Impact of embryo density on the proportion of good quality cleavage embryos / 解剖学报

Objective To investigate the real correlation between embryo density and developmental outcome of cleavage embryos on day 3 by adjusting covariates. Methods Data of 1196 embryos from 206 couples undergoing in vitro fertilization and embryo transfer(IVF-ET) treatment were retrospectively analyzed. Embryos were hypoxia-cultivated in a fixed 30 μl microdrop in culture dishes. Embryo quality on day 3 was evaluated and proportion of good quality cleavage embryos on day 3 was used as the endpoint. Maternal age, paternal age, antral follicles, level of anti-mullerian hormone (AMH), type of infertility, controlled ovarian stimulation(COS) protocol, length of stimulation, number of retrieved oocytes, and type of insemination were chosen as covariates. Results A total of 1196 embryos were included and analyzed. Three embryo densities were routinely used: 30 μl/ embryo [1 embryo/ (30 μl·drop)], 15 μl/ embryo [2 embryos / (30 μl·drop)] and 10 μl/ embryo [3 embryos/ (30 μl·drop)]. The number of embryos assigned into these three groups were 434, 646 and 116 embryos separately. The average proportion of good quality embryos on day 3 in 10 μl/ embryo group were lower than that in both 15 and 30 μl/ embryo group (29. 31% vs 40. 25%,P 0. 05). In the regression analysis, without adjusting any covariables, the good quality embryos rate on day 3 of the 10 μl/ embryo group was 43% lower than that of the 30 μl/ embryo group (0. 57, 95% CI 0. 32, 1. 03), and there was no statistical difference (P>0. 05). In the minimum-adjusted model 2 (adjusted the level of AMH and type of insemination), proportion of good quality embryos on day 3 in group of 10 μl/ embryo significantly decreased by 51% (0. 49, 95% CI 0. 27,0. 90, P < 0. 05) compared with that in group of 30 μl/ embryo. Conclusion In a 30 μl microdrop, compared with individual cul turing, group culturing with the density of 10 μl / embryo did not benefit the development of the cleavage embryos and 30 μl / embryo was the optimal embryo density.

Antifungal resistance-modifying multiplexing action of Momordica charantia protein and phosphorylated derivatives on the basis of growth-dependent gene coregulation in Candida albicans.

Fungal growth-dependent gene coregulation is strongly implicated in alteration of gene-encoding target proteases ruling with an antifungal resistance niche and biology of resistant mutants. On the basis of multi-alterative processes in this platform, the resistance-modifying strategy is designed in ketoconazole resistant Candida albicans and evaluated with less selective Momordica charantia protein and allosterically phosphorylated derivatives at the Thr102, Thr24 and Thr255 sites, respectively. We demonstrate absolutely chemo-sensitizing efficacy regarding stepwise-modifying resistance in sensitivity, by a load of only 26.23-40.00 µg/l agents in Sabouraud's dextrose broth. Five successive modifying-steps realize the decreasing of ketoconazole E-test MIC50 from 11.10 to a lower level than 0.10 mg/l. With the ketoconazole resistance-modifying, colony undergoes a high-frequency morphological switch between high ploidy (opaque) and small budding haploid (white). A cellular event in the first modifying-step associates with relatively slow exponential growth (ie, a 4-h delay)-dependent action, mediated by agents adsorption. Moreover, multiple molecular roles are coupled with intracellularly and extracellularly binding to ATP-dependent RNA helicase dbp6; the 0.08-2.45 fold upregulation of TATA-box-binding protein, rRNA-processing protein and translation initiation factor 5A; and the 7.52-55.33% decrease of cytochrome P450 lanosterol 14α-demethylase, glucan 1, 3-ß glucosidase, candidapepsin-1 and 1-acylglycerol-3-phosphate O-acyltransferase. Spatial and temporal gene coregulation, in the transcription and translation initiation stages with rRNA-processing, is a new coprocessing platform enabling target protease attenuations for resistance-impairing. An updated resistance-modifying measure of these agents in the low-dose antifungal strategic design may provide opportunities to a virtually safe therapy that is in high dose-dependency. LAY SUMMARY: A new platform to modify resistance is fungal growth-dependent gene coregulation. MAP30 and phosphorylated derivatives are candidate resistance-modifying agents. Low-dose stepwise treatment absolutely modifies azole resistance in model fungus.

