Objective To compare the performance and efficacy of prognostic models constructed by different machine learning algorithms in predicting the survival period of lung transplantation (LTx) recipients. Methods Data from 483 recipients who underwent LTx were retrospectively collected. All recipients were divided into a training set and a validation set at a ratio of 7:3. The 24 collected variables were screened based on variable importance (VIMP). Prognostic models were constructed using random survival forest (RSF) and extreme gradient boosting tree (XGBoost). The performance of the models was evaluated using the integrated area under the curve (iAUC) and time-dependent area under the curve (tAUC). Results There were no significant statistical differences in the variables between the training set and the validation set. The top 15 variables ranked by VIMP were used for modeling and the length of stay in the intensive care unit (ICU) was determined as the most important factor. Compared with the XGBoost model, the RSF model demonstrated better performance in predicting the survival period of recipients (iAUC 0.773 vs. 0.723). The RSF model also showed better performance in predicting the 6-month survival period (tAUC _{6 months} 0.884 vs. 0.809, P = 0.009) and 1-year survival period (tAUC _{1 year} 0.896 vs. 0.825, P = 0.013) of recipients. Based on the prediction cut-off values of the two algorithms, LTx recipients were divided into high-risk and low-risk groups. The survival analysis results of both models showed that the survival rate of recipients in the high-risk group was significantly lower than that in the low-risk group (P<0.001). Conclusions Compared with XGBoost, the machine learning prognostic model developed based on the RSF algorithm may preferably predict the survival period of LTx recipients.

Objective To investigate the relationship between kinase insert domain receptor(KDR)rs2305948 polymorphism and clopidogrel resistance(CR)in patients with acute coronary syndrome after receiving percutaneous coronary intervention(PCI).Methods A total of 468 patients with acute coronary syndrome,who were admitted to the Zhangjiakou Municipal First Hospital of China from September 2022 to September 2023,were selected as the subjects of study.All patients received PCI treatment and took medication of clopidogrel after the treatment.The occurrence of CR was recorded.The factors influencing the occurrence of CR were analyzed.The clinical significance of KDR rs2305948 polymorphism in predicting CR in patients with acute coronary syndrome after receiving PCI was evaluated.Results Of 468 patients with acute coronary syndrome,116(24.79％)developed CR.Logistic multivariate regression analysis indicated that low-density lipoprotein cholesterol(LDL-C,95％CI=1.420-8.390,OR=3.452),type 2 vascular endothelial growth factor receptor(VEGFR-2,95％CI=1.374-8.118,OR=3.340),KDR rs2305948 T/T genotype(95％CI=1.677-9.905,OR=4.076),and T allele(95％CI=1.390-8.207,OR=3.377)were the independent factors influencing the occurrence of CR inpatients with acute coronary syndrome after receiving PCI(all P＜0.05).Receiver operating characteristic(ROC)curve analysis showed that the sensitivity,specificity,and area under ROC curve(AUC)of the T/T genotype of KDR rs2305948 in predicting CR in patients with acute coronary syndrome after receiving PCI were 75.86％,70.45％,and 0.773(95％CI=0.666-0.880)respectively.Conclusion In patients with acute coronary syndrome after receiving PCI,the risk of developing CR is higher.The KDR rs2305948 polymorphism is correlated with CR in patients with acute coronary syndrome after receiving PCI,and it has a certain predictive value for CR.

