Insights into the Roles of Natural Killer Cells in Osteoarthritis.

Osteoarthritis (OA) is now widely acknowledged as a low-grade inflammatory condition, in which the intrinsic immune system plays a significant role in its pathogenesis. While the involvement of macrophages and T cells in the development of OA has been extensively reviewed, recent research has provided mounting evidence supporting the crucial contribution of NK cells in both the initiation and advancement of OA. Accumulated evidence has emerged in recent years indicating that NK cells play a critical role in OA development and progression. This review will outline the ongoing understanding of the utility of NK cells in the etiology of OA, focusing on how NK cells interact with chondrocytes, synoviocytes, osteoclasts, and other immune cells to influence the course of OA disease.

An Online Survey on the Relationship Between Positive Coping and Post-Traumatic Stress Symptoms (PTSS) of Medical Students in China During the COVID-19 Pandemic: The Mediating Role of Social Support.

BACKGROUND The COVID-19 pandemic has caused varying degrees of psychological stress among medical students. This research explored the post-traumatic stress symptoms (PTSS) of medical students in China and their relationship with positive coping and social support. MATERIAL AND METHODS In the form of cross-sectional online survey, 2280 medical students locked down at home were selected by random cluster method to investigate social support, coping style, and PTSS using the Social Support Rating Scale (SSRS), Simplified Coping Style Questionnaire (SCSQ), and Post-traumatic Stress Disorder (PTSD) Checklist-Civilian Version (PCL-C), respectively. RESULTS This research found that the PTSS detection rate in medical students was 10.42% during the COVID-19 pandemic. The PTSS scores of females were significantly higher than that of the males. However, the PTSS detection rate in females (9.71%) was not significantly different from that in males (11.24%). Compared with those of the non-PTSS group, the total score and its all-factor score of social support, the total score of coping style and the positive coping score of the PTSS group were much lower, while the negative coping score of the PTSS group was much higher (P<0.01). Positive coping was positively correlated with social support, while positive coping and social support were negatively correlated with PTSS. The total effect of positive coping on PTSS was -0.310 (P<0.001), the direct effect was -0.128 (P<0.01), and the indirect effect was -0.182 (P<0.001). Social support played a mediating role between positive coping and PTSS, with the mediating effect accounting for 58.81% of the total effect. CONCLUSIONS Social support plays a mediating role between positive coping and post-traumatic stress symptoms. Objective support and positive coping are the 2 main protective factors of PTSS.

Ruxolitinib attenuates intimal hyperplasia via inhibiting JAK2/STAT3 signaling pathway activation induced by PDGF-BB in vascular smooth muscle cells.

BACKGROUND: Cardiovascular diseases are associated with proliferation and phenotypic switch. Platelet-derived growth factor-BB (PDGF-BB) is a major initiating factor for proliferative vascular diseases, such as neointimal lesion formation, restenosis after angioplasty, and atherosclerosis. Ruxolitinib, a potent Janus kinase (JAK) 1 and 2 inhibitor, has been reported to significantly block the proliferation-related signaling pathway of JAK2/signal transducers and activators of transcription 3 (STAT3) and harbor a broad spectrum of anti-cancer activities, including proliferation inhibition, apoptosis induction, and anti-inflammation. However, the role of ruxolitinib in regulating PDGF-BB-induced VSMC proliferation remains to be elucidated. Thus, this study investigates the role of ruxolitinib in regulating PDGF-BB-induced VSMC proliferation and its underlying mechanisms. METHODS: In vivo, the medial thickness of the carotid artery was evaluated using a mouse carotid ligation model, ruxolitinib was administered orally to the mice every other day, and the mice were euthanized on day 28 to evaluate the therapeutic effects of ruxolitinib. Cell proliferation markers were measured using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. In vitro, VSMCs were treated with ruxolitinib with or without PDGF-BB at an indicated time and concentration. Cell proliferation and apoptosis were measured using Cell Counting Kit-8 assay, MTS assays and flow cytometry. The JAK2/STAT3 signaling pathway involved in the effects of ruxolitinib on VSMCs was detected by western blotting with the specific pathway inhibitor AG490. RESULTS: In vivo, ruxolitinib significantly decreased the ratio-of-intima ratio (I/M ratio) by inhibiting the expression of PCNA and cyclinD1 (p <0.05). In vitro, ruxolitinib inhibited PDGF-BB-induced VSMC proliferation compared with the PDGF-BB treatment group (p <0.05). In addition, ruxolitinib inhibited the PDGF-BB-induced activation of the JAK2/STAT3 signaling pathway and decreased the expression of proliferation related-proteins cyclinD1 and PCNA in VSMCs (p <0.05). CONCLUSION: Our findings suggest that ruxolitinib inhibits VSMC proliferation in vivo and in vitro by suppressing the activation of the JAK2/STAT3 signaling pathway. Therefore, ruxolitinib has a therapeutic potential for proliferative vascular diseases.

