[Establishment of an auxiliary diagnosis system of newborn screening for inherited metabolic diseases based on artificial intelligence technology and a clinical trial].

Objective: To establish a disease risk prediction model for the newborn screening system of inherited metabolic diseases by artificial intelligence technology. Methods: This was a retrospectively study. Newborn screening data (n=5 907 547) from February 2010 to May 2019 from 31 hospitals in China and verified data (n=3 028) from 34 hospitals of the same period were collected to establish the artificial intelligence model for the prediction of inherited metabolic diseases in neonates. The validity of the artificial intelligence disease risk prediction model was verified by 360 814 newborns' screening data from January 2018 to September 2018 through a single-blind experiment. The effectiveness of the artificial intelligence disease risk prediction model was verified by comparing the detection rate of clinically confirmed cases, the positive rate of initial screening and the positive predictive value between the clinicians and the artificial intelligence prediction model of inherited metabolic diseases. Results: A total of 3 665 697 newborns' screening data were collected including 3 019 cases' positive data to establish the 16 artificial intelligence models for 32 inherited metabolic diseases. The single-blind experiment (n=360 814) showed that 45 clinically diagnosed infants were detected by both artificial intelligence model and clinicians. A total of 2 684 cases were positive in tandem mass spectrometry screening and 1 694 cases were with high risk in artificial intelligence prediction model of inherited metabolic diseases, with the positive rates of tandem 0.74% (2 684/360 814)and 0.46% (1 694/360 814), respectively. Compared to clinicians, the positive rate of newborns was reduced by 36.89% (990/2 684) after the application of the artificial intelligence model, and the positive predictive values of clinicians and artificial intelligence prediction model of inherited metabolic diseases were 1.68% (45/2 684) and 2.66% (45/1 694) respectively. Conclusion: An accurate, fast, and the lower false positive rate auxiliary diagnosis system for neonatal inherited metabolic diseases by artificial intelligence technology has been established, which may have an important clinical value.

Time-to-progression following conventional compared with drug-eluting-bead transcatheter arterial chemoembolisation in patients with large hepatocellular carcinoma.

AIMS: To identify the optimal transarterial chemoembolisation (TACE) approach in patients with large hepatocellular carcinoma (HCC; >5 cm) by comparing conventional TACE (cTACE) and drug-eluting-bead (DEB)-TACE. MATERIALS AND METHODS: This retrospective study included 63 consecutive HCC patients who received TACE at a single medical centre from September 2009 to October 2015. Primary endpoints were 3-year overall survival (OS) rate and time-to-progression (TTP). Hazard ratios (HRs) from Kaplan-Meier curves were calculated to compare survival estimates. RESULTS: The median OS was shorter in the cTACE group, but was not significantly different from the DEB-TACE group (33.9 versus 35.6 months, respectively; p=0.52). The mean TTP was shorter in the cTACE group than in the DEB-TACE group (13.9 versus 17.5 months, respectively; p=0.01). There was no difference in 3-year survival (HR=0.95, 95% confidence interval [CI]: 0.51-1.78; p=0.880) and TTP (HR=0.70, 95% CI: 0.42-1.16; p=0.147) between the groups; however, patients treated with DEB-TACE were more likely to have longer TTP in the first 2 years following treatment (HR=0.51, 95% CI: 0.29-0.88; p=0.009). CONCLUSION: Although DEB-TACE is not superior in terms of TTP or OS in patients with large HCC, it may have greater efficacy in the first 24 months following therapy.

Myomectomy through the uterine cervix using forceps under sonographic guidance.

OBJECTIVES: To evaluate the feasibility of a novel method of forceps myomectomy under sonographic guidance. METHODS: Between June 2005 and August 2006, we performed a prospective study to evaluate the feasibility of forceps myomectomy under sonographic guidance in patients with submucosal myomas. Patients were enrolled into the study if, on transvaginal sonographic or hysteroscopic examination, their myomas were found to have an intramural extension < 75%, absence of 'sinking' and a mean diameter < 8 cm. RESULTS: There were 28 patients with submucosal myomas including Types 0 (n = 18), 1 (n = 6) and 2 (n = 4). In 26/28 (92.8%; 95% CI, 82.6-100) patients the myomas were removed completely. The mean operating time and intraoperative blood loss were 27.3 min and 33.5 mL, respectively. The median follow-up time was 15 months. There were no perioperative complications. No patient subsequently underwent myomectomy or hysterectomy. CONCLUSIONS: In our experience, this novel method of forceps myomectomy is feasible for the removal of Type 0 and Type 1 submucosal myomas as well as selected Type 2 myomas.