ObjectiveTo observe the effects and underlying mechanisms of Fagopyri Dibotryis Rhizoma extract on the proliferation， apoptosis， and autophagy of human colorectal cancer HCT-116 cells. MethodFirstly， cellular activity was detected by the cell proliferation and activity-8 （CCK-8） assay， and the half inhibition rate （IC₅₀） was calculated. Blank group and Fagopyri Dibotryis Rhizoma group （2， 4， 8 mg·L^-1） were set. The effect of Fagopyri Dibotryis Rhizoma on the proliferation of HCT-116 cells was observed by cloning experiments， and that of Fagopyri Dibotryis Rhizoma on apoptosis was observed by flow cytometry. The expressions of autophagy-related proteins， p38 mitogen-activated protein kinase （p38 MAPK）， extracellular signal-regulated kinase （ERK）， c-Jun amino-terminal kinase （JNK）， phosphorylated （p）-p38， p-ERK， p-JNK， and other proteins were detected by Western blot. Finally， flow cytometry instrumentation and fluorescence microscopy were used to analyze the changes in reactive oxygen species （ROS）， and a ROS scavenger （NAC） was adopted for verification. ResultCompared with the blank group， the activity of HCT-116 cells was significantly decreased in the Fagopyri Dibotryis Rhizoma group （P<0.05， P<0.01）. The apoptosis rate of HCT-116 cells in the Fagopyri Dibotryis Rhizoma group was significantly increased （P<0.01）. The expression of autophagy-related protein ubiquitin-binding protein （p62） was decreased， but that of autophagy-specific genes （Beclin1） and autophagic microtubule-associated protein 1 light-chain 3B （LC3B） was enhanced （P<0.05， P<0.01）. Compared with the Fagopyri Dibotryis Rhizoma group， the apoptosis rate of HCT-116 cells in the Fagopyri Dibotryis Rhizoma + NAC group was significantly reduced （P<0.01）. The expression of related autophagy protein Beclin1 was significantly reduced （P<0.01）， and that of LC3B protein was reduced （P<0.01）. In addition， the expression of MAPK pathway-related proteins ERK and JNK was decreased in the Fagopyri Dibotryis Rhizoma group （P<0.05， P<0.01）， and that of p-ERK and p-JNK was enhanced （P<0.05， P<0.01）. ConclusionFagopyri Dibotryis Rhizoma can inhibit the proliferation of HCT-116 cells and induce apoptosis and autophagy through the ROS/MAPK signaling pathway.

OBJECTIVE: To compare the prevalence of chromosomal aneuploidies and pregnancy outcomes of D5 and D6 blastocysts subjected to preimplantation genetic testing for aneuploidy (PGT-A). METHODS: Clinical and laboratory data of 268 couples who underwent PGT-A at the Reproductive Center of the First Affiliated Hospital of Zhengzhou University from September 2018 to September 2020 were collected. The prevalence of chromosomal aneuploidies and pregnancy outcomes of D5/D6 biopsied blastocysts were compared. RESULTS: Compared with D6 blastocysts, the euploidy rate of D5 blastocysts was significantly higher (49.1% vs. 41.1%, P = 0.001 1), whilst their aneuploidy rate was significantly lower (50.9% vs. 58.9%, P = 0.001 1). The rate of numerical abnormalities of D6 blastocysts was significantly higher than that of D5 blastocysts (27.9% vs. 20.2%, P = 0.000 5). For patients under 35 years old, the euploidy rate of D5 blastocysts was significantly higher than that of D6 blastocysts (53.8% vs. 44.3%, P = 0.001), whilst the numerical abnormality rate was significantly lower (16.3% vs. 23.9%, P = 0.001). For both D5 and D6 blastocysts, the euploidy rates for patients <= 35 were significantly higher than those for > 35. The elder group had the lowest rates for aneuploidies and live births. Compared with those receiving D6 blastocysts transplantation, the pregnancy rate, implantation rate and live birth rate for those receiving thawed D5 blastocysts transplantation were significantly higher (60.2% vs.37.0%, P = 0.000 3; 59.1% vs.37.0%, P = 0.000 6; 47.7% vs. 28.3%, P = 0.002). CONCLUSION For patients undergoing PGT-A, the chromosomal euploidy rate for D5 blastocysts is higher than that for D6 blastocysts, and the clinical outcome of D5 blastocysts with normal signal is better than that of D6 blastocysts. Elder patients have a higher rate of aneuploidies.
Female ; Pregnancy ; Humans ; Aged ; Adult ; Pregnancy Outcome ; Aneuploidy ; Blastocyst ; Genetic Testing ; Laboratories

The gross specimens and tissue slices used for traditional experimental pathology curriculum are fragile, and some specimens or slices are difficult to be supplemented. Besides, the classroom and schedule for experimental pathology teaching are inflexible. Therefore, the teaching effects for experimental pathology course are limited. The development of digital technology has promoted the teaching reform of medical experimental curriculum. We have digitalized the gross specimens and tissue slices to preserve and expand the samples, and constructed pathological sample repository containing both physical samples and digital samples. Furthermore, we have established a platform for remote access, and thus improved the flexibility and autonomy of study for experimental pathology curriculum. Additionally, we have integrated clinical information of the teaching samples, and interpreted the specimens with the assistance of two-dimensional code technology and voice broadcast technology, to realize human-computer interactive learning. The questionnaire shows that the application of pathological sample repository in experimental teaching has improved student learning effect and recognition.

