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Ying Ni Lin,1,2,* Xiao Fei Lan,1,3,* Zhuo Ran Liu,4,* Ya Ru Yan,1,2 Jian Ping Zhou,1,2 Ning Li,1,2 Xian Wen Sun,1,2 Qing Yun Li1,2 1Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People’s Republic of China; 2Institute of Respiratory Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People’s Republic of China; 3Department of Respiratory Medicine, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200335, People’s Republic of China; 4Department of Thyroid and Vascular Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qing Yun LiDepartment of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People’s Republic of ChinaTel +86-21-64370045Email liqingyun68@hotmail.comPurpose: Chronic intermittent hypoxia (CIH) contributes to the increased risk of cardiovascular diseases in obstructive sleep apnea (OSA). We previously reported the anti-apoptotic effects of estradiol (E2) on IH-exposed human umbilical vein endothelial cells (HUVECs). Herein, we employed a proteomic analysis to elucidate the mechanisms of the protective effects of E2 under IH exposure.Methods: HUVECs were divided into three groups: control, IH, and IH+E2 group. Isobaric tags for relative and absolute quantification (iTRAQ) were performed to compare protein profiles among the groups. Some of the identified proteins were validated by Western blotting.Results: A total of 185 proteins were differentially expressed in the IH+E2 group compared to the IH group. Bioinformatics analysis indicated that the effects of E2 may be linked to the regulation of cellular stress response. Among the differentially expressed proteins, we identified that serine-protein kinase ataxia telangiectasia mutated (ATM) and its downstream target, cellular inhibitor of apoptosis protein 1 (c-IAP1), were up-regulated by E2. We also observed that E2 decreased the level of cleaved caspase-3 and inhibited cell apoptosis in IH-exposed HUVECs. The inhibition of ATM abolished the anti-apoptotic effect of E2.Conclusion: The ATM-c-IAP1 pathway is involved in the cardioprotective effects of E2 in HUVECs exposed to IH.Keywords: estradiol, obstructive sleep apnea, OSA, intermittent hypoxia, IH, endothelial dysfunction, proteomics

Objective: To study the applied anatomy of the vascular and muscular innervations related to vascularized fibular grafts.Methods: Thirty-four cadaveric lower extremities were dissected for this study. The observations included fibular length, fibular nutrient artery, arcuate arteries, and innervation of fibular muscles. The fibulas were averagely divided into four segments and the locations of relevant vessels and nerves were ascertained.Results: All specimens had 1 fibular nutrient artery and 4-9 arcuate arteries except 1 specimen which had only 1 arcuate artery. The fibular nutrient artery and the first three arcuate arteries were constantly located between the distal half of the 1/4 segment and 2/4 segment of the fibula. The muscular branch of the superficial peroneal nerve passed through the surface of the periosteum in the 2/4 segment of the fibula.Conclusions: The most proximal osteotomy point locates at the midpoint of the 1/4 segment by which it ensure the maximal potential for preserving the nutrient vessels. The muscular branch of the superficial peroneal nerve is fragile to injury at the 2/4 segment of the fibula. [ABSTRACT FROM AUTHOR]

Background: Apatinib is an oral small-molecule tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptor-2. Oral vinorelbine is a semisynthetic chemotherapeutic agent of vinorelbine alkaloids. Apatinib and oral vinorelbine have been proved to be effective in the treatment of metastatic breast cancer (mBC). At present, several small sample clinical trials have explored the efficacy of apatinib combined with oral vinorelbine in the treatment of mBC., Methods: This retrospective study included 100 human epidermal growth factor receptor-2 (HER2)-negative mBC patients who received low-dose apatinib (250 mg orally per day) plus oral vinorelbine until disease progression or intolerance during February 2017 and March 2023. The progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), and safety were analyzed by SPSS 26.0 software and GraphPad Prism 8 software. Cox proportional hazards regression model for univariate and multivariate was used to identify factors significantly related to PFS and OS., Results: The median follow-up time for this study was 38.1 months. Among 100 patients with HER2-negative mBC, 66 were hormone receptor (HR)-positive/HER2-negative and 34 were triple-negative breast cancer (TNBC). The median PFS and OS were 6.0 months (95% CI, 5.2-6.8 months) and 23.0 months (95% CI, 19.9-26.1 months). There were no statistical differences in PFS (p = 0.239) and OS (p = 0.762) between the HR-positive /HER2-negative and TNBC subgroups. The ORR, CBR, and DCR were 21.0%, 58.0%, and 78.0%, respectively. Ninety-five patients (95.0%) experienced varying grades of adverse events (AEs) and 38.0% of patients for Grades 3-4. The most common Grades 3-4 AEs that we observed were neutropenia (30.0%) and leukopenia (25.0%)., Conclusion: Low-dose apatinib combined with oral vinorelbine demonstrates potential efficacy and well tolerated for pretreated HER2-negative mBC., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Potentially substantial impacts on the prognosis have been observed in individuals undergoing endovascular treatment due to cytochrome P450 2c19 (C YP2C19 ) polymorphism. In an attempt to improve prognosis and lower the recurrence rate, this study investigated the CYP2C19 polymorphism in acute ischemic stroke patients., Materials and Methods: A retrospective analysis was performed on 292 patients with cerebral infarction who had acute endovascular recanalization at the Department of Neurology of Chongqing Hospital of Traditional Chinese Medicine between May 2017 and 2019. The patients were categorized into rapid-, medium-, and slow-metabolism groups based on CYP2C19 gene polymorphism, and their prognosis was monitored. In addition, the prognosis of 188 patients selectively receiving carotid artery stenting at a selected time was also observed., Results: Among the 292 cerebral infarction cases receiving acute endovascular recanalization, the patients in the CYP2C19 rapid-metabolism group regularly took clopidogrel and aspirin combined with antiplatelet therapy and suffered from reoccurrence of apoplexy and cerebral hemorrhage; the 90-day good prognosis had a statistical difference ( P < 0.05, prognostic assessment includes hospitalization and 6 months after discharge) and the other adverse events had no statistical difference (including mortality). The 188 patients selectively receiving carotid artery stenting had a recurrence of apoplexy, cerebral hemorrhage, and restenosis rate with a statistical difference ( P < 0.05), and the other adverse events had no statistical difference., Conclusions: In conclusion, the findings of the current study indicate that irrespective of whether patients are undergoing selective carotid artery stenting or acute endovascular recanalization, those with rapid CYP2C19 metabolism have a significantly lower likelihood of experiencing adverse prognostic events compared to those with intermediate and slow metabolism. Furthermore, this group also has a more favorable prognosis than the other two groups., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Annals of Indian Academy of Neurology.)

