Five influencing factors of the polymerization process of glutaraldehyde with hemoglobin were studied in cluding the approach of feeding glutaraldehyde, hemoglobin concentration, the molar ratio of glutaraldehyde and hemoglobin, reaction time and temperature, in order to reduce the average molecular weight and to improve the effective polymerization ratio. The results showed that the optimal process reduced the average molecular weight of hemoglobin based oxygen carriers (HBOCs) from (350.20 +/- 35.45)kD to (158.60 +/- 8.70)kD and improved the effective polymerization ratio from 53.27% +/- 4.95% to 69.50% +/- 3.70%. When the experiments expanded 30 folds, the results of the effective polymerization ratio and the average molecular weight mentioned above could be achieved.
Female ; Glutaral ; chemistry ; Hemoglobins ; chemistry ; Humans ; Molecular Weight ; Oxygen ; chemistry ; Placenta ; Polymerization ; Pregnancy

Objective To study the optimization process of matching conditions using glutaraldehyde (GDA) as crosslinking agent of hemoglobin based oxygen carriers (HBOCs),to further reduce the average molecular weight and the content of super-weight molecular,and improve the conversion ratio of polymerization.Methods The orthogonal designs were done on the basis of the previous single influencing factor research of human placenta hemoglobin crosslinking GDA.Three factors were selected including molar ratio of GDA to hemoglobin,mass concentration of hemoglobin and the rate of the feeding GDA.Results The molar ratio of GDA to hemoglobin is the most important influencing factor on the molecular weight distribution of polymerized hemoglobin,followed by the mass concentration of hemoglobin and the rate of feeding GDA.When analyzing the impact on the mean molecular weight,there were significant differences between mean molecular weight corresponding to different molar ratios of GDA to hemoglobin (P＜0.05),while there was no statistical significance between mean molecular weight corresponding to different mass concentrations of hemoglobin and the rates of feeding GDA (P＞0.05).When analyzing the impact on the effective conversion ratio,there were significant differences between effective conversion ratios corresponding to different molar ratios of GDA to hemoglobin and different mass concentrations of hemoglobin (P＜0.05),while there were no statistical significances between effective conversion ratios corresponding to different rates of feeding GDA (P＞0.05).When analyzing the impact on the content of super-weight molecular,there were significant differences between content of super-weight molecular corresponding to different molar ratios of GDA to hemoglobin,while there were no statistical significances between content of super-weight molecular corresponding to different mass concentrations of hemoglobin and different rates of feeding GDA.Conclusions The optimal matching conditions of hemoglobin polymerization process were determined by orthogonal designs.

Objective: Investigate the clinicopathological features for secretory carcinoma of breast (SCB). Methods: The clinical data of 3 SCB cases were collected, immunohistochemical staining was performed by the streptavidin-peroxidase (SP) method to test the expression of the antibodies: ER, PR, HER-2, Ki-67, S100, CK5/6, p63, SMA, calponin, GCDFP-15, and EGFR. Fluorescence in situ hybridization (FISH) was used to detect the ETV6-NTRK3 gene fusion. Results: ER was focal weakly positive in case 1 and case 2 (about 5%) , and negative in case 3. PR was focal weakly positive in case 1 (about 5%) and completely negative in case 2 and case 3. Three cases showed that HER-2, SMA, calponin, GCDFP-15 were negative, while S100, CK5/6, EGFR were diffuse strongly positive. The proliferation index was nearly 15% in case 1 and case 2, and 10% in case 3. p63 was negative in mostly tumor cells of case 1, and focal positive expression in the nucleus and cytoplasm. In case 2, p63 was completely negative. However, p63 was observed positive in the cytoplasm as well as some secretory material in case 3. ETV6-NTRK3 gene fusion detection by FISH was positive in all cases. Conclusions SCB is a rare low grade triple-negative breast cancer with the unique pathomorphologic features, while its recurrent t (12; 15) (p13; q25) translocation resulting in ETV6 -NTRK3 gene fusion. It has the indolent clinical behavior and good prognosis.