Objective:To explore the newborn birth weight and its influencing factors of polycystic ovary syndrome (PCOS) patients during fresh embryo transfer cycle.Methods:In this retrospective cohort study, the clinical data of 5087 patients with singleton live births who underwent in vitro fertilization and embryo transfer (IVF-ET) in the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University from January 2014 to December 2019 were analyzed. The patients were categorized into PCOS group ( n=1095) and non-PCOS group (referred to as control group, n=3992) according to the cause of infertility. The general conditions and birth weight of the two groups were compared, and logistic regression analysis was performed to identify the factors affecting birth weight. Results:For embryo transfer on the 3rd day (day 3, D3), the clinical pregnancy rate [69.0% (1248/1808)] and the implantation rate [49.0% (1742/3555)] in PCOS group were higher than those in control group [59.1% (5661/9572) and 42.0% (7577/18 040), all P<0.001], while the live birth rate [37.0% (670/1810)] was lower than that in control group [49.0% (4697/9585), P<0.001]. For blastocyst transfer on the 5th day (day 5, D5), the implantation rate [63.1% (500/793)] and the live birth rate [54.0% (425/787)] in PCOS group were higher than those of control group [59.0% (1066/1806), P=0.042; 48.0% (876/1825), P=0.013]. The birth weight of the infants [(3 459.76±527.11) g] and the proportion of overweight infants [14.35% (61/425)] in PCOS group of D5 blastocyst transfer were higher than those in control group [(3 391.61±521.38) g, P=0.028; 8.22% (72/876), P<0.001] and PCOS group of D3 embryo transfer [(3 389.24±555.06) g, P=0.018; 9.25% (62/670), P=0.009], but the proportion of low weight infants [2.35% (10/425)] was lower than that in control group of the D5 blastocyst transfer [4.91% (43/876), P=0.029] and PCOS group of D3 embryo transfer [4.78% (32/670), P=0.042]. Logistic regression analysis showed that the level of female body mass index (BMI) affects the birth weight of D5 blastocyst transfer ( OR=1.12, 95% CI=0.052-0.175, P<0.001). Developmental timing of transferred embryos affects birth weight in PCOS patients ( OR=1.52, 95% CI=0.019-0.819, P=0.040). Conclusion:For PCOS patients, choosing D5 blastocyst transfer can obtain a higher rate of live birth and a lower proportion of low birth weight infants. It is recommended that blastocyst transfer be performed for PCOS patients in fresh cycle.

Objective:To explore the newborn birth weight and its influencing factors of polycystic ovary syndrome (PCOS) patients during fresh embryo transfer cycle.Methods:In this retrospective cohort study, the clinical data of 5087 patients with singleton live births who underwent in vitro fertilization and embryo transfer (IVF-ET) in the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University from January 2014 to December 2019 were analyzed. The patients were categorized into PCOS group ( n=1095) and non-PCOS group (referred to as control group, n=3992) according to the cause of infertility. The general conditions and birth weight of the two groups were compared, and logistic regression analysis was performed to identify the factors affecting birth weight. Results:For embryo transfer on the 3rd day (day 3, D3), the clinical pregnancy rate [69.0% (1248/1808)] and the implantation rate [49.0% (1742/3555)] in PCOS group were higher than those in control group [59.1% (5661/9572) and 42.0% (7577/18 040), all P<0.001], while the live birth rate [37.0% (670/1810)] was lower than that in control group [49.0% (4697/9585), P<0.001]. For blastocyst transfer on the 5th day (day 5, D5), the implantation rate [63.1% (500/793)] and the live birth rate [54.0% (425/787)] in PCOS group were higher than those of control group [59.0% (1066/1806), P=0.042; 48.0% (876/1825), P=0.013]. The birth weight of the infants [(3 459.76±527.11) g] and the proportion of overweight infants [14.35% (61/425)] in PCOS group of D5 blastocyst transfer were higher than those in control group [(3 391.61±521.38) g, P=0.028; 8.22% (72/876), P<0.001] and PCOS group of D3 embryo transfer [(3 389.24±555.06) g, P=0.018; 9.25% (62/670), P=0.009], but the proportion of low weight infants [2.35% (10/425)] was lower than that in control group of the D5 blastocyst transfer [4.91% (43/876), P=0.029] and PCOS group of D3 embryo transfer [4.78% (32/670), P=0.042]. Logistic regression analysis showed that the level of female body mass index (BMI) affects the birth weight of D5 blastocyst transfer ( OR=1.12, 95% CI=0.052-0.175, P<0.001). Developmental timing of transferred embryos affects birth weight in PCOS patients ( OR=1.52, 95% CI=0.019-0.819, P=0.040). Conclusion:For PCOS patients, choosing D5 blastocyst transfer can obtain a higher rate of live birth and a lower proportion of low birth weight infants. It is recommended that blastocyst transfer be performed for PCOS patients in fresh cycle.