Objective: To evaluate the efficacy and safety of microwave ablation (MWA) plus ethanol ablation (EA) for different types of benign mixed thyroid nodules., Methods: A total of 81 patients with 81 benign mixed thyroid nodules were enrolled into the study; 39 were divided to the MWA group and 42 to the combined group (MWA combined with EA). Nodule ablation rate, volume reduction rate (VRR) and surgical complications of all patients were analyzed before and after treatment., Results: The mean ablation rate were 86.49 ± 6.68% and 90.09 ± 5.79% in the microwave and combined groups respectively, and the ablation rate of nodule decreased as the nodule volume increased. For nodules ≥15 ml in volume, the mean ablation rate of the combined group was higher than that of the microwave group (all P < 0.05). The mean VRR at 12 months postoperatively was 89.58 ± 4.32% in the microwave group and 92.92 ± 3.49% in the combined group, showing statistical significantly different between both arms (P = 0.001). The combined group decreased in volume more significantly than the microwave group for nodules with 20-50% or 50-80% cystic proportions or >15 ml in volume (all P < 0.05). The complication rate was 23.08% and 2.38% respectively., Conclusion: MWA combined with EA is more effective than MWA for treating mixed thyroid nodules. MWA combined with EA may be the first approach for nodules with >20% cystic proportions or volume >15 ml., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: This study aims to investigate the differences in safety and antidepressant effects of multi-infusion ketamine treatment between elderly and young adults with depression., Methods: The safety, antidepressant, and anti-suicidal effects of multi-infusion ketamine were compared between 19 elderly (≥50 years) and 116 younger (<50 years) adults with depression; all were treated with six ketamine infusions (0.5 mg/kg). Montgomery-Åsberg Depression Rating Scale (MADRS) was used to measure the depressive symptoms, and suicidal ideation was measured with Beck Scale for Suicide Ideation (SSI)-part 1, Hamilton Rating Scale for Depression (HAMD) item 3, and (MADRS) item 10. Dissociative and psychotomimetic symptoms were evaluated based on the Clinician-Administered Dissociative States Scale (CADSS) and the Brief Psychiatric Rating Scale (BPRS)-four items., Results: Multi-Ketamine infusions resulted in a lower (trend) antidepressant response (37.1 % versus 57.8 %) and antidepressant remission (15.8 % versus 47.4 %) in elderly patients with depression compared with younger patients with depression (all ps > 0.05). Interestingly, elderly patients with depression had a higher MADRS score after six ketamine infusions compared with younger patients (p = 0.04). No significant differences in SSI-part 1 scores, HAMD item 3 scores, MADRS item 10 scores, CADSS scores, and BPRS-four items scores were found between the two groups at any assessment point (all ps > 0.05)., Conclusion: Our study shows that repeated-dose infusions of ketamine may be a feasible treatment strategy in elderly Chinese patients with depression; however, elderly patients with depression may be less responsive to ketamine compared with younger adults with depression., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: Accumulating evidence suggests that the effects of ketamine administered intravenously at subanaesthetic doses on both anhedonic symptoms and suicidal ideation occur independently of depressive symptoms in major depressive disorder (MDD) and bipolar disorder (BD). This study sought to determine the relationship between anhedonia and suicidal ideation after serial ketamine infusions., Methods: A total of 79 subjects with either treatment-refractory MDD ( n  = 60) or BD ( n  = 19) were included in a clinical ketamine study. The Montgomery-Åsberg Depression Rating Scale (MADRS) anhedonia factor and the first five items of the Scale for Suicidal Ideations (SSI-Part I) were used to assess anhedonia symptoms and suicidal ideation, respectively., Results: At baseline, anhedonia, as measured by the MADRS, was not significantly associated with suicidal ideation or specific suicide-related ideation as measured by SSI-Part I (all p 's > 0.05). Only the 'wish to die' and 'desire to make a suicide attempt' items were positively associated with anhedonia at two weeks after the sixth ketamine infusion, which was independent of the reductions in depressive symptoms (all p 's < 0.05)., Conclusion: Anhedonia as measured by the MADRS appeared to not be positively related to suicidal ideation after serial ketamine infusions.KEY POINTSSerial ketamine (0.5 mg/kg) infusions have shown quick and dramatic antisuicidal and antianhedonic effects in patients with depression.The association between anhedonia and suicidal ideation after serial ketamine infusions is unclear.Anhedonia appeared to not be positively related to suicidal ideation after serial ketamine infusions.

Background: Anlotinib is a novel oral small-molecule tyrosine kinase inhibitor (TKI), which can inhibit angiogenesis. The purpose of this study was to evaluate the efficacy and safety of anlotinib combined with chemotherapy in patients with metastatic triple-negative breast cancer (TNBC)., Methods: This phase II clinical trial included 40 patients with metastatic TNBC who had previously received anthracycline and/or taxane treatment. All patients received anlotinib combined with chemotherapy. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR) and safety., Results: During May 1, 2019 and April 30, 2022, there were 40 patients enrolled in this study. The median PFS and median OS were 8.8 months (95% confidence interval [CI] 6.5-11.1 months) and 19.0 months (95% CI, 12.1-25.9 months), respectively. The ORR, CBR and DCR were 40.0% (16/40), 85.0% (34/40) and 95.0% (38/40), respectively. Cox univariate and multivariate analyses demonstrated that having more than 3 metastatic sites (p = 0.001; p = 0.020) was an independent and meaningful unfavorable prognostic factor for PFS. 37.5% of patients had grade 3 to 4 treatment-related adverse events (TRAEs). The grade 3 to 4 TRAEs included neutropenia (22.5%), leukopenia (20.0%), secondary hypertension (10.0%), hand-foot syndrome (5.0%), vomiting (5.0%), proteinuria (5.0%) and thrombocytopenia (2.5%). None of the patients withdrew from the study or died due to TRAEs., Conclusion: In this single-arm study, the treatment of metastatic TNBC with anlotinib combined with chemotherapy showed certain efficacy, and its toxicity was acceptable., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huang, Xie, Chen, Zhang, Chen, Bai, Lan, Song, Guo and Du.)

Purpose: A substantial need for effective and safe treatment options is still unmet for patients with heavily pre-treated human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). Herein, we assessed the efficacy and safety of pyrotinib plus trastuzumab and chemotherapy in patients with heavily treated HER2-positive MBC., Methods: In this single-arm exploratory phase II trial, patients with HER2-positive MBC previously treated with trastuzumab plus lapatinib or pertuzumab, received pyrotinib plus trastuzumab and chemotherapy. The primary end point was progression-free survival (PFS) in the total population (TP). Secondary end points included PFS in the subgroup with brain metastases (Sub-BrM), confirmed objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), exploration of predictive factors of PFS, and safety., Results: Between November 1, 2018, and March 31, 2021, 40 patients were eligible for this study. The median PFS reached 7.5 months (95% confidence interval [CI] 4.7 to 9.9 months) and 9.4 months (95% CI 6.6 to 12.1 months) in the TP and Sub-BrM, respectively. ORR was 50.5% (20/40). CBR was 75.5% (30/40) and DCR reached 97.5% (39/40). Cox univariate and multivariate analyses demonstrated that liver or/and lung metastases was the significant adverse prognostic factor for PFS (p = 0.018; p = 0.026; respectively). The most frequent grade 3 or 4 treatment-related adverse events were diarrhea, neutropenia and leukopenia. No new safety signals were observed., Conclusion: Pyrotinib plus trastuzumab and chemotherapy offered a promising option with manageable safety profile for heavily pre-treated HER2-positive MBC, especially for those without liver or/and lung metastases., (© 2022. The Author(s).)

