Changes of photopic negative response of multifocal electroretinogram after treatment with Aflibercept in patients with diabetic macular edema / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To observe the changes of photopic negative response(PhNR)of multifocal electroretinogram(mf-ERG)in patients with diabetic macular edema(DME)before and after treatment with Aflibercept.METHODS: A total of 37 patients(37 eyes)with DME who visited the Aier Eye Hospital of Wuhan University(Wuhan Aier Eye Hospital)from May 2019 to June 2022, and 0.05 mL of aflibercept was injected per month for consecutive 3mo were included in this retrospective cohort study. Another 20 cases(20 eyes)with normal physical examination to exclude related eye diseases were selected as the control group. The PhNR amplitude of mf-ERG, best-corrected visual acuity(BCVA; LogMAR), central retinal thickness(CRT), capillary plexus in macular area and vessel density(CPVD)of the participants between the two groups were compared before and after treatment.RESULTS: The PhNR amplitude of mf-ERG in DME patients before treatment(201.69±80.92nV)was significantly lower than that in the normal control group(398.87±77.92nV; P<0.01), and the average PhNR amplitude of mf-ERG in DME patients at 6mo after treatment was significantly higher than that before treatment(P=0.036), but it was still significantly lower than the normal control group at 6mo after treatment(P=0.031). In addition, the BCVA(LogMAR)of DME patients increased from 0.64±1.33 to 0.37±1.39(P=0.021)at 6mo after treatment, and CPVD significantly increased compared to that before treatment(P=0.029). Meanwhile, the PhNR amplitude of mf-ERG in DME patients at 6mo after treatment was positively correlated with CPVD at 6mo after treatment(r=0.448, P=0.043), and negatively correlated with BCVA(LogMAR)and CRT(r=-0.647, P=0.011; r=-0.337, P=0.032).CONCLUSION: The PhNR amplitude of mf-ERG in DME patients increased significantly after receiving aflibercept, and it can be used to observe and evaluate the functional changes of retinal ganglion cells in DME patients.

Application of ureteral access sheath in the operation of middle and lower ureteral calculi in patients with massive benign prostatic hyperplasia / 中华外科杂志

Objective: To examine the effectiveness and safety of application of the ureteral access sheath in the treatment of middle or lower ureteral calculi in patients with large-volume benign prostatic hyperplasia above grade Ⅲ, which is expected to avoid the simultaneous or staged treatment of benign prostatic hyperplasia via eliminate the difficult angle and resistance of ureteroscopy caused by severe prostatic hyperplasia. Methods: From April 2018 to December 2020, the clinical data of 27 patients with massive benign prostatic hyperplasia above grade Ⅲ and middle and lower ureteral calculi treated with indwelling ureteral access sheath plus ureteroscopy holmium laser lithotripsy at Department of Urology, Zhejiang Quhua Hospital were retrospectively analyzed and followed up. All the patients were male, aged (69.7±12.8) years (range: 55 to 87 years). Prostate volume measured by transrectal ultrasound was (94.8±16.2) cm3 (range: 85 to 186 cm3). The ureteral access sheath was indwelled in advance, and then the semirigid ureteroscopy was introduced through the working channel of the sheath. Holmium laser lithotripsy was performed, and intraoperative and postoperative complications were recorded. Urinary abdominal plain X-ray or CT urography were performed at 1-and 2-month postopaerative to evaluate the residual stones and clinical efficacy. Results: The ureteral access sheath was placed and holmium laser lithotripsy under a semirigid ureteroscopy was performed successfully in all the 27 patients. In 2 patients, a second session of auxiliary procedure was required due to the large load of preoperative stones and residual stones after surgery, among whom 1 patient received extracorporeal shock wave lithotripsy and 1 patient underwent extracorporeal shock wave lithotripsy plus ureteroscopic lithotripsy. The stone free rate at 1-and 2-month postoperative were 92.6% (25/27) and 100% (27/27), respectively. There were no severe complications such as ureteral avulsion and perforation, perirenal hematoma, septic shock, severe hematuria, urinary retention, iatrogenic ureteral stricture occurred during and after the surgery. The ureteral calculus was wrapped by polyps heavily in 1 patient, he was diagnosed as ureteral stenosis 1 month postoperative, receiving laparoscopic resection of ureteral stricture plus anastomosis 3 months postoperative. Conclusions: In the operations of middle and lower ureteral calculi in patients with large-volume prostatic hyperplasia above grade Ⅲ, the ureteral access sheath can be placed first to effectively eliminate the difficult angle and resistance of ureteroscopy caused by severe prostatic hyperplasia, and then semirigid ureteroscopic lithotripsy can be safely performed. It could avoid the treatment of benign prostatic hyperplasia at the same time or by stages.