Rubiadin-1-methyl ether from Morinda officinalis How. Inhibits osteoclastogenesis through blocking RANKL-induced NF-κB pathway.

Rubiadin-1-methyl ether (RBM) is a natural anthraquinone compound isolated from the root of Morinda officinalis How. In our previous study, RBM was found to have inhibitory effects on the TRAP activity of osteoclasts, which means that RBM may be a candidate for therapy of bone diseases characterized by enhanced bone resorption. However, the further effect of RBM on osteoclasts and the underlying mechanism remain unclear. In the present study, we investigated the effects of RBM isolated from Morinda officinalis How. on osteoclasts derived from bone marrow macrophages (BMMs) and the underlying mechanism in vitro. RBM at the dose that did not affect the viability of cells significantly inhibited RANKL-induced osteoclastogenesis and actin ring formation of osteoclast, while RBM performed a stronger effect at the early stage. In addition, RBM downregulated the expression of osteoclast-related proteins, including nuclear factor of activated T cells cytoplasmic 1 (NFATc1), cellular oncogene Fos (c-Fos), matrix metallopeptidase 9 (MMP-9) and cathepsin K (CtsK) as shown by Western blot. Furthermore, RBM inhibited the phosphorylation of NF-κB p65 and the degradation of IκBα as well as decreased the nuclear translocation of p65. Collectively, the results suggest that RBM inhibit osteoclastic bone resorption through blocking NF-κB pathway and may be a promising agent for the prevention and treatment of bone diseases characterized by excessive bone resorption.

Pharmacokinetics and tissue distribution of monotropein and deacetyl asperulosidic acid after oral administration of extracts from Morinda officinalis root in rats.

BACKGROUND: Iridoid glycosides (IGs), including monotropein (MON) and deacetyl asperulosidic acid (DA) as the main ingredients, are the major chemical components in Morinda officinalis How. (MO) root, possessing various pharmacological properties including anti-osteoporosis, anti-inflammation and anti-rheumatism activities.The aim of the present study was to further elucidate the pharmacological actions of MO by investigating the pharmacokinetics and tissue distribution of IGs in MO. METHODS: An ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS) method was developed and validated for simultaneous determination of MON and DA levels in plasma and various tissues of Wistar rats. MON, DA and acetaminophen (ACE) as the internal standard (IS) were extracted from rat plasma and tissue samples by direct deproteinization with methanol. The rats were administered orally at 1650 mg/kg MO and 25, 50 and 100 mg/kg MO iridoid glycosides (MOIGs) or intravenously at MOIG 25 mg/kg for pharmacokinetic study of MON and DA. In addition, 100 mg/kg MOIG was administered orally for tissue distribution study of MON and DA. Non-compartmental pharmacokinetic profiles were constructed. Tissue distributions were calculated according to the validated methods. RESULTS: Significant differences in the pharmacokinetic parameters were observed in male and female rats. The AUC0-t, Cmax and bioavailability of MON and DA in female rats were higher than those in male rats. MON and DA mainly distributed in the intestine and stomach after oral administration, and noteworthily high concentrations of MON and DA were detected in the rat hypothalamus. CONCLUSION: The results of the present study may shed new lights on the biological behavior of MOIGs in vivo, help explain their pharmacological actions, and provide experimental clues for rational clinical use of these IGs extracted from the MO root.

Effects of Electroacupuncture at Governor Vessel Acupoints on Neurotrophin-3 in Rats with Experimental Spinal Cord Injury.

