[Progress in methodological research on bridging the efficacy-effectiveness gap of clinical interventions(2): to improve the extrapolation of efficacy].

Objective: Randomized controlled trials (RCT) usually have strict implementation criteria. The included subjects' characteristics of the conditions for the intervention implementation are quite different from the actual clinical environment, resulting in discrepancies between the risk-benefit of interventions in actual clinical use and the risk-benefit shown in RCT. Therefore, some methods are needed to enhance the extrapolation of RCT results to evaluate the real effects of drugs in real people and clinical practice settings. Methods: Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results: A total of 12 articles were included. Three methods in the included literature focused on: ①improving the design of traditional RCT to increase population representation; ②combining RCT Data with real-world data (RWD) for analysis;③calibrating RCT results according to real-world patient characteristics. Conclusions: Improving the design of RCT to enhance the population representation can improve the extrapolation of the results of RCT. Combining RCT data with RWD can give full play to the advantages of data from different sources; the results of the RCT were calibrated against real-world population characteristics so that the effects of interventions in real-world patient populations can be predicted.

[Progress in methodological research on bridging the efficacy-effectiveness gap of clinical interventions (1): to improve the validity of real-world evidence].

Objective: Differences between randomized controlled trial (RCT) results and real world study (RWS) results may not represent a true efficacy-effectiveness gap because efficacy-effectiveness gap estimates may be biased when RWS and RCT differ significantly in study design or when there is bias in RWS result estimation. Secondly, when there is an efficacy- effectiveness gap, it should not treat every patient the same way but assess the real-world factors influencing the intervention's effectiveness and identify the subgroup likely to achieve the desired effect. Methods: Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results: Ten articles were included to discuss how to use the RCT research protocol as a template to develop the corresponding RWS research protocol. Moreover, based on correctly estimating the efficacy-effectiveness gap, evaluate the intervention effect in the patient subgroup to confirm the subgroup that can achieve the expected benefit-risk ratio to bridge the efficacy-effectiveness gap. Conclusion: Using real-world data to simulate key features of randomized controlled clinical trial study design can improve the authenticity and effectiveness of study results and bridge the efficacy-effectiveness gap.

[Real-world evidence and randomized controlled trials: the initiation, implementation, progress interpretation and revelation of RCT DUPLICATE (part 1)].

In recent years, researchers, pharmaceutical companies, and political makers gradually using more real-world data (RWD) to produce real-world evidence (RWE) for policy-making. A research team of Harvard University launched the RCT DUPLICATE project in 2018, aiming to replicate 30 randomized controlled trials using the medical claims database in order to explore methods for quantifying the efficacy-effectiveness gap and explain its potential sources, to enhance the credibility of the RWE. This paper reviews the background of RCT DUPLICATE Initiative, highlights the research purposes, research design and implementation process of the RCT DUPLICATE Initiative, to help domestic scholars better understand the scope and application value of RWE.

[Real-world evidence and randomized controlled trials: the initiation, implementation, progress interpretation and revelation of RCT DUPLICATE (part 2)].

With the promotion and application of big medical data, non-interventional real-world evidence (RWE) has been used by regulators to assess the effectiveness of medical products. This paper briefly introduces the latest progress and research results of the RCT DUPLICATE Initiative launched by the research team of Harvard University in 2018 and summarizes relevant research experience based on the characteristics of China's medical service to provide inspiration and reference for domestic scholars to conduct related RWE research in the future.

[Perioperative factors affecting the length of hospital stay after cesarean section of pregnant women with heart disease].

