Objective:To analyse the clinical significance of selective single embryo transfer by time-lapse mo-nitoring(TLM)or conventional morphology assessment(CMA)in vitro fertilization/intracytoplasmic sperm in-jection and embryo transfer(IVF/ICSI-ET),and to initially explore the predictive value of Raman spectral analy-sis of embryo culture medium for clinical pregnancy rate.Methods:The study is a prospective randomized con-trolled clinical trial.We assigned 139 patients treated with IVF/ICSI-ET in Reproductive and Genetics Center of Suzhou Municipal Hospital from April 2019 to July 2020,which were randomly assigned to either the CMA or the TLM group.We performed selective single-embryo transfer(fresh cycle and FET)after selecting the optimal em-bryos with TLM or CMA respectively.If the patient's first embryo transfer was unsuccessful,a second one would be performed to compare the differences in the cumulative live birth rate of embryo transfer and other pregnancy outcomes between the two groups.Meanwhile,we collected 15 μl of embryo culture medium at day 3 after IVF/ISCI fertilization for Raman spectroscopy analysis.Results:There were no differences in cumulative live birth,cu-mulative clinical pregnancy,cumulative premature birth,cumulative early spontaneous abortion,cumulative ectopic pregnancy and LGA or SGA between TLM and CMA groups(P＞0.05).The Neonatal sex ratio in the TLM group was lower than that in the CMA group,but the difference was not significant(P＞0.05).Raman spectros-copy analysis of embryo culture medium predicted the clinical pregnancy rate with 67.21％accuracy.Conclu-sions:In young women with a good ovarian reserve,the advantage of using TLM to evaluate embryos is not obvi-ous,so we should remain vigilant that embryo selection based on morphokinetic parameters may affect the sex ratio.Raman spectroscopic analysis of embryo culture medium is not yet able to effectively predict the planting ability of embryos.

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.

To investigate the correlation of polymorphisms at the rs1837253 and rs3806933 loci of the thymic stromal lymphopoietin(TSLP)gene with asthma susceptibility and Eos,IgE,and FeNO levels in children.A total of 143 asthmatic children were selected as the study group,and 112 healthy children undergoing routine health examinations at the same hospital were chosen as the control group.The MassARRAY SNP genotyping technology was used to detect the genotypes at two loci,while serum IgE levels were determined by using the turbidimetric scattering method.The distribution differences in genotype and allele frequencies between the two groups were analyzed,along with the effects of different genotypes on Eos,IgE,and FeNO levels.There was no statistically significant difference in the distribution of rs1837253 allele and genotype frequencies as well as rs3806933 allele frequencies between the two groups(P＞0.05).However,asthma group rs3806933 CT genotype frequency was higher than the control group,and CC genotype frequency was lower than the control group(P＜0.05).Compared with the wild-type genotypes,children who carried rs1837253 CT+CC and rs3806933 CT,CT+TT genotypes had an increased risk of asthma(CT+CC vs TT:OR=2.737,95%CI:1.514-4.945;CT vs CC:OR=2.058,95%CI:1.194-3.543;CT+TT vs CC:OR=1.843,95%CI:1.109-3.062).There was an overall statistical difference in Eos counts among the three genotypes at the rs1837253 locus in the asthma group(P＜0.05,correction for multiple comparisons P＞0.05),but not in the control group(P＞0.05).There were no statistically significant differences in Eos%,IgE,and FeNO levels among the genotypes at the two loci and no significant difference in Eos counts among genotypes at the rs3806933 loci(P＞0.05).Taken together,polymorphisms at rs1837253 and rs3806933 loci in the promoter region of the TSLP gene are associated with asthma susceptibility in children.rs3806933 CT genotype may serve as a potential genetic marker for asthma,and rs1837253 CT+CC and rs3806933 CT+TT genotypes are risk factors for asthma in children;the rs1837253 locus polymorphism tended to affect blood Eos counts,while the two SNPs were not associated with Eos%,serum IgE,and FeNO levels.

Objective To explore the effects of sodium oligomannate combined with high-frequency repetitive transcranial magnetic stimulation on the activity of daily living and intelligence level of patients with Alzheimer's disease.Methods A total of 100 patients with Alzheimer's disease admitted to Henan Provincial Staff Hospital from September 2021 to September 2023 were selected as the research subjects.These patients were divided into an observation group and a control group according to the random number table method,with 50 patients in each group.Patients in the control group were given high-frequency repetitive transcranial magnetic stimulation,and patients in the observation group were given sodium oligomannate combined with high-fre-quency repetitive transcranial magnetic stimulation.Enzyme-linked immunosorbent assay was used to detect the levels of amyloid β-protein(Aβ)142,tumor necrosis factor-a(TNF-a)and interleukin-6(IL-6)in patients of the two groups before and after treatment.Chemiluminescence was used to detect the levels of neurotransmitters in patients of the two groups before and after treatment.The mental symptoms of patients in the two groups before and after treatment were evaluated by the behavioral pathology in Alzheimer's disease rating scale,the intelligence level of patients in the two groups before and after treatment was evaluated by the mini-mental state examination(MMSE)scale and the Montreal cognitive assessment(MoCA)scale,the activity of daily living of patients in the two groups before and after treatment was evaluated by Alzheimer's disease cooperative study-activity of daily living(ADCS-ADL),and the quality of life of patients in the two groups before and after treatment was evaluated by the quality of life-Alzheimer's disease scale.Results Before treatment,the two groups showed no significant difference in the levels of Aβ1-42,TNF-α and IL-6(P＞0.05);after treatment,the levels of Aβ1-42,TNF-α and IL-6 in both groups were lower than those before treatment,and the levels of Aβ1-42,TNF-α and IL-6 in the observation group were lower than those in the control group(P＜0.05).Before treatment,there were no statistically significant differences in the levels of 5-hydroxytryptamine(5-HT),acetylcholine(ACh),γ-aminobutyric acid(GABA),and Alzheimer-associated neuronal thread protein(AD7c-NTP)between the two groups(P＞0.05);after treatment,the levels of 5-HT,ACh,and GABA in the two groups were higher than those before treatment,while the AD7c-NTP level was lower than that before treatment(P＜0.05);after treatment,the levels of 5-HT,ACh,and GABA in the observation group were higher than those in the control group,while the AD7c-NTP level was lower than that in the control group(P＜0.05).Before treatment,there were no significant differe-nces in the scores of paranoid and delusional ideas,hallucinations,behavioral disorders,aggressive behaviors,daily rhythm disorders,emotional disorders,anxiety and fear,and the total scores between the two groups(P＞0.05);after treatment,the scores of paranoid and delusional ideas,hallucinations,behavioral disorders,aggressive behaviors,daily rhythm disorders,emotional disorders,anxiety and fear,and the total scores of patients in the two groups were lower than those before treatment,and the scores of paranoid and delusional ideas,hallucinations,behavioral disorders,aggressive behaviors,daily rhythm disorders,emotional disorders,anxiety and fear,and the total scores of patients in the observation group were lower than those in the control group(P＜0.05).Before treatment,there were no significant differences in MMSE,MoCA and ADCS-ADL scores of patients between the two groups(P＞0.05);after treatment,the MMSE,MoCA and ADCS-ADL scores of patientsin the two groups were higher than those before treatment,and the MMSE,MoCA and ADCS-ADL scores of patientsin the observation group were higher than those in the control group(P＜0.05).Before treatment,there were no significant differences in the scores of physiological function,mental function,behavioral ability and interpersonal relationship,and the total scores of patients between the two groups(P＞0.05).After treatment,the scores of physiological function,mental function,behavioral ability and interpersonal relationship,and the total scores of patients in the two groups were higher than those before treatment,and the scores of physiological function,mental function,behavioral ability and interpersonal relationship,and the total scores of patients in the observation group were higher than those in the control group(P＜0.05).Conclusion Sodium oligomannate combined with high-frequency repetitive transcranial magnetic stimulation can improve the inflammatory state of patients with Alzheimer's disease,regulate neurotransmitter levels,alleviate psychiatric symptoms,enhance the intelligence level and the activity of daily living,and increase the quality of life.

Obesity is increasingly prevalent globally, searching for therapeutic agents acting on adipose tissue is of great importance. Equisetin (EQST), a meroterpenoid isolated from a marine sponge-derived fungus, has been reported to display antibacterial and antiviral activities. Here, we revealed that EQST displayed anti-obesity effects acting on adipose tissue through inhibiting adipogenesis in vitro and attenuating HFD-induced obesity in mice, doing so without affecting food intake, blood pressure or heart rate. We demonstrated that EQST inhibited the enzyme activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), a therapeutic target of obesity in adipose tissue. Anti-obesity properties of EQST were all offset by applying excessive 11β-HSD1's substrates and 11β-HSD1 inhibition through knockdown in vitro or 11β-HSD1 knockout in vivo. In the 11β-HSD1 bypass model constructed by adding excess 11β-HSD1 products, EQST's anti-obesity effects disappeared. Furthermore, EQST directly bond to 11β-HSD1 protein and presented remarkable better intensity on 11β-HSD1 inhibition and better efficacy on anti-obesity than known 11β-HSD1 inhibitor. Therefore, EQST can be developed into anti-obesity candidate compound, and this study may provide more clues for developing higher effective 11β-HSD1 inhibitors.

Objective:To explore the efficacy of doctor-nurse co-led care involving education and engagement of patients on improving compliance of patients, and a treat-to-target urate-lowering rate for gout.Methods:Nurses were trained in practice management of gout. Patients diagnosed with gout in the departments of rheumatology and immunology of Anqing Municipal Hospital in Anhui Province were prospectively enrolled from January 1 to June 30, 2019. The patients were divided into the continuous-care group and the conventional management group by random number table method. The patients of continuous-care group received telephone follow-up, WeChat tracking and regular face-to-face communication. The patients of conventional management group were told to follow up regularly in the outpatient department, and the nurses did not follow up. Patients were evaluated before intervention and 12 months after intervention. The treat-to-target rate of blood uric acid and the frequency of gout flares were observed.Results:After 12 months of intervention, the patients of serum uric acid concentrations below 360 μmol/L were 92.39% (85/92) in the continuous-care group, and 26.74% (23/86) in the conventional management group. There was significant difference ( χ2 value was 80.282, P<0.001). After 12 months of intervention, the average serum uric acid concentration of patients in the continuous-care group was (301.6±61.4) μmol/L, and that in the conventional management group was (419.0±98.0) μmol/L, both of which were significantly lower than before intervention, continuous-care group (466.1±119.7) μmol/L, conventional management group (477.8±113.1) μmol/L. But the average serum uric acid concentration of patients in the continuous-care group was significantly lower than that in the conventional management group. There was significant difference between them ( t value was 96.678, P<0.001). At the end of 12 months, the patients of uric-acid-lowering therapy increased in both groups. The proportion of patients was 94.56% (87/92) in the continuous-care group, which was significantly higher than that in the conventional management group (58.14%, 50/86), there was significant difference ( χ2 value was 33.260, P<0.001). Conclusions:The mode of continuing nursing combined with specialized physician-led treatment can significantly improve the compliance and the control rate of treat-to-target for gout, and this management method is simple and feasible which provides a new management concept for clinical treatment of gout.

Objective To evaluate the efficacy of acetate Ringer's solution for fluid therapy in the patients with dangerous placenta previa undergoing cesarean section. Methods One hundred fifty-two pa-tients, aged 22-41 yr, with body mass index of 20-30 kg/m2 , of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, scheduled for elective cesarean section under general anesthesia, were allocated to 2 groups ( n=76 each) using a random number table method: acetate Ringer's solution group ( group AR) and lactated Ringer's solution group ( group LR) . Acetate Ringer's solution and lactated Ringer's so-lution 500 ml were intravenously infused at an initial rate of 15 ml·kg-1 ·h-1 followed by an infusion of 10 ml·kg-1·h-1 until patients leaved the operating room in two groups. Blood samples were collected from the left radial artery immediately before fluid replacement, at the end of fluid replacement and at 6 h after sur-gery for blood gas analysis. The development of arrhythmia was recorded during fluid replacement. The postpartum hemorrhage at 2 h after surgery was calculated. Results Compared with group LR, the Mg2+level was significantly increased and blood glucose was decreased at the end of fluid replacement, the inci-dence of arrhythmia was decreased ( P ＜ 0. 05) , and no significant change was found in each parameter of blood gas analysis at 6 h after surgery, postpartum hemorrhage at 2 h after surgery or consumption of ephed-rine in group AR ( P＞0. 05) . Conclusion Acetate Ringer's solution can be effectively used for fluid ther-apy, maintain the internal environment stable and prevent the occurrence of arrhythmia effectively during cesarean section in the patients with dangerous placenta previa.

Objective To study the clinicopathological features and differential diagnosis of bizarre parosteal osteochondromatous proliferation (BPOP). Methods The clinicopathological features of 3 patients with BPOP were analyzed , and related literature was reviewed. Results 3 patients included 2 males and 1 female with an average age 40 years old (24-53 years old). The lesions in three patients were located in the left side of the distal radius, the left side of the little finger inside and the right side of ulna coracoid, respectively. Histologically, characterized by unusual mineralized cartilaginous matrix (`blue bone'), the lesion was composed of a heterogeneous mixture of bone, cartilage and fibrous tissue. Conclusion BPOP is a rare benign surface osteocartilaginous lesion, and its diagnosis and differential diagnosis mainly depend on radiographic and histopathologic features.

Objective To investigate the influence of isoquercitrin on the inflammatory factors in LPS-induced RAW264.7 cells.Methods MTT method was used to detect inhibition ratio of RAW264.7 cells induced by isoquercitrin.The level of TNF-α in culture medium was measured by ELISA.Nitric oxide (NO) was detected by Nitrate Assay Kit.Western blotting was used to investigate the influence on the productions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2).Results The half inhibitory concentration (IC50) of isoquercitrin was 65.73 μmol·L-1.LPS had no inhibitory effect on the cells.Compared with LPS group,the level of TNF-α was decreased to 74.80% and 60.57% in isoquercitrin (20,10 μmol·L-1) groups in a dose-dependent manner.The results measured by Nitrate Assay Kit revealed that isoquercitrin (20,10 μmol·L-1) could suppress production of NO,the level of NO decreased to 79.34% and 68.81%(P<0.05).The Western blotting results showed that isoquercitrin (20,15,10 μmol·L-1) inhibited the productions of iNOS and COX-2 (P<0.05).Conclusion Isoquercitrin has anti-inflammatory effects by inhibiting the productions of TNF-α,NO,iNOS and COX-2,and the most effective dose for the inhibition is 10 μmol·L-1.

Aim To study the inhibitory effect of isoquercitrin on Raf/MEK/ERK signaling pathway in HepG2 cells.Methods MTT was used to detect the proliferation of human liver cancer HepG2 cells after the treatment of isoquercitrin.The morphology and growth of cells were observed under inverted microscope after the different concentrations of isoquercitrin(0, 40, 80, 160, 320 μmol·L-1) to treat HepG2 cells for 24 and 48 h.Cell cycle was assessed by flow cytometry.Ras, Raf, MEK, ERK expression was assayed by Western blot, and mRNA expression was detected by quantitative fluorescence PCR.Results Isoquercitrin could inhibit the growth of HepG2 cells in a concentration-and time-dependent manner.Typical morphological changes of apoptosis were observed by inverted microscopy after HepG2 cells were treated with different concentrations of of isoquercitrin for 24 h or 48 h.The cell cycle assay showed that with the increasing concentration of isoquerditrin, the number of cells that was arrested in G1 phase gradually increased.Compared with the blank group, the expressions of Ras, Raf, MEK, ERK mRNA were down-regulated, and related proteins expression were also down-regulated(P<0.05), and these results had statistical significance.Conclusion Isoquercitrin can induce the apoptosis of HepG2 cells, which may be related to the Raf/MEK/ERK signaling pathway.