BACKGROUND: Epidermal growth factor receptor (EGFR) sensitive mutation is one of the effective targets of targeted therapy for non-small cell lung cancer (NSCLC). However, due to the difficulty of obtaining some primary tissues and the economic factors in some underdeveloped areas, some patients cannot undergo traditional genetic testing. The aim of this study is to establish a machine learning (ML) model using non-invasive peripheral blood markers to explore the biomarkers closely related to EGFR mutation status in NSCLC and evaluate their potential prognostic value. METHODS: 2642 lung cancer patients who visited Jiangsu Cancer Hospital from November 2016 to May 2023 were retrospectively enrolled and finally 175 NSCLC patients with complete follow-up data were included in the study. The ML model was constructed based on peripheral blood indicators and divided into training set and test set according to the ratio of 8:2. Unsupervised learning algorithms were used for clustering blood features and mutual information method for feature selection, and an ensemble learning algorithm based on Shapley value was designed to calculate the contribution of each feature to the model prediction result. The receiver operating characteristic (ROC) curve was used to evaluate the predictive ability of the model. RESULTS: Through the feature extraction and contribution analysis of the predictive results of the interpretable ML model based on the Shapley value, the top ten indicators with the highest contribution were: pathological type, phosphorus, eosinophils, monocyte count, activated partial thromboplastin time, potassium, total bilirubin, sodium, eosinophil percentage, and total cholesterol. The area under the curve (AUC) of the model was 0.80. In addition, patients with hyponatremia and squamous cell carcinoma group had a poor prognosis (P<0.05). CONCLUSIONS The interpretable model constructed in this study provides a new approach for the prediction of EGFR mutation status in NSCLC patients, which provides a scientific basis for the diagnosis and treatment of patients who cannot undergo genetic testing.
Humans ; Carcinoma, Non-Small-Cell Lung/diagnosis* ; Machine Learning ; Lung Neoplasms/diagnosis* ; Male ; Female ; Mutation ; Middle Aged ; ErbB Receptors/genetics* ; Prognosis ; Aged ; Retrospective Studies ; Adult ; Biomarkers, Tumor/genetics*

Objective:To investigate the impact of the progesterone concentration on human chorionic gonadotropin (hCG) trigger day in fresh cycles versus thawed transfer cycles (the freeze-all strategy) with an antagonist protocol, and to compare the differences in clinical outcomes.Methods:This retrospective cohort study included a total of 2 165 cycles conducted at Henan Provincial People′s Hospital with cleavage-stage embryo (at least one top-quality) transfer between January 2017 and December 2023, with serum progesterone levels on hCG trigger day all≤6.34 nmol/L (i.e. 2 ng/ml). Multivariate logsitic regression analysis and curve fitting were performed based on different serum progesterone levels on hCG trigger day [≤3.17 nmol/L (i.e. 1 ng/ml) or 1-2 ng/ml].Results:Multivariate regression analysis, by using cycle type (either fresh or frozen-thawed cycle) as the exposure variable, showed that the clinical pregnancy rate (≤1 ng/ml: OR=0.93, 95% CI: 0.75-1.14; 1-2 ng/ml: OR=1.05, 95% CI: 0.58-1.87) and live birth rate (≤1 ng/ml: OR=0.90, 95% CI: 0.71-1.13; 1-2 ng/ml: OR=1.53, 95% CI: 0.79-3.00) had no statistically significant differences in group of progesterone concentration ≤1 ng/ml or in group of 1-2 ng/ml. Using serum progesterone levels on hCG trigger day as a continuous variable for curve fitting analysis, the clinical pregnancy rate in fresh or thawed cycles showed no significant changes with increasing progesterone levels. Conclusions:In the antagonist protocol with cleavage-stage embryo transfer (at least one top-quality), when the serum progesterone level on hCG day is ≤2 ng/ml, there are no significant differences in clinical outcomes between thawed cycles and fresh cycles, including clinical pregnancy rate and live birth rate. Transferred in fresh cycles or choosing the freeze-all strategy could be selected based on the actual situation of the patients.