Objective: To explore the related factors influencing the length of hospital stay(LOS) of pregnant women with heart disease (PWHD) after cesarean section. Methods: A total of 306 patients with PWHD who underwent cesarean section from January 2012 to March 2019 were collected. Among them, 203 patients had not undergone heart surgery (uncorrected group) and 103 patients who had undergone heart surgery (corrected group) during the same period. Demographic, perioperative and postoperative data were recorded. Predictors associated with postoperative LOS were determined using univariate and multivariate linear regression analysis models. Results: (1) The median LOS after cesarean section in the uncorrected group was 6 days (5-8 days). The results of univariate linear regression analysis showed that 38 parameters had significant impact on LOS (P<0.05). The results of multivariate linear regression analysis showed that 5 parameters were independent risk factors for prolonged LOS in the uncorrected group; among them, the median LOS in uncorrected group with hypertensive disorders of pregnancy was 3 days longer than that in patients with PWHD alone [7 days (5-8 days) vs 4 days (4-5 days), ß=0.195, P=0.001]; the median LOS in uncorrected group with high serum creatinine was 3 days longer than normal patients [7 days (5-13 days) vs 4 days (4-5 days), ß=0.145, P=0.015]; the LOS of patients who chose general anesthesia was 2 days longer than that of patients who chose spinal anesthesia [6 days (4-8 days) vs 4 days (4-5 days), ß=0.154, P=0.007]; the LOS of patients with postoperative pulmonary infection was 4 days longer than that of patients without pulmonary infection [8 days (5-15 days) vs 4 days (4-5 days), ß=0.269, P<0.01]; the LOS of patients who admitted to ICU after surgery was 2 days longer than that not admitted patients [6 days (5-8 days) vs 4 days (4-5 days), ß=0.268, P<0.01]. (2) The median LOS after cesarean section in corrected group was 4 days (4-5 days). The results of univariate linear regression analysis showed that 8 parameters had significant impact on the LOS (all P<0.05). The results of multivariate linear regression analysis showed that 2 parameters, which were American Society of Anesthesiologists (ASA) grade (ß=0.198, P=0.028) and intraoperative blood loss (ß=0.285, P=0.003), were the independent risk factors for prolonged LOS in corrected group. Conclusion: Preoperative with hypertensive disorders of pregnancy, preoperative creatinine increase, intraoperative general anesthesia, postoperative pulmonary infection, and postoperative admission to ICU are independent predictors of prolonged LOS in uncorrected patients with PWHD; ASA classification and intraoperative bleeding are independent predictor of prolonged postoperative LOS in patients with corrected PWHD.

RETRACTED: Proton transport enabled by a field-induced metallic state in a semiconductor heterostructure.

Tuning a semiconductor to function as a fast proton conductor is an emerging strategy in the rapidly developing field of proton ceramic fuel cells (PCFCs). The key challenge for PCFC researchers is to formulate the proton-conducting electrolyte with conductivity above 0.1 siemens per centimeter at low temperatures (300 to 600°C). Here we present a methodology to design an enhanced proton conductor by means of a Na x CoO2/CeO2 semiconductor heterostructure, in which a field-induced metallic state at the interface accelerates proton transport. We developed a PCFC with an ionic conductivity of 0.30 siemens per centimeter and a power output of 1 watt per square centimeter at 520°C. Through our semiconductor heterostructure approach, our results provide insight into the proton transport mechanism, which may also improve ionic transport in other energy applications.

[Effectiveness of eradication regimen based on the bacterial susceptibility and CYP2C19 genotype in children with refractory Helicobacter pylori infection].

Objective: To evaluate the effectiveness of eradication therapy based on Helicobacter pylori (Hp) susceptibility and CYP2C19 genotype in children with refractory Hp infection. Methods: In this prospective observational cohort study, 156 children with Hp refractory to amoxicillin+clarithromycin+omeprazole triple regimen in Baoding Children's Hospital from December 2017 to May 2018 were enrolled. Ninety-two of them underwent Hp culture and CYP2C19 detection. Seventy-five cases with positive Hp culture were defined as culture successful group and were treated according to Hp susceptibility and CYP2C19 genotype. Seventeen cases with negative Hp culture were defined as culture failed group and were treated only based on the results of CYP2C19 genotype. Sixty-four children who did not have Hp culture and CYP2C19 gene testing were defined as the empirical eradication therapy group and were treated with quadruple regimen (amoxicillin+metronidazole+omeprazole+bismuth). Bacterial resistance, CYP2C19 polymorphism and therapeutic effectiveness between the three groups were compared using chi-square test. Results: Among the 75 positive Hp culture results, 72 (96%) were resistant to clarithromycin, 3 (4%) were resistant to metronidazole, 5 (7%) were resistant to levofloxacin, 5 (7%) were resistant to rifampicin, 1 (1%) was resistant to tetracycline, and none was resistant to amoxicillin and furazolidone. The CYP2C19 polymorphism in 92 patients showed that 43 (47%) were extensive metabolizer (EM), 9 (10%) were poor metabolizer (PM), and 40 (43%) were intermediate metabolizer (IM). In terms of the effectiveness, eradication rate in the culture successful group,culture failed group and empirical eradication therapy group were 99% (74/75), 88% (15/17) and 72% (46/64), respectively (χ(2)=21.325, P<0.05). The eradication rate in the culture successful group was significantly higher than that in empirical eradication therapy group (χ(2)=21.005, P<0.05), while there was no difference between empirical eradication therapy group and culture failed group (χ(2)=1.154, P=0.283). Conclusion: Eradication regimen based on bacterial susceptibility and CYP2C19 genotype should be considered in children with refractory Hp infection.