Correlation between color and content of eight components of Gardeniae Fructus at different harvest time / 中国中药杂志

This research is to establish an HPLC method for determination of geniposidic acid, genipin-1-β-D-gentiobioside, geniposide, p-trans-coumaroylgenipin gentiobioside, chlorogenic acid, crocin-Ⅰ, crocin-Ⅱ and crocin-Ⅲ in Gardeniae Fructus at different harvest time. The detection wavelength was 238, 320 and 440 nm. Principal component analysis(PCA), correlation analysis, regression analysis and partial least squares(PLS) analysis were used to explore the relationship of color and content of eight components in Gardeniae Fructus. The result showed that the trend of the eight components in Gardeniae Fructus at harvest time in different three years was varied similarly. According to the variation of eight components at different harvest time, the mature and immaturate Gardeniae Fructus were discriminated. The content of crocin-Ⅰwas correlated positively with a~* of color significance. The redder color of Gardeniae Fructus showed the higher value of a~* and content of crocin-Ⅰ, indicating the better quality of Gardeniae Fructus. This method provided reference for justifying the color and quality of Gardeniae Fructus and scientific evidence for "assessing quality by distinguishing color".

Effect of Arisaema Rhizoma and Pinelliae Pedatisectae Rhizoma on Water Metabolism and Hemorheology in Rats / 中国实验方剂学杂志

Objective:To discuss the effect of Arisaema Rhizoma and Pinelliae Pedatisectae Rhizoma on water metabolism and hemorheolog in rats. Method:A total of 50 healthy SD rats were randomly divided into 5 groups, namely normal group, high-dose Arisaema Rhizoma group (1.2 g·kg·d-1), low-dose Arisaema Rhizoma group (1.2 g·kg·d-1), high-dose Pinelliae Pedatisectae Rhizoma group (1.2 g·kg·d-1) and low dose Pinelliae Pedatisectae Rhizoma group (0.3 g·kg·d-1), with 10 rats in each group. The effects of Arisaema Rhizoma and Pinelliae Pedatisectae Rhizoma on water metabolism and hemorheology were compared, with the micturition index, fecal volume, fecal water content, pathological morphology of submandibular gland, aquaporin (AQP2) content in kidney, adenosine cyclic 3′,5′-(hydrogen phosphate)/current good manufacture practices (cAMP/cGMP) and Na+-K+-ATP enzyme content in serum as the evaluation indexes of water metabolism, and the whole blood viscosity (WBV) and erythrocyte aggregation index (RE) as the evaluation indexes of hemorheolog. Result:Compared with normal group, the fecal volume, fecal water content and AQP2 expression decreased significantly， acinus of submandibular gland were atrophied， micturition index, cAMP/cGMP and Na+-K+-ATP enzyme content in serum were increased significantly， WBV and RE were increased significantly in high-dose Arisaema Rhizoma and Pinelliae Pedatisectae Rhizoma groups（P<0.05）, but with no significant difference between them. Conclusion:High-dose Arisaema Rhizoma and Pinelliae Pedatisectae Rhizoma groups had significant effects on water metabolism and hemorheology in rats, suggesting that attention shall be given to the safety of Arisaema Rhizoma and Pinelliae Pedatisectae Rhizoma. And this study provides a theoretical basis for the rational use of the two traditional Chinese medicines in clinic.

