[The role of Sabin inactivated poliovirus vaccine in the final phase of global polio eradication].

Global polio eradication has entered its final phase, but still faces enormous challenges. The Polio Eradication and Endgame Strategic Plan (2013-2018) set the target for making the world polio-free by 2018. Meanwhile, the World Heath Organization Global Action Plan (GAP Ⅲ) recommended that polioviruses be stored under strict conditions after eradication of the wild poliovirus. At least one dose of inactivated poliovirus vaccine (IPV) would be required for each newborn baby in the world to ensure successful completion of the final strategy and GAP Ⅲ. The Sabin IPV has a high production safety and low production cost, compared with the wild-virus IPV and, therefore, can play an important role in the final stage of global polio eradication.

Effects of high intensity exhaustive exercise on SOD, MDA, and NO levels in rats with knee osteoarthritis.

The aim of this study was to investigate the impact of high intensity exhaustive exercise on nitric oxide (NO), malondialdehyde (MDA), and superoxide dismutase (SOD) expression in rats with knee osteoarthritis. Sprague Dawley rats were randomly divided into control (N = 5) and model (N = 35) groups; the model group was further divided into quiet (N = 5), low- (N = 15) and high- (N = 15) intensity exhaustive exercise groups. The low- and high-intensity groups were randomly divided into pre-exercise (N = 5), immediate post-exercise (N = 5), and 24-h post-exercise (N = 5) groups according to different time points for detection. NO, MDA, and SOD levels were compared between each group. The SOD levels in the quiet, low-, and high-intensity exhaustive exercise groups were lower than that in the control group, whereas the NO and MDA levels were higher in the former groups than in the controls (P < 0.05). The SOD level in the 24-h post-low intensity exhaustive exercise group was higher than that in the 24-h post-high intensity exhaustive exercise group, whereas the NO and MDA levels were lower in the 24-h post-low intensity than in the post-high intensity exercise group (P < 0.05). Overall, the results demonstrated that with the increase of exercise intensity, the SOD activity in the rats with knee osteoarthritis decreased gradually, whereas the MDA and NO levels gradually increased. Thus, the greater the exercise intensity, the more serious the impact on knee osteoarthritis.

Effect of high-intensity exercise on interleukin-15 expression in rabbit synovia.

The objective of this study was to examine the effect of high-intensity exercise on interleukin-15 (IL-15) expression in rabbit synovia. We utilized 24 New Zealand white rabbits, which were randomly divided equally into high-intensity exercise and control groups. The former were forced to run for 60 min/day over 4 weeks at the speed of 30 m/min. The histological changes of cartilage and knee joint synovia were investigated with hematoxylin and eosin staining. Immunohistochemistry and enzyme-linked immunosorbent assays were performed to measure IL-15 expression. From these analyses, we identified knee articular cartilage damage and synovitis in the high-intensity exercise group. This group also exhibited higher IL-15 expression in their synovial fluid and tissues than was observed in the control group (P < 0.05). These results suggested that high-intensity exercise might lead to synovitis and articular cartilage damage, and that IL-15 overexpression in synovia might be associated with post-traumatic osteoarthritis.

Protective effect and mechanism of probucol in the treatment of spinal cord injury.

To investigate the effects of probucol on the treatment of spinal cord injury in rat, 80 rats were randomly divided into two groups of 40: a group treated with probucol and a control group. Allen's method was used to establish a rat model of spinal cord injury. After establishment, probucol (500 mg·kg(-1)·day(-1)) was intraperitoneally injected into the treatment group rats for 1 week, while the same amount of saline was used to treat the control group. On days 1, 7, 14, 21, and 28 after treatment, the function of rats' spinal cord was evaluated according to the Bresnahan locomotor rating scale. Serum protein and mRNA levels of the cytokines [interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-17] were measured using enzyme-linked immunosorbent assay and quantitative polymerase chain reaction, respectively. Protein levels of IFN-γ, TNF-α, IL-17, and the downstream markers signal transducer and activator of transcription (STAT)-1 and STAT-3 were measured using western blot. In addition, the oxidative stress-related parameters, superoxide dismutase (SOD) and malondialdehyde (MDA), were also measured. It was found that compared to control group, rats from the treatment group had significantly lower levels of IFN-γ, TNF-α, and IL-17 (P < 0.05) on days 1 and 7, as well as lower MDA levels and higher SOD activity on days 7, 21, and 28 (P < 0.05). In summary, probucol improved the recovery of locomotion function after spinal cord injury in rats through downregulation of inflammation and upregulation of anti-oxidative activity.