In an effort to explore new, noninvasive treatment options for spinal cord injuries (SCI), this study investigated the effects of electroacupuncture (EA) for SCI rat models. SCI was induced by a modified Allen's weight-drop method. We investigated the response of EA at Dazhui (GV 14) and Mingmen (GV 4) acupoints to understand the effects and mechanisms of EA in neuroprotection and neuronal function recovery after SCI. BBB testing was used to detect motor function of rats' hind limbs among groups, and EA was shown to promote the recovery of SCI rats' motor function. Nissl staining showed a restored neural morphology and an increase in the quantity of neurons after EA. Also, the antiapoptosis role was exposed by TUNEL staining. Western blotting analysis was used to determine the protein expression of neurotrophin-3 (NT-3) in spinal cord tissue. Compared to the sham group, the expression levels of NT-3 were significantly decreased and EA was shown to upregulate the expression of NT-3. The present study suggests that the role of EA in neuroprotection and dorsal neuronal function recovery after SCI in rats, especially EA stimulation at GV 14 and GV 4, can greatly promote neuronal function recovery, which may result from upregulating the expression of NT-3.

Anti-inflammatory constituents from the root of Litsea cubeba in LPS-induced RAW 264.7 macrophages.

Context Litsea cubeba (Lour.) Pers. (Lauraceae) has long been used as a folk remedy in Traditional Chinese Medicine (TCM) for the treatment of rheumatic diseases. Previous studies from our laboratory indicated that L. cubeba extract showed anti-arthritic activity in rats. Objective To study L. cubeba chemically and biologically and to find the potential constituents responsible for its anti-arthritic effect. Materials and methods The compounds were isolated from the root of L. cubeba by column chromatography which eluted with PE:EtOAc gradient system, and the structures were elucidated by detailed spectroscopic data analysis; the anti-inflammatory activity of the isolated compounds was evaluated by lipopolysaccharide (LPS)-induced RAW 264.7 cells and the TNF-α and NO level were measured by ELISA (commercial kit); The iNOS and COX-2 mRNA expression were measured by RT-PCR and the phosphorylation of IκBα, IKKß, P38 and Akt were determined by western blots. Results A novel 9-fluorenone, 1-ethoxy-3,7-dihydroxy-4,6-dimethoxy-9-fluorenone (1), together with 4 known compounds, namely pinoresinol (2), syringaresinol (3), 9,9'-O-di-(E)-feruloyl-meso-5,5'-dimethoxysecoisolariciresinol (4) and lyoniresinol (5) were isolated from the root of L. cubeba for the first time. The IC50 for NO inhibition on compounds 1 and 4 were 56.1 ± 1.2 and 32.8 ± 2.3 µM, respectively. The IC50 for TNF-α inhibition were 28.2 ± 0.9 and 15.0 ± 1.0 µM, respectively. Both 1 and 4 suppress mRNA expression of iNOS, COX-2 and protein phosphorylation of IκBα, IKKß in LPS-induced RAW 264.7 cells. Discussion and conclusion Compounds 1 and 4 isolated from L. cubeba exhibited potent anti-inflammatory activity through the NF-κB signal pathway.

A preliminary analysis of microRNA as potential clinical biomarker for schizophrenia.

MicroRNAs (miRNA, miR) have been implicated as promising blood-based biomarkers for schizophrenia patients. This study aimed to clinically validate miRNA as potential schizophrenia biomarkers. Plasma levels of 10 miRNAs were analyzed using qPCR in a cohort of 61 schizophrenia patients and 62 normal controls, as well as 25 patients particularly selected for a six-week antipsychotic treatment course. Positive And Negative Syndrome Scale (PANSS), Global Assessment Scale (GAS) and Clinical Global Impression (CGI) were administered to assess the clinical symptoms. The results demonstrated that a panel of miRNAs consisting of miR-30e, miR-181b, miR-34a, miR-346 and miR-7 had significantly increased expression levels with significant combined diagnostic value (AUC:0.713; sensitivity:35.5%; specificity:90.2%). In response to pharmacological treatment, expression levels of miR-132, miR-181b, miR-432 and miR-30e were significantly decreased. In addition, the improvement of clinical symptomatology was significantly correlated with the changes of miR-132, miR-181b, miR-212 and miR-30e expression levels. Furthermore, the decreases of plasma levels of miR-132 and miR-432 were significantly greater in high-effect subgroup than those in low-effect subgroup after six-week treatment course. We conclude that miR-30e, miR-181b, miR-34a, miR-346 and miR-7 combined as a panel are potentially useful non-invasive biomarkers for schizophrenia diagnosis. Markers miR-132, miR-181b, miR-30e and miR-432 are potential indicators for symptomatology improvements, treatment responses and prognosis for schizophrenia patients.