A valid protective immune response elicited in rhesus macaques by an inactivated vaccine is capable of defending against SARS-CoV-2 infection

With the relatively serious global epidemic outbreak of SARS-CoV-2 infection, public concerns focus on not only clinical therapeutic measures and public quarantine for this disease but also the development of vaccines. The technical design of our SARS-CoV-2 inactivated vaccine provides a viral antigen that enables the exposure of more than one structural protein based upon the antibody composition of COVID-19 patients convalescent serum. This design led to valid immunity with increasing neutralizing antibody titers and a CTL response detected post-immunization of this vaccine by two injections in rhesus macaques. Further, this elicited immunoprotection in macaques enables not only to restrain completely viral replication in tissues of immunized animals, compared to the adjuvant control and those immunized by an RBD peptide vaccine, but also to significantly alleviate inflammatory lesion in lung tissues in histo-pathologic detection, compared to the adjuvant control with developed interstitial pneumonia. The data obtained from these macaques immunized with the inactivated vaccine or RBD peptide vaccine suggest that immunity with a clinically protective effect against SARS-CoV-2 infection should include not only specific neutralizing antibodies but also specific CTL responses against at least the S and N antigens.

Advance in Effect of Occupational Therapy on Quality of Life of Patients with Malignant Tumors (review) / 中国康复理论与实践

In recent years, the mortality rate of patients with malignant tumors gradually decreases, but brought low quality of life from the adverse reactions and complications. Occupational therapy plays a significant role in improving the quality of life of the patients with malignant tumors. There are many quality-of-life scales for evaluation, such as the general quality of life evaluation scale, cancer-specific quality of life evaluation tools and cancer-specific quality of life evaluation tools,which provide a basis for subsequent treatment. Occupational therapy may work to relief the pain after surgery, maintain or improve the motor function, the activities of daily living, strengthen endurance and cardiopulmonary function, reduce anxiety and depression, promote the return to work or school, for the family, provide suggestions for community environment adjustment, and guide the training for lymphedema. Some problems still remained, such as the insufficient rehabilitation service, the medicine-based model, and insufficient rehabilitation therapists.

The expression and significance of Th17 cell/regulatory T cells in peripheral blood of patients with idiopathic inflammatory myopathy / 中华风湿病学杂志