Polymorphism analysis of the intron one of insulin-like growth factor 2 receptor gene (IGF2R) in FFRC strain common carp (Cyprinus carpio L.) and its relationship with growth performance.

The insulin-like growth factor 2 receptor gene (IGF2R) encodes a transmembrane protein receptor and acts to sequester and degrade excess circulating insulin-like growth factor 2, which is critical for normal mammalian growth and development. Thus, IGF2R may serve as a candidate gene underlying growth trait in the common carp. In this study, we isolated the intron one of common carp IGF2R and detected the diversity in 3 continuous generations of FFRC strain common carp. A total of 8 loci were detected within this region, which were named in accordance with their location (i.e., Loc84, Loc106, Loc119, Loc130, Loc145, Loc163, Loc167, and Loc265). Loc106, Loc119, and Loc145 were moderately polymorphic; while Loc84, Loc130, Loc163, Loc167, and Loc265 exhibited slight level of polymorphism. However, significant differences between polymorphism information content values were not observed among the different generations. For Loc145, all generations deviated from Hardy-Weinberg equilibrium. The total number of significant linkage disequilibria for all generations equaled 40. Among them, 4 pairs were detected in each population, while 8 pairs were found in the 2nd and 3rd generations. For Loc130, the G/T genotype exhibited higher body weight when compared to that of the G/G genotype. The frequency of the homozygous G/G genotype reached 87.96%; thus, we can improve FFRC strain common carp growth performance by increasing the percentage of the G/T genotype within a breeding population. Therefore, the G/T genotype could be used as a molecular marker for superior growth traits.

Does sperm morphology affect the outcome of intrauterine insemination in patients with normal sperm concentration and motility?

The aim of this study was to assess the correlation of sperm morphology with the intrauterine insemination (IUI) outcome in patients with normal sperm concentration and motility. About 412 couples who underwent 908 IUI cycles were involved in the present study. A total of 110 clinical pregnancies were achieved with a pregnancy rate of 12.11% per cycle. The pregnancy rates per cycle were 7.60%, 12.67%, 13.62% and 13.13% in patients with <5%, 5-9%, 10-14% and >14% normal forms, respectively. The lowest pregnancy rate (7.60%) was obtained in the group with normal forms below 5%. However, this rate was not significantly different from other subgroups. Moreover, no pregnancies occurred in women >35 years old with normal sperm forms below 5%, in comparison with that in other subgroups of the same age. For women younger than 35 years old, no significant difference in pregnancy rate was observed in terms of different level of morphologically normal sperm. Our results show that for patients with normal sperm concentration and motility, IUI is recommended for first-line treatment when the woman is younger than 35 years, or morphologically normal sperm is ≥ 5%. IVF/ICSI should be performed when the normal forms are <5% and female age is > 35 years.

[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.

Mycoplasma genitalium incidence, treatment failure, and resistance: a retrospective survey of men of infertile couples from a hospital in China.

BACKGROUND: Mycoplasma genitalium infection is significantly associated with an increased risk of male infertility. To date, few large M. genitalium studies have been conducted in China. OBJECTIVE: This study aimed to estimate the M. genitalium incidence and treatment failure and to provide information regarding the resistance of M. genitalium to macrolide and tetracycline antibiotics among men of infertile couples in China. MATERIALS AND METHODS: This study was performed as a retrospective survey of seminal and meatus urinarius secreta specimens of 30,094 men of infertile couples collected and used for microbiological tests for the evaluation of genital tract infections (Mycoplasma genitalium, Chlamydia trachomatis, and Neisseria gonorrhoeae) between October 2016 and December 2017. Mycoplasma genitalium RNA was detected using novel simultaneous amplification testing. Macrolide and tetracycline resistance screening was introduced using polymerase chain reaction (PCR) and Sanger sequencing. RESULTS: The incidence of M. genitalium was 2.49% (749 of 30,094; 95% confidence interval (CI), 2.31-2.66%). After antibiotic treatment, the mean values of semen parameters increased from those measured before treatment. The overall incidence of treatment failure was 17.56% (82/467; 95% CI, 14.10%-21.02%) (112-26-4 = 82), irrespective of the drug used. Resistance to macrolide and tetracycline antibiotics was detected in 58 samples (58/60, 96.67%; 95% CI, 91.99-101.34%) and 27 samples (27/60, 45.00%; 95% CI, 32.04-57.96%), respectively. CONCLUSIONS: Although the M. genitalium incidence was relatively low, the detection of macrolide antibiotic resistance in >96.67% of the treatment failure samples most likely explained the high azithromycin treatment failure rate (73/195, 37.44%) in our study. These findings indicate the need to provide resistance testing and to reappraise the recommended antimicrobial options in China.

