Objective: To investigate the correlations among clinicopathological features, histopathological growth patterns and prognosis of extrapulmonary multiple metastatic(stage ⅣB) pulmonary adenocarcinoma with epidermal growth factor receptor(EGFR) mutations. Methods : A total of 488 eligible patients with adenocarcinoma of stage ⅣB. Clinicopathological data,EGFRgene mutation subtypes, metastatic sites, histopathological growth patterns and survival information were collected. The chi-square test(χ2test) and Fisher's exact probability method were used to detect the correlation between the metastasis status and various clinical characteristics; the Kaplan-Meier method was used to conduct survival analysis on the median Progression-Free Survival(PFS) under different clinical characteristics. Cox univariate and multivariate regression analyses were conducted to evaluate the impact of various clinical characteristics on prognosis. Results : The metastatic patterns of stage ⅣB pulmonary adenocarcinoma withEGFRmutations was correlated with histopathological growth patterns(P<0.05). In the group with multiple metastases in a single organ, the proportion of micropapillary type in the group with multiple metastases in a single organ was higher than that in the group with multiple-organ metastases(51.1%vs41.1%), while the proportion of solid type in the group with multiple-organ metastases was higher than that in the group with multiple metastases in a single organ(23.8%vs14.2%). Multiple brain or multiple bone metastases were correlated with histopathological growth patterns and tumor differentiation degree. Compared with the multiple bone metastases group, the proportion of acinar type decreases in the multiple brain metastasis group, while the proportion of micropapillary type increased. Moreover, the proportion of poorly differentiated tumors increased significantly(P<0.05). Compared with multiple bone metastases, the proportion of poorly differentiated tumors significantly increases in the group with multiple brain metastases. The median progression-free survival(PFS) of patients with a predominant solid growth pattern was shorter than that of patients with other growth patterns(12.7 monthsvs17.8 months,P<0.05). The PFS of patients in the poorly differentiated group was worse than that in the moderately differentiated group(15.6 monthsvs17.8 months,P<0.05). There were significant differences in PFS among patients with common sensitive mutations and rare mutationsEGFR(17.3 monthsvs10.2 months,P<0.01). Cox proportional hazards regression model suggested that solid growth pattern, poor differentiation and rare single gene mutation were adverse prognostic factors. Conclusion In stage ⅣB pulmonary adenocarcinoma patients withEGFRmutations, both the metastatic patterns and metastatic sites are significantly correlated with the histopathological growth patterns of tumors. Moreover, theEGFRmutation subtypes as well as the histopathological growth patterns and differentiation degree of tumors significantly affect the prognosis of patients.

Objective:To observe the therapeutic efficacy of point catgut-embedding therapy combined with cupping therapy in treating simple obesity due to stomach heat and dampness obstruction,as well as its effects on Chinese medicine symptoms,obesity indicators,and blood lipid parameters.Methods:A total of 135 cases with simple obesity due to stomach heat and dampness obstruction were allocated into an embedding group,a cupping group,and a combined group using the random number table method,with 45 cases in each group.The embedding group received point catgut-embedding therapy alone,the cupping group was treated with cupping therapy alone,while the combined group underwent both embedding therapy and cupping therapy.The same points were used in the three groups.The treatment was performed once daily,and consecutive 28-day treatment was taken as 1 treatment course.The therapeutic efficacy was evaluated,and the changes in the traditional Chinese medicine(TCM)symptom score,obesity indicators[body mass(BM),body mass index(BMI),body fat percentage(BFP),waist circumference,and waist-to-hip ratio],and blood lipid parameters[triglyceride(TG)and total cholesterol(TC)]were observed after 3 consecutive courses.Results:After 3-course treatment,the total effective rate in the combined group was 93.3%,higher than 82.2%in the embedding group and 73.3%in the cupping group(P<0.05),and the total effective rate of the embedding group was higher than that of the cupping group(P<0.05).Compared to those before treatment,the TCM symptom score,obesity indicators,and blood lipid parameters reduced significantly in the three groups(P<0.05 or P<0.01),and indicators in the combined group were lower than those in the other two groups(P<0.05).Conclusion:The synergistic application of point catgut-embedding therapy and cupping therapy can improve TCM symptoms,obesity-related indicators,and blood lipid parameters of patients with simple obesity due to stomach heat and dampness obstruction;compared to the use of either point catgut-embedding therapy or cupping therapy alone,the combined application of the two therapies shows a more significant therapeutic effect.

Objective:To observe the therapeutic efficacy of point catgut-embedding therapy combined with cupping therapy in treating simple obesity due to stomach heat and dampness obstruction,as well as its effects on Chinese medicine symptoms,obesity indicators,and blood lipid parameters.Methods:A total of 135 cases with simple obesity due to stomach heat and dampness obstruction were allocated into an embedding group,a cupping group,and a combined group using the random number table method,with 45 cases in each group.The embedding group received point catgut-embedding therapy alone,the cupping group was treated with cupping therapy alone,while the combined group underwent both embedding therapy and cupping therapy.The same points were used in the three groups.The treatment was performed once daily,and consecutive 28-day treatment was taken as 1 treatment course.The therapeutic efficacy was evaluated,and the changes in the traditional Chinese medicine(TCM)symptom score,obesity indicators[body mass(BM),body mass index(BMI),body fat percentage(BFP),waist circumference,and waist-to-hip ratio],and blood lipid parameters[triglyceride(TG)and total cholesterol(TC)]were observed after 3 consecutive courses.Results:After 3-course treatment,the total effective rate in the combined group was 93.3%,higher than 82.2%in the embedding group and 73.3%in the cupping group(P<0.05),and the total effective rate of the embedding group was higher than that of the cupping group(P<0.05).Compared to those before treatment,the TCM symptom score,obesity indicators,and blood lipid parameters reduced significantly in the three groups(P<0.05 or P<0.01),and indicators in the combined group were lower than those in the other two groