A nomogram diagnostic cardiovascular disease in patients with erythrodermic psoriasis in Chinese.

Objective: Patients with erythrodermic psoriasis (EP) are associated with an increased risk of cardiovascular disease (CVD), because of the more severe inflammation in the skin areas. This study aimed to develop a diagnostic model for the risk of CVD in EP patients based on the available features and multidimensional clinical data. Methods: A total of 298 EP patients from Beijing Hospital of Traditional Chinese Medicine were retrospectively included in this study from May 5th, 2008, to March 3rd, 2022. Of them, 213 patients were selected as the development set by random sampling, and clinical parameters were analyzed by univariate and backward stepwise regression. Whereas the remaining 85 patients were randomly selected as the validation set. The model performance was later assessed in terms of discrimination, calibration, and clinical usefulness. Results: In the development set, the CVD rate was 9%, which was independently correlated with age, glycated albumin (GA>17%), smoking, albumin (ALB<40 g/L), and lipoprotein(a) (Lp(a)>300 mg/L). The area under the ROC curve (AUC) value was 0.83 (95% confidence interval CI, 0.73,0.93). For the validation set of EP patients, the AUC value was 0.85 (95%CI, 0.76,0.94). According to decision curve analysis, our model exhibited favorable clinical applicability. Conclusion: EP patients with age, GA>17%, smoking, ALB<40 g/L, and Lp(a)>300 mg/L are associated with a higher risk of CVD. The nomogram model performs well in predicting the probability of CVD in EP patients, which may help improve perioperative strategies and good treatment outcomes.

Transplanting Human Neural Stem Cells with ≈50% Reduction of SOX9 Gene Dosage Promotes Tissue Repair and Functional Recovery from Severe Spinal Cord Injury.

Neural stem cells (NSCs) derived from human pluripotent stem cells (hPSCs) are considered a major cell source for reconstructing damaged neural circuitry and enabling axonal regeneration. However, the microenvironment at the site of spinal cord injury (SCI) and inadequate intrinsic factors limit the therapeutic potential of transplanted NSCs. Here, it is shown that half dose of SOX9 in hPSCs-derived NSCs (hNSCs) results in robust neuronal differentiation bias toward motor neuron lineage. The enhanced neurogenic potency is partly attributed to the reduction of glycolysis. These neurogenic and metabolic properties retain after transplantation of hNSCs with reduced SOX9 expression in a contusive SCI rat model without the need for growth factor-enriched matrices. Importantly, the grafts exhibit excellent integration properties, predominantly differentiate into motor neurons, reduce glial scar matrix accumulation to facilitate long-distance axon growth and neuronal connectivity with the host as well as dramatically improve locomotor and somatosensory function in recipient animals. These results demonstrate that hNSCs with half SOX9 gene dosage can overcome extrinsic and intrinsic barriers, representing a powerful therapeutic potential for transplantation treatments for SCI.

Xiyanping injection combined with acitretin for psoriasis vulgaris: A systematic review and meta-analysis.

Background: Psoriasis represents the chronic, recurrent and inflammatory disorder. The Traditional Chinese Medicine Xiyanping injection (XYP) is extensively applied in China for treating diverse inflammatory disorders, such as bronchitis, viral pneumonia or upper respiratory tract infection. XYP may offer a potential treatment for psoriasis vulgaris (PV). This study focused on analyzing whether XYP combined with acitretin was effective and safe. Methods: The present meta-analysis was carried out in line with guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). This systematic review was registered in PROSPERO (CRD42022333273). Besides, relevant randomized controlled trials (RCTs) that compared XYP plus acitretin with acitretin alone for treating PV were searched from several databases from their inception till May 2022. In addition, this work utilized RevMan5.4 to conduct risk assessment as well as meta-analysis. Results: This meta-analysis selected altogether 10 RCTs including 815 subjects. Upon quality assessment, the RCTs mainly had low or unclear risk. According to our meta-analysis results, relative to acitretin monotherapy, XYP plus acitretin increased the total clinical effective rate, as evidenced by Psoriasis area and severity index score (PASI)-20, PASI-30 and PASI-60 in patients with PV [risk ratio (RR) = 1.23 Z = 4.87, p < 0.00001, 95% confidence interval (CI): 1.13-1.34; RR = 1.29, Z = 3.89, p = 0.009, 95% CI: 1.07 to 1.55; and RR = 1.31, Z = 3.89, p = 0.0001, 95% CI: 1.14-1.49]; the reduced levels of TNF-α, MCP-1 and RANTES, the alleviated side effects resulting from acitretin like itchiness (RR = 0.54, 95% CI: 0.4 to 0.74, Z = 3.94, p < 0.0001), and the increased levels of aminotransferases and dyslipidemia (RR = 0.5, 95%CI = 0.29, 0.86, p = 0.01; and RR = 0.41, 95% CI = 0.23, 0.75, p = 0.004). Conclusion: As suggested in the present meta-analysis, XYP combined with acitretin effectively and safely treats PV. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022333273, identifier PROSPERO 2022 CRD42022333273.