Antibiotic treatment for threatened abortion during the early first trimester in women with previous spontaneous abortion.

BACKGROUND: We retrospectively examined the usefulness of antibiotic therapy for management of first-trimester threatened abortion in women with previous spontaneous abortion. METHODS: From 1993 through 1999, women with first-trimester threatened abortion received antibiotic therapy. Only those with gestational age less than 9 weeks and previous spontaneous abortion were included in this analysis. Women with mild abdominal cramping received amoxicillin plus erythromycin for 1 week; those with severe abdominal pain received amoxicillin plus clindamycin for 1 week. Recurrence was documented on the basis of either lower abdominal pain or vaginal bleeding. RESULTS: Of the 23 women included, 15 (65%) had abnormal vaginal flora (a score above 4, Nugent's criteria). Seven of 16 women who received amoxicillin plus clindamycin and three of seven who received amoxicillin plus erythromycin had complete resolution of lower abdominal pain and vaginal bleeding without recurrence (p=1). The recurrence rate was higher, though not significantly, in women with abnormal bacterial vaginal flora (8/15 vs. 2/8, p=0.379). Twenty-two (96%) of the 23 pregnancies were carried to term, with no identifiable neonatal anomalies. CONCLUSIONS: These results suggest the usefulness of early antibiotic therapy in preventing pregnancy loss in women with threatened abortion early in the first trimester, and warrant further clinical trials.

Implications of asymptomatic endocervical leukocytosis in infertility.

Genital tract infection is a known cause of male and female infertility. In this retrospective study, we investigated the effect of treatment of asymptomatic cervical leukocytosis on pregnancy rates. Twenty-five infertile women with asymptomatic cervical leukocytosis received broad-spectrum antibiotic treatment (100 mg doxycycline, 200 mg ofloxacin, and 500 mg metronidazole twice a day for 7-10 days). Pregnancy rates and resolution of leukocytosis were evaluated 6 months after treatment. Eleven patients (44%) had persistent cervical leukocytosis and 16 (64%) had become pregnant within 6 months after treatment. Successful treatment of cervical leukocytosis resulted in an increase in the pregnancy rate: 13 of the 14 patients (93%) who were cured of leukocytosis became pregnant, while 3 of the 11 (27%) who did not become pregnant were cured (p = 0.002). Patients who did not achieve pregnancy were older (p = 0. 002) than those who did. Patients who were not cured were also older than those who were (p = 0.014). Our findings suggest that the treatment for cervical leukocytosis is less effective for older patients than for younger patients. However, treatment of asymptomatic cervical leukocytosis appears to help preserve the fertility of patients with this disease.

Sonographically guided intralesional antibiotic injection for treatment of a recalcitrant pelvic abscess: a case report.

A pelvic abscess occurred in an infertile woman with an endocervical gonococcal infection after hysterosalpingographical examination. The pelvic abscess was not cured despite rigorous antimicrobial chemotherapy until two intra-abscess ceftriaxone injections were administered. This shows that antibiotics administered systemically may not reach therapeutic concentration in an abscess and an intra-abscess antibiotic injection may help to cure it.

Sperm head agglutination induced by V3 peptide does not occur through a CD4 receptor.

BACKGROUND: Although recent studies have shown that HIV (human immunodeficiency virus) can attach to sperm, the mechanism by which it does this is not yet understood. It has been shown that CD4 receptors on T4 cells are responsible for the binding of gp120 (glycoprotein 120) to HIV; however, the existence of CD4 receptors on sperm is controversial. The V3 peptide is part of gp120 and crucial for the syncytium formation by CD4 receptors. In this study we used an anti-CD4 antibody to block V3 peptide-induced sperm head agglutination in an attempt to gain a further understanding of the mechanism of HIV attachment to sperm. METHODS: Ten semen samples from 10 healthy men were studied. A sperm head fixation method (SHFM) was used to evaluate the blocking effect of anti-CD4 antibody (Q4120) of V3 peptide-induced sperm head agglutination in phosphate-buffered saline solution. RESULTS: While the sperm swam out of the micropipette, as occurs in SHFM, the V3 peptide induced an average of 53.2 +/- 10.8 (mean +/- SEM) head-to-head bound sperm (in the 10 semen samples. The sperm that had been preincubated with anti-CD4 antibody induced an average of 54.1 +/- 11.6 head-to-head bound sperm. There was no significant difference found between sperm that had been preincubated or not preincubated with anti-CD4 antibody, in terms of sperm head agglutination. CONCLUSIONS: The anti-CD4 antibody can block the binding of gp120 and CD4 positive T cells in a low concentration, but it did not block V3 peptide-induced sperm head agglutination. Therefore, V3 peptide-induced sperm head agglutination may not occur through a CD4 receptor.