[Progress in study of spectrum-effect relationship of traditional Chinese medicine and discussions].

Spectrum-effect relationship of traditional Chinese medicine is a scientific method based on fingerprint of traditional Chinese medicine, which studied the correlations between fingerprint and activity. The method revealed the activity related peaks and clarified the active components. It provided directions and thoughts for the clarification of pharmacodynamic material basis and establishment of evaluation method to reflect the inherent quality of traditional Chinese medicine. In this text we would make a systematic review about the progress in the study of spectrum-effect relationship of traditional Chinese medicine after summarized the latest years of investigations from researchers at home and abroad, including the establishment of fingerprint, efficacy evaluation, and data processing. The key problems in each part were clarified and corresponding discussions were made, providing thoughts and advices for the following study of spectrum-effect relationship of traditional Chinese medicine. At last we made a expecting on the development trend of spectrum-effect relationship of traditional Chinese medicine.

[Fingerprint and spectrum-effect relationships on Tripterygium glycosides preparation].

Tripterygium glycosides preparation which extracted from the traditional Chinese herb Tripterygium wilfordii (TWHY), was widely used to treat the autoimmune diseases. Previous works demonstrated that TWHF had potent anti-inflammatory and immunosuppressive properties. But the different quality and high incident rate of side effects of different manufactures inhibited its clinical application. Since TWHF had been generally known to play a therapeutical effect by synergism of multiple constituents, it was necessary to build the relationship between the HPLC fingerprint and bioactivity so as to ensure the quality safety and efficacy. The HPLC fingerprint showed that description and content of peaks from different manufactures were diverse. Only 11 common peaks were found. In this study, mice spleen cells stimulated by Con A were used to test the proliferation inhibition bioactivity of TWHF preparations, which were incubated with 30, 15, 7.5, 3.75, 1.88 and 0.94 mg x L(-1) TWHF preparations for 48 h. The results showed that mice spleen cells proliferation was inhibited by all TWHF preparations significantly compared with the control group, which suggested the TWHF preparations showed immune suppress activity. The TWHF preparations from 7 manufacture showed different IC50 value, which might belong to different contents which showed in the HPLC fingerprint. Moreover, a relationship between the HPLC fingerprint and the bioactivity were established to identify important constituents by grey relational analysis (GRA). The result showed that all the contents were relative with the IC50, especially No. 5 and 10 peaks, but No. 1 peak, which was proved to be triptolide, had few contribute to the inhibition of mice spleen cells proliferation. The study of relationship between the HPLC fingerprint and the IC50 by GRA could help to investigate mechanism of bioactive and provide an evidence for the quantification of multi-constituents.

[Isolation, purification and identification of polysaccharides from Gynura divaricata].

The purpose of this study was to isolate and purify polysaccharide from Gynura divaricata and analyze its monosaccharide composition. A water-soluble crude polysaccharide was obtained by hot water extraction, ethanol precipitation and deproteinization after degreasing. The crude polysaccharide then purified with DEAE-Sepharose Fast Flow column chromatography and dialysis. The monosaccharide composition and structure were analyzed by HPLC, UV spectrophotometer and 1H-NMR. The results showed that the purity and molecular weight of GDPS-2 and GDPS-3 were 87.3%, 2.03 x 10(4) Da and 90.9%, 4.29 x 10(4) Da, respectively. The UV spectrophotometer and 1H-NMR data suggested that glycosidic bond of GDPS-2 and GDPS-3 were a type. Both GDPs-2 and GDPs-3 were homogeneous polysaccharides, and GDPs-2 was mainly composed of glucuronic acid and xylose at a molar ratio of 1.1:0.63. GDPs-3 was mainly composed of rhamnose, glucuronic acid, galactose, xylose and galacturonic acid at a molar ratio of 0.32:6.0:0.21:1.75:4.3.

