OBJECTIVE To study the effect of fluoropezil on embryo-fetal developmental toxicity and toxicokinetics in rabbits,and provide reference for clinical medication.METHODS According to the sequence of pregnancy,pregnant rabbits were divided into five groups:vehicle control group(1%hydroxy-propyl methylcellulose+1.5%polyethylene glycol 400 aqueous solution),positive control group(cyclo-phosphamide 18 mg·kg-1),and fluoropezil(3.6,9.0 and 22.5 mg·kg-1)groups.The vehicle control group and the fluoropezil groups were ig administrated on the 6th to 18th day of gestation(GD6-18)while the positive control group was ig given cyclophosphamide on GD6-20.The pregnant rabbits were sacri-ficed on GD28,and the embryo-fetal development was detected.Sex hormone levels of pregnant rabbits on GD5,GD18 and GD28 were detected by ELISA method.Blood samples with toxokinetics were collected for concomitant toxic generation at the first and last administration,and drug concentrations in fetal,placenta and amniotic fluid were detected with liquid chromatography tandem mass spectrometry(LC-MS/MS).RESULTS Fluoropezil 3.6,9.0 and 22.5 mg·kg-1 had no significant effect on body mass,mass gain,food consumption,pregnancy outcomes,fetal appearance,viscera,skeletal and physical growth and development of pregnant rabbits.Only on GD18 or GD28,the levels of follicle stimulating hormone,estra-diol and progesterone in each dose group fluctuated to some extent.The combined toxokinetics results indicated that fluoropezil could cross the placental barrier of the rabbits,but did not accumulate in preg-nant rabbits or fetuses.Fetal mass,crown-rump length and uterus mass in the cyclophosphamide group were lower than those in the vehicle control group.The appearance and bone of the cyclophos-phamide group were positive.CONCLUSION The no observed adverse effect level(NOAEL)of fluoro-pezil toxicity on rabbit embryo-fetal development is 22.5 mg·kg-1,which is 125 times of the effective dose.At the dosage level of 22.5 mg·kg-1,Cmax is 1093 μg·L-1,and AUC(0-24 h)6650 μg·h·L-1 on GD18.

Humans ; COVID-19/genetics* ; SARS-CoV-2/genetics* ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics* ; CRISPR-Cas Systems/genetics* ; RNA, Viral/genetics*

Inducing durable and effective immunity against severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) via vaccination is essential to combat the current pandemic of coronavirus disease 2019 (COVID-19). It has been noticed that the strength of anti-COVID-19 vaccination-induced immunity fades over time, which calls for an additional vaccination regime, as known as booster immunization, to restore immunity among previously vaccinated populations. Here we report a pilot open-label trial of a third dose of BBIBP-CorV, an inactivated SARS-CoV-2 vaccine (Vero cell), on 136 participants aged between 18 to 63 years. Safety and immunogenicity in terms of neutralizing antibody titers and cytokine/chemokine responses were analyzed as the main endpoint until day 28. While systemic reactogenicity was either absent or mild, SARS-CoV-2-specific neutralizing antibody titers rapidly arose in all participants within 4 weeks, surpassing the peak antibody titers elicited by the initial two-dose immunization regime. Broad increases of cellular immunity-associated cytokines and chemokines were also detected in the majority of participants after the third vaccination. Furthermore, in an exploratory study, a newly developed recombinant protein vaccine, NVSI-06-08 (CHO Cells), was found to be safe and even more effective than BBIBP-CorV in eliciting humoral immune responses in BBIBP-CorV-primed individuals. Together, these results indicate that a third immunization schedule with either homologous or heterologous vaccine showed favorable safety profiles and restored potent SARS-CoV-2-specific immunity, providing support for further trials of booster vaccination in larger populations.
Adolescent ; Adult ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19/prevention & control* ; COVID-19 Vaccines/adverse effects* ; China ; Humans ; Immunogenicity, Vaccine ; Middle Aged ; SARS-CoV-2 ; Vaccination ; Young Adult