The efficacy and tolerability of eribulin mesylate, a synthetic halichondrin B analog, in patients with metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes have been established. Acute-on-chronic liver failure (ACLF) is a clinical syndrome manifesting as acute and severe hepatic derangement resulting from varied insults in patients with established chronic liver disease or cirrhosis who did not previously receive eribulin. A middle-aged woman diagnosed with MBC and diffuse liver metastases who was pretreated with multi-line chemotherapy received eribulin as eighth-line chemotherapy and presented with hepatic encephalopathy, rapid bilirubin elevation, and significant coagulation dysfunction on day 4 in cycle 1. The patient was diagnosed with ACLF induced by eribulin. Therefore, ACLF may be a lethal and rare adverse event when patients with chronic liver metastases receive eribulin treatment, and clinicians' awareness should be increased for optimal prevention and prompt diagnosis and treatment.

Objectives: Accumulating evidence supports a role for vascular endothelial growth factor (VEGF) in the pathogenesis of depression, but its relationship with the antisuicidal effects of ketamine is not clear. Our objective was to determine whether there was an association between the plasma VEGF (pVEGF) concentrations and the antisuicidal response to serial ketamine infusions., Methods: Six ketamine infusions (0.5 mg/kg) over a 12-day period were administered to sixty depressed individuals suffering from suicidal ideation. The Hamilton Depression Rating Scale (HAMD) suicide item, the Montgomery-Åsberg Depression Rating Scale (MADRS) suicide item, and the Beck Scale for Suicide Ideation (SSI-part I) were used to assess suicidal ideation at baseline, 1 day after the first infusion (day 1), 1 day following the last infusion (day 13), and again 2 weeks post-infusion (day 26). For this purpose, plasma was obtained at baseline, day 13 and 26., Results: The rates of antisuicidal response to ketamine were 61.7% (37/60), 81.7% (49/60), and 73.3% (44/60) at days 1, 13, and 26, respectively. The linear mixed model revealed significant time effects on suicidal ideation and pVEGF concentrations over time (all Ps < 0.05). Antisuicidal responders did not have significantly altered pVEGF concentrations compared with non-responders on day 13 and day 26 (all Ps > 0.05). No significant correlation was found between the baseline pVEGF concentration and suicidal ideation as measured by the SSI part 1, HAMD suicide item and MADRS suicide item on days 1, 13, and 26 (all ps > 0.05)., Conclusion: This preliminary finding does not support a role for VEGF in the antisuicidal effects of serial ketamine treatments in individuals with depression and suicidal ideation. Further research is needed to confirm and expand these findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zheng, Gu, Zhou, Wang, Lan, Zhang and Ning.)

Objectives: Anhedonia is a common, persistent, and disabling phenomenon in patients with major depressive disorder (MDD) and bipolar depression (BD). This study was conducted to investigate the comparative effectiveness of repeated ketamine infusions in treating anhedonia in Chinese individuals suffering from MDD and BD., Methods: Ninety-seven individuals suffering from MDD (n = 77) or BD (n = 20) were treated with six intravenous infusions of ketamine (0.5 mg/kg) administered over 40 min. Anhedonia was measured through the Montgomery-Åsberg Depression Rating Scale (MADRS). The antianhedonic response and remission were defined as ≥ 50% and ≥ 75% reduction in MADRS anhedonia subscale score one day after the sixth infusion, respectively., Results: Anti-anhedonic response and remission rates after the sixth ketamine infusion were 48.5% (95% confidence interval =  38.3%-58.6%) and 30.9% (95% confidence interval = 21.6%-40.3%), respectively. When compared to baseline, a significant reduction in the MADRS anhedonia subscale score was observed at 4 h after the first infusion and was maintained with repeated infusions at any time point (all Ps < 0.05). The anti-anhedonic effect of ketamine did not differ between the MDD and BD groups., Conclusion: This preliminary study found that repeated ketamine infusions appeared to be effective at rapidly ameliorating anhedonia, with similar efficacy in MDD and BD., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: To first explore the role of plasma vascular endothelial growth factor (VEGF) concentrations in ketamine's antianhedonic effects, focusing on Chinese patients with treatment-refractory depression (TRD). Methods: Seventy-eight patients with treatment-refractory major depressive disorder (MDD) or bipolar disorder (BD) were treated with six ketamine infusions (0.5 mg/kg). Levels of anhedonia were measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) anhedonia item at baseline, day 13 and 26. Plasma VEGF concentrations were examined at the same time points as the MADRS. Results: Despite a significant reduction in anhedonia symptoms in individuals with treatment-refractory MDD ( n = 59) or BD ( n = 19) after they received repeated-dose ketamine infusions ( p < 0.05), no significant changes in plasma VEGF concentrations were found at day 13 when compared to baseline ( p > 0.05). The alteration of plasma VEGF concentrations did not differ between antianhedonic responders and non-responders at days 13 and 26 (all p s > 0.05). Additionally, no significant correlations were observed between the antianhedonic response to ketamine and plasma VEGF concentrations (all p s > 0.05). Conclusion: This preliminary study suggests that the antianhedonic effects of ketamine are not mediated by VEGF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zheng, Gu, Zhou, Wang, Lan, Zhang, Shi, Wang and Ning.)

LianhuaQingwen capsule, prepared from an herbal combination, is officially recommended as treatment for COVID-19 in China. Of the serial pharmacokinetic investigations we designed to facilitate identifying LianhuaQingwen compounds that are likely to be therapeutically important, the current investigation focused on the component Glycyrrhiza uralensis roots (Gancao). Besides its function in COVID-19 treatment, Gancao is able to induce pseudoaldosteronism by inhibiting renal 11β-HSD2. Systemic and colon-luminal exposure to Gancao compounds were characterized in volunteers receiving LianhuaQingwen and by in vitro metabolism studies. Access of Gancao compounds to 11β-HSD2 was characterized using human/rat, in vitro transport, and plasma protein binding studies, while 11β-HSD2 inhibition was assessed using human kidney microsomes. LianhuaQingwen contained a total of 41 Gancao constituents (0.01-8.56 μmol/day). Although glycyrrhizin (1), licorice saponin G2 (2), and liquiritin/liquiritin apioside (21/22) were the major Gancao constituents in LianhuaQingwen, their poor intestinal absorption and access to colonic microbiota resulted in significant levels of their respective deglycosylated metabolites glycyrrhetic acid (8), 24-hydroxyglycyrrhetic acid (M2 D ; a new Gancao metabolite), and liquiritigenin (27) in human plasma and feces after dosing. These circulating metabolites were glucuronized/sulfated in the liver and then excreted into bile. Hepatic oxidation of 8 also yielded M2 D . Circulating 8 and M2 D , having good membrane permeability, could access (via passive tubular reabsorption) and inhibit renal 11β-HSD2. Collectively, 1 and 2 were metabolically activated to the pseudoaldosterogenic compounds 8 and M2 D . This investigation, together with such investigations of other components, has implications for precisely defining therapeutic benefit of LianhuaQingwen and conditions for its safe use., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