Knockdown of long noncoding RNA growth arrest-specific transcript 5 regulates forkhead box O3 to inhibit lipopolysaccharide-induced human bronchial epithelial cell pyroptosis.

Pyroptosis is a novel proinflammatory programmed cell death process. This study was designed to investigate the functional mechanisms of long noncoding RNA growth arrest-specific transcript 5 (lncRNA GAS5) on lipopolysaccharide (LPS)-induced human bronchial epithelial cell (HBEC) pyroptosis. LPS was used to induce pyroptosis in HBECs, followed by the detection of the expression of GAS5, forkhead box O3 (FOXO3), and nuclear factor E2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) signaling pathway-related factors. Cell viability was evaluated using CCK-8 assay, lactate dehydrogenase (LDH) release was assessed by LDH assay kit and caspase-1 activity by flow cytometry. Furthermore, expression of NOD-like receptor family pyrin domain containing 3 and pyroptosis-related proteins was evaluated using Western blot analysis, while enzyme-linked immunosorbent assay was used to determine the levels of inflammatory factors. The interaction between GAS5 and FOXO3 was confirmed using bioinformatic prediction, RNA immunoprecipitation assay, RNA pull-down, and dual-luciferase reporter gene assay. Treatment of HBECs with LPS upregulated the expression of GAS5 and FOXO3, resulting in the inactivation of the Nrf2/HO-1 signaling pathway. On the other hand, inhibition of both GAS5 and FOXO3 promoted cell viability, reduced LDH release, pyroptosis, and inflammatory response in LPS-induced HBECs. Furthermore, FOXO3 could interact with GAS5, while FOXO3 overexpression reversed the inhibitory effect of GAS5 knockdown on cell pyroptosis. Thus, mechanistically, inhibition of FOXO3 activates the Nrf2/HO-1 pathway to suppress LPS-induced pyroptosis in HBECs. This study revealed that GAS5 knockdown attenuates FOXO3 expression thereby activating the Nrf2/HO-1 pathway to inhibit LPS-induced pyroptosis in HBECs. These findings may contribute to identifying novel targets that inhibit pyroptosis in HBECs.

Genetic analysis of potential biomarkers and therapeutic targets in ferroptosis from psoriasis.

Introduction: Ferroptosis is associated with multiple pathophysiological processes. Inhibition of ferroptosis has received much concern for some diseases. Nonetheless, there is no study comprehensively illustrating functions of ferroptosis-related genes (FRGs) in psoriasis. Methods: In this study, FRGs together with psoriasis-associated data were obtained in Ferroptosis Database (FerrDb) and gene expression omnibus (GEO) database separately. This work identified altogether 199 psoriasis-associated DE-FRGs, and they were tightly associated with immunity and autophagy modulation. Thereafter, the present study utilized SVM-RFE and LASSO algorithms to identify NR5A2, CISD1, GCLC, PRKAA2, TRIB2, ABCC5, ACSF2, TIMM9, DCAF7, PEBP1, and MDM2 from those 199 DE-FRGs to be marker genes. As revealed by later functional annotation, the marker genes possibly had important effects on psoriasis through being involved in diverse psoriasis pathogenesis-related pathways such as cell cycle, toll-like receptor (TLR), chemokine, and nod-like receptor (NLR) pathways. Moreover, altogether 37 drugs that targeted 11 marker genes were acquired. Besides, based on CIBERSORT analysis, alterations of immune microenvironment in psoriasis cases were possibly associated with PRKAA2, PEBP1, CISD1, and ACSF2. Discussion: Taken together, this work established the diagnostic potency and shed more lights on psoriasis-related mechanism. More investigations are warranted to validate its value in diagnosing psoriasis before it is applied in clinic.