Objective To explore the expression and their significance of peripheral Th17 cells and regulatory T cells (Tregs) in idiopathic inflammatory myopathy,and analyze the relationship between the expression and clinical indicators,imaging and pathological changes.Methods Clinical data,laboratory tests,imaging and pathological changes of IIM cases (n=85) and healthy controls (n=70) were enrolled.Clinical data included the classification,age,gender,course of the disease;laboratory tests including erythrocyte sedimentation rate (ESR),C-reactive protein (CRP),creatine kinase (CK),creatine kinase isoenzyme-MB (CKMB),lactate dehydrogenase (LDH),hydroxybutyrate dehydrogenase (HBDH).The level of peripheral Th17,Treg cells and clinical indicators,laboratory tests,imaging and pathological changes were analyzed retrospectively.Since the data was disregarded from the normal distribution,the median four quantile method was used for statistical description.Two samples were compared with Mann-Whitney U test,and the correlation between variables was Spearman rank correlation analysis.Results ①) The levels of Th17 cells in the case group was not significantly different from that in the control group [6.18(3.42,13.65) cell/μl vs 7.42(5.02,11.13) cell/μl,P＞0.05],the levels of Treg cells in patients was significantly lower than that in the control group [21.25(12.48,35.67) cell/μl vs 36.95(30.37,47.12) cell/μl,P＜0.05],the ratio of Th17/Treg was also significantly higher than that in the control group [0.31(0.21,0.47) vs 0.18(0.14,0.31),P＜0.05].② Peripheral Treg cells levels were not correlated with ESR,CRP,CK-MB,LDH and HBDH (P＞0.05).Peripheral Treg cells levels were negatively correlated with CRP (r=-0.279,P＜0.05),but no correlated with ESR,CK-MB,LDH and HBDH (P＞0.05).③ According to the involvement of important organs,patients were classified into two groups:organ involvement group and non-organ involvement group.The levels of Treg cells in the organ involvement group was fewer than that in non-organ involvement group [16.54(8.84,27.34) cell/ul vs 24.87(14.44,43.37) cell/ul,P＜0.05],and the ratio of Th17/Treg in the organ involvement group was significantly higher than that in non-organ involvement group [0.41(0.29,0.68) vs 0.29(0.19,0.39),P＜0.05].④) Peripheral Th17 cells levels in patients with skeletal muscle inflammatory edema was significantly higher than that of non-inflammatory edema patients [10.70 (4.11,14.51) cell/μl vs 3.10 (1.27,5.15) cell/μl,Z=-2.460,P＜0.05].⑤ The levels of Th17,Treg cells and ratio of Th17/Treg did not correlate with pathological features of inflammatory infiltration (P＞0.05).Conclusion The absolute number of peripheral Treg cells decreases significantly in IIM,and correlates with CRP.Patients with organ involvement have fewer Treg cells,and there is imbalance between Th17 and Treg.When muscle MRI presents with inflammatory edema,patients may have high level of Th17 cells.Our results suggest that Treg cells may play an important role in the pathogenesis of IIM.

Correlation of serum C-telopeptide cross-linked collagen type Ⅰ with bone mineraI density in a rat modeI of disuse osteoporosis / 中国组织工程研究

BACKGROUND: C-telopeptide and N-telopeptide cross-linked collagen type Ⅰ (CTx and NTx, respectively) are specific biochemical bone markers that can reflect bone formation and resorption. OBJECTIVE: To analyze the association of CTx with disuse osteoporosis. METHODS: Male Sprague-Dawley rats, weighing 180-220 g, were randomly divided into control and disuse osteoporosis groups. Right hind limbs of the rats in the disuse osteoporosis group were immobilitzed for 4 weeks by ankle-tail fixation to establish the rat model of disuse osteoporosis. Peritoneal venous blood was collected before and after modeling, and the femur was then removed to measure the serum CTx level and bone mineral density of the bilateral femurs. RESULTS AND CONCLUSION: The serum CTx level did not differ significantly between groups before modeling (P > 0.05). At 4 weeks after modeling, the serum CTx level in the disuse osteoporosis group was significantly higher than that in the control group and at baseline (P <0.01). The serum CTx level showed no significant change in the control group before and after modeling (P > 0.05). The increment of serum CTx in the disuse osteoporosis group exhibited a negative correlation with the bone mineral density of the bilateral femurs (r=0.426, P < 0.01). The bone mineral density of the right femur in the disuse osteoporosis group was significantly lower than that of the left one in the disuse osteoporosis group and the right one in the control group (P < 0.01), and there was no significant difference in the bone mineral density between left and right femurs in the control group (P > 0.05). These results imply that the model of disuse osteoporosis by ankle-tail fixation is established successfully. Disuse osteoporosis can promote the production of CTx further reducing bone mineral density; CTx is positively correlated with the degree of bone loss, so it can be used for therapeutic assessment and diagnosis of osteoporosis.