Rolling adhesion of HL-60 cells treated with all-trans retinoic acid on E-selectin / 中国组织工程研究

BACKGROUND: All-trans retinoic acid (ATRA) is an ideal therapy for acute promyelocytic leukemia, which can induce promyelocytes to differentiate to mature granulocytes. However, differentiation syndrome is still a high risk for the patients undergoing ATRA therapy. Occurrence of this complication is closely related with cellular morphology change and expression and function of cellular adhesion molecules, especially selectin and integrin families. OBJECTIVE: To reveal rolling adhesion behavior and mechanical mechanism of ATRA treated HL-60 cells on the substrate coated with E-selectin under different fluid shear forces. METHODS: Using the equipment of parallel plate flow chamber, untreated and ATRA treated HL-60 cells were driven to roll on E-selectin-coated substrate. The mean rolling velocity and mean stop time were calculated. Here, the HL-60 cells were incubated in the medium containing 1×10-6mol/L ATRA for 0, 48, 72, 96 hours. The substrates were captured with 40 μg/L E-selectin overnight and the shear stresses were set to 0.02, 0.04, 0.06 Pa. RESULTS AND CONCLUSION: The velocity of untreated/treated HL-60 cells decreased firstly and then increased with monotonously increasing shear stress. On the contrary, the mean stop time and factional stop time increased firstly and then decreased. Therefore, we deduced that the flow enhanced rolling adhesion was regulated by the catch bond for the HL-60 cells rolling on E-selectin under flow. On the other side, rolling velocities decreased under the same shear stress even if treated with or without ATRA, and the mean stop time and factional stop time increased inversely, which further illustrate the rolling velocity is mainly regulated by stop time.

Application of ETDRS chart and mfERG in assessing pathologic myopia combined with macular CNV after treatment / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM: To evaluate the efficacy of anti - vascular endothelial growth factor ( VEGF ) and photodynamic therapy ( PDT) on pathological myopia ( PM) combined with choroidal neovascularization ( CNV ) using ETDRS chart and multifocal electroretinogram (mfERG). ·METHODS: Forty-three patients ( 45 eyes) diagnosed by fundus fluorescein angiography ( FFA ), indocyanine green angiograph ( ICGA ) and optical coherence tomography (OCT) with PM combined with macular CNV were recruited in this study. The patients were randomly divided into two groups for different treatments, intravitreal injection with Ranibizumab ( 20 patients, 22 eyes) and PDT (23 patients, 23 eyes). After treatment, all patients had been followed up monthly for 12mo. The further treatments were operated according to referral situations. The best corrected visual acuity ( BCVA) was recorded with the ETDRS chart and mfERG. At the last follow-up, the therapy efficacy was determined by ETDRS numbers and mfERG and analyzed. ·RESULTS: Before treatment, there was no significant difference on the baseline in ETDRS and mfERG latency of N1 wave, latency and the density values of P1 wave between ranibizumab group and PDT group. After 12mo treatment, the ETDRS number in ranibizumab group (39. 23± 20. 06) significantly increased to the baseline by 5. 88±9. 03(P<0. 05), and in PDT group (37. 38±16. 95) was not significantly improved by 0. 33±6. 94(P>0. 05). There was no significant difference in latency of N1 wave, latency and the density values of P1 wave from treatment response of mfERG in the two groups (P>0. 05). · CONCLUSION: In the treatment of macular CNV complicated by the PM, ranibizumab injection can improve visual function better than PDT, while similar on macular.

Evaluation of Ranibizumab and PDT for patients with pathologic myopia and macular CNV / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM: To evaluate the efficacy of anti - vascular endothelial growth factor (VEGF) and photodynamic therapy (PDT) on pathological myopia (PM) combined with choroidal neovascularization (CNV). ·METHODS: Forty-three patients (45 eyes) diagnosed by fundus fluorescein angiography (FFA), indocyanine green angiography ( ICGA ) and optical coherence tomography (OCT) with PM combined with macular CNV were recruited in this study. The patients were randomly divided into two groups for different treatments, intravitreal injection with Ranibizumab (20 patients, 22 eyes) and PDT(23 patients,23 eyes). After treatment,all patients had been followed up monthly for 12mo. The further treatments were operated according to referral situations. The best corrected visual acuity (BCVA) was recorded with the ETDRS chart and the mean defect(MD) of the center 10° visual field was measured. At the last follow-up,the therapy efficacy was determined by ETDRS numbers and MD and analyzed. ·RESULTS: Before treatment, there was no significant difference on the baseline in ETDRS and MD between ranibizumab group and PDT group (P>0.05). After 12mo treatment, the ETDRS number in ranibizumab group (39.23±20.06) significantly increased (by 5.88 ± 9.03, P<0.05), but the PDT group (37. 38 ± 16. 95) was not significantly improved(by 0.33±6.94,P>0.05). The MD in ranibizumab group decreased significantly (P<0.05), and no significant change was found in PDT group(P>0.05). · CONCLUSION: In the treatment of macular CNV complicated by the PM, ranibizumab injection can improve visual function better than PDT.

Effect of Integration of Habitat Processing and Pieces Processing on Anti-inflammatory of Cortex Fraxini / 世界科学技术-中医药现代化

Objective: To compare the anti-inflammatory effect of Fraxini Cortex pieces between integrated production process and traditional processing method. Methods: The model of rat paw swelling induced by carrageenan was used to study the anti-inflammatory and swelling reliving effects of water extracts of Cortex Fraxini with different methods. The main chemical components of the 2 kinds of Cortex Fraxini herbal pieces were determined by high performance liquid phase. Results: Compared with the blank group, the water extracts of the 2 kinds of Cortex Fraxini could reduce the swelling of the rats and improve the various indicators of inflammation. However, the anti-inflammatory and swelling reliving effects of the integrated processing of Cortex Fraxini were more significant. The contents of 4 main active ingredients of esculine, fraxin, aesculetin and fraxetin in the integrated processing of Cortex Fraxini were higher than that of the traditionally processed Cortex Fraxini. The total amount of 4 kinds of coumarins in the integrated Cortex Fraxini was about 1.5 times that of the traditionally processed water extract of Cortex Fraxini. Conclusion: The integrated processing and traditional processing of Cortex Fraxini have similar effects on anti-inflammatory effects, and have the superiority of reducing the loss of active ingredients, which is worthy of popularization and application.

VWF-A1A2A3-mediated expression of P-selectin in platelets under flow shear stress / 医用生物力学

Objective To investigate the effect of fluid shear stress (FSS) on VWF-A1A2A3-mediated expression of platelet surface P-selectin. Methods Using a parallel plate flow chamber system and mouse anti-human CD62P: FITC as the indicator of P-selectin expression, the alteration of platelet P-selectin expression level with increasing exposure time under different FSS conditions (0, 1, 2 Pa) specifically mediated by VWF-A1A2A3 was observed and analyzed by fluorescence microscope to obtain the activation characteristics. Results FSS triggered platelet activation and P-selectin expression. The activation ratio of platelet was positively regulated by FSS and their exposure time, reaching the maximum value, 9.42% and 14.59% under FSS of 1 Pa and 2 Pa, respectively. The level of P-selectin expression exhibited two-phase tendency with the shear stress-exposure time increasing, uplifted at first, then decreased, with the best action time at 7.5 min. The fluorescence peak intensity increased when FSS was enhanced. Conclusions The level of platelet P-selectin expression is co-regulated by VWF-A1A2A3 and FSS, and is closely related to force-signaling exposure time.