Structural Engineering of Organic D-A-π-A Dyes Incorporated with a Dibutyl-Fluorene Moiety for High-Performance Dye-Sensitized Solar Cells.

Structural engineering of the light-harvesting dyes employed in DSSCs (dye-sensitized solar cells) with a systematic choice of the electron-donating and -accepting groups as well as the π-bridge allows the (photo)physical properties of dyes to match the criteria needed for improving the DSSC efficiency. Herein, we report an effective approach of molecular engineering of DSSC sensitizers, aiming to gain insights on the configurational impact of the fluorenyl unit on the optoelectronic properties and photovoltaic performance of DSSCs. Five new organic dyes (GZ116, GZ126, GZ129, MA1116, and MA1118) with a D-A-π-A framework integrated with a fluorenyl moiety were designed and synthesized for DSSCs. The fluorenyl unit is configured as part of the π-spacer for the GZ series, whereas it connected on the electron-deficient quinoxaline motif for the MA series. The devices fabricated from the MA1116 sensitizer produced the best performance under standard AM 1.5 G solar conditions as well as dim-light (300-6000 lx) illumination. The devices fabricated from MA1116 displayed a PCE of 8.68% (Jsc = 15.00 mA cm-2, Voc = 0.82 V, and FF = 0.71) under 1 sun and 26.81% (Jsc = 0.93 mA cm-2, Voc = 0.68 V, and FF = 0.76) under 6000 lx illumination. The device efficiency based on dye MA1116 under 1 sun outperformed that based on the standard N719 dye, whereas a comparable performance between devices based on MA1116 and N719 was achieved under dim-light conditions. A combination of enhancing the charge separation, suppressing dye aggregation, and providing better insulation that prevents the oxidized redox mediator from approaching the TiO2 surface all contribute to the superior performance of DSSCs fabricated based on these light-harvesting dyes. The judicious integration of the fluorenyl unit in a D-A-π-A-based DSSC would be a promising strategy to boost the device performance.

Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial.

Importance: Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19), but further data from randomized clinical trials are needed. Objective: To evaluate the efficacy and adverse effects of convalescent plasma therapy for patients with COVID-19. Design, Setting, and Participants: Open-label, multicenter, randomized clinical trial performed in 7 medical centers in Wuhan, China, from February 14, 2020, to April 1, 2020, with final follow-up April 28, 2020. The trial included 103 participants with laboratory-confirmed COVID-19 that was severe (respiratory distress and/or hypoxemia) or life-threatening (shock, organ failure, or requiring mechanical ventilation). The trial was terminated early after 103 of a planned 200 patients were enrolled. Intervention: Convalescent plasma in addition to standard treatment (n = 52) vs standard treatment alone (control) (n = 51), stratified by disease severity. Main Outcomes and Measures: Primary outcome was time to clinical improvement within 28 days, defined as patient discharged alive or reduction of 2 points on a 6-point disease severity scale (ranging from 1 [discharge] to 6 [death]). Secondary outcomes included 28-day mortality, time to discharge, and the rate of viral polymerase chain reaction (PCR) results turned from positive at baseline to negative at up to 72 hours. Results: Of 103 patients who were randomized (median age, 70 years; 60 [58.3%] male), 101 (98.1%) completed the trial. Clinical improvement occurred within 28 days in 51.9% (27/52) of the convalescent plasma group vs 43.1% (22/51) in the control group (difference, 8.8% [95% CI, -10.4% to 28.0%]; hazard ratio [HR], 1.40 [95% CI, 0.79-2.49]; P = .26). Among those with severe disease, the primary outcome occurred in 91.3% (21/23) of the convalescent plasma group vs 68.2% (15/22) of the control group (HR, 2.15 [95% CI, 1.07-4.32]; P = .03); among those with life-threatening disease the primary outcome occurred in 20.7% (6/29) of the convalescent plasma group vs 24.1% (7/29) of the control group (HR, 0.88 [95% CI, 0.30-2.63]; P = .83) (P for interaction = .17). There was no significant difference in 28-day mortality (15.7% vs 24.0%; OR, 0.59 [95% CI, 0.22-1.59]; P = .30) or time from randomization to discharge (51.0% vs 36.0% discharged by day 28; HR, 1.61 [95% CI, 0.88-2.95]; P = .12). Convalescent plasma treatment was associated with a negative conversion rate of viral PCR at 72 hours in 87.2% of the convalescent plasma group vs 37.5% of the control group (OR, 11.39 [95% CI, 3.91-33.18]; P < .001). Two patients in the convalescent plasma group experienced adverse events within hours after transfusion that improved with supportive care. Conclusion and Relevance: Among patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment, compared with standard treatment alone, did not result in a statistically significant improvement in time to clinical improvement within 28 days. Interpretation is limited by early termination of the trial, which may have been underpowered to detect a clinically important difference. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2000029757.