Objective:To explore the related factors of poor ovarian response (POR) in patients receiving controlled ovarian stimulation (COS) and to establish the nomogram for predicting POR in patients who received in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI).Methods:In this retrospective research, clinical data of 17 164 cycles of patients who received IVF/ICSI treatment at Henan Provincial People′s Hospital from September 1st, 2016 to September 1st, 2020 were analyzed. Independent correlative factors affecting the occurrence of POR were screened by logistic regression, which were the model enrollment variables in the prediction model. Totally 13 266 cycles with well-record of enrollment variables were screened, and these data were randomly divided into model group (9 896 patients) and validation group (3 370 patients) according to 3∶1. The nomogram was established according to the regression coefficient of the relevant variables. The prediction accuracy of the nomogram was evaluated by calculating area under the receiver operating characteristic curve (AUC).Results:Multivariate logistic regression analysis showed age, infertility type, body mass index, anti-Müllerian hormone, basal follicle stimulating hormone, basal estrogen, antral follicle number, previous times of POR, history of ovarian surgery, ovulation stimulation protocol and average amount of gonadotropin were independent correlative factors affecting the occurrence of POR (all P<0.05). In the model group, according to the above factors, the prediction model and nomogram of POR risk were constructed and the validation group verified the model. The AUC of the model group was 0.893 (95% CI: 0.885-0.900), and the AUC of the validation group was 0.890 (95% CI: 0.878-0.903). Conclusion:The influencing factors of POR after COS in patients treated by IVF/ICSI are screened, and the nomogram for predicting POR established in this study is proved to be effective, simple, intuitive and clear in predicting the occurrence of POR.

Objective:To explore the clinical outcomes of top-quality blastocysts transfer developed from cleavage embryos with different grading and determine whether the cleavage stage embryo morphology grading should be taken into consideration when transferring the embryo at the blastocyst stage.Methods:A number of 3 059 cycles were included with single top-quality blastocyst transfer dating from January 2017 to May 2021 in Henan Provincial People′s Hospital. According to the number of cleavage sphere and degree of fragmentation, all cleavage stage embryos were divided into three groups: top D3 embryo (8 cells, ≤5% fragments)-TB group, suboptimal D3 embryo (8 cells, 5%0.05); and the early abortion rate were 10.74%, 12.54% and 12.62%, respectively ( P>0.05). After adjusting for confounders, logistic regression showed that no significant associations were found between cleavage stage embryo morphology grading and clinical pregnancy rate (suboptimal D3 embryo-TB group: OR=1.02, 95% CI: 0.76-1.38, P=0.879; normal D3 embryo-TB group: OR=0.84, 95% CI: 0.61-1.14, P=0.262) and early abortion rate (suboptimal D3 embryo-TB group: OR=1.18, 95% CI: 0.77-1.82, P=0.445; normal D3 embryo-TB group: OR=1.26, 95% CI: 0.81-1.98, P=0.309). The results of threshold effect analysis showed that when a single top-quality blastocysts was transferred, the effect of age on the clinical pregnancy rate showed a curve relationship, when the age was≥33 years old, the clinical pregnancy rate decreased significantly with age increased ( OR=0.89, 95% CI: 0.83-0.95, P=0.007); and there was no significant change in early abortion rate ( OR=1.01, 95% CI: 0.97-1.06, P=0.628). Conclusions:Cleavage stage embryo grading is not found to correlate with clinical outcomes in single top-quality blastcyst tranfer. Therefore, when considering blastocyst transfer, its morphology at blastocyst stage is more relevant. The effect of age on pregnancy outcomes of single blastocyst transfer should be considered.

Objective:To investigate the effect of endometrial thickness(EMT) on the clinical outcome of blastocyst hormone replacement freeze-thawed embryo transfer (HRT-FET) on the first progesterone day, and to analyze the threshold and optimal thickness interval corresponding to ideal clinical pregnancy rate by statistical method.Methods:The endometrial preparation protocols of 2 825 blastocyst HRT-FET cycles from January 2013 to December 2016 in Henan Provincial People′s Hospital and the Second Hospital of Hebei Medical University were studied retrospectively. According to EMT on the first progesterone day, they were divided into 5 subgroups: group Q1(EMT: 3.5-7.9 mm), group Q2(EMT: 8.0-8.9 mm), group Q3(EMT: 9.0-9.5 mm), group Q4(EMT: 9.6-10.7 mm), group Q5(EMT: 10.8-21.0 mm). Univariate analysis, classification multivariate Logistic regression analysis, curve fitting and threshold effect analysis were used to investigate the effect of endometrial thickness on clinical outcome of blastocyst HRT-FET.Results:Group Q1 was set as the control group in classification multivariate Logistic regression analysis, after adjusting for confounding factors, the clinical pregnancy rate and live birth rate in other groups were higher than the control group. The clinical pregnancy rate and live birth rate in group Q3 and Q4 were significantly increased and the differences were statistically significant(all P<0.05). The cut-off value of the endometrial thickness was 9.6 mm. When endometrial thickness was less than 9.6 mm, with 1 mm increase of endometrial thickness, the clinical pregnancy rate increased by 23%( OR=1.23, 95% CI=1.11-1.36) and the live birth rate increased by 21%( OR=1.21, 95% CI=1.10-1.33). When the endometrial thickness was thicker than the threshold, the clinical pregnancy rate did not increase significantly( OR=0.92, 95% CI=0.84-1.02), and the live birth rate showed a downward trend( OR=0.88, 95% CI=0.81-0.96). Conclusions:In the blastocyst HRT-FET cycle, endometrial thickness showes a curvilinear relationship with clinical outcome. The optimal endometrial thickness range for ideal clinical outcome is 9.0-11.0 mm.