Shear force-induced activation of integrin LFA-1 by chemokine CXCL12 under flows / 医用生物力学

Objective To explore the activate process of lymphocyte function-associated antigen 1 (LFA-1) triggered by chemokine under shear stresses. Methods Jurkat cells were perfused over ICAM-1 in the parallel-plate flow under 10-30 mPa shear stresses. The effects of soluble and immobilized Chemokines on transient adhesion behavior of Jurkat cells were observed and analyzed to obtain their tether characteristics. Results The immobilized CXCL12 could mediate brief tether (0.13-0.2 s) of Jurkat cells under flow. Only immobilized CXCL12 could effectively activate LFA-1 on Jurkat cells to bind ICAM-1, and then enhance cell adhesion fraction and greatly prolong the tether time (0.8-1.2 s). Two distinct activation states of LFA-1/ICAM-1 were reflected by their dissociation rate k1 (1.09-1.24 s-1) and k2 (0.28-0.7 s-1), respectively. The shear stress would affect the transient adhesion behavior of cells through regulation of k2 and β (the contribution ratio of high affinity to total tether time). Conclusions Shear stress can rapidly trigger LFA-1 activation in 0.2 s through G protein coupled receptors induced by chemokine CXCL12, and further regulate the whole adhesion process of leukocyte. These research findings will contribute to further understanding the integrin activation mechanism of chemokine-force cooperative regulation.

Shear force-induced activation of integrin LFA-1 by chemokine CXCL12 under flows / 医用生物力学

Objective To explore the activate process of lymphocyte function-associated antigen 1 (LFA-1) triggered by chemokine under shear stresses.Methods Jurkat cells were perfused over ICAM-1 in the parallel-plate flow under 10-30 mPa shear stresses.The effects of soluble and immobilized Chemokines on transient adhesion behavior of Jurkat cells were observed and analyzed to obtain their tether characteristics.Results The immobilized CXCL12 could mediate brief tether (0.13-0.2 s) of Jurkat cells under flow.Only immobilized CXCL12 could effectively activate LFA-1 on Jurkat cells to bind ICAM-1,and then enhance cell adhesion fraction and greatly prolong the tether time (0.8-1.2 s).Two distinct activation states of LFA-1/ICAM-1 were reflected by their dissociation rate k1 (1.09-1.24 s-1) and k2 (0.28-0.7 s-1),respectively.The shear stress would affect the transient adhesion behavior of cells through regulation of k2 andβ (the contribution ratio of high affinity to total tether time).Conclusions Shear stress can rapidly trigger LFA-1 activation in 0.2 s through G protein coupled receptors induced by chemokine CXCL12,and further regulate the whole adhesion process of leukocyte.These research findings will contribute to further understanding the integrin activation mechanism of chemokine-force cooperative regulation.

VWF-A1A2A3-mediated expression of P-selectin in platelets under flow shear stress / 医用生物力学

Objective To investigate the effect of fluid shear stress (FSS) on VWF-A1A2A3-mediated expression of platelet surface P-selectin.Methods Using a parallel plate flow chamber system and mouse anti-human CD62P:FITC as the indicator of P-selectin expression,the alteration of platelet P-selectin expression level with increasing exposure time under different FSS conditions (0,1,2 Pa) specifically mediated by VWF-A1A2A3 was observed and analyzed by fluorescence microscope to obtain the activation characteristics.Results FSS triggered platelet activation and P-selectin expression.The activation ratio of platelet was positively regulated by FSS and their exposure time,reaching the maximum value,9.42％ and 14.59％ under FSS of 1 Pa and 2 Pa,respectively.The level of P-selectin expression exhibited two-phase tendency with the shear stress-exposure time increasing,uplifted at first,then decreased,with the best action time at 7.5 min.The fluorescence peak intensity increased when FSS was enhanced.Conclusions The level of platelet P-selectin expression is co-regulated by VWF-A1A2A3 and FSS,and is closely related to force-signaling exposure time.