Study on optimal model of hypothetical work injury insurance scheme / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore an optimal model of hypothetical work injury insurance scheme, which is in line with the wishes of workers, based on the problems in the implementation of work injury insurance in China and to provide useful information for relevant policy makers.</p><p><b>METHODS</b>Multistage cluster sampling was used to select subjects: first, 9 small, medium, and large enterprises were selected from three cities (counties) in Zhejiang Province, China according to the economic development, transportation, and cooperation; then, 31 workshops were randomly selected from the 9 enterprises. Face-to-face interviews were conducted by trained interviewers using a pre-designed questionnaire among all workers in the 31 workshops.</p><p><b>RESULTS</b>After optimization of hypothetical work injury insurance scheme, the willingness to participate in the scheme increased from 73.87%to 80.96%; the average willingness to pay for the scheme increased from 2.21% (51.77 yuan) to 2.38% of monthly wage (54.93 Yuan); the median willingness to pay for the scheme increased from 1% to 1.2% of monthly wage, but decreased from 35 yuan to 30 yuan. The optimal model of hypothetical work injury insurance scheme covers all national and provincial statutory occupational diseases and work accidents, as well as consultations about occupational diseases. The scheme is supposed to be implemented worldwide by the National Social Security Department, without regional differences. The premium is borne by the state, enterprises, and individuals, and an independent insurance fund is kept in the lifetime personal account for each of insured individuals. The premium is not refunded in any event. Compensation for occupational diseases or work accidents is unrelated to the enterprises of the insured workers but related to the length of insurance. The insurance becomes effective one year after enrollment, while it is put into effect immediately after the occupational disease or accident occurs.</p><p><b>CONCLUSION</b>The optimal model of hypothetical work injury insurance scheme actually realizes cross-regional mobility of workers, minimizes regional differences, and embodies the fairness. The proposed model will, to some extent, protect the rights and interests of enterprises, as well as the healthy rights and interests of workers when they are unemployed.</p>

Part IV. Synthesis and antitumor evaluation of s-triazolothiadiazines and pyrazolo s-triazoles derived from ciproxacin / 药学学报

An efficient modified route based on the targeting mechanism of antibacterial fluoroquinolones for the shift from the antibacterial activity to the antitumor one was further developed. Using a fused heterocyclic ring, s-triazolothiadiazine as a carboxyl bioisostere of ciprofloxacin, the title compounds, 1-cyclopropyl-6-fluoro-7-piperazin-1-yl-3-(6-substituted-phenyl-7H-[1, 2, 4]triazolo[3, 4-b][1, 3, 4]thiadiazin-3-yl)-quinolin-4(1H)-ones (5a-5e) and their corresponding N-acetyl products (6a-6e), were designed and synthesized, separately. Meaningfully, a ring-contraction of fused six-membered thiadiazine occurred by a sulfur extrusion reaction gave new tri-acetylated fused heterocycles related to pyrazolo[5, 1-c][1, 2, 4] triazoles (7a-7e). The in vitro antitumor activity against L1210, CHO and HL60 cell lines was also evaluated for the synthesized fifteen heterocycles compared to parent ciprofloxacin by methylthiazole trazolium (MTT) assay. Interestingly, the results displayed that fifteen fused heterocyclic compounds showed more significant growth inhibitory activity (IC50 < 25.0 micromo x L(-1)) than that of parent ciprofloxacin (IC50 > 150.0 micromol x L(-1)), and the active order decreased from 7a-7e to 5a-5e to 6a-6e, respective.

Part IV: Design, synthesis and antitumor activity of fluoroquinolone C-3 heterocycles: bis-oxadiazole methylsulfide derivatives derived from ciprofloxacin / 药学学报

To explore an efficient strategy for further development of anticancer fluoroquinolone candidates derived from ciprofloxacin, a heterocyclic ring as the bioisosteric replacement of C3 carboxyl group led to a key intermediate, oxadiazole thiol (5), which was further modified to the bis-oxadiazole methylsulfides (7a-7h) and the corresponding dimethylpiperazinium iodides (8a-8h), respectively. Structures were characterized by elemental analysis and spectra data, and their anticancer activities in vitro against CHO, HL60 and L1210 cancer cells were also evaluated by MTT assay. The preliminary results show that piperazinium compounds (8) possess more potent activity than that of corresponding free bases (7).