Astrocyte elevated gene-1 mediates glycolysis and tumorigenesis in colorectal carcinoma cells via AMPK signaling.

To investigate the role of AEG-1 in glycolysis and tumorigenesis, we construct myc-AEG-1 expression vector and demonstrate a novel mechanism that AEG-1 may increase the activity of AMPK by Thr172 phosphorylation. The higher expression levels of AEG-1 in colorectal carcinoma cells were found but showed significant difference in different cell lines. To study the role of AEG-1 in colorectal cells, myc-AEG-1 vector was constructed and transfected into NCM460 colonic epithelial cells. We observed consistent increasing of glucose consumption and lactate production, typical features of anaerobic glycolysis, suggesting that AEG-1 may promote anaerobic glycolysis. Moreover, we noted that AMPK phosphorylation at Thr172 as well as pPFK2 (Ser466) was increased in NCM460 cells overexpressing AEG-1. Compound C may block AMPK and PFK2 phosphorylation in both control and AEG-1-overexpressed cells and decrease the glucose consumption and lactate production. The present findings indicated that reduced AEG-1 protein levels by RNAi may decrease the glucose consumption and lactate production in HCT116 colorectal carcinoma cells. The present identified AEG-1/AMPK/PFK2 glycolysis cascade may be essential to cell proliferation and tumor growth. The present results may provide us with a mechanistic insight into novel targets controlled by AEG-1, and the components in the AEG-1/AMPK/PFK2 glycolysis process may be targeted for the clinical treatment of cancer.

Psychosomatic conditions of the children and adolescents exposed to 5.12 Wenchuan earthquake.

BACKGROUND: A devastating earthquake registering 8.0 on the Richter Scale struck Wenchuan County in Northwest Sichuan Province in China on May 12, 2008, claiming over 69,200 lives, seriously wounding more than 374,600 people, and rendering more than 18,400 people missing. The epicenter was close to Yingxiu Township in Wenchuan County. PURPOSE: This study aimed to investigate the psychosomatic conditions of the children and adolescents exposed to the devastating earthquake and explore the risk factors for psychosomatic symptoms. METHOD: A total of 1,828 participants aged 6 to 16 years, of whom 842 from the affected area and 986 from non-affected area, were administered a Psychosomatic Conditions Scale. RESULTS: Each factor score, total somatic score, total psychological score, and total psychosomatic score of the experimental group were significantly higher than those of the control group (P < 0.001). Positive correlation was found between the psychological state and somatic symptoms in the experimental group(r = 0.157 ~ 0.489, P < 0.01). Respiratory system, cardiovascular system, nervous system, digestive system, urogenital system, emotion, behavior, and language, combined as a panel, were significantly differentiated between the two groups, accounting for 73.4% of the total difference. In the experimental group, the factor scores of anxiety, behavior, total psychological score, and total psychosomatic score of the girls were obviously higher than those of the boys (P < 0.01 ~ 0.05); most somatic factors and psychological factors, total somatic score, total psychological score, and total psychosomatic score of the elder adolescents were significantly higher than those of the younger children (P < 0.01 ~ 0.05). CONCLUSION: The children and adolescents exposed to 5.12 earthquake greatly suffered from terrible psychosomatic conditions, among whom the elder girls had more severe symptoms, particularly in terms of anxiety and behavior.

Progress of animal research on electro-acupuncture treatment for depression(△).

This paper summarized the Chinese literatures in the previous 5 years about the pre-clinical animal researches on the application of electro-acupuncture (EA) treatment for depression, searched in China National Knowledge Infrastructure (CNKI). The efficiency of EA treatment for depression and the mechanism of it were discussed, to shed light on new ideas and new fronts for the further research on depression in clinical or pre-clinical fields.

[Effect of CYP3A4*18B, CYP3A5*3 gene polymorphism on dosage and concentration of tacrolimus in renal transplant patients].