VWF-A1A2A3-mediated expression of P-selectin in platelets under flow shear stress / 医用生物力学

Objective To investigate the effect of fluid shear stress (FSS) on VWF-A1A2A3-mediated expression of platelet surface P-selectin.Methods Using a parallel plate flow chamber system and mouse anti-human CD62P:FITC as the indicator of P-selectin expression,the alteration of platelet P-selectin expression level with increasing exposure time under different FSS conditions (0,1,2 Pa) specifically mediated by VWF-A1A2A3 was observed and analyzed by fluorescence microscope to obtain the activation characteristics.Results FSS triggered platelet activation and P-selectin expression.The activation ratio of platelet was positively regulated by FSS and their exposure time,reaching the maximum value,9.42％ and 14.59％ under FSS of 1 Pa and 2 Pa,respectively.The level of P-selectin expression exhibited two-phase tendency with the shear stress-exposure time increasing,uplifted at first,then decreased,with the best action time at 7.5 min.The fluorescence peak intensity increased when FSS was enhanced.Conclusions The level of platelet P-selectin expression is co-regulated by VWF-A1A2A3 and FSS,and is closely related to force-signaling exposure time.

A collective review of syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis / 解放军医学杂志

The syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) is characterized by recurrent attacks of paroxysmal headache, accompanying with neurological deficits and lymphocytic pleocytosis. Clinical features of the syndrome are nonspecific that it is bound to be confused with transient ischemic attack, intracranial tumor, viral encephalitis, migraine and other diseases. In fact, it is usually mis-diagnosed at the initial visits. So far, there is only one HaNDL case reported in China. Therefore the etiology, clinical features, diagnosis, and treatment are herewith reviewed to improve the knowledge regarding this syndrome.

Mechanism of affinity alterations in VWF-A1 domain mutant G561S studied by molecular dynamics simulation / 医用生物力学

Objective To investigate the mechanism of affinity down-regulation between Von Willebrand factor mutant G561S and its ligand. Methods Three molecular systems were constructed for WT-A1, G561S-A1, and R543Q-A1, respectively. G561S-A1 mutant was constructed by replacing the Gly561 with Ser561 in the wild-type A1 domain. The crystal structures of WT-A1 and R543Q-A1 were downloaded from Protein Data Base (PDB). Free molecular dynamics simulation was performed to observe the changes of conformation, alterations of flexibility, and the formation and evolution of hydrogen bond and/or salt bridge, among the three A1 domains (WT-A1, G561S-A1, and R543Q-A1). ResultsG561S mutation lowered the localized dynamic properties of α2 helix and increased the interactions between the N-terminal arm and body region in A1 domain, thus leading to the decreased binding affinity with its ligand GPIbα. However, the Gain-of-function mutation R543Q followed the pathway which was contrary to G561S. ConclusionsThe change of localized dynamic properties of α2 helix is a potential mechanism in the regulation of the binding affinity of A1, and this research finding is helpful in developing allosteric drugs against the activated A1 domain and relevant anti-thrombus drugs.

Mechanism of force-induced activation of integrin LFA-1 under circulating flows / 医用生物力学

Objective To reveal the mechanical regulation mechanism for activation of lymphocyte function-associated antigen 1 (LFA-1). Methods The LFA-1 expressed on Jurkat cell surface was pre-activated by Mg2+ from quiescent-to intermediate-affinity state, and the tether events of Jurkat cells under different wall shear stresses (4.5-10 mPa) were observed and analyzed by flow chamber experiment. Meanwhile, a probabilistic model of integrin affinity jumping was established. Results The affinity jumping model was well fitted with the data obtained from flow chamber experiment. Under flowing loads, LFA-1 from intermediate to high-affinity state was observed, with prolonging of the adhesion bonds. The probability of tether event was 15%-26%. LFA-1 at high-affinity state contributed a significant fraction (about 26%-40%) of the bond lifetime. The off-rate of LFA-1 at high-affinity state was slower by 19%-65% as compared to that at intermediate-affinity state. Dissociating of ICAM-1 from LFA-1 was force-dependent and governed either by slip-bond at intermediate-affinity state or by catch-slip bond at high-affinity state. Conclusions The force-induced activation of LFA-1 mediates the slower rolling and firm adhesion of the cells. This research finding will further the understanding of inflammatory response events of circulating leukocytes, and contribute to the discovery of new antibody drug targets for the associated diseases.