Asymmetric localization of DLC1 defines avian trunk neural crest polarity for directional delamination and migration.

Following epithelial-mesenchymal transition, acquisition of avian trunk neural crest cell (NCC) polarity is prerequisite for directional delamination and migration, which in turn is essential for peripheral nervous system development. However, how this cell polarization is established and regulated remains unknown. Here we demonstrate that, using the RHOA biosensor in vivo and in vitro, the initiation of NCC polarization is accompanied by highly activated RHOA in the cytoplasm at the cell rear and its fluctuating activity at the front edge. This differential RHOA activity determines polarized NC morphology and motility, and is regulated by the asymmetrically localized RhoGAP Deleted in liver cancer (DLC1) in the cytoplasm at the cell front. Importantly, the association of DLC1 with NEDD9 is crucial for its asymmetric localization and differential RHOA activity. Moreover, NC specifiers, SOX9 and SOX10, regulate NEDD9 and DLC1 expression, respectively. These results present a SOX9/SOX10-NEDD9/DLC1-RHOA regulatory axis to govern NCC migratory polarization.

Chemo-, Regio-, and Stereoselective Construction of Core Skeleton of Furo[2,3-b]pyrrole via Multicomponent Bicyclization Reaction.

An efficient and straightforward N-ethyldiisopropylamine (DIPEA)-catalyzed multicomponent bicyclization reaction was developed to synthesize furo[2,3-b]pyrrole derivatives from ß-ketothioamides, glyoxals, and ethyl cyanacetate in EtOH at rt for 1.5 h. This was achieved via a sequential Knoevenagel condensation, Michael addition, and double cyclization, resulting in continuous formation of four chemical bonds (two C-C, two C-O, and one C-N bonds), two five-membered cycles, and three stereogenic centers in a one-pot operation.

Direct Construction of 2-Aryliminochromenes from Arynes, N,S-Keteneacetals, and DMF.

A concise and direct synthetic strategy for the construction of 2-aryliminochromene skeleton by cascade three-component coupling reaction of arynes, N,S-keteneacetals, and DMF in good yields has been disclosed. The process demonstrates the first example of aryne chemistry combined with N,S-keteneacetals. Using this strategy, an expeditious synthesis of biologically important arylimino-2H-chromene-3- carboxamides was achieved.

[Impact of CHA2DS2 VASc score on substrate for persistent atrial fibrillation and outcome post catheter ablation of atrial fibrillation].

OBJECTIVE: To explore if CHA2DS2 VASc score can predict substrate for persistent atrial fibrillation ( AF) and outcome post catheter ablation of AF. METHODS: From January 2011 to December 2012,116 patients underwent catheter ablation of persistent AF in our department and were enrolled in this study. CHA2DS2VASc score was calculated as follows: two points were assigned for a history of stroke or transient ischemic attack and age ≥ 75 and 1 point each was assigned for age ≥ 65, a history of hypertension, diabetes,recent cardiac failure, vessel disease, female. Left atrial geometry ( LA) was reconstructed with a 3.5 mm tip ablation catheter with fill-in threshold 10 in CARTO system. The mapping catheter was stabled at each endocardial location for at least 3 seconds for recording. The electrogram recordings at each endocardial location were analyzed with a custom software embedded in the CARTO mapping system. Interval confidence level (ICL) was used to characterize complex fractionated atrial electrograms (CFAEs) . As the default setting of the software, ICL more than or equal to 7 was considered sites with a highly repetitive CFAEs complex. CFAEs index was defined as the fraction of area of ICL more than or equal to 7 to the left atrial surface. The CFAEs index and outcome of catheter ablation among different CHA2DS2VASc groups were compared. RESULTS: Of the 116 patients, CHA2DS2VASc was 0 in 33 patients, 1 in 31 patients and ≥ 2 in 52 patients. Left atrial surface ((121.2 ± 18.9) cm2, (133.6 ± 23.8) cm2, (133.9 ± 16.1) cm2, P = 0.008), left atrial volume ((103.6 ± 24.8) ml, (118.3 ± 27.8) ml, (120.9 ± 20.9) ml, P = 0.005) and CFAEs index (44.6% ± 22.4%, 54.2% ± 22.2%, 58.7% ± 23.1%, P = 0.023) increased in proportion with increasing CHA2DS2VASc. ICLmax, ICLmin and CFAEs spatial distribution were similar among the three groups. During the mean follow-up of (13 ± 8) months, the recurrence rate were 36.4%, 35.5%, 55.8% among the three groups (P = 0.025). CONCLUSION: A high CHA2DS2VASc score is associated with extensive AF substrate and higher recurrence rate post catheter ablation of persistent AF.