Objective:To compare the effects of two embryo culture reagents on embryonic developmental time dynamics, embryonic development potential and clinical pregnancy outcomes.Methods:The data of patients undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) were retrospectively analyzed at the Center for Reproductive Medicine of the First Affiliated Hospital of Zhengzhou University from September 2016 to May 2018. According to the different embryo culture reagents, they were divided into Vitrolife group and Cook group, comparing the embryonic time dynamics parameters, embryo development potential and clinical pregnancy outcomes of 470 patients who met the criteria. Results:There were significant differences in the kinetic parameters of embryo development between the two different embryo culture reagents. Compared with Cook group, Vitrolife group had shorter time in pronuclei appeare and disappear, and time of development to 3-cell and 8-cell embryos [tPNa: (7.12±2.71) h vs. (7.40±2.61) h, tPNf: (23.83±4.33) h vs. (24.21±4.74) h, t3: (35.75±6.03) h vs. (36.64±6.16) h, t4: (38.30±6.25) h vs. (38.92±6.06) h, t5: (47.59±7.85) h vs. (49.01±7.86) h, t6: (50.77±7.17) h vs. (52.12±6.99) h, t7: (53.05±6.31) h vs. (54.33±6.37) h, t8: (55.35±6.89) h vs. (56.31±6.41) h, all P<0.05]. There was no significant difference in cell cycle s2 and had a significant difference in cc2 [9.71±4.60) h vs.(10.33±4.28) h, P<0.001], synchronized in cell cycle in the sexual comparison. Cook group had a longer cell cycle, cell development time interval t5-t4 [(10.60±5.65) h vs. (11.20±5.90) h], t8-t4 [(18.45±5.76) h vs. (19.28±5.18) h] with statistically significant differences, all P<0.05, but there was no significant difference at t2 and t4-t2. Comparing the embryo development potential of the two embryo culture reagents, embryo utilization rate (59.9% vs. 63.9%, P=0.017) and day 3 (D3) high-quality embryo rate (65.4% vs. 69.5%, P=0.011) in Cook group were higher than those in Vitrolife group. There were no significant differences in implantation rate, embryo implantation rate, blastocyst implantation rate, fertilization rate and cleavage rate ( P>0.05). The clinical pregnancy rate, the continuous pregnancy rate (OPR), the abortion rate, the delivery rate, the live birth rate, the fetal malformation rate, the male to female ratio, the embryo pregnancy rate, and the blastocyst pregnancy rate were not statistically different ( P>0.05). Conclusion:According to the actual situation of the center, each center should find out the embryo time kinetic parameters suitable for the embryo culture reagent of the center, and establish the selection standard of the best embryo culture reagent, so as to improve the clinical pregnancy rate and live birth rate of the patients in the center.

