstly described a case in which CZA was administered as 2.5 g after each time of IHD, and a dose of 1.25 g was added on the 48th-hour for the 72-h interdialytic interval. Plasma concentrations of CZA measured at different time indicated that > 50% of administered ceftazidime and avibactam were removed during the 4-h hemodialysis. In addition, we described another case on continuous venovenous hemodialysis (CVVHD), in which CZA was administered as 2.5 g q12h in 2-h infusions. The dose regimen for these two cases could achieve trough concentration of ceftazidime higher than fourfold of the MIC and trough concentration of avibactam higher than the threshold of 1 µg/mL during the treatment, and exert efficient antimicrobial effect.

Intraventricular colistin sulphate as a last resort therapy in a patient with multidrug-resistant Acinetobacter baumannii induced post-neurosurgical ventriculitis.

Limited therapeutic options exist for multidrug-resistant/extensively drug-resistant Acinetobacter baumannii (MDR/XDR-Ab) meningitis/ventriculitis. A combination of intravenous and intraventricular (IVT)/intrathecal (IT) polymyxins achieves good therapeutic outcomes for cases of healthcare-associated MDR/XDR-Ab meningitis/ventriculitis. Colistin is commercially available as colistin sulphate and its sulphomethylated derivative. However, the effect and safety of colistin sulphate in the treatment of MDR/XDR-Ab meningitis/ventriculitis has not been reported. We report on a 66-year-old male patient who developed post-neurosurgical ventriculitis caused by MDR-Ab. IVT concomitant intravenous colistin sulphate was used as a last-resort antimicrobial therapy, the patient's ventriculitis was dramatically improved, and the concentrations of CSF colistin were higher than the MIC breakpoint throughout the treatment. Meanwhile, no nephrotoxicity or neurotoxicity was observed during the treatment.

(C7H18N2)PbI4: A 2D Hybrid Perovskite Solid-State Phase Transition Material with Semiconducting Properties.

Two-dimensional organic-inorganic hybrid perovskites (OIHPs) have gained attention as a result of their flexibility and adjustability of the structure. However, the large band gap of two-dimensional perovskites limits their application in the photoelectric field. In the present work, we report a two-dimensional organic-inorganic hybrid compound of (C7H18N2)PbI4 (1) with a narrow band gap, which consists of [PbI4]2-n layers and N-(2-aminoethyl)piperidinium cations. 1 exhibits semiconducting properties with a narrow optical band gap of ∼2.02 eV and a photoelectric response with a ratio of photocurrent to dark current of ∼100. In addition, it exhibits a reversible solid-state phase transition at 228 K. This finding should inspire research into more 2D layered OIHPs with the combination of phase transition and semiconductor properties.

A-site cation with high vibrational motion in ABX3 perovskite effectively induces dielectric phase transition.

Organic-inorganic hybrid ABX3 perovskite (OIHPs) with phase transition have considerable application potential in multifunctional devices for their structural tunability and excellent photo/electric performance. Because the interaction between molecules during the crystallization process is difficult to predict and control, exploring targeted chemical design methods to synthesize phase change materials has been an interesting and challenging problem. As per the synergistic effect of anion and cation, we assemble a cation with high vibrational activity and an inorganic anion with large voids to successfully design a one-dimensional OIHPs phase change material. [FMPD][Cd(SCN)3] (FMPD = 1-fluoroethyl-1-methylpiperidinium) undergoes two reversible phase transitions above room temperature with the substitution of methyl with fluoroethyl increasing the energy barrier of molecular motion. The individual crystal diffraction structures show that, unlike the phase change caused by the reorientation of organic cations in majority of known perovskites, this phase transition is triggered by the order/disorder of cations and anions related to the vibration increase by the introduction of fluoroethyl. The results provide a new design idea for the design and assembly of novel OIHPs-type phase change materials.

[Expert consensus on Tongsaimai Tablets/Capsules in treatment of peripheral vascular diseases in clinical practice].