Properties of the target registration error for surface matching in neuronavigation.

OBJECTIVE: Surface matching is a relatively new method of spatial registration in neuronavigation. Compared to the traditional point matching method, surface matching does not use fiducial markers that must be fixed to the surface of the head before image scanning, and therefore does not require an image acquisition specifically dedicated for navigation purposes. However, surface matching is not widely used clinically, mainly because there is still insufficient knowledge about its application accuracy. This study aimed to explore the properties of the Target Registration Error (TRE) of surface matching in neuronavigation. MATERIALS AND METHODS: The surface matching process was simulated in the image space of a neuronavigation system so that the TRE could be calculated at any point in that space. For each registration, two point clouds were generated to represent the surface extracted from preoperative images (PC(image)) and the surface obtained intraoperatively by laser scanning (PC(laser)). The properties of the TRE were studied by performing multiple registrations with PC(laser) point clouds at different positions and generated by adding different types of error. RESULTS: For each registration, the TRE had a minimal value at a point in the image space, and the iso-valued surface of the TRE was approximately ellipsoid with smaller TRE on the inner surfaces. The position of the point with minimal TRE and the shape of the iso-valued surface were highly random across different registrations, and the surface registration error between the two point clouds was irrelevant to the TRE at a specific point. The overall TRE tended to increase with the increase in errors in PC(laser), and a larger PC(laser) made it less sensitive to these errors. With the introduction of errors in PC(laser), the points with minimal TRE tended to be concentrated in the anterior and inferior part of the head. CONCLUSION: The results indicate that the alignment between the two surfaces could not provide reliable information about the registration accuracy at an arbitrary target point. However, according to the spatial distribution of the target registration error of a single registration, enough application accuracy could be guaranteed by proper visual verification after registration. In addition, surface matching tends to achieve high accuracy in the inferior and anterior part of the head, and a relatively large scanning area is preferable.

Classification and analysis of the errors in neuronavigation.

There are many different types of errors in neuronavigation, and the reasons and results of these errors are complex. For a neurosurgeon using the neuronavigation system, it is important to have a clear understanding of when an error may occur, what the magnitude of it is, and how to avoid it or reduce its influence on the final application accuracy. In this article, we classify all the errors into 2 groups according to the working principle of neuronavigation systems. The first group contains the errors caused by the differences between the anatomic structures in the images and that of the real patient, and the second group contains the errors occurring in transforming the position of surgical tools from the patient space to the image space. Each group is further divided into 2 subgroups. We discuss 16 types of errors and classify each of them into one of the subgroups. The classification and analysis of these errors should help neurosurgeons understand the power and limits of neuronavigation systems and use them more properly.

Redefinition of hypervariable region I in mitochondrial DNA control region and comparing its diversity among various ethnic groups.

The hypervariable region I (HVR-I) of the mitochondrial DNA control region described in the literature is variable in its 5'and 3' ends as well as in its length, causing a problem when data from different ethnic groups are to be compared. To redefine HVR-I, which should be highly polymorphic yet relatively short in length, we analyzed 1437 reported sequences distributed among 11 geographic areas in the world. The results showed that the 237-bp (nts 16126-16362) redefined HVR-I (rHVR-I) had a global genetic diversity of 0.9905 and the 154-bp (nts 16209-16362) short HVR-I (sHVR-I) had a global diversity of 0.9735. Being flanked by a stretch of highly conservative sequences, both rHVR-I and sHVR-I can be produced by PCR, even if extracted from badly degraded specimens. Comparing the genetic diversity among 3870 sequences from 25 countries, we found that the genetic diversity of rHVR-I was 0.9869+/-0.0133 in Asian countries, 0.9685+/-0.0193 in African countries, 0.9299+/-0.0664 in European countries, and 0.8477+/-0.1857 in American countries, whereas that of sHVR-I was 0.9689+/-0.0284 in Asian countries, 0.9504+/-0.0334 in African countries, 0.8721+/-0.0911 in European countries, and 0.8230+/-0.1693 in American countries. The difference in genetic diversity among these countries is consistent with the notion that genetic diversity roughly reflects the genetic history of a given ethnic group. Our results indicate that a polymorphic, short, and PCR-producible HVR-I can be defined, making the comparison among various ethnic groups possible.