Oxymatrine therapy inhibited epidermal cell proliferation and apoptosis in severe plaque psoriasis.

BACKGROUND: Psoriasis is a chronic skin disorder that manifests as epidermal keratinocyte hyperplasia. OBJECTIVES: We examined the effect of oxymatrine treatment on cell proliferation and apoptosis in skin lesions of psoriasis. PATIENTS AND METHODS: Patients with severe plaque psoriasis were treated with oxymatrine or with acitretin. The skin lesions were stained with proliferating cell nuclear antigen (PCNA), Ki-67 and Bcl-2, as well as examined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL). We performed correlations of the Psoriasis Area and Severity Index (PASI) and the proliferation and apoptosis index. RESULTS: Oxymatrine significantly reduced the psoriasis lesions as demonstrated by the reduced PASI score after treatment [6·91; 95% confidence interval (CI) 5·00-8·81, P < 0·001]. In the oxymatrine group, the mitotic index was 26·15 (95% CI 24·80-27·49) before oxymatrine treatment, decreasing to 14·52 (95% CI 13·82-15·25; P < 0·001) after treatment, but remained higher than the normal group (6·24; 95% CI 5·87-6·61, P < 0·001). Oxymatrine also inhibited the proliferation of epidermal cells in the skin lesion as indicated by the reduced proliferation index after treatment (P < 0·01). In addition, oxymatrine treatment reduced cellular apoptosis as shown by increased Bcl-2 expression and a decrease in TUNEL-positive cells. The PASI score was positively correlated with mitotic index, proliferation index and apoptotic index (TUNEL), but negatively correlated with Bcl-2 expression. CONCLUSIONS: Oxymatrine treatment reduced proliferation but inhibited apoptosis of cells in the skin lesion. The balance between cell proliferation and turnover may contribute to the significant alleviation of psoriasis by oxymatrine. What's already known about this topic? Psoriasis manifests as epidermal keratinocyte hyperplasia with proliferation, keratinocyte maturation and turnover rates. Current drugs for psoriasis may inhibit cell proliferation but could not adjust the balance of cell division, differentiation and apoptosis. What does this study add? We studied the efficacy of oxymatrine in the treatment of psoriasis and analysed the correlation of skin lesions, proliferation and apoptosis index before and after oxymatrine treatment. What is the translational message? Our study has demonstrated that oxymatrine is effective in the treatment of severe plaque psoriasis. It has comparable efficacy with acitretin. Because acitretin treatment was sometimes associated with metabolic abnormalities, our study suggests oxymatrine therapy as an alternative treatment for psoriasis in the context of acitretin allergy or adverse reactions.

Infection Status with Plerocercoid of Ligulid Tapeworm in Cyprinid Fish from Three Lakes in Republic of Korea.

We have investigated freshwater cyprinid fish for its current infection status with plerocercoid of ligulid tapeworm in the Republic of Korea. A total of 6,049 (517 Euiam Lake and 4,071 Hoengseong Lake in Gangweon-do and 1,461 Chungju Lake in Chungcheongbuk-do) fish were examined by dissecting the peritonial cavity between March 2015 and December 2016. Totally 45 (0.74 %) fish in of 5 (26.3 %) species (8 Squalidus japonicus coreanus, 6 Squalidus gracilis majimae, 7 Opsariichthys uncirostris amurensis, 15 Zacco platypus and 9 Erythroculter erythropterus) were infected with plerocercoids of ligulid tapeworm. The infection density with plerocercoids in Erythroculter erythropterus was 12 - 26 per fish infected in Erythroculter erythropterus, and 1 - 2 in other 4 fish species. The plerocercoid was ivory-white and 26.2 - 57.8 cm long. The prevalence value in this survey was 0.9 % (45/6,049). The genetic analysis in this study was conducted to identify plerocercoid species. Based on genetic analysis with data in GenBank, these plerocercoids were identified as the L. intestinalis.

Efficacy of oxymatrine for treatment and relapse suppression of severe plaque psoriasis: results from a single-blinded randomized controlled clinical trial.