Objective To explore the value of anti-Müllerian hormone (AMH) and age in predicting outcomes of patients undergoing in vitro fertilization and embryo transfer treatment. Methods In this retrospective study, 6 328 Chinese patients who underwent the first in vitro fertilization or intracytoplasmic sperm injection and embryo transfer treatment in Henan Provincial People′s Hospital between July 2016 and July 2018 were analyzed. All the patients were categorized into two groups according to pregnancy or not. Baseline data and outcomes of two groups were compared. The regression analysis was conducted to identify the independent factors of clinical pregnancy rates. Furthermore, correlation analysis was performed between AMH and other factors. Results (1) The total clinical pregnancy rate was 56.86% (3 547/6 238). Age, AMH, basal FSH, antral follicle number (AFC), starting dose of gonadotropin (Gn), total doses of Gn, duration of Gn, number of oocytes, transferable cleavage embryos and transferred embryos were significantly different (all P<0.01). (2) Correlation analysis showed that AMH had significant passive correlation with age, basal FSH, starting dose of Gn and total doses of Gn (all P<0.01), while showed significant positive correlation with AFC, body mass index, duration of Gn, number of oocytes and transferable cleavage embryos (all P<0.01). Of all the factors, AMH had the strongest correlation with AFC (P<0.01). (3) Multivariate logistic regression analysis suggested that age was the independent influencing factor of clinical pregnancy rate ( OR=0.938, 95%CI : 0.824-0.952, P<0.01), while AMH not ( OR=1.004, 95%CI : 0.984-1.024, P=0.687). In the subgroups according to age, the advanced group (age>35 years old) had lower clinical pregnancy rate and higher cancellation rate for no available embryos. Conclusions AMH has no predictive value of clinical pregnancy outcomes for patients with in vitro fertilization and embryo transfer treatment, while age has certain predictive value of pregnancy outcomes. AMH level may have indictive value for the evaluation of ovarian reserve.

Objective To evaluate the role of transvaginal color Doppler ultrasound measurements of endometrial thickness,endometrium and subendometrial blood distribution patterns and flow index in predicting endometrial receptivity and pregnancy outcome of freezing embryo transfer(FET).Methods 468 cycles FET were analysed retrospectively.Endometrial thickness,endometrium and subendometrial blood distribution patterns,pulsatility index (PI),resistance index (RI),systolic /diastolic ratio (S/D) of endometrial and subendometrial blood flows with transvaginal ultrasonography were measured on the day of progesterone initiation.Based on the clinical pregnancy or not,patients were divided into two groups.The comparison of these indicators were carried out between pregnant group and non pregnant group.Results The endometrium and subendometrial blood distribution patterns had statistical difference between the two groups(P ＜0.05),the clinical pregnancy rate of Ⅰ,Ⅱ,Ⅲ blood distribution patterns were 31.0％,62.5％,79.0％ respectively.In the pregnancy group,the S/D,PI,and RI of endometrium were significantly lower than those in the nonpregnant group (P ＜ 0.05),and there was no significant difference between the pregnant group and nonpregnant group in endometrial thickness(P ＞0.05).Conclusions Endometrium and subendometrial blood distribution patterns and flow index measured with transvaginal color Doppler ultrasound could assess endometrial receptivity and guide the time selecting of FET transplantation.