The co-transplantation of human bone marrow stromal cells and embryo olfactory ensheathing cells as a new approach to treat spinal cord injury in a rat model.

BACKGROUND: Both bone marrow stromal cells (BMSC) and olfactory ensheathing cells (OEC) have been demonstrated experimentally as promising for therapy of spinal cord injury (SCI). However, clinical use may be constrained by the margin neuronal differentiation capacity of BMSC as well as the limited number of isolatable OEC. This study therefore tested the efficacy of co-grafting human BMSC and OEC in treating thoracic SCI. METHODS: Rat SCI models were created with cushion forces. OEC were labeled with Hoechst 33342 and BMSC with BrdU or GFP. BMSC, OEC and BMSC plus OEC were injected into the injured sites of rat spinal cords. Histologic, electrophysiologic and functional approaches were applied to assess the effects of transplantation of these cell types. RESULTS: Behavioral evaluation showed an improvement in animals with all cell-based treatments. The co-graft led to significantly higher gait scaling. The latency of transcranial magnetic motor-evoked potential (tcMMEP) responses was also better restored in the co-graft group. Larger numbers and sizes of axon bundles through the transitional zone between the normal and injured regions were observed in the co-graft animals in comparison with all other animals. Transplanted bone marrow stromal cells were identified as neurofilament-positive in the co-grafted animals although the number of glial fibrillary acidic protein-positive cells remained the same in all groups. DISCUSSION: Taken together, our results suggest that the combined use of BMSC and OEC may provide an improved approach for the treatment of SCI.

Cloning, characterization and identification of Rcet1-v1 and Rcet1-v2, two novel splice variants of mouse Rcet1 related to Cres subgroup of family 2 cystatins.

Cystatins are physiological cysteine proteinase inhibitors. We used digital differential display (DDD) to clone two novel splice variants Rcet1-v1 and Rcet1-v2 which were isolated from adult mouse testis cDNA library. Sequence analysis revealed that Rcet1-v1 and Rcet1-v2 cDNAs are 454 and 610 bp in length, respectively, and each has four exons, but the lengths of their second and third exons are different, with the results that these cDNAs encoded two different putative proteins. The deduced proteins were 88 amino acid residues (RCET1-v1) and 140 residues (RCET1-v2) in length and have one potential signal peptide and one cystatin domain, respectively, but lack part critical consensus sites important for cysteine protease inhibition. These characteristics are seen in CRES subgroup, which related to the family 2 cystatins and primarily expressed in reproductive tract. RT-PCR analysis showed that Rcet1-v1 and Rcet1-v2 were specifically expressed in adult mouse testis, epididymis and cerebrum, but higher in testis than in epididymis and cerebrum. RT-PCR analysis also showed that Rcet1-v1 and Rcet1-v2 were specifically expressed in adult mouse pituitary and spermatogonium, but not expressed in spermatozoa. Results of in situ hybridization showed that Rcet1 gene expressed abundantly in mouse spermatogonium, spermatocytes and round spermatids; did not expressed in spermatozoa. At mouse testis different development stages, Rcet1-v1 and Rcet1-v2 were expressed very low from postnatal 1 day to postnatal 3 weeks; after postnatal 4 weeks, expressed steadily increased from postnatal 4 to 7 weeks, highest in postnatal 7 to 8 weeks, then keeping on the expressing level of postnatal 6 weeks in postnatal 13-57 weeks. All these indicated that Rcet1-v1 and Rcet1-v2 primarily expressed in mouse male reproductive tract and may play important roles in mouse spermatocytes and round spermatid development. Rcet1-v1 and Rcet1-v2 may be new members of Cres subgroup of the family 2 cystatins.

Comparative Proteomics Reveal the Association between SPANX Proteins and Clinical Outcomes of Artificial Insemination with Donor Sperm.