Dendritic cell-based cancer vaccines (DC vaccines) have been proved efficient and safe in immunotherapy of various cancers, including melanoma, ovarian and prostate cancer. However, the clinical responses were not always satisfied. Here we proposed a novel strategy to prepare DC vaccines. In the present study, a fusion protein SNU containing a secretin-penetratin (SecPen) peptide, NY-ESO-1 and ubiquitin was designed and expressed. To establish the DC vaccine (DC-SNU), the mouse bone marrow-derived DCs (BMDCs) were isolated, pulsed with SNU and maturated with cytokine cocktail. Then peripheral blood mononuclear cells (PBMCs) from C57BL/6 mice inoculated intraperitoneally with DC-SNU were separated and cocultured with MC38/MC38

Objective:To explore the diagnostic value of transrectal ultrasound(TRUS)/multiparametric magnetic resonance imaging(mpMRI) fusion targeted biopsy(FTB) for clinically significant prostate cancer(PCa) detection by using both biopsy histopathology and radical prostatectomy histopathology as reference standards.Methods:A total of 303 consecutive patients with suspicious lesions detected by mpMBI and underwent prostate biopsy at Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine between November 2017 to January 2020 were retrospectively analyzed. All the suspicious lesions were sampled by TRUS/mpMRI FTB in addition with standard 12-core systematic biopsy(SB). The clinically significant PCa detection rates by TRUS/mpMRI FTB and SB were compared by using both biopsy histopathology and radical prostatectomy histopathology as reference standards.Results:The diagnosis of PCa was histologically confirmed in 189 of 303 patients, including 178 patients with clinically significant PCa and 11 patients with clinically insignificant PCa. With biopsy histopathology as reference standard, the clinically significant PCa detection rate of TRUS/mpMRI FTB was statistically higher than SB (57.1% vs 45.9%, P<0.001). Among 189 patients with biopsy proven PCa, 80 patients underwent radical prostatectomy, and the radical prostatectomy histopathology confirmed 79 patients with clinically significant PCa.With radical prostatectomy as reference standard, the clinically significant PCa detection rate of TRUS/mpMRI FTB was statistically higher than SB (91.1% vs 74.7%, P<0.001). Conclusions:Compared with SB, MRI/US FTB can offer more accurate sampling of suspicious lesions on mpMRI, and consequently improve the clinically significant PCa detection rate.

Objective:To assess the utility of contrast-enhanced ultrasound (CEUS) targeted biopsy (TB) for clinically significant prostate cancer (PCa) detection.Methods:A total of 983 consecutive patients scheduled for prostate biopsy from October 2015 to March 2019 in Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine were enrolled in this retrospective study. All patients had suspicious lesions on CEUS, defined as increased focal contrast enhancement, rapid contrast enhancement and low enhancement lesions with ill-defined borders. Suspicious lesions on CEUS were sampled in addition with standard 12-core systematic biopsy(SB). Clinically significant PCa was defined using Epstein criteria. The clinically significant PCa detection rate by CEUS-TB and combined biopsy was evaluated in comparison with SB.Results:In 502 of the 983 patients, the diagnosis of PCa was histologically confirmed, including 445 patients with clinically significant PCa and 57 patients with clinically insignificant PCa. The clinically significant PCa by CEUS-TB and combined biopsy were 41.9% (412/983) and 45.3% (445/983) respectively, which was significantly higher than SB (36.8%, 362/983)(all P<0.001). CEUS-TB resulted in additional 83 cases of clinically significant PCa, including 61 patients missed by SB and 22 patients under-graded by SB. Conclusions:CEUS is helpful in the detection of PCa lesions. Combined CEUS-TB and SB can improve the clinically significant PCa detection rate.

Objective To retrospectively investigate the value of contrast enhanced ultrasound ( CEUS) in breast cancer biopsy . Methods A total of 49 consecutive patients with biopsy confirmed breast cancer were retrospectively analyzed . All patients underwent CEUS and biopsies were thus performed targeting both the high perfusion and low/non‐perfusion regions on CEUS . T he diagnostic performance and core cancer involvement of the biopsy cores taken from the high perfusion regions were compared with those from the low/non‐perfusion . Results A total of 53 breast cancer lesions were biopsy confirmed in 49 patients .CEUS revealed homogeneous enhancement in 8 lesions ( 15 .1% ) ,and heterogeneous enhancement in 45 lesions ( 84 .9% ) . T he diagnostic accuracy rate for biopsy cores taken from the high perfusion regions was significantly higher than that from the low/non‐perfusion regions ( 98 .5% vs 72 .9% , P ＜0 .01) . T he core cancer involvement was also higher in high perfusion lesions ( 55% vs 30% , P ＜0 .01) . Conclusions CEUS can differentiate the active area and necrotic fibrosis area of breast tumors by displaying the microvessels ,thus contributing to the selection of biopsy sites .