BACKGROUND: Drugs that are currently used in the treatment of psoriasis are associated with drawbacks such as rapid recrudescence, high costs and unwanted side-effects. Oxymatrine has a long history of clinical use in the treatment of hepatitis and cancer in China. OBJECTIVES: To explore the efficacy and safety of intravenous oxymatrine in patients with severe plaque psoriasis. METHODS: A total of 67 patients were randomly allocated to receive oxymatrine injections (0.6 g per day for 8 weeks) or acitretin capsules (0.75 mg kg-1 per day from week 0 to week 2 and 20-30 mg per day from week 3 to week 8) and followed up for another 24 weeks. The primary end point was the percentage of patients with ≥ 50% reduction of Psoriasis Area and Severity Index (PASI 50) at week 32. The secondary end points included the skin classification grade and the Dermatology Quality of Life Index (DLQI) score. Side-effects were recorded throughout the whole study to assess the safety profile. RESULTS: Treatment with oxymatrine or acitretin for 8 weeks significantly decreased PASI score, skin classification grade and DLQI score (P < 0.001), with no significant differences between the oxymatrine and acitretin groups in terms of PASI 50. However, at week 32, the relapse rate in the oxymatrine group was significantly lower than that of the acitretin group (P < 0.001). Moreover, while there was an increase in the number of patients with metabolic abnormalities in the acitretin group, a significant reduction was observed in the oxymatrine group. Furthermore, rates of adverse reactions were significantly decreased in the oxymatrine group compared with that of the acitretin group (P < 0.001). CONCLUSIONS: Treatment with oxymatrine effectively ameliorated severe plaque psoriasis, and was accompanied by only minor adverse effects.

Significance of platelet distribution width as a severity marker of erectile dysfunction.

Mean platelet volume (MPV) and Platelet distribution width (PDW) are potential markers in platelet activation. In present study, we aimed to evaluate MPV and PDW as potential severity markers for those patients who are complaining erectile dysfunction (ED). A total of 358 participants were enrolled in this study. The whole cohort was asked to complete the International Index of Erectile Function-5 (IIEF-5) questionnaire. The participants were classified into 3 groups: control group (n = 120), mild ED (n = 118) and severe ED (n = 120). We found in our cohort MPV and PDW were significantly higher in both mild ED group and severe ED group than control group (9.24 ± 0.70 and 9.71 ± 0.80 versus 8.56 ± 0.62 for MPV; 14.48 ± 1.29 and 14.98 ± 1.60 versus 12.86 ± 1.13 for PDW respectively). The MPV and PDW increased as the disease progressed. In the mild and severe ED groups, a significant inverse correlation was detected between the mean values of IIEF-5 score and PDW. Furthermore, in the receiver operating characteristic curve analysis, the area under the curve of the MPV and PDW to predict severe ED was 0.818 and 0.848 respectively. Our study establishes a dose-dependent association between the PDW and ED. Therefore, the PDW can serve as a potential marker for predicting the severity of ED.

Serum levels of PSA, ALP, ICTP, and BSP in prostate cancer patients and the significance of ROC curve in the diagnosis of prostate cancer bone metastases.

Bone metastasis is a common complication in prostate cancer patients that can cause bone pain and pathological fracture. This study tested serum levels of prostate specific antigen (PSA), alkaline phosphatase (ALP), bone sialoprotein (BSP), collagen type I pyridine crosslinking peptide (ICTP) in prostate cancer patients and the significance of the receiver operator characteristic (ROC) curve in the diagnosis of prostate cancer bone metastases. Eighty-three prostate cancer patients were enrolled including 42 in the bone metastases group and 41 in the non-bone metastases group. Serum levels of BSP, ALP, ICTP, and PSA were highest in the bone metastases group followed by the non-bone metastases group, hyperplasia group, and then the control group (P < 0.05). Based on Gleason score, serum levels were highest in the poorly differentiated group followed by moderately differentiated and well-differentiated groups (P < 0.05). ROC curve analysis revealed that the diagnostic efficiency of the biomarkers in turn was BSP, PSA, ICTP, and ALP. The sensitivity of BSP, ALP, ICTP, and PSA in the diagnosis of prostate cancer bone metastases were 80.95, 57.14, 69.05, 71.43%, respectively, and the specificity of the same markers were 72.80, 64.80, 76.80, and 88.80%, respectively. Combined detection of the four markers improved sensitivity to 97.62% and the negative-predictive value increased to 97.60%. PSA + BSP showed the best efficiency when combining two markers. In conclusion, serum levels of BSP, ALP, ICTP, and PSA increased in patients with bone metastases, and combined detection of all markers could improve the positive-predictive value.