Aims: Growing evidence suggests that vascular endothelial growth factor (VEGF) may be involved in the neuronal mechanisms underlying both depression aetiology and the response to ketamine treatments. The aim of this study was to examine whether changes in plasma VEGF levels are associated with the antidepressant effects of repeated ketamine infusions in patients with depression., Methods: Ninety-six patients with depression were enrolled and received six ketamine infusions during a 12-day period. Depressive symptom severity and plasma VEGF levels were measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) and an enzyme-linked immunosorbent assay (ELISA) respectively, at baseline, 13 days and 26 days., Results: Despite a significant improvement in MADRS scores after patients received six ketamine infusions ( p  < 0.001), no changes in plasma VEGF levels were observed at 13 days when compared with baseline. Moreover, no significant difference in plasma VEGF levels at baseline and 13 days was found between ketamine responders and nonresponders. No association was found between the antidepressant effects of repeated ketamine treatments and plasma VEGF levels., Conclusion: This study indicated that VEGF may not be a potential predictor of antidepressant response to repeated intravenous administration of ketamine in patients with depression., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2021.)

Objectives: Accumulating evidence has implicated that brain derived neurotrophic factor (BDNF) is thought to be involved in the pathophysiology of depression, but its correlation with ketamine's antidepressant efficacy focusing on Chinese individuals with depression is not known. This study was aim to determine the correlation of plasma BDNF (pBDNF) concentrations and ketamine's antidepressant efficacy., Methods: Ninety-four individuals with depression received six intravenous infusions ketamine (0.5 mg/kg). Remission and response were defined as Montgomery-Asberg Depression Rating Scale (MADRS) scores less than 10 and a reduction of 50% or more in MADRS scores, respectively. Plasma was collected at baseline and at 24 h and 2 weeks after completing six ketamine infusions (baseline, 13 d and 26 d)., Results: A significant improvement in MADRS scores and pBDNF concentrations was found after completing six ketamine infusions compared to baseline (all ps  < 0.05). Higher baseline pBDNF concentrations were found in ketamine responders/remitters (11.0 ± 6.2/10.1 ± 5.8 ng/ml) than nonresponders/nonremitters (8.0 ± 5.5/9.2 ± 6.4 ng/ml) (all ps  < 0.05). Baseline pBDNF concentrations were correlated with MADRS scores at 13 d ( t  =  - 2.011, p  = 0.047) or 26 d ( t  =  - 2.398, p  = 0.019) in depressed patients (all ps  < 0.05). Subgroup analyses found similar results in individuals suffering from treatment refractory depression., Conclusion: This preliminary study suggests that baseline pBDNF concentrations appeared to be correlated with ketamine's antidepressant efficacy in Chinese patients with depression., Competing Interests: The authors declare there are no competing interests., (©2021 Zheng et al.)

Background: Ketamine produces significant rapid-onset and robust antidepressant effects in patients with major depressive disorder. However, this drug also has transient cardiovascular stimulatory effects, and there are limited data about potential predictors of these cardiovascular effects., Methods: A total of 135 patients with unipolar and bipolar depression received a total of 741 ketamine infusions (0.5 mg/kg over 40 min). Blood pressure and pulse were monitored every 10 min during the infusions and 30 min after the infusions. Depressive, psychotomimetic and dissociative symptom severity was assessed at baseline and 4 hours after each infusion., Results: The maximum blood pressure and pulse values were observed at 30-40 min during infusions. The largest mean systolic/diastolic blood pressure increases were 7.4/6.0 mmHg, and the largest mean pulse increase was 1.9 beats per min. No significant change in blood pressure and pulse was found in the second to sixth infusions compared with the first infusion. Patients who were older (age⩾50 years), hypertensive and receiving infusions while exhibiting dissociative symptoms showed greater maximal changes in systolic and diastolic blood pressure than patients who were younger (age<50 years), normotensive and without dissociative symptoms (all p < 0.05). Hypertensive patients had less elevation of pulse than normotensive patients ( p < 0.05). Ketamine dosage was positively correlated with changes in systolic and diastolic blood pressure (all p < 0.05)., Conclusions: Blood pressure and pulse elevations following subanaesthetic ketamine infusions are transient and do not cause serious cardiovascular events. Older age, hypertension, large ketamine dosage and dissociative symptoms may predict increased ketamine-induced cardiovascular effects.

Background: This study is the first to examine the association between plasma levels of brain-derived neurotrophic factor (BDNF) and the antisuicidal effects of repeated ketamine infusions in depressed patients with suicidal ideation., Methods: Fifty-seven depressed patients with suicidal ideation received six ketamine infusions (0.5 mg/kg) during a 12 days period. Suicidality was measured with the Scale for Suicidal Ideations (SSI-part 1), item 10 of the Montgomery-Åsberg Depression Rating Scale (MADRS), and item 3 of the Hamilton Depression Rating Scale (HAMD) at baseline, 1 day after the first infusion (1 day), 1 day after the sixth infusion (13 days), and at 2 weeks after the last infusion (26 days). Plasma levels of BDNF were measured by enzyme-linked immunosorbent assay at baseline, 13 days, and 26 days., Results: Overall, 46 (80.7%) depressed patients with suicidal ideation had an antisuicidal response at 13 days. Despite a significant reduction in suicidal symptoms over time, no changes in plasma levels of BDNF were found after ketamine treatment when compared with baseline. Correlation analysis showed that no significant association was observed between the plasma levels of BDNF and the changes in the severity of suicidal symptoms as measured by SSI-part 1, item 10 of the MADRS, or item 3 of the HAMD at 1 day, 13 days, and 26 days (all p  < 0.05)., Conclusion: Our results indicated that plasma levels of BDNF may not serve as a biomarker for determining the antisuicidal effects of six ketamine infusions in depressed patients with suicidal ideation., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