Implication of sperm head agglutination induced by a V3 peptide (fragment 307-330, HIV-1 envelope protein gp120) solution.

Human semen is the main vehicle for the transmission of human immunodeficiency virus (HIV); therefore, the interaction of HIV with the sperm is worthy of study. The motile sperm head fixation method was used as an in vitro model system to demonstrate the interaction of sperm with the peptide of HIV envelope protein. A micropipette loaded with semen was put into phosphate-buffered saline (PBS) containing V3 peptide (HIV-1IIIB envelope protein, fragment 307-330) or C2 peptide (HIV-1IIIB envelope protein, fragment 254-274). The V3 peptide caused a significant number of head-to-head binding sperm while the C2 peptide did not. This V3 peptide carries a high positive charge, which may overcome the electrostatic resistance on the cell to bring the sperm together. An HIV-CD4+ cell attachment inhibitor, dextran sulfate (DS, molecular weight about 5000), enhanced the sperm head agglutination induced by the V3 peptide. DS is presumed able to bind with specific sites near the V3 domain of gp120 to induce conformational change so as to prevent the binding of anti-V3 monoclonal antibodies or CD4+ cells to the V3 domain. This study suggests that DS interacts directly with the V3 peptide to enhance the sperm head agglutination.

Biosynthesis of N-acetylsphingosine by platelet-activating factor: sphingosine CoA-independent transacetylase in HL-60 cels.

We have previously identified a novel CoA-independent transacetylase in the membrane fraction of HL-60 cells that transfers the acetate group from platelet activating factor (PAF) to a variety of lysophospholipid acceptors (Lee, T.-c., Uemura, Y., and Snyder, F. (1992) J. Biol. Chem. 267, 19992-20001). In the present study, we demonstrate that a similar transacetylase can transfer the acetate group from PAF to sphingosine forming N-acetylsphingosine (C2-ceramide). The chemical structure of the reaction product, C3-ceramide, was established by its identical Rf value with authentic C2-ceramide standard on thin-layer plate, sensitivity to acid treatment, resistance to alkaline hydrolysis, and ability to form the C2-ceramide dibenzoate derivative. Nonspecific transfer of the acetate from PAF to sphingosine in the absence of enzyme and nonlinearity of the reaction rates were rectified by complexing sphingosine to bovine serum albumin in a 1:1 molar ratio. Under these conditions, the apparent Km for PAF is 5.4 microM, which is in the same range as the Km (12.0 microM) when lysoplasmalogen is the acetate acceptor. PAF:sphingosine transacetylase has a narrow substrate specificity and strict stereochemical configuration requirements. Ceramide, sphingosylphosphocholine, stearylamine, sphingosine 1-phosphate, or sphingomyelin are not substrates, whereas sphinganine has a limited capacity to accept the acetate from PAF. Also, only the naturally synthesized D-erythroisomer but not the synthetic L-erythro-, D-threo-, or L-threosiomers of sphingosine can serve as a substrate. PAF transacetylase activity is widely distributed among several tissues and may involve histidine and cysteine for its catalytic activity due to inhibitory effects to the enzyme by diethyl pyrocarbonate and N-ethylmaleimide, respectively. C2-ceramide is produced via PAF:sphingosine transacetylase, and physiological levels of C2-ceramide are detected in both undifferentiated and differentiated intact HL-60 cells. Collectively, because C2-ceramide has many biological activities that differ from that of PAF and sphingosine, the CoA-independent, PAF-dependent transacetylase serves as a modifier of PAF, and sphingosine functions by generating a variant lipid mediator, C2-ceramide.

Potential etiologic role of PAF in two major septic complications; disseminated intravascular coagulation and multiple organ failure.