Proteomic analysis revealed the altered kidney protein profile of a Cyld knockout mouse model.

The aim of this study was to compare the proteomics pattern of the kidneys from Cyld knockout mice with that from normal mouse kidneys and establish a preliminary understanding of the role of Cyld in the kidney. Proteins from the kidneys of knockout Cyld mice and wild-type mice were extracted, isobaric tags for relative and absolute quantitation (iTRAQ) was performed, and the proteomics patterns of the two groups were compared. The genotypes of the mice were verified by polymerase chain reaction. A total of 1748 proteins with a local false discovery rate of ≤5% were identified, among which 1437 proteins were reliably recognized and quantified. The expression of two dysregulated proteins was confirmed by Western blotting. Gene ontology and pathway analyses indicated that the proteins identified were involved in biological processes, cell components, and molecular functions, and participated in different pathways. Some of the proteins identified were relevant to renal function or kidney diseases. The difference between the proteomics profiles of kidneys from Cyld knockout mice and wild-type mice was prominent, which correlates to kidney dysfunction and the development of renal diseases.

Nonlinear and threshold of the association between meteorological factors and bacillary dysentery in Beijing, China.

Previous studies examining the weather-bacillary dysentery association were of a large time scale (monthly or weekly) and examined the linear relationship without checking the linearity assumption. We examined this association in Beijing at a daily scale based on the exposure-response curves using generalized additive models. Our analyses suggested that there were thresholds for effects of temperature and relative humidity, with an approximately linear effect for temperature >12·5 °C [excess risk (ER) for 1 °C increase: 1·06%, 95% confidence interval (CI) 0·63-1·49 on lag day 3] and for relative humidity >40% (ER for 1% increase: 0·18%, 95% CI 0·12-0·24 at lag day 4); and there were linear effects of rainfall (ER for 1-mm increase: 0·22%, 95% CI 0·12-0·32), negative effects for wind speed (ER: -2·91%, 95% CI -4·28 to -1·52 at lag day 3) and sunshine duration (ER: -0·25% 95% CI -0·43 to -0·07 at lag day 4). This study suggests that there are thresholds for the effects of temperature and relative humidity on bacillary dysentery, and these findings should be considered in its prevention and control programmes.

Epidural anaesthetic effect of the 8% emulsified isoflurane: a study in rabbits.

BACKGROUND: Studies have shown that local use of volatile anaesthetics produce local anaesthetic effects such as local infiltration anaesthesia (in rats and humans) and spinal anaesthesia (in dogs). However, there is still no report on the epidural anaesthetic effect of volatile anaesthetics. The aim of the present study was to evaluate the epidural anaesthetic effect of the 8% emulsified isoflurane in rabbits. METHODS: Forty rabbits chronically instrumented with an epidural catheter were randomly divided into four groups of 10 rabbits each. According to group assignment, rabbits received epidural administration of 8% emulsified isoflurane (v/v) 1 ml in the E-isoflurane group, 1% lidocaine 1 ml in the Lidocaine group, 30% lipid emulsion 1 ml in the Itralipid group, or normal saline 1 ml in the NS group. The sensory and motor functions and the state of consciousness were assessed at baseline and at predetermined regular intervals. Then, the rabbits were continuously observed for 2 weeks to examine the possible long-term neurological complications. RESULTS: The sensory blockade onset time, motor blockade onset time, and motor blockade duration in the E-isoflurane group [1.4 (0.7), 1.6 (0.7), and 34 (10) min, respectively] were similar to those in the Lidocaine group [1.3 (0.5), 1.7 (0.8), and 38 (8), min, respectively]. The sensory blockade duration in the E-isoflurane group was longer than that in the Lidocaine group [68 (13) vs 49 (13) min, P<0.01]. No epidural anaesthetic effects occurred in the NS group and the Intralipid group. None of the rabbits showed an abnormal consciousness after the epidural drug administration. None of the rabbits showed any long-term neurological deficits during a 2 week observation. CONCLUSIONS: The present study demonstrates that epidural administration of the 8% emulsified isoflurane produces completely a reversible epidural anaesthetic effect that does not affect the level of consciousness in rabbits.

2,6-Bis(diphenylphosphino)pyridine-bridged hetero-polynuclear complexes consolidated by Fe-->M (M = Ag, Hg) dative bonding.