Objective: The N-methyl-D-aspartate subtype glutamate receptor antagonist ketamine has rapid antidepressant and antisuicidal effects in treating treatment-resistant bipolar depression (TRBD). The neurocognitive effects of repeated ketamine infusions in TRBD are not known., Methods: Six intravenous infusions of ketamine (0.5 mg/kg over 40 min) were administered on a Monday-Wednesday-Friday schedule during a 12-day period on 16 patients with TRBD followed by a 2-week observational period. The assessment of neurocognitive function was conducted using the MATRICS Consensus Cognitive Battery at baseline, 13 and 26 days. Tasks were designed to test speed of processing, working memory, visual learning and verbal learning., Results: A significant improvement was found only in scores of speed of processing ( F = 9.9, p = 0.001) after a 2-week observational period, which was accounted for by the improvement of depression symptoms. There were no significant changes over time in terms of working memory, visual learning and verbal learning. Pearson correlation analysis showed that the improvement of depression symptoms through six ketamine infusions was greater among TRBD patients with lower working memory at baseline ( r = 0.54, p = 0.03). In multiple regression analysis, the significant correlation was still maintained (beta = 0.67, t = 2.2, p = 0.04)., Conclusion: This preliminary study indicated that six ketamine infusions were not harmful but were slightly beneficial for speed of processing in TRBD. However, this change was mainly accounted for the improvement of depression symptoms over time. Lower baseline working memory appears to be associated with greater antidepressant response after completion of six ketamine infusions in patients with TRBD., Competing Interests: The authors declare that they have no competing interests., (© 2020 Zheng et al.)

Background: Evidences suggest that inflammatory marker-mediated neuroplasticity contributes critically to brain changes following antidepressant treatment. To date, no study has examined the relationship between changes in hippocampal volume, depressive symptoms, and inflammatory markers following repeated ketamine treatment., Methods: Forty-four patients with major depressive disorder received six intravenous ketamine (0.5 mg/kg) infusions over 12 days. The Montgomery-Asberg Depression Rating Scale (MADRS) was used to assess depressive symptoms, and peripheral blood was collected to test multiple cytokines and tryptophan (TRP) metabolites at baseline, 24 h and 14 days after the sixth infusion (day 13 and day 26). Magnetic resonance imaging (MRI) scans were carried out at baseline and day13, and FreeSurfer software was used to process the T1 images and analyze hippocampal volume., Results: Following ketamine, a significant improvement in depressive symptoms, a small increase in right hippocampal volume and alterations in inflammatory markers was found. No significant association was found between changes in inflammatory markers and changes in hippocampal volume from baseline to day 13 (P>0.05), while a weak association was found between TRP metabolite changes and other cytokine changes from baseline to day 26 (beta=-0.357, t=-2.600, P = 0.013)., Limitations: The patients continued receiving previous medications during ketamine treatment, which may have impacted hippocampal volume and inflammatory markers., Conclusions: Hippocampal volume increase following ketamine was an independent neurobiological effect that was not associated with changes in peripheral inflammatory markers, suggesting a likely complex neurobiological mechanism of the antidepressant effect of ketamine., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: Ketamine has shown rapid antidepressant effects in depressed patients. However, the antidepressant and antisuicidal effects of repeated ketamine infusions in patients with treatment-resistant bipolar depression (TRBD) are not known., Methods: TRBD patients received six intravenous infusions of 0.5 mg/kg ketamine over 40 min on a Monday-Wednesday-Friday schedule during a 12-day period followed by a 2-week follow-up period. Depressive symptoms were measured by the Montgomery-Asberg Depression Rating Scale (MADRS) at baseline and at each follow-up visit., Results: Nineteen patients with TRBD were enrolled in the study, and 16 patients (84.2%) received all six ketamine infusions. After the first infusion, the rates of response and remission were 21.1% (95% CI: 0.9 to 21.2) and 15.8% (95% CI: 0 to 33.9), respectively, and after the sixth infusion, the rates of response and remission were 73.7% (95% CI: 51.9 to 95.5) and 63.2% (95% CI: 39.3 to 87.0), respectively. The average times for nineteen patients who responded and remitted were 9.1 and 12.5 days, respectively. There were large decreases in the scores on the MADRS and the Scale for Suicidal Ideation-part 1 within 4 h after the first infusion, and the decreases were maintained across subsequent infusions. There were no significant increases in dissociative and psychotomimetic symptoms as measured by the Clinician-Administered Dissociative States Scale (CADSS) and the Brief Psychiatric Rating Scale (BPRS)-4 items, respectively., Conclusion: These pilot findings suggest the feasibility of repeated ketamine infusions at subanaesthetic doses for patients with TRBD. Future controlled studies are needed to confirm and expand these findings., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest concerning this paper., (Copyright © 2020. Published by Elsevier B.V.)

Abnormal subcortical structures have been associated with major depressive disorder (MDD) and could be reversed by antidepressant treatment. To date no study has examined the relationship between subcortical volumes and repeated ketamine treatment. The current study investigated volume changes in specific subcortical structures and hippocampal subfields after six ketamine infusions. Forty-four patients with MDD received six subanesthetic dose infusions of ketamine. Depressive symptoms were assessed and magnetic resonance imaging scans were performed before and after six ketamine infusions. FreeSurfer software was used to process the T1 images and analyze the volumes of the subcortical regions and hippocampal subfields. After six ketamine infusions, increases were observed in the volumes of the left amygdala; the right hippocampus; the cornu ammonis 4 body, granule cell and molecular layer of the dentate gyrus body in the left hippocampus; and the cornu ammonis 4 head and molecular layer head in the right hippocampus. Positive correlations were found between symptom improvement and the pretreatment volumes of the right thalamus (r = 0.501; P = 0.001) and left subiculum head of the hippocampus (r = 0.471; P = 0.002), and changes in the volumes of the left amygdala (r = -0.452; P = 0.003) and the left cornu ammonis 4 body (r = -0.537; P < 0.001). Our findings provided evidence for critical roles of the amygdala and specific hippocampal subfields in the antidepressant effect of repeated ketamine treatment. Relatively larger volumes in right thalamus and left subiculum head in the hippocampus can predict a superior clinical outcome of ketamine treatment in MDD patients.

We investigate whether slag and biochar applications have subsequent effects on greenhouse gas emissions from paddy fields by applying biochar (B), slag (S), and a biochar-slag mix (BS) to paddy fields in the Fuzhou Plain, China. Applications of the three treatments along with a control (CK) of no amendment were made in 2015 before early and late rice seedlings were transplanted. Two years later in 2017, the CO 2 , CH 4 , and N 2 O emissions in the different treatments and control were measured in the early and late rice growing seasons. The results showed that, in the rice growing season, the averaged CO 2 emission in the control, biochar, slag, and mixed applications were (1723.66±194.56), (1245.52±155.05), (1140.29±79.68), and (1055.83±62.13) mg·(m 2 ·h) -1 , respectively. The CO 2 emissions from the three treatments were significantly lower than the control group ( P <0.05), and the reduction ratios of each treatment to the control were 27.74%, 33.84%, and 38.75%, respectively. The averaged CH 4 emissions in the control, biochar, slag, and mixed applications were (0.45±0.03), (0.40±0.05), (0.36±0.10), and (0.25±0.04) mg·(m 2 ·h) -1 , respectively, which were lower, but not significantly so ( P >0.05), than the control. The ratios of CH 4 emissions from each treatment to the control were 11.11%, 20.00%, and 44.44%, respectively. The averaged N 2 O emissions from the control, biochar, slag, and mixed applications were (62.47±27.00), (115.09±30.94), (79.75±24.98), and (112.68±23.59) μg·(m 2 ·h) -1 , respectively. In comparison to the control, the biochar, slag, and mixed treatments increased the N 2 O emissions by 84.23%, 27.66%, and 80.37%, respectively. The global comprehensive warming potential indicated that the application treatments increased the comprehensive warming potential of the early and late rice paddy ecosystems; after 2 years of applying slag and biochar treatments, their effect on the emission reductions were not obvious.