Semen analysis is used for diagnosing male infertility and evaluating male fertility for more than a century. However, the semen analysis simply represents the population characteristics of sperm. It is not a comprehensive assessment of the male reproductive potential. In this study, 20 semen samples from human sperm bank with distinctive artificial insemination with donor sperm (AID) clinical outcomes were collected and analyzed using a two-dimensional differential in-gel electrophoresis (2D-DIGE); 45 differentially expressed protein spots were obtained, and 26 proteins were identified. Most differentially expressed proteins were related to sperm motility, energy consumption, and structure. These identified proteins included several sperm proteins associated with the nucleus on the X chromosome (SPANX) proteins. This prospective study aimed to investigate the association between the expression levels of SPANX proteins and the AID clinical outcomes. The proteins identified in this study provided a reference for the molecular mechanism of sperm fertility and revealed a predictive value of the SPANX proteins.

Mycoplasma and ureaplasma infection and male infertility: a systematic review and meta-analysis.

The relationship between mycoplasma and ureaplasma infection and male infertility has been studied widely; however, results remain controversial. This meta-analysis investigated the association between genital ureaplasmas (Ureaplasma urealyticum, Ureaplasma parvum) and mycoplasmas (Mycoplasma hominis, Mycoplasma genitalium), and risk of male infertility. Differences in prevalence of ureaplasma and mycoplasma infection between China and the rest of the world were also compared. Study data were collected from PubMed, Embase and the China National Knowledge Infrastructure. Summary odds ratio (OR) with 95% confidence interval (CI) was applied to assess the relationship. Heterogeneity testing and publication bias testing were also performed. A total of 14 studies were used: five case-control studies with 611 infertile cases and 506 controls featuring U. urealyticum infection, and nine case-control studies with 2410 cases and 1223 controls concerning M. hominis infection. Two other infection (U. parvum and M. genitalium) were featured in five and three studies, respectively. The meta-analysis results indicated that U. parvum and M. genitalium are not associated with male infertility. However, a significant relationship existed between U. urealyticum and M. hominis and male infertility. Comparing the global average with China, a significantly higher positive rate of U. urealyticum, but a significantly lower positive rate of M. hominis, was observed in both the infertile and control groups in China.

An asymptotic solution for the contact of two biphasic cartilage layers.

This study addresses the hypothesis that interstitial fluid plays a major role in the load support mechanism of articular cartilage. An asymptotic solution is presented for two contacting biphasic cartilage layers under compression. This solution is valid for identical thin (i.e. epsilon = h'/a'0 << 1), frictionless cartilage layers, and for the 'early' time response (i.e. t' << (h')2/HAk) after the application of a step load. An equilibrium asymptotic solution is also presented (i.e.t'-->infinity). Here h' is the thickness, a'0 is a characteristic contact radius, HA is the aggregate modulus and k is the permeability of the cartilage layer. A main conclusion from this analysis is that the fluid phase of cartilage plays a major role in providing load support during the first 100-200 s after contact loading. Further, the largest component of stress in cartilage is the hydrostatic pressure developed in the interstitial fluid. For tissue fluid volume fraction (porosity) in the range 0.6 < or = phi f < or = 0.8, k = O(10(-15) m4/Ns) and HA = O(1 MPa), the peak magnitude of the principal effective (or elastic) stress may be as low as 14% of the peak hydrostatic pressure within the tissue, or the contact stress at the surface. In effect, the interstitial fluid shields the solid matrix from high normal stresses and strains. The asymptotic solution also shows that pressure-sensitive film measurements of intra-articular contact stress do not measure the elastic stress at the surface, but they rather provide a measure of the interstitial fluid pressure. Finally, this analysis provides strong support for the hypothesis that, if sudden loading causes shear failure within the cartilage-bone layer structure, this failure would take place at the cartilage-bone interface, and the plane of failure would be either parallel or perpendicular to this interface.

Biphasic indentation of articular cartilage--II. A numerical algorithm and an experimental study.

Part I (Mak et al., 1987, J. Biomechanics 20, 703-714) presented the theoretical solutions for the biphasic indentation of articular cartilage under creep and stress-relaxation conditions. In this study, using the creep solution, we developed an efficient numerical algorithm to compute all three material coefficients of cartilage in situ on the joint surface from the indentation creep experiment. With this method we determined the average values of the aggregate modulus. Poisson's ratio and permeability for young bovine femoral condylar cartilage in situ to be HA = 0.90 MPa, vs = 0.39 and k = 0.44 x 10(-15) m4/Ns respectively, and those for patellar groove cartilage to be HA = 0.47 MPa, vs = 0.24, k = 1.42 x 10(-15) m4/Ns. One surprising finding from this study is that the in situ Poisson's ratio of cartilage (0.13-0.45) may be much less than those determined from measurements performed on excised osteochondral plugs (0.40-0.49) reported in the literature. We also found the permeability of patellar groove cartilage to be several times higher than femoral condyle cartilage. These findings may have important implications on understanding the functional behavior of cartilage in situ and on methods used to determine the elastic moduli of cartilage using the indentation experiments.