Objective:To compare the effects of two embryo culture reagents on embryonic developmental time dynamics, embryonic development potential and clinical pregnancy outcomes.Methods:The data of patients undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) were retrospectively analyzed at the Center for Reproductive Medicine of the First Affiliated Hospital of Zhengzhou University from September 2016 to May 2018. According to the different embryo culture reagents, they were divided into Vitrolife group and Cook group, comparing the embryonic time dynamics parameters, embryo development potential and clinical pregnancy outcomes of 470 patients who met the criteria. Results:There were significant differences in the kinetic parameters of embryo development between the two different embryo culture reagents. Compared with Cook group, Vitrolife group had shorter time in pronuclei appeare and disappear, and time of development to 3-cell and 8-cell embryos [tPNa: (7.12±2.71) h vs. (7.40±2.61) h, tPNf: (23.83±4.33) h vs. (24.21±4.74) h, t3: (35.75±6.03) h vs. (36.64±6.16) h, t4: (38.30±6.25) h vs. (38.92±6.06) h, t5: (47.59±7.85) h vs. (49.01±7.86) h, t6: (50.77±7.17) h vs. (52.12±6.99) h, t7: (53.05±6.31) h vs. (54.33±6.37) h, t8: (55.35±6.89) h vs. (56.31±6.41) h, all P<0.05]. There was no significant difference in cell cycle s2 and had a significant difference in cc2 [9.71±4.60) h vs.(10.33±4.28) h, P<0.001], synchronized in cell cycle in the sexual comparison. Cook group had a longer cell cycle, cell development time interval t5-t4 [(10.60±5.65) h vs. (11.20±5.90) h], t8-t4 [(18.45±5.76) h vs. (19.28±5.18) h] with statistically significant differences, all P<0.05, but there was no significant difference at t2 and t4-t2. Comparing the embryo development potential of the two embryo culture reagents, embryo utilization rate (59.9% vs. 63.9%, P=0.017) and day 3 (D3) high-quality embryo rate (65.4% vs. 69.5%, P=0.011) in Cook group were higher than those in Vitrolife group. There were no significant differences in implantation rate, embryo implantation rate, blastocyst implantation rate, fertilization rate and cleavage rate ( P>0.05). The clinical pregnancy rate, the continuous pregnancy rate (OPR), the abortion rate, the delivery rate, the live birth rate, the fetal malformation rate, the male to female ratio, the embryo pregnancy rate, and the blastocyst pregnancy rate were not statistically different ( P>0.05). Conclusion:According to the actual situation of the center, each center should find out the embryo time kinetic parameters suitable for the embryo culture reagent of the center, and establish the selection standard of the best embryo culture reagent, so as to improve the clinical pregnancy rate and live birth rate of the patients in the center.

Objective: To investigate the effects and the underlying mechanisms of betulinic acid (BEA) on sensitizing pancreatic cancer cell lines Panc-1 and Miapaca-2 to gefitinib. Methods: After the cell culture was completed, Panc-1 and Miapaca-2 cells were randomly divided into 4 groups: control group (without treatment), BEAgroup, gefitinib group and BEAcombined with gefitinib group, respectively.The sensitization effect of BEAon gefitinib-insensitive pancreatic cancer cells was detected by MTS assay. The treatment effects of combined treatment of gefitinib and BEA against Panc-1 and Miapaca-2 cells were evaluated by colony formation assay. Flow cytometry was used to examine the effect of BEAon apoptosis of Panc-1 cells while WB was applied to determine the effect of BEAonapoptosis-related proteins. Surface plasmon resonance (SPR) experiment was used to detect the direct combination between signal transducer and activator of transcription 3(STAT3) and BEA; Molecular docking and molecular dynamics simulation experiments were adopted topredict the combining mode between STAT3 and BEA. Results: BEA synergistically enhanced the gefitinib-sensitivity of pancreatic cancer Panc-1 and Miapaca-2 cells (P<0.05), and IC50 of gefitinib on two cells were reduced by over 50%. Compared with single treatment, the combined treatment of BEA and gefitinib promoted the apoptosis and up-regulated the expressions of apoptosis-relatedproteins (cleaved-PARP and Bax), but reduced the apoptosis-inhibitory protein Bcl-2 (all P<0.05 or P<0.01). Moreover, the inhibitory effect of BEA on STAT3 activation in Panc-1 cells was in a dose-dependent mannar (P<0.01). BEA stabilizes its binding to STAT3 by forming hydrogen bonds with Lys-591 and Ser-613 of STAT3; in the meanwhile, BEA stabilized inthebinding site of STAT3, there by blocking STAT3 dimerization to enhance the drug sensitivity. Conclusion: Combined use of BEA and gefitinib could significantly inhibit the proliferation and induce apoptosis of Panc-1 and Miapaca-2 cells, which might be mediated by the inhibition of BEA on STST3.