Objective: To investigate the application value of superb microvascular imaging (SMI) in the diagnosis of penile vascular ED., Methods: Seventy-two ED patients underwent SMI and color Doppler flow imaging (CDFI), all ultrasonographically diagnosed with penile vascular ED. We compared SMI and CDFI in detecting the grades of blood flow in the cavernous artery and the lengths of time needed to obtain satisfactory blood flow spectrum from the patients., Results: SMI mainly revealed grades Ⅲ and Ⅳ blood flow, in 43 and 20 of the 72 patients (87.5%), while CDFI chiefly manifested grades Ⅰ and Ⅱ blood flow, in 26 and 32 cases respectively (80.6%). The former showed significantly better manifestations of the penile cavernous artery than the latter. It took less time to obtain the spectrums of grades Ⅲ and Ⅳ blood flow (［1.52 ± 0.18］ and ［1.21 ± 0.11］ min) than grades Ⅰ and Ⅱ (［5.23 ± 0.44］ and ［4.46 ± 0.65］ min), and SIM took significantly less time than CDFI (［1.32 ± 0.42］ vs ［4.53 ± 0.67］ min, P < 0.05)., Conclusions: SMI is superior to CDFI in better manifesting the blood flow of the penile cavernous artery and shortening the examination time, and therefore deserves a wide application in the diagnosis of vascular ED.

Chronic intermittent hypoxia (IH) contributes to obstructive sleep apnea (OSA)-related cardiovascular diseases through increasing oxidative stress. It has been widely recognized that estradiol decreases the risk for cardiovascular disease, but the estrogen replacement therapy is limited for its side effects. Thioredoxin (Trx) and its endogenous inhibitor, thioredoxin-interacting protein (Txnip), are associated with the protective effect of estradiol in some conditions. In this study, we aimed to explore whether estradiol could protect against IH-induced vascular injury, and the possible effect of Trx-1/Txnip in this process. Forty-eight adult female C57/BL6J mice were randomly divided into 4 groups, ovariectomy combined with IH group, sham operation combined with IH group, IH group and the control group. The mice treated with IH for 8 hrs/day, and 28 days. IH induced the injury of aorta, and ovariectomized mice were more prone to the IH-induced aortic injury, with higher level of oxidative stress. In vitro, estradiol increased Trx-1 level, but decreased the level of Txnip and oxidative stress in human umbilical vein endothelial cells (HUVECs) treated with IH for 16 hrs. Knock-down of Txnip by specific siRNA rescued oxidative stress and apoptosis. In conclusion, estradiol protects against IH-induced vascular injury, partially through the regulation of Trx-1/Txnip pathway.

Objective: To explore the correlation between intermittent hypoxia (IH)-induced apoptosis of human umbilical vein endothelial cells (HUVECs) and release of cytochrome C (cytC) from mitochondria., Methods: HUVECs in IH groups were exposed to repetitive cycles (1% O2 5 min alternating with 21% O2 5 min, 37 ℃, 5% CO2) for different exposure time (8, 16 and 24 h, respectively), while the control group were placed in an ordinary incubator (21% O2, 37 ℃, 5% CO2) for 24 h. Apoptosis rate of HUVECs were determined by using Annexin V-FITC/PI apoptosis detection kit. The mitochondria ultrastructure was observed under transmission electron microscope (TEM). The mitochondria and cytoplasm of HUVECs were isolated by differential centrifugation, and the expression cytC in two separations were detected by Western blot. The correlation between the release of cytC and apoptosis rate was analyzed., Results: TEM showed that mitochondria in HUVECs treated with IH appeared significant swelling, cristae rupture and vacuolization, compared with intact mitochondria in control group. Apoptosis rates in IH groups of 8, 16 and 24 h were significantly higher than control group[(6.710±0.599)%, (8.863±1.190)% and (9.607±1.266)% vs (2.450±0.795)%]in a time-dependent manner (all P<0.05). Apoptosis rates in IH groups positively correlated with cytC expression in cytoplasm (r=0.741, P=0.022)., Conclusion: IH-induced cytC release from mitochondria promotes apoptosis of HUVECs, which participates in IH-induced endothelial injury.

Objective: To detect platelet anti-HPA-1a and -1b antibodies using recombinant GPIIIa fragments coupled to Luminex beads., Methods: The sensitivity of 2 techniques, monoclonal antibody specific immobilization of platelet antigen (MAIPA) and Luminex bead assay, was compared using 12 twofold-serial dilutions (from neat to 1 in 2048) of an anti-HPA-1a WHO international standard. The specificity of Luminex assay to identify anti-HPA-1a and -1b antibodies was assessed using 8 negative or positive controls and 36 blinded samples provided by WHO Platelet Workshop., Results: The sensitivity of MAIPA and Luminex bead assay to detect anti-HPA-1a was dilution 1/64 (i.e. 1.56 IU/ml) and far more than dilution 1/2048 (i.e. 0.049 IU/mL), respectively. The Luminex bead assay could specifically identify negative and positive controls of anti-HPA-1a and -1b. All results of 36 blinded samples by Luminex assay were accordant to reference results except one sample which contained high concentration antithetical antibody and resulted in false positive of anti-HPA-1b. Cross-reactivity was also not observed with the samples containing HLA, ABO or other platelet antibodies., Conclusion: The Luminex beads coupled with recombinant GPIIIa fragments can be used to detect HPA-1 system antibodies with sufficient sensitivity and specificity, that is suitable for the detection of platelet alloantibodies in clinical alloimmune thrombocytopenia.