The effect of CYP3A4*18B and CYP3A5*3 on concentration/dosage x body surface area ratios (C/D'), adverse effects and acute rejection of tacrolimus in renal transplant patients were investigated. The CYP3A4*18B genotypes of 227 renal transplant patients were determined by PCR-RFLP method. The differences of C/D' ratios, adverse reactions and acute rejection were compared among all of the genotype groups treated with tacrolimus. The frequencies of CYP3A4*18 and CYP3A5*3 alleles in renal transplant patients were 30.8% and 74.2%, respectively. No significant association was found between the C/D's of tacrolimus and CYP3A4*18B genotypes when they were classified by two CYP3A5 genotypes (P > 0.05). While after the effects of CYP3A4*18B genotype were eliminated, the C/D' ratio of tacrolimus in patients with CYP3A5*1/*1 and *1/*3 genotype group was significantly lower than those with CYP3A5*3/*3 genotype groups (P < 0.01). There is no significant difference in adverse effects and acute rejection among different genotypes (P > 0.05).

[Validation and comparison of pharmacogenetics-based warfarin dosing algorithms in Han Chinese patients].

OBJECTIVE: To assess whether the existing three types of pharmacogenetics-based Warfarin dosing algorithms appropriately predict the actual maintenance dose in Han Chinese mechanical heart valve replacement patients (n = 130). METHODS: The patients' CYP2C9 and VKORC1 genetic polymorphisms were detected by PCR-RFLP. The genotype of CYP2C9, VKORC1 and other information were used to calculate predicted doses. Accuracy of the models was assessed using the absolute value of the difference between predicted dose and actual dose, calculated on both an absolute and percentage basis. Actual weekly dose was also regressed on predicted weekly dose, from which we obtained R(2) values. Clinical accuracy of the predictions was assessed by computing the proportion in which the predicted dose was 20% or more below the actual dose (under dosed), within 20% of the actual dose (ideally dosed), or 20% or greater above the actual dose (over dosed). RESULTS: The average absolute error is the smallest for the predictions made by the Wen model (3.74 mg/wk), followed by the Ohno model (4.07 mg/wk) and IWPC model (5.05 mg/wk). R(2) was 40.2% in the Wen model, 38.2% in the Ohno model and 26.7% in the IWPC model. When comparing the percentage of patients for whom the predicted doses were ideal, the Wen model works the best (50.0%) in low-dose group (≤ 21 mg/wk), but the Ohno model works the best (85.29%) in middle-dose group (21 - 49 mg/wk), followed by the Wen model. CONCLUSION: The best accuracy is achieved by the Wen model and the best clinical accuracy is obtained by the Ohno model for predicting the actual maintenance dose in Han Chinese mechanical heart valve replacement patients.

Curcumin protects PC12 cells from a high glucose-induced inflammatory response by regulating the miR-218-5p/TLR4 axis.

BACKGROUND: Curcumin exerts a protective effect on diabetic encephalopathy (DN), It is known for its potent neuroprotective, anti-inflammatory, antioxidant, and anticancer properties. However, the underlying mechanisms of curcumin's neuroprotective effects resulting from high glucose (HG)-induced injuries remain unknown. The purpose of this study is to identify the protective mechanism of Curcumin in the DN. METHODS: In this study, pheochromocytoma cells (PC12 cells) were pretreated with different concentrations of Curcumin and then co-treated with Curcumin and glucose for 48 hours, and the cell viability was evaluated by CCK-8, the expression of the inflammatory mediators were detected by ELISA, the miR-218-5p and toll-like receptors (TLR4) level were examined by both quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, the potential target genes of miR-218-5p were identified using luciferase reporter assay. RESULTS: The viability of PC12 cells treated with HG was significantly reduced in a dose- and time-dependent manner. Cotreatment of curcumin with HG significantly increased cell viability. Curcumin inhibited the expression of the inflammatory mediators, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), and induced the expression of the anti-inflammatory mediator interleukin-10 (IL-10). Curcumin upregulated the levels of miR-218-5p and downregulated the expression of TLR4 in HG-treated PC12 cells. The curcumin-induced anti-inflammatory effect was abrogated by a miR-218-5p inhibitor and overexpression of TLR4. The results suggest that curcumin ameliorates the inflammatory response by upregulating miR-218-5p levels in PC12 cells. CONCLUSIONS: Our results indicate a protective role for curcumin in PC12 cells and suggest that it should be considered for the prophylactic treatment of DN in the future.

Population pharmacokinetics and dosing optimization of unbound teicoplanin in Chinese adult patients.