Objective To investigate the pregnancy outcome of frozen-thawed embryos transfer in different endometrial progesterone preparation time.Methods From January to December 2012,pregnant outcome of 1 103 frozen-thawed embryo transfer cycles using artificial periodic endometrial preparation were studied retrospectively in Reproductive Medical Center of Henan Provincial People's Hospital.It was divided into 4 groups:group 3-3 (n =543,3 days after endometrial progesterone preparation and transfer D3 embryo),group 4-3(n =330,4 days after endometrial progesterone preparation and transfer D3 embryo),group 5-5 (n =150,5 days after endometrial progesterone preparation and transfer D5 blastula),group 6-5 (n =80,6 days after endometrial progesterone preparation and transfer D5 blastula).The rate of implantation,pregnancy,ectopic pregnancy,multiple pregnancy,and first trimester abortion were compared among those groups.Results (1) With the different endometrial progesterone preparation methods and transfer D3 embryos,implantation rate [group 3-3:39.9％ (429/1 074) ; group 4-3:44.1％ (286/648)],pregnancy rate [group 3-3:56.0％ (304/543) ; group 4-3:59.4％ (196/330)],ectopic pregnancy rate [group 3-3:3.3％ (10/304) ; group 4-3:2.6％ (5/196)],multiple pregnancy rate [group 3-3:38.5％ (117/304) ; group 4-3:43.4％ (85/196)]and early abortion rate[group 3-3:13.5％ (41/304); group 4-3:13.3％ (26/196)] had no significant differences between group 3-3 and group 4-3 (all P ＞ 0.05).(2) With the different endometrial progesterone preparation methods and transfer D5 blastocysts,implantation rate [group 5-5:64.7％ (191/295) ; group 6-5:69.4％ (100/144)],pregnancy rate [group 5-5:80.7％ (121/150) ; group 6-5:78.8％ (63/80)],ectopic pregnancy rate [group 5-5:2.5％ (3/121) ; group 6-5:0],multiple pregnancy rate[group 5-5:55.4％ (67/121) ; group 6-5:46.3％ (37/80)] and early abortion rate[group 5-5:5.8％ (7/121); group 6-5:7.9％ (5/63)].However,there were no significantly differences between group 5-5 and group 6-5 (all P ＞ 0.05).Conclusions The two different progesterone transformed endometrial methods can obtain satisfactory clinical outcome with D3 embryo or D5 blastocysts transfor.It is convenient to clinical and laboratory work arrangements.

Objective To study the effect of estradiol supplementation during the luteal phase on mouse endometrial expression of leukaemia inhibitory factor and pinopodes in controlled ovarian stimulation cycles.Methods Female mice were randomly divided into four groups:group A[controlled ovarian stimulation(COS)group],group B(COS group with progesterone for luteal-phase-support),group C(COS group with progesterone and estradiol for luteal-phase-support),and group D of natural cycle group.Pinopodes were investigated by scanning electronic microscopy(SEM)in the uterine endometrium of pregnant mice on pregnancy days(pa)3-5.LEukaemia inhibitory factor(LIF)protein Was determined by immunohistochemistry in the uterine endometrium of pregnant mice on pd 3-5.Results (1)In groups B,C,and D,there were small developed pinopodes in the endometrial surface of pregnant mouse on day 3;there were large fully developed pinopodes in endometrial surface,which Was smooth with well defined borders resembling a mushroom on day 4.The regressing pinopodes were observed on day 5.In group A,there were small developed pinopodes in endometrial surface of pregnant mouse on day 3.The regressing pinopodes were seen on day 4.(2)In the pregnant mice of groups C and D,the level of LIF protein on days 3-5 ( 138.5±20. 3,143.1±19. 0) was significantly higher than group A ( 103. 2 ± 5.0, P < 0. 05 ), and strong immunostaining of LIF protein was found on day 4 of gestation. In group B, the level of LIF protein on days 3-5 ( 123.5±10. 8)was significantly higher than group A (P <0. 05), but significantly lower than groups C and D ( P <0. 05 ). Strong immunostaining of LIF protein was found on day 4 of gestation. In group A, weak immunostaining of LIF protein peaked on day 3 of gestation. In groups B, C, and D, the level of LIF protein on day 4 was significantly higher than group A on day 3 ( F = 55.76, P < 0. 01 ). Conclusions Estradiol supplementation during the luteal phase can improve the expression of LIF and pinopodes in mouse endometrium in controlled ovarian stimulation cycles and redress the harmful effect on implantation window by COS. Therefore, estradiol supplementation can improve the endometrial receptivity.

Objective To study the optimal laparoscopic procedure and its indication for remove of common bile duct stone. Methods Analysis was made on the clmical data of 124 cases of laparoscopic choledocholithotomy and T tube drainage in our center.Results 82 patients underwent the improved laparoscopic procedure, alternation to open operation in 4 cases (4.9%),and the mean operating time was (80?30) min. While 42 patients were operated with traditional laparoscopic method,changing to open operation in 6 cases (14.3%),and the mean operating time was (170?40) min . The improved method could shorten the operation time and reduce the open operation rate significantly than traditional method did (P