Tongsaimai Tablets/Capsules are composed of Lonicerae Japonicae Flos, Angelicae Sinensis Radix, Achyranthis Bidentatae Radix, Codonopsis Radix, Dendrobii Caulis, Astragali Radix, Scrophulariae Radix, and Glycyrrhizae Radix et Rhizoma, and are effective in promoting blood circulation, removing blood stasis, supplementing Qi, and nourishing Yin. It is widely used in the treatment of peripheral vascular diseases. With 40 years of clinical application, it has accumulated substantial research data and application experience. Its good clinical efficacy and pharmacoeconomic benefits in improving the clinical symptoms of peripheral vascular diseases have been confirmed by relevant research. Meanwhile, this drug has also been recommended by many expert consensus, guidelines, and teaching materials, serving as one of the most commonly used Chinese patent medicines in clinical practice. To further improve the understanding of the drug among clinicians and properly guide its clinical medication, the China Association of Chinese Medicine took the lead and organized experts to jointly formulate this expert consensus. Based on the questionnaire survey of clinicians and the systematic review of research literature on Tongsaimai Tablets/Capsules with clinical problems in the PICO framework, the consensus, combined with expert experience, concludes recommendations or consensus suggestions by GRADE system with the optimal evidence available through the nominal group technique. This consensus defines the indications, usage, dosage, course of treatment, medication time, combined medication, and precautions of Tongsaimai Tablets/Capsules in the treatment of peripheral vascular diseases, and explains the safety of its clinical application. It is recommended for clinicians and pharmacists in the peripheral vascular department(vascular surgery), traditional Chinese medicine surgery(general surgery), and endocrinology department of hospitals at all levels in China.

Cyclic tensile forces enhance the angiogenic properties of HUVECs by promoting the activities of human periodontal ligament cells.

BACKGROUND: This study aimed to investigate whether human periodontal ligament (PDL) cells secrete pro-angiogenic factors that induce the vascularization of surrounding bone tissue under tensile stress. METHODS: Quantitative real-time PCR and Western blotting were used to analyze the mRNA and protein expression levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), Angiopoietin-I (Ang-I), connective tissue growth factor （CTGF）, and macrophage colony-stimulating factor (M-CSF) in PDL cells after tensile force treatments of different durations. Enzyme-linked immunosorbent assay was used to measure the VEGF concentration in the supernatants of cell cultures. Cell viability assay, wound healing assay, and tube formation assay were performed to evaluate the angiogenic behaviors of human umbilical vein endothelial cells (HUVECs). RESULTS: The mRNA expression and protein expression of VEGF, bFGF, Ang-I, and M-CSF was increased in the cells that received 6 to 48 hours of tensile force treatment. And, the VEGF level in the supernatant significantly increased in the human PDL cell cultures stressed for 6 to 48 hours. The abilities of HUVECs to proliferate, migrate, and form tubes were enhanced in media conditioned with tensile-stressed human PDL cells. Hence, tensile force induced human PDL cells to express and release pro-angiogenic factors enhancing the proliferation, migration, and angiogenic capacity of HUVECs. CONCLUSION: Tensile stress induced human PDL cells to express and release pro-angiogenic factors, including VEGF, bFGF, Ang-I, and M-CSF, thereby enhancing the proliferation, migration, and angiogenic capacity of HUVECs.

A comparative study on the clinical effect of the treatment of pathological scars in young and middle-aged women with the combination of Chinese and western medicine.

INTRODUCTION: Pathological scar is the abnormal manifestation of skin fiber hyperplasia caused by the failure of normal healing after skin damage. At present, there are many clinical treatments for pathological scars. However, there is no cure for clinically effective pathological scars with high recurrence rate. In this study, we will use a combination of Chinese and western medicine treatment methods to evaluate the clinical efficacy and related indicators of young and middle-aged female patients who meet pathological scars, looking for an objective and effective treatment method for pathological scars. METHODS/DESIGN: In this study, we will use our own front-to-back clinical research method. We plan to include 120 young and middle-aged female patients who meet the diagnostic criteria for pathological scars. The untreated pathological scars of the enrolled patients will be used as blank controls. The intervention group will be given conventional western medicine treatment and combined Chinese and western medicine treatment. The assessment of scar area, color, hardness, thickness, itching, and pain was recorded for 8 weeks of treatment. DISCUSSION: This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of traditional Chinese medicine for patients with pathological scars. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2000032187, Registered on April 22, 2020.

Clinical observation for acupuncture treatment of a small area of hyperplastic scars in young and middle-aged women.