Objectives: To develop a population pharmacokinetic (PopPK) model describing unbound teicoplanin concentrations in Chinese adult patients and perform Monte Carlo simulations to optimize the dosing regimens. Methods: The raw data for PopPK analysis in this study were collected from Chinese adult patients. A PopPK model of unbound teicoplanin was developed and Monte Carlo simulations were used to optimize the dosing regimens. The trough concentrations of unbound teicoplanin were targeted at 0.75 mg/L and 1.13 mg/L for most infection induced by Gram-positive bacteria and endocarditis or severe infections, respectively. Results: A total of 103 teicoplanin unbound concentrations were collected from 72 Chinese adult patients. A one-compartment pharmacokinetic model with first-order elimination was established. The typical values of clearance and the volume of distribution were 11.7 L/h and 811 L, respectively. The clearance and volume of distribution of unbound teicoplanin were positively correlated with estimated glomerular filtration rate (eGFR) and serum albumin concentrations, respectively. Dosing simulation results showed that standard dosing regimens were unable to meet the treatment needs of all patients, and the dosing regimen need optimize based on eGFR and serum albumin concentrations. The high eGFR and serum albumin concentration were associated with reduced probability of achieving target unbound trough concentrations. Conclusion: We successfully characterized the pharmacokinetics of unbound teicoplanin in Chinese adult patients. Importantly, we further highlight the importance of guiding dosing through unbound drugs. To achieve safe and effective treatment, the dosing regimens need to be adjusted according to eGFR and serum albumin concentrations.

Investigation on the psychological status of college students during the coronavirus disease-2019 epidemic.

This study is designed to investigate the mental health status of college students under the current coronavirus disease-2019 (COVID-19) pandemic and explore potential influential factors. We surveyed 1128 people including 435 medical students and 693 nonmedical students by a self-designed questionnaire containing general demographic characteristics, Self-Rating Anxiety Scale, Self-Rating Depression Scale, and Chinese Perceived Stress Scale. SPSS 23.0 software was used for statistical analysis. The incidence of anxiety, depression, and perceived stress were 8.4, 22.7, and 42.9% among college students during the COVID-19, respectively. Pearson correlation analysis showed that sex, specialty, and Family conflict were all positively associated with SAS, SDS, and CPSS (p<0.05). Stepwise linear retrospective analysis showed that family conflicts and specialty were the influencing factors of SAS, SDS, and CPSS. There were significantly differences between medical students and nonmedical students in the frequency of SDS abnormality score (Z=-4.125, p<0.001) and the frequency of CPSS abnormality (χ2=7.836, p=0.005). According to the results, we can come to the conclusion that college students have different degrees of psychological problems during the COVID-19. Family conflicts and specialty were the influencing factors of anxiety, depression, and perceived stress.

Population pharmacokinetic analysis for dabigatran etexilate in Chinese patients with non-valvular atrial fibrillation.

We aimed to develop a pharmacokinetic (PK) and pharmacodynamic (PD) model from healthy Chinese subjects and real-world non-valvular atrial fibrillation (NVAF) patients. We also investigated meaningful intrinsic and extrinsic factors and related biomarkers for bleeding events. We characterized the integrated PK/PD models based on rich PK/PD data [dabigatran concentration, activated partial thromboplastin time (APTT), prothrombin time (PT), and anti-factor IIa (anti-FIIa) activity] from 118 healthy volunteers and sparse PD data [APTT, PT, and anti-FIIa] from 167 patients with NVAF after verifying the model extrapolation performance. We also documented the correlations between PD biomarkers and clinically relevant bleeding events over one year. Next, we used the final integrated PK/PD model (a two-compartment, linear model with first-order absorption) to evaluate the influence of dosage and individual covariates on PD parameters. The age, high-density liptein cholesterol (HDL-C), and creatinine clearance (CrCL) improved the PK model fit. The linear direct-effects PD model described the correlation between APTT, PT, and anti-FIIa and plasma concentration. CrCL improved the PD model fit. Anti-FIIa was more sensitive to the increase in dabigatran exposure than APTT and PT in the PD model. Therefore, fixed dabigatran doses could be prescribed for patients with NVAF without adjusting for age and HDL-C. We observed an elevated bleeding tendency with higher peak and trough values of APTT, PT, and anti-FIIa. Randomized studies should be performed to evaluate the efficacy and safety of low-dose dabigatran in Chinese patients with NVAF.