Synthesis and biological evaluation of a new angiotensin II receptor antagonist.

The design, synthesis, in vitro and in vivo evaluation of (2 R,6 S)-4-({1-[2-(1 H-tetrazol-5-yl)phenyl]-1 H-indol-4-yl}methyl)-2,6-dimethylmorpholine, compound 1, as a novel angiotensin II receptor antagonist is outlined. Radioligand binding assays showed that 1 displayed a high affinity for the angiotensin II type 1receptor with IC50 value of 0.82 nM. It acted as a potent anti-hypertensive derivative (maximal reduction of mean arterial pressure of 47 mm Hg at 10 mg/kg po in spontaneously hypertensive rat producing a dose-dependent fall in blood pressure following oral administration lasting beyond 10 h. Acute toxicity tests measured the LD50 of 1 value as 2431.7 mg/kg, which is higher than Losartan (LD50=2248 mg/kg). In addition further testing showed that 1 also demonstrated efficient anti-proliferative activity in vitro and anti-prostate cancer activity in vivo were also found. Taken together this compound could be considered as an effective and durable anti-hypertension drug candidate with additional anti-prostate cancer activity. These encouraging results are deserved of further investigation towards its use for therapeutic benefit.

Successful use of the dilated right spermatic cord vein for renal transplantation in a patient with congenital hypoplasia of the inferior vena cava.

A 29-year-old man was admitted to our department with renal failure secondary to glomerulonephritis. No history of deep venous thromboses was reported, and no iliac vessel abnormality was evident on routine ultrasound (B-mode) examination before the operation. Transplantation of his mother's left kidney revealed occlusion of his common iliac vein and distal inferior vena cava (IVC). The right spermatic cord vein was noted to be dilated and suitable for venous drainage of the allograft, which was accomplished by an end-to-side anastomosis between the renal vein and the right spermatic cord vein. The allograft showed immediate function; serum creatinine was decreased to a normal value at 5 days after surgery. After the operation, a vascular spiral computerized tomographic 3-dimensional reconstruction showed absence of the infrarenal IVC with the right spermatic cord vein draining into the end of IVC. Physical examination revealed a right-side varicocele with dilated epigastric vein. The donor kidney slower normal values upon routine follow-up at 2 years after the operation.

Clinical analysis of living related renal transplantation with donors older than 50 years in China.

OBJECTIVE: The objective of this study was to investigate whether kidney grafts from living related donors older than 50 years were safe for the donors and recipients in the long term. METHODS: One hundred seven living related donor kidney transplantations were performed in our center from April 1994 to December 2007. No prisoners or organs from prisoners were used in the collection of these data. Donors were divided into 2 groups: >50 years of age (range, 51-78 years), designated as the study group, and ≤50 years of age (range, 21-50 years), designated as the control groups. The mean time of follow-up was 49 months (range, 12-180 months). Clinical data were compared, including donor serum creatinine (Scr) levels, glomerular filtration rates (GFR) before and after the procedures operative complications, and postoperative short-term and long-term recovery of renal function in recipients as well as their complications and recipient and kidney survivals. RESULTS: All operations were successfully performed. Before the operation, the mean Scr and GFR were 82.16 ± 10.86 umol/L and 85.82 ± 6.26 mL/min, respectively, in the study group versus 78.66 ± 10.41 umol/L and 88.74 ± 9.44 mL/min, respectively, in the control group. There were no significant differences in mean Scr or GFR values between the groups at various preoperative or postoperative times (P > .05). No severe perioperative complications occurred, and no subsequent renal function failure was observed upon long-term follow-up of donors in the 2 groups. Comparisons of recipient age, gender ratio, duration on dialysis, HLA matches, cold/warm ischemia times, and immunosuppression therapy showed a correlations between the 2 groups. Mean Scr levels of recipients, which were compared from 1 week to 3 years following surgery, were slightly higher among the control than the study group, but the difference was not significant (P > .05). There were no significant differences between the study and control groups in 1-,3-,5-, and 8-year recipient/graft survival rates (P > .05). CONCLUSIONS: Long-term follow-up showed that transplantations using grafts from donors older than 50 years of age yielded similar results to those with younger donors.