Objective To investigate the level of finger systolic blood pressure (FSBP) in healthy young adults. Methods A total of 28 healthy young adults were selected as the study subjects by convenient sampling method. The FSBP of the study subjects was detected at 30 and 10 ℃, and the FSBP index (F_i) was calculated. Results The FSBP of the study subjects at 30 and 10 ℃ were (102.0±16.5) and (104.4±15.2) mmHg, respectively. The FSBP in male group at 30 and 10 ℃ was (99.6±18.6) and (107.2±17.0) mmHg, respectively. The FSBP in female group at 30 and 10 ℃ was (104.4±13.9) and (101.5±2.8) mmHg, respectively. The results of factorial analysis showed that the interaction between gender and temperature on FSBP was statistically significant (P<0.05). FSBP in male group was higher at 10 than 30 ℃ (P<0.05) and higher than female group at 10 ℃ (P<0.05). There was no statistical significance for the main effect of gender, temperature, finger, or the interaction effect of gender and finger, temperature and finger for FSBP (all P>0.05). The average F_i of the study subjects was (98.0±16.6)%, with males and females having the average F_i of (100.7±20.7) % and (95.2±10.6) % respectively. The results of factorial analysis of variance showed that there was no significant difference on F_i in the main effect gender and fingers or the interaction effect between them(all P>0.05). Conclusion The FSBP test could be used as a detection method for assessing peripheral microcirculation function in Chinese population. However, further research is needed to establish reference ranges and influencing factors.

OBJECTIVE To mine adverse drug event （ADE） signals of lacosamide， and to provide references for clinically safe drug use. METHODS ADE data for lacosamide reported to the United States FDA adverse event reporting system from January 1， 2009， to December 31， 2022， were collected. Data mining was conducted using the reporting odds ratio method and Bayesian confidence propagation neural network method. Classification statistics were performed using the system organ class （SOC） and preferred terms （PT） from ADE terminology set of Medical Dictionary for Regulatory Activities （Version 25.0）. RESULTS A total of 21 360 lacosamide ADE reports were received， identifying 203 ADE signals across 24 SOCs， with 19 signals not included in the drug’s instruction. The top five PTs ranked by occurrence frequency were medication overdose， technical errors during device use， product use issues， intentional product misuse， and therapy discontinuation. The top five PTs ranked by signal strength were changes in seizure presentation type， congenital hypoplasia of depressor anguli oris muscle， multidrug resistance， brain surgery， and vagus nerve stimulator implantation. ADEs not recorded in the drug instruction included congenital hypoplasia of depressor anguli oris muscle， multidrug resistance， mitochondrial DNA mutation， dissociative identity disorder， and congenital auricular anomaly. CONCLUSIONS For lacosamide-induced ADEs that occur frequently and are already listed in the drug’s instructions， such as bradycardia and atrioventricular block， the clinical application should be careful and attentive， adjusting the dosage timely according to the patient’s condition to avoid severe ADEs. Newly discovered suspect ADEs， such as congenital hypoplasia of depressor anguli oris muscle， mitochondrial DNA mutation， overmature infant， dissociative identity disorder， pigmenturia， behavioral disorders， and dissociative disorders， should be vigilantly recognized to ensure the safety of drug use.