The bridging phosphine ligand 2,6-bis(diphenylphosphino)pyridine (L) was used to synthesize a new, neutral organometallic ligand [Fe(CO)(4)](2)(micro-L) 1, which exhibits eclipsed and staggered conformations in two crystalline forms. This Fe,N,Fe-tridentate ligand reacts with silver perchlorate to form the hetero-trinuclear complex [[Fe(CO)(4)](2)Ag(micro-L)](ClO(4)) 2, in which the central silver(I) atom bridges a pair of iron(0) atoms at Fe-Ag distances of 2.627(3) and 2.652(3) A; the Fe-Ag-Fe angle is 170.98(9) degrees. The reaction of 1 with mercury(II) chloride gives [Fe(CO)(4)](2)Hg(2)Cl(4)(micro-L), 3. The ligand also reacts with mercury(II) acetate to form a hetero-octanuclear complex [[Fe(CO)(3)Hg](2)(micro-L)](2) 4 and a novel hetero-heptanuclear complex Fe(3)(CO)(8)Hg(4)(micro-L)(2)(MeCO(2))(2) 5. Complex 4 displays a square metallic core in which the iron and mercury atoms occupy the corners and the centers of the edges, respectively. The metal atoms in 5 are linked to form a kinky line with bends at the iron atoms.

A novel luminescent copper(I) complex containing an acetylenediide-bridged, butterfly-shaped tetranuclear core.

A novel luminescent acetylenediide-bridged tetranuclear copper(I) complex [Cu4(mu-Ph2Ppypz)4(mu 4-eta 1,eta 2-C identical to C)]-(ClO4)2 [Ph2Ppypz = 2-(diphenylphosphino-6-pyrazol-1-yl)pyridine] has been synthesized and structurally characterized by X-ray crystallography.

Late fertilization of unfertilized human oocytes in in vitro fertilization and intracytoplasmic sperm injection cycles: conventional insemination versus ICSI.

PURPOSE: The aim of this study was to evaluate the efficacy of intracytoplasmic sperm injection (ICSI) in comparison with conventional reinsemination using fertilization failed oocytes by conventional in vitro fertilization (IVF). METHODS: Oocytes were collected from patients of IVF or ICSI cycles. Patients were grouped by fertilization techniques: group 1: conventional IVF; group 2: reinsemination after conventional IVF failure; group 3: regular ICSI; group 4: 1-day-old ICSI after conventional IVF failure; group 5: 2-day-old ICSI after conventional IVF failure; group 6: re-ICSI after regular ICSI failure. RESULTS: In different insemination groups, normal fertilization rate was higher (P < 0.001) in 1-day-old ICSI (47.1%) and 2-day-old ICSI groups (40.0%) than in reinsemination (14.7%). Abnormal fertilization rate was higher (P < 0.05) in re-ICSI group (21.7%) than any other groups (range: 0-8%). Cleavage rate was higher in 1-day-old (36.7%) and 2-day-old ICSI groups (36.0%) than in reinsemination (5.3%, P < 0.001) or re-ICSI groups (17.4%, P < 0.05). Pregnancy rate was 27.6% and 20.0% in conventional IVF and regular ICSI groups, respectively. However, 1-day-old ICSI (group 4) and 2-day-old ICSI (group 5) were attempted once embryo transfer (ET) but failed pregnancy occurred in each group. CONCLUSIONS: In fertilization failure cycles, late ICSI increases the rate of fertilization and embryonic development and may rescue the completely failed attempt of pregnancy.

Further investigation on the role of selenium deficiency in the aetiology and pathogenesis of Keshan disease.

Selenium supplements were not able to restore the ultrastructural changes in the myocardium of latent Keshan disease patients taken by using cardiac catheter endomyocardial biopsy. Observations on the changes of selenium status and the incidence of Keshan disease showed that new latent and naturally-occurring chronic cases were found in the endemic area even after selenium levels had been elevated in the residents to the levels typical in the non-endemic area. These results indicate that although selenium deficiency might be a primary pathogenetic geogen in the occurrence of Keshan disease, it is rather a conditional predisposing factor than a specific or initiative aetiologic factor for the occurrence of Keshan disease. Selenium supplementation could apparently alleviate the higher platelet responsiveness of residents in the endemic area, which might contribute to eliminating the basis for the occurrence of the multifocal perivascular necroses in myocardium of acute and subacute Keshan disease.