Purpose: Obstructive sleep apnea hypopnea syndrome (OSAHS) is an independent risk factor for development of hypertension. Epidemiological surveys have found that risk of cardiovascular diseases increased in postmenopausal women. However, it is not well known about the profiles of hypertension of women with OSAHS in their different reproductive stages. This study aimed to investigate the difference of blood pressure profile between pre and postmenopausal women with OSAHS., Methods: Women who were tested by polysomnography (PSG) (n = 207) in Ruijin Hospital were recruited in the study. The subjects were divided into two groups of premenopausal women (24 with and 30 without OSAHS), and two groups of postmenopausal women (116 with and 37 without OSAHS). Among the groups, the differences of demographic and PSG variables were compared. The factors influencing blood pressure were further studied., Results: The prevalence of hypertension (56.9 %) in postmenopausal OSAHS patients was higher than the other three groups. Among OSAHS patients, both average systolic blood pressure (SBP) and diastolic blood pressure (DBP) of postmenopausal women were higher than those of premenopausal ones [(129.9 ± 16.16 mmHg vs. 123.7 ± 18.89), (84.96 ± 9.88 mmHg vs. 78.81 ± 10.34), P = 0.05, P < 0.01, respectively], with the elevation of DBP being more pronounced. For premenopausal women, body mass index (BMI) was the only factor affecting blood pressure (p < 0.05); in postmenopausal women, BMI was a factor affecting SBP, while BMI and apnea hypopnea index (AHI) affecting DBP (P < 0.05)., Conclusion: Blood pressure profile of postmenopausal women with OSAHS was affected by both BMI and AHI. But those of premenopausal ones were predominantly related to BMI.

The individual with the deficiency of CD36 antigen on platelet displayed the risk of anti-CD36 immune reaction induced by transfusion, which is one of the reasons for platelet transfusion refractoriness (PTR). This study was purposed to detect the expression level of CD36 antigen on platelet by flow cytometry among apheresis platelet donors of Hangzhou area, and the frequency of CD36 deficiency was analyzed. Platelet-rich plasma (PRP) was separated from fresh anticoagulant whole blood by centrifugation, then the platelets were washed and adjusted to 1×10(6). The platelets were incubated with FITC-labeled CD36 and PE-labeled CD41 monoclonal antibodies, then the expression level of CD36 was detected by flow cytometry. The CD36 expression on monocytes for the samples of CD36-deficiency on the platelets was further analyzed. The results showed that 7 samples with CD36 antigen deficiency were found in 192 apheresis platelet donors. The frequency of CD36 deficiency was 3.6% and all of them were typeII deficiency. The significant difference of CD36 antigen expression was observed in the platelet donors of Hangzhou population, among them 59 individuals with low expressed CD36 antigen and 126 individuals with highly expressed CD36 antigen were found according to the geometric mean fluorescence intensity. It is concluded that the CD36 antigen deficient phenotype existed in the population, these data will provide the information for research of the CD36 antigen distribution and help to solve the platelet transfusion refractoriness.

The fluorescence properties of imidacloprid was studied based on the basic theory that organic molecules can emit fluorescence as they are excited by rays. The fluorescence spectra were obtained under the condition of different content of imidacloprid in apple juices and pure apple juices respectively through fluorescence spectrometer, and the relation between their fluorescence intensity and content of imidacloprid was analyzed. The experiment results show that the most intensive fluorescence (373 nm) was found in the spectrum of imidacloprid, while the fluorescence was not found in the pure apple juices with 234 nm as the excitation wavelength. Then the imidacloprid solution was added to the fruit juices increasingly. The best prediction model was obtained for the contend of imidacloprid in the apple juices, the coefficient of determination is 0.99674, and the accuracy is higher than 90%. As a result, it is fast and feasible to carry out the detection and analysis of the pesticide residue of imidacloprid in the apple juices.

Polarized three-dimensional fluorescence spectra of different kinds of milk were measured, including pure milk, milk with high calcium, and milk with high calcium but low fat produced by YiLi and MengNiu. It was found that the fluorescence intensity is stronger when excitation and emission polarizer orientation is parallel. The angle between excitation dipole and emission dipole of all kinds of milk equivalent chromophore was estimated by a simple model, indicating that they all less than 40 degrees. The angle for milk with high calcium but low fat is less than that of pure milk and milk with high calcium. And in the experiment, the polarized fluorescence intensity of milk with high calcium but low fat is significantly greater than the others, which fitted with the model estimation.

This study was aimed to investigate the distribution of rare blood group in Zhejiang Han population. The H(-) (H system), GPA(-) and s(-) (MNS), Rhnull, Rhmod, D--, CCDEE, CCdEE (variations of Rh), GPC(-) (Gerbich), i(+) (I), Lu(b-) (Lutheran), Js(b-) and k(-) (Kell), Fy(a-) (Duffy), Ok(a-) (Ok), Di(b-) (Diego) phenotypes were screened by serological or molecular methods. Jk (a-b-) phenotype was detected by urea hemolytic test. The results showed that one Di (a+b-) individual was found in 1618 blood donors, three Fy (a-b+) individuals in 1007 donors and one CCdEE individual in 633 Rh negative donors. No Jk (a-b-), H(-), GPA(-), s(-), GPC(-), i(+) (adult), Lu(b-), k(-), Js(b-), Lu(b-) and Ok(a-) phenotypes were found in this large scale survey. It is concluded that Di (a+b-), Fy (a-b+), CCdEE phenotypes are confirmed in the blood donors and this study provides the distribution data of erythrocyte rare blood group in Zhejiang Han population.

Objective: To analyze the molecular basis for an individual with ABx09 phenotype of ABO subtype., Methods: The ABO group antigens on red blood cells of the proband were identified by monoclonal antibodies, and the ABO antibody in serum was detected by standard A, B, O cells. The exons 1 to 7 of ABO gene were amplified by polymerase chain reaction (PCR) respectively and the PCR products were sequenced directly. The amplified products for exons 5 to 7 were also cloned by TOPO TA cloning sequencing kit to split the two alleles apart, selected colonies were sequenced bidirectionally for exons 5 to 7 of the ABO gene. The samples of the proband's parents were collected, then serological test of the blood group and sequence analysis for exons 6 and 7 of ABO gene were preformed., Results: Both A and B antigens were detected on red blood cells of the proband and there was anti-B antibody in the serum. There was no G deletion at position 261, while 297AG in exon 6, 467CT, 526CG, 657CT, 703GA, 796CA, 803GC, 889GA and 930GA heterozygote in exon 7 were detected by direct DNA sequencing, which can be assigned for A102Bx09 genotype. After cloning and sequencing, two alleles A102 and Bx09 were obtained. The sequence of Bx09 had one nucleotide changes (G to A) at position 889 compared with that of B101, which resulted in an amino acid change of Glu to Lys at 297 position. The Bx09 in the proband was inherited from her mother by family investigation., Conclusion: G to A at nt889 of alpha-1,3 galactosyltransferasegene can result in Bx09 phenotype, with the presence of anti-B antibody in serum.