BACKGROUND:Reducing the rate of abnormal fertilization is an effective approach to improving the efficacy of in vitro fertilization and reducing patients'financial strain.However,the current research on abnormal fertilization has focused on exploring the types of prokaryotic nuclei and their generation mechanisms,as well as analyzing embryos formed by abnormal fertilization,chromosomal ploidy and utilization value.There is a lack of clinical prediction models for abnormal fertilization based on retrospective studies. OBJECTIVE:To construct a nomogram model to predict abnormal female factors in in vitro fertilization. METHODS:A total of 5 075 patients undergoing treatment for conventional in vitro fertilization at Nanxishan Hospital of Guangxi Zhuang Autonomous Region from March 2017 to March 2022 were retrospectively analyzed.The male confounders were calibrated on a 1:1 propensity score with a match tolerance of 0.02,and 1 672 cases were successfully matched.According to the Vienna Consensus,patients with≥60%normal fertilization capacity were included in the normal fertilization group(n=836)and those with<60%normal fertilization capacity were included in the abnormal fertilization group(n=836).The model and validation groups were obtained by random sampling at a ratio of 7:3.Factors related to the occurrence of abnormal fertilization following conventional in vitro fertilization in the model group were screened using univariate analysis and the best matching factors were selected using the Least Absolute Shrinkage and Selection Operator(LASSO)and included in a multifactorial forward stepwise Logistic regression to identify their independent influencing factors and plot a nomogram.Finally,the prediction model was validated for discrimination,accuracy and clinical application efficacy using receiver operating characteristic curves,calibration curves,clinical decision curves and clinical impact curves. RESULTS AND CONCLUSION:The univariate analysis indicated the factors influencing the occurrence of abnormal fertilization were age,controlled ovarian hyperstimulation protocol,number of assisted pregnancies,years of infertility,infertility factors,anti-mullerian hormone,sinus follicle count,basal luteinizing hormone,luteinizing hormone concentration on the human chorionic gonadotropin day,and estradiol level on human chorionic gonadotropin injection day(P<0.05).LASSO regression further identified the best matching factors,including age,microstimulation protocol,number of assisted pregnancies,years of infertility,anti-mullerian hormone,luteinizing hormone level on human chorionic gonadotropin injection day,and estradiol level on human chorionic gonadotropin injection day(P<0.05).Multifactorial forward stepwise Logistic regression results showed that age,microstimulation protocol,number of assisted conceptions,years of infertility,anti-mullerian hormone,and estradiol level on human chorionic gonadotropin injection day were independent influencing factors for the occurrence of abnormal fertilization following conventional in vitro fertilization.The receiver operating characteristic curves showed an area under the curve of 0.761(0.746,0.777)for the model group and 0.767(0.733,0.801)for the validation group,indicating that the model has good discrimination.The mean absolute error of the calibration curve was 0.044,and the Hosmer-Lemeshow test indicated that there was no significant difference between the predicted probability of abnormal fertilization and the actual probability of abnormal fertilization(P>0.05),indicating the prediction model has good consistency and accuracy.The clinical decision curves and clinical impact curves showed that the model and validation groups had the maximum net clinical benefit at valve probability values of 0.00-0.52 and 0.00-0.48,respectively,and there was a good clinical application efficacy in this valve probability range.To conclude,the nomogram model has good discrimination and accuracy as well as clinical application efficacy for predicting the occurrence of abnormal fertilization in women undergoing conventional in vitro fertilization based on age,microstimulation protocol,number of assisted conceptions,years of infertility,anti-mullerian hormone,and estradiol level on human chorionic gonadotropin injection day.

【Objective】 To study the red blood cell substitute preparation method of glutaraldehyde(GDA) and Bis(3, 5-dibromosalicyl) fumarate(DBBF) double polymerized, and also observe its curative effect. 【Methods】 The affecting factors of the crosslink of DBBF and human placental hemoglobin(Hb) were selected, including solution pH, inositol hexaphosphoric acid concentration, and molar ratios of DBBF/Hb. The changes of P50, Hill Co and methemoglobin(MetHb) content during the preparation process were studied and the molar ratio of GDA to DBBF-Hb were determined. The final product was obtained through the steps of ultrafiltration, filtration, and deoxygenation, etc., and the final product was subjected to a study on the curative effect of anti-hemorrhagic shock in rats. 【Results】 Under the condition of pH 8.0, the concentration of inositol hexaphosphoric acid was 10mM/L, the molar ratio of DBBF/hemoglobin was 6∶1, the content of dimer was(22.67±3.28)%, the content of tetramer was (74.64±7.05)%, and its P50 was (25.25±2.31) mmHg. As the molar ratio of DBBF/Hb increased, P50 and MetHb content would gradually increase, while the Hill Co will gradually decrease. The molar ratio of GDA and DBBF-Hb was 7∶1, the content of dimer was (8.23±0.79)%, the content of tetramer was (27.87±3.63)%, the content of super-macromolecule was (1.05±0.31)%. As the molar ratio of GDA and DBBF/Hb increased, MetHb content would increase, while the P50 and Hill Co would gradually decrease. The 24h survival rate of the product in rats with hemorrhagic shock was 83.33%(10/12), which was significantly higher than that in the negative control group[41.67%(5/12)], while similar with the positive control group [91.67%(11/12)]. 【Conclusion】 The red blood cell substitutes with GDA and DBBF double polymerized can effectively reduce the dimer content, which is more conducive to industrial production, and has a positive effect on the treatment of hemorrhagic shock.