A possible role of platelet-activating factor (PAF) in the occurrence of the two septic complications, i.e., disseminated intravascular coagulation (DIC) and multiple organ failure (MOF) was investigated, employing a rabbit model and a novel PAF antagonist E5880. By an instillation of fecal suspension into the common bile duct of the rabbit, manifestations of DIC and MOF were observed with high reproducibility by 9 hours after the septic insult. E5880 was intravenously administered to 12 rabbits for 1 hour after the septic insult at dose of 1 mg/kg (n = 6) or 3mg/kg (n = 6). All the rabbits were subjected to observation of vital signs and serial determination of laboratory tests for 9 hours and then lung, liver and kidney were removed for histological examination. Blood endotoxin level increased significantly by 9 hours after the septic insult. Although administration of E5880 did not affect the endotoxemia, the antagonist attenuated in a dose related manner laboratory manifestation of DIC such as thrombocytopenia and prolonged prothrombin time as well as that of MOF such as increase in serum bilirubin and creatinine level. The beneficial effect of E5880 on MOF was also confirmed by the histological evaluation. These observations indicated that PAF is deeply involved in the occurrence of DIC and MOF due to sepsis and E5880 may be one of the modalities to treat or prevent these two major septic complications.

Acrosome reaction in the head-attached human sperm.

The physiological acrosome reaction of the sperm occurs on the surface of the oocyte. Although its occurrence on the zona pellucida is considered to be a specific response to zona compounds, whether the simple attachment itself could influence the reaction of motile spermatozoa to a fixed surface and promote onset of the reaction is questioned. A motile human sperm head fixation method was developed recently, through which a group of head-attached sperm can be established easily. These head-attached sperm were investigated for their acrosome reactions. After staining by fluorescein iso-thiocyanate conjugated peanut lectin (FITC-PNA), many head-attached spermatozoa (75.7%) were found to have undergone an acrosome reaction.

Tail beat frequency of human sperm: evaluated with sperm head fixation method and computer-assisted semen analysis.

Tail beat frequency (TBF) of individual sperm in 15 semen samples was evaluated with a sperm head fixation method (SHFM). Motility parameters of the semen samples were also measured with computer-assisted semen analysis (CASA). The TBF obtained from SHFM correlated best with beat cross-frequency obtained from CASA. The TBF measured soon after sperm head fixation also correlated well with total motility and rapid motility, but not with progress motility and critical motility measured with CASA. SHFM is a simple method for the study of tail beat frequency and the TBF of individual sperm is closely related to the overall motility in a semen sample.

A motile human sperm head fixation method.

In a solution containing less than 5% seminal fluid, human sperm has a tendency to attach its head on the smooth surface of an object. Based on such a phenomenon, a simple method was developed to fix sperm head on the surface of glass slide. This method was demonstrated by studying caffeine effect on the tail movement of human sperm in phosphate buffered saline. By analysing the images recorded on a videocassette, caffeine, a well known stimulator of human sperm motility, was shown to induce an immediate increase of sperm TBF (tail beat frequency) and the amplitude of TBF increase was found to be larger in sperm with lower basal TBF value. This method can provide a flock of head-fixed motile sperm for a precise sperm tail movement assessment or for other purposes.

Modification of septic processes by beta-glucan administration.

The effect of glucan (lentinan), beta(1----3)-glucan derived from Lentinus edodes, was evaluated in a clinically relevant septic model. Male, Japanese, white rabbits were intravenously injected with lentinan (1 mg/body) just before septic insult, induced by injecting fecal suspension into the ligated choledochus. In septic animals without lentinan treatment, platelet counts dropped serially following the septic insult and a paracoagulation test, measured by protamine gelation, turned positive. Plasma bilirubin and creatinine elevated significantly in comparison with control animals injected with saline, at 9 h and at 6 and 9 h. respectively. In lentinan-treated septic animals, platelet counts did not decrease and a significant difference was found at 9 h, compared to the untreated septic animals. The degree of positive paracoagulation was less prominent. The elevation of plasma bilirubin and creatinine levels was also less prominent and a significant difference was found at 9 h. Plasma endotoxin elevated significantly at 9 h in the untreated septic animals in comparison with lentinan-treated septic and control animals. The findings suggest a modification of the septic processes by the administration of glucan.

Amniotic fluid lecithin/sphingomyelin ratio in high risk pregnancy.

The amniotic fluid lecithin/sphingomyelin (L/S) ratio from 128 cases of high risk pregnancies were measured by using high performance liquid chromatography (HPLC). The L/S ratio was found to be increased in patients with pre-eclampsia, hypertension, intrauterine growth retardation (IUGR), prolonged rupture of membranes (PROM), and twin gestation, but decreased in patients with diabetes from gestational diabetes to class C. In patients with placenta previa, the L/S ratio was not affected.