The objective of this study was to analyze the molecular genetic basis for 2 individuals with A2B phenotype of ABO subtype. The ABO group antigens on red blood cells were identified by monoclonal antibodies and the ABO antibodies in serum were detected by the standard A, B, O cells. The exon 5 to exon 7 coding region of ABO gene was amplified by polymerase chain reaction (PCR) and the PCR product was sequenced directly after the enzymes digested. The amplified product was also cloned by TOPO TA cloning sequencing kit to split the 2 alleles apart and chosen colonies were sequencing bidirectionally for exon 6 to 7 of ABO gene. The results showed that both A and B antigen were identified on red blood cells of the individuals and there was anti-A1 antibody in their serum. There was no 261G deletion and showed 297A/G, 467C/T, 526C/G, 657C/T, 703G/A, 742C/T, 796C/A, 803G/C, 930G/A heterozygotes by direct DNA sequencing. After cloning and sequencing, it was obtained the B101 and one novel A allele. The novel allele has one nucleotide change at 742 position C to T compared with A102, which results in an amino acid Arg to Cys at 248 position and was nominated as A213. It is concluded that C742T mutation of the α1, 3 N-acetyl-D-galactosaminyl-transferase gene can lead to A2 phenotype and with anti-A1 antibody in serum.

Objective: To investigate the polymorphisms of platelet membrane glycoprotein genes related to human platelet alloantigen (HPA)-1 to 17w., Methods: The DNA segments of platelet membrane glycoprotein genes related to HPA-1 to 17w were amplified using author's designed primers. The amplification products were purified and directly sequenced to identify the HPA genotype and glycoprotein gene polymorphisms., Results: Thirteen new single nucleotide polymorphisms (SNPs) and a micro-satellite sequence were found in the glycoprotein genes from the 112 random samples, in which two SNPs (1333G/A and 1960G/A) in ITGB3 gene result in two amino acid change (V419M and E628K) on glycoprotein GPIIIa., Conclusion: New variants in platelet membrane glycoprotein genes were identified, which may lead to structure change of platelet membrane glycoprotein and affect the accuracy of partial HPA genotyping method.

Objective: To clone and investigate the polymorphism of the 5'-untranslated region (5'-UTR) of the human ABO gene, in order to provide the basis for exploring the transcriptional regulation of the human ABO histo-blood group genes., Methods: ABO phenotypes of 30 unrelated healthy blood donors were determined by serological technique, their genotypes were analyzed by sequencing the exons 6 and 7 of the ABO gene. Nearly 5 kb of the 5'-UTR of ABO gene was obtained by PCR amplification and sequencing was performed bidirectionally. Haplotypes of samples with heterozygous sites in the 5'-UTR of ABO gene were separated and analyzed after cloning., Results: Twenty polymorphic sites were identified in these samples where ABO genotypes were consistent with serological phenotypes. It included sixteen nucleotide sequence variations, one 8 bp deletion, one 6 bp deletion/insertion, one 36 bp insertion and one 43 bp repeats. Among them, 11 were novel polymorphic sites. Seven different haplotypes of 5'-UTR of ABO gene were defined to the cis/trans linkage of those mutations., Conclusion: There were polymorphisms in the 5'-UTR of ABO gene and the nucleotide sequences near the proximal promoter were conservative.

This study was purposed to investigate the molecular basis of a para-Bombay phenotype for screening and identification of rare blood group. ABO and H phenotypes of the proband were identified by serological techniques. The exon 6 to exon 7 of ABO gene and full coding region of α-1,2-fucosyltransferase (fut1) gene of the proband were analyzed by polymerase chain reaction and direct sequencing of the amplified fragments. The haplotype of compound heterozygote of fut1 was also identified by cloning sequencing. The results indicated that a rare para-Bombay phenotype was confirmed by serological techniques. Two deletion or insertion variant sites near nucleotide 547 and 880 were detected in fut1 gene. The results of cloning sequence showed that one haplotype of fut1 gene was two bases deletion at 547-552 (AGAGAG→AGAG), and another one was two bases deletion at position 880-882 (TTT→T). Both two variants caused a reading frame shift and a premature stop codon. It is concluded that a rare para-Bombay phenotype is found and confirmed in blood donor population. The molecular basis of this individual is compound heterozygote of two bases deletion on fut1 gene which weaken the activity of α-1, 2-fucosyltransferase.

In order to explore the effects of 35C > T and 682A > G mutations on the activity of alpha-(1,2) fucosyltransferase, the coding region of fut1 gene was amplified by polymerase chain reaction (PCR) from genomic DNA. PCR product was ligated into expression vector using TOPO TA cloning kit to obtain the recombinant plasmids. The recombinant plasmids were transfected into COS-7 cells by liposome method. After screening by using G418, H antigen expression on the COS-7 was tested by flow cytometry and fut1 mRNA was detected by real-time PCR. The results indicated that three kinds of recombinant plasmids pcDNA3.1/V5-His-wild (35C + 682A), pcDNA3.1/V5-His-35T and pcDNA3.1/V5-His-35T-682G were successfully constructed. After transfection, the H antigen expressed on membrane of COS-7 cells at the second day, with the maximum level of expression at the fourth day. When compared with pcDNA3.1/V5-His-wild transfected cells, the H antigen expression level of the 35T and 682G + 35T recombinant plasmids in the transfected cells was 52.7% and 13.3% on the fourth day, respectively. Although the level of fut1 mRNA decreased with prolonging of time, the mRNA expressed on the pcDNA3.1/V5-His-35T-682G transfected cells reached to 14% of the wild plasmids on the first day. It is concluded that 682A > G mutation obviously reduces the activity of alpha-(1,2) fucosyltransferase, while 35C > T mutation leads to partial reduction of H antigen in vitro expression.

The cholesterol with different concentration in hypercholesterolemia serum was studied by the method of spectroscopy technology. The absorption and fluorescence spectra of normal human serum and hypercholesterolemia serum were obtained respectively; the spectral characteristic of each sample and the difference between two kinds of samples were discussed too. The results indicate that the absorption and fluorescence spectra of hypercholesterolemia serum are different from those of normal human serum. The absorptivity and the fluorescence intensity of hypercholesterolemia serum are both higher than those of normal human serum. Besides, there are new absorptive peaks and new fluorescence peaks in the spectrogram. Thus, the abnormalism of cholesterol in serum can be judged by comparing the absorption and fluorescence spectra. The researches in the present paper provide an experimental foundation for the diagnosis of cholesterol in blood.

Ethanol solution can emit visible fluorescence when induced by UV light. With emission spectral profiles similar on the whole, the peaks are red-shifted distinctly when the excitation light alters from 200 to 250 nm. And the spectral profiles of ethanol solutions with different concentrations are also red-shifted when induced by the same wavelength of excitation light. A thorough analysis of the rule of spectrum peaks that are red-shifted is carried out and discussed in theory and in experiment. Investigation on the intrinsic fluorescence spectrum of ethanol solution and its characteristics will contribute to the study of the fluorescence spectra when ethanol serves as a solute and hydrolysis catalyst. Especially, this study will also help to offer a sensitive method of the determination of ethanol.