A kind of exponential model of seasickness habituation / 医用生物力学

Objective To provide a quantitative analysis tool by building a mathematical model of seasickness habituation to make adaptive training plans scientifically for anti-seasickness purpose. Methods Based on the regular pattern of seasickness habituation, an exponential model of motion sickness incidence (MSI) was established to extract such seasickness habituation parameters as anti-motion sickness incidence (AMSI) and anti-motion sickness rate (μ) through making the seasickness habituation data fitting into the corresponding training, and the effects of AMSI and μ on MSI was also simulated. Results The data from two marine adaptive trainings were well fitted with the MSI model, and the fitting results of AMSI and μ were 0.87 and 0.048 for intermittent training, or 0.81 and 0.34 for continuous training. Effects of seasickness habituation training would be enhanced by increasing the value of AMSI and μ. Conclusions The present model of MSI is suitable for evaluating the effect of training on anti-seasickness and making the optimal strategy for such seasickness habituation training.

A novel approach for identifying the critical amino acid residues on binding site of GPIbα and vWF-A1 domain through molecular dynamics simulation / 医用生物力学

Objective To develop a novel computer method for identifying the critical amino acid residues in the receptor-ligand interactions. Methods GPIbα/vWF-A1 crystal structure was taken from Protein Data Bank (PDB code 1SQ0). Free molecular dynamics simulations were performed to observe the formation and evolution of hydrogen bonding and salt bridge on the binding sites of GPIbα and vWF-A1 by VMD. A residue interaction index, which was scored with the survival ratios of salt bridges and/or hydrogen bonds involved in interaction of a residue to other(s), was used as a criterion of the residue’s role in interaction between the receptor and ligand. Results In the interface, 21 residues in GPIbα and 21 residues in vWF-A1 were significantly identified to participate in the interaction between GPIbα and vWF-A1; 20 of these 42 key residues were verified by previous mutagenesis experiments. Conclusions This novel approach is useful for computationally identifying the key residues involved in GPIbα-vWF interaction, and has potential in developing new strategy for the traditional mutagenesis experiments and the antithrombotic mAbs drug design.

vWF-A1A2A3-mediated rolling of circulating platelets in flows / 医用生物力学

Objective To reveal the shear stress regulation mechanism on vWF-A1A2A3-mediated rolling of platelets in flows. Methods Platelets were perfused with various flow rates over 200 μg/mL vWF A1A2A3 in parallel-plate flow chamber. The rolling events of platelets near the bottom of chamber were observed and analyzed to obtain the rolling characteristics. Results The mean rolling velocity and time, stop frequency and fractional stop time of platelets were all found to be biphasic dependent on wall shear stress, with all the threshold/inflection points occurring under the fluid stress of 0.8 Pa. Increasing shear stress below the threshold would slow and stabilize cell rolling in flows. Conclusions Wall shear stress regulates velocity of A1A2A3-mediated cell rolling by adjusting the cell stop time, suggesting that a catch-to slip-bond transition serves as a mechanical regulation mechanism for platelet rolling through A1A2A3 GPIbα interaction in flows.

Disseminated cryptococcal lymphadenitis with negative latex agglutination test / 中华医学杂志(英文版)

We reported an unusual case of disseminated cryptococcal lymphadenitis in an immunocompetent host who presented with fever and lymphadenopathy, which were the only two symptoms and signs. Latex agglutination test of serum and cerebrospinal fluid (CSF) were negative, while lymph node biopsy showed Cryptococcus neoformans. A diagnosis of disseminated cryptococcal lymphadenitis was made. Then the patient was treated with amphotericin B for 15 days as initial therapy and itraconazole for 6 months as maintenance therapy respectively. The patient received re-examination per 6 months and was followed up for 2 years. Swollen lymph nodes diminished gradually, and no fever or other symptoms were found. Latex agglutination test of serum and CSF were negative throughout the follow-up period, and anti-HIV, syphilis and tuberculosis antibody were all negative.