Cloning of genes expressed in cell quiescence: a new function of the ras-recision/lysyl oxidase gene.

The mechanism governing cell quiescence remains to be elucidated, albeit some tumor suppressor genes are known to be involved in this process. If more genes belonging to this regulatory circuit are identified, we will have a better understanding on cell quiescence. For this purpose, the present study was designed to clone genes preferentially expressed in cell quiescence. Using the method of differential display, we cloned ras-recision gene (rrg), also known as lysyl oxidase gene (lox), from BALB/c 3T3T cells, which were rendered quiescent by serum deprivation. Northern blot analysis showed that the induction of rrg/lox gene could be detected as early as 12 h following serum deprivation and it was dramatically elevated from 24 hours on after serum starvation. Induction of rrg/lox was also observed in cells rendered quiescent by contact inhibition, indicating that rrg/lox is induced by cell quiescence in general rather than specific to serum deprivation. Because rrg/lox gene products are known to be involved in extracellular matrix maturation, and function as tumor suppressors against ras oncogene, our finding suggests that quiescence-associated cell physiology is partly mediated by induction of rrg/lox.

Incidence of gastrointestinal stromal tumor: a retrospective study based on immunohistochemical and mutational analyses.

The aim of this study is to estimate the incidence of the gastrointestinal stromal tumor after the previous diagnoses were confirmed and/or revised by both immunohistochemical and mutational analyses. We reviewed 17,858 surgically excised gastrointestinal lesions in our hospital from 1998 to 2004. All mesenchymal tumors were examined for CD117 expression by immunohistochemistry, and every CD117-negative mesenchymal tumors were further subjected to mutational analysis for KIT and PDGFRA exons. The results showed that approximately 35% of gastrointestinal stromal tumors were misdiagnosed if immunohistochemical analysis of CD117 expression was not performed; and approximately 15% misdiagnosed if mutation analysis was not available. Because approximately 4.72% of patients with gastrointestinal malignancies in Taiwan were treated in our hospital and the average of newly diagnosed gastrointestinal stromal tumors in our hospital was 14.33 cases per year, the estimated annual incidents of gastrointestinal stromal tumor in Taiwan were 303.60. Therefore, the annual incidence of gastrointestinal stromal tumor is 13.74 per million Taiwanese.

Pharmacokinetics of multiple intravenous instillation of levofloxacin in Chinese healthy subjects.

AIM: To study the pharmacokinetics of multiple doses intravenous infusion of levofloxacin instillation in Chinese healthy volunteers. METHODS: Intravenous infusion of levofloxacin instillation 200 mg within 60 min was given to 10 male healthy volunteers for 7 d, on d 1 and d 7, once-daily, from 2-6 d twice-daily dosing. The concentrations of levofloxacin in serum and urine were assayed by HPLC. RESULTS: The main pharmacokinetic parameters af ter the first dosing were as follows: Cmax was (2.4+/-0.4) mg/L; AUC0- was (16.1 +/- 1.4) mg . h . L-1; T1/2beta was (6.3 +/- 0.3) h. The concentration in serum reached steady state within 72 h. The main parameters after the last dosing were as follows: Cssmax was (2.9 +/- 0.4) mg/L; Cssmin was (0.71 +/- 0.19) mg/L; Cav was (1.40 +/- 0.29) mg/L; AUCss0-12 was (17 +/- 3) mg . h . L-1; T1/2beta was (6.2 +/- 0.8) h. The 24-h cumulative urinary excretion rate was (88 +/- 5) %. From the calculation, the cumulative rate was 1.20; the fluctuation index was 1.30. The difference of T1/2beta and AUC between the first dosing and the last dosing was not significant, and the elimination rate of levofloxacin was not changed after multiple dosing. No clear adverse events were noted during this study. CONCLUSION: There was no accumulation of drug after the repeated intravenous infusion with 200 mg levofloxacin instillation for 7 d.