Association of single nucleotide polymorphisms in VEGF gene with the risk of endometriosis and adenomyosis / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association of single nucleotide polymorphisms (SNPs) in VEGF gene with the risk of endometriosis and adenomyosis.</p><p><b>METHODS</b>Genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 344 endometriosis patients, 174 adenomyosis patients, 360 frequency-matched control women of endometriosis and 199 frequency-matched control women of adenomyosis.</p><p><b>RESULTS</b>No significant difference was found in allele frequencies and genotype distributions of the -460C/T polymorphism between patients (endometriosis and adenomyosis) and control women (all P value > 0.05). However, there were significant differences in genotype and allele distributions of the VEGF -1154G/A polymorphism between patients (endometriosis and adenomyosis) and control women (all P value < 0.05). The genotype frequencies of the VEGF -1154 AA, GA, and GG in endometriosis patients and control women were 1.7%, 28.8%, 69.5% and 5.8%, 32.8%, 61.4%, respectively; and the A and G allele frequencies in the two groups were 16.1%, 83.9% and 22.2%, 77.8%, respectively. The genotype frequencies of the VEGF -1154 AA, GA, and GG in adenomyosis patients and control women were 2.9%, 23.6%, 73.6% and 7.0%, 34.2%, 58.8%, respectively; and the A and G allele frequencies in the two groups were 14.7%, 85.3% and 24.1%, 75.9% respectively. Compared with GA+ AA genotype, GG genotypes could significantly increase the risk of endometriosis (OR:1.43,95%CI:1.05-1.96) and adenomyosis (OR:1.95,95%CI:1.26-3.03).</p><p><b>CONCLUSION</b>The VEGF -1154G/A polymorphism was associated with susceptibility to endometriosis and adenomyosis, and the GG genotype could significantly increase the risk of developing endometriosis and adenomyosis. However, the VEGF -460C/T polymorphism was not associated with susceptibility to endometriosis and adenomyosis in the population studied.</p>

Association of polymorphism on HLA-DRB1*04 alleles with outcome of hepatitis B virus infection / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the relation between the alleles of HLA-DRB1*04 and outcome of HBV infection.</p><p><b>METHODS</b>The alleles of HLA-DRB1*04 were detected by polymerase chain reaction-sequence specific primer (PCR-SSP). The frequency of allele of HLA-DRB1*04 in four groups[106 asymptomatic HBsAg carriers (group ASC), 93 chronic hepatitis B patients (group CHB), 77 patients with hepatitis B cirrhosis and 102 cases of spontaneous recovery after HBV infection (control group)] were studied, and the frequency of that in different replication of HBV was also studied.</p><p><b>RESULTS</b>The frequency of allele of HLA-RB1*04 in groups ASC, CHB and hepatitis B cirrhosis was markedly higher than that of control group (25.94%, 26.34%, 27.92% respectively versus 14.22%, P< 0.01); the frequency of HLA-DRB1*0401 in groups ASC, CHB and hepatitis B cirrhosis was also higher than that of control group (20.91%, 24.49%, 22.09% respectively versus 8.62%, P< 0.05, P< 0.01,P< 0.05 respectively); the frequency of HLA-DRB1*0405 in groups ASC, CHB and hepatitis B cirrhosis was lower than that of control group (3.64%, 2.04%, 3.49% respectively versus 15.52%, P< 0.01, P< 0.01, P< 0.05 respectively ). There was no statistical significance in the allele frequency of HLA-DRB1*04 among groups ASC, CHB and hepatitis B cirrhosis (P> 0.05), and the same result was observed in different replication of HBV (P> 0.05).</p><p><b>CONCLUSION</b>HLA-DRB1*04 gene is one of the factors which determine the outcomes of HBV infection, while it has no influence on HBV replication.</p>