INTRODUCTION: Hypertrophic scars are a common disease in plastic surgery, which is the reaction of skin connective tissue to trauma beyond the normal range. Although scholars around the world have explored the tissue structure and formation mechanism of HS for decades, they are not satisfactory the result of. No effective treatment has been found. Therefore, the search for safe and effective treatments for HS has always been the focus of medical attention and research. Acupuncture therapy has a definite effect on HS and has unique advantages. METHODS/DESIGN: In this study, we will use our own front-to-back clinical research method. We plan to include 120 young and middle-aged female patients who meet the diagnostic criteria for HS. The untreated HS of the enrolled patients will be used as blank controls. The intervention group will be given acupuncture treatment. The assessment of scar area, color, hardness, thickness, itching and pain will be recorded for 30 days of treatment. DISCUSSION: This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of Acupuncture for patients with HS. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2000032624, Registered on 04 May 2020.

A newly characterized exopolysaccharide from Sanghuangporus sanghuang.

Sanghuangporus sanghuang is a well-known pharmacodynamic and economically important edible fungus associated with mulberry (Morus spp.). A distinctly new exopolysaccharide (EPS), designated SHP-2 was obtained from S. sanghuang P0988 broth, and its structure and anti-aging prosperity were characterized. SHP-2 was found to be composed of a back-bone of →4)-ß-Manp-(1→4)-α-Araf-(1→3,4)-α-Glcp(1→3,4)-α-Glcp-(1→3,4)-α-Glcp-(1→3,4)-α-Glcp-(1→3,4)-α-Glcp-(1→6)-α-Galp-(1→4)-ß-Manp-(1→ and five branches, including four α-D-Glcp-(1→ and one α-D-Manp-(1→SHP-2 was shown to increase antioxidant enzyme activities including catalase (CAT) and superoxide dismutase (SOD) activities, as well as trolox equivalent antioxidant (TEAC) capacity in serum of mice pre-treated with D-Gal, while reducing lipofuscin levels. SHP-2 exerted a favorable influence on immune organ coefficients and ameliorated the histopathological hepatic lesions and apoptosis in hepatocytes of D-galactose-aged mice almost in a dose-dependent manner. Using the same analytical methods, on comparison with previously studied EPS compounds (i.e. SHP-1), SHP-2 was found to have more complex structure, larger molecule weight, and different anti-aging properties. The results presented here suggest that not only does EPS bioactivity vary with respect to molecular structures and molecule weight, but that multiple structures with different activity can be expressed by a single fungal strain. These results may help understanding the anti-aging prosperity of these polysaccharides for use in health foods or dietary supplements.

Nell-1 Enhances Osteogenic Differentiation of Pre-Osteoblasts on Titanium Surfaces via the MAPK-ERK Signaling Pathway.

BACKGROUND/AIMS: This study aimed to investigate the effect of Nell-1 on the osteogenic behaviors of pre-osteoblasts on titanium (Ti) surfaces and to identify the underlying signaling pathway. METHODS: Nell-1 at different concentrations was added to culture medium to stimulate MC3T3-E1 subclone 14 on Ti surfaces. A CCK-8 colorimetric assay was used to detect cell proliferation. Alkaline phosphatase activity (ALP) assay and enzyme-linked immunosorbent assay (ELISA) were used to evaluate ALP activity and the osteocalcin (OCN) secretion, respectively. Indicators of osteoblastic differentiation were assessed using real-time polymerase chain reaction analysis (RT-PCR). Western blot (WB) assay was used to analyze the expression changes of the osteogenic proteins and the mitogen-activated protein kinase (MAPK) pathway. RESULTS: Nell-1 significantly increased the osteogenic gene and protein expression levels of ALP, OCN, Runx2, osteoprotegerin (OPG), collagen type I (Col-I), and Osterix (Osx) in pre-osteoblasts on Ti surfaces. The optimal concentration of Nell-1 was 100 ng/ ml. In addition, Nell-1 activated ERK and JNK, but not P38, in MC3T3-E1 cells on the Ti surface. Except for ALP and Col-I, the promotive effects of Nell-1 on the expression of osteogenic markers were suppressed by ERK inhibitor U0126. CONCLUSION: Certain concentrations of Nell-1 can promote the osteogenic differentiation of pre-osteoblasts on Ti surfaces by activating the MAPK/ERK signaling pathway.