Objective: To retrospectively investigate the value of contrast enhanced ultrasound (CEUS) in breast cancer biopsy. Methods: A total of 49 consecutive patients with biopsy confirmed breast cancer were retrospectively analyzed. All patients underwent CEUS and biopsies were thus performed targeting both the high perfusion and low/non-perfusion regions on CEUS. The diagnostic performance and core cancer involvement of the biopsy cores taken from the high perfusion regions were compared with those from the low/non-perfusion. Results: A total of 53 breast cancer lesions were biopsy confirmed in 49 patients.CEUS revealed homogeneous enhancement in 8 lesions (15.1%), and heterogeneous enhancement in 45 lesions (84.9%). The diagnostic accuracy rate for biopsy cores taken from the high perfusion regions was significantly higher than that from the low/non-perfusion regions (98.5% vs 72.9%, P<0.01). The core cancer involvement was also higher in high perfusion lesions (55% vs 30%, P<0.01). Conclusions CEUS can differentiate the active area and necrotic fibrosis area of breast tumors by displaying the microvessels, thus contributing to the selection of biopsy sites.

In this study, we attempted to establish a culture system for in vitro spermatogenesis from spermatogonial stem cells (SSCs) of Bama mini-pig. Dissociated testicular cells from 1-month-old pigs were co-cultured to mimic in vivo spermatogenesis. The testicular cells were seeded in minimum essential medium alpha (α-MEM) supplemented with Knockout serum replacement (KSR). Three-dimensional colonies formed after 10 days of culture. The colonies showed positive staining for SSC-associated markers such as UCHL1, PLZF, THY1, OCT4, Dolichos biflorus agglutinin, and alkaline phosphatase. Induction of SSCs was performed in α-MEM + KSR supplemented with retinoic acid, bone morphogenetic protein 4, activin A, follicle-stimulating hormone, or testosterone. The results showed that STRA8, DMC1, PRM1, and TNP1 were upregulated significantly in the colonies after induction compared to that in testis from 1-month-old pigs, while expression levels of those genes were significantly low compared to those in 2-month-old testis. However, upregulation of ACROSIN was not significant. Replacement of α-MEM and KSR with Iscove's modified Dulbecco's medium and fetal bovine serum did not upregulate expression of these genes significantly. These results indicate that SSCs of Bama mini-pig could undergo differentiation and develop to a post-meiotic stage in α-MEM supplemented with KSR and induction factors.
Acrosin ; Activins ; Alkaline Phosphatase ; Bone Morphogenetic Protein 4 ; Dolichos ; Follicle Stimulating Hormone ; Humans ; In Vitro Techniques ; Infant ; Infant, Newborn ; Spermatogenesis ; Stem Cells ; Swine ; Testis ; Testosterone ; Tretinoin ; Up-Regulation

Objective To retrospectively evaluate the influence of prostate volume on prostate cancer detection using elastography targeted transperineal biopsy. Methods A total of 573 consecutive patients suspicious for prostate cancer were enrolled in this study. Patients underwent combined elastography-targeted biopsy and 10 core-systematic transperineal biopsy.In correlation with prostate biopsy pathology, the sensitivity of elastography-targeted biopsy and systematic biopsy were compared among four subgroups with different prostate volume.Results The overall prostate cancer detection rate was 42.9% (246/573). The increase in cancer detection rate by elastography-targeted biopsies was 9.1% (52/573).In patients with prostate volume of ≤30 ml,30-50 ml,50 -80 ml and >80 ml,the sensitivity of elastography targeted biopsy were 91.1% (72/79),81.3% (87/107),70.5% (31/44) and 50.0% (8/16),respectively ( P =0.000).The sensitivity of systematic biopsy were 77.2% (61/79),77.6% (83/107),86.4% (38/44) and 75.0% (12/16),respectively,in comparison among these four groups ( P = 0.601). For patients with prostate volume ≤30 ml,the sensitivity of elastography targeted biopsy was significantly higher than that of systematic biopsy (P= 0.028). Conclusions Prostate cancer detection rate can be improved by elastography targeted biopsy. Prostate volume is correlated with the accuracy of elastography. The sensitivity of elastography targeted biopsy is higher in patients with a smaller prostate gland.