【Objective】 To explore the protective effects of hemoglobin base on oxygen carries (HBOCs) with different oxygen affinity on isolated rat hearts. 【Methods】 Using Langendorff isolated heart perfusion model, 45 adult male SD rats (SPF grade), perfused with 30 min KH solution baseline, were randomly divided into sham operation group and control group: St. Thomas (STS) solution perfusion volume was 3mL/100g body weight; high P50 HBOCs group: [STS + high P50 HBOCs (P50=35.0 mmHg, 2.5 mg/100 g) product] perfusion volume was 3mL/100g body weight; medium P50 HBOCs group: [STS + medium P50HBOCs (P50=26.5.0 mmHg, 2.5 mg/100 g) product] perfusion volume was 3 mL/100 g body weight; low P50 HBOCs group: [STS + low P50 HBOCs (P50=11.0 mmHg, 2.5 mg/100 g) product] perfusion volume was 3mL/100g body weight, and the heart was arrested and placed in a 37℃ water bath to make the heart ischemic for 35 minutes, and then reperfused for 2 hours. The left ventricular development pressure (LVDevP), left ventricular end diastolic pressure (LVEDP), the rate of change of left ventricular pressure (LVPCR) and heart rate (HR) in the rat heart during reperfusion were observed and recorded. 1 min perfusion fluid from each rat in the basic and reperfusion phase was taken, and blood gas analyzer was used to measure the blood gas indexes of rats, and the myocardial injury marker enzymes [cardiac enzyme creatine kinase (CK-MB), lactate dehydrogenase (LDH) and the release of α-hydroxybutyrate dehydrogenase (α-HBDH)] were measured by ELISA kit. 【Results】 The cardiac function and the release of myocardial enzymes in the 5 groups of rats in the basal cardiac perfusion stage were similar (P>0.05). However, in the reperfusion stage, except for the insignificant changes in HR (P>0.05), the heart LVDevP (mmHg) of the three P50 HBOCs groups and the control group were 10.69±3.65 vs 8.50±2.88, 23.26 ±5.62 vs 8.50±2.88, 35.60±3.82 vs 8.50±2.88, LVEDP (mmHg) were 43.34±8.08 vs 54.64±7.42, 39.43±8.30 vs 54.64±7.42, 31.46±4.11 vs 54.64±7.42, dp/dt were 12.09±9.96 vs 6.09±0.98, 25.65±8.87 vs 6.08±0.98, 35.32±9.33 vs 6.09±0.98, -dp/dt were 17.53±11.28 vs 11.39±2.16, 28.80±13.70 vs 11.39±2.16, 43.36±3.83 vs 11.39±2.16, respectively (all P<0.05); the rebound situation and the release of CK-MB, LDH, and α-HBDH in the three P50 HBOCs groups were better than those in the control group (P<0.05). Among the three P50HBOCs products, the low P50HBOCs group had the best cardiac function indexes. The myocardial enzyme indexes of the high, medium and low HBOCs groups were CK-MB (ng/mL): 110.47±4.04, 90.2±2.46, 77.1±3.51; LDH (U/L): 162.23±7.71, 135.13±23.69, 92.20±4.21; a-HBDH (U/L): 228.00±8.03, 172.30±8.99, 131.00±2.02. 【Conclusion】 STS solution containing HBOCs products can improve the function of the reperfused heart at normal temperature ischemia for 35 min and 2 h reperfusion, and reduce heart damage. The STS solution containing low P50 HBOCs has the most obvious protective effect in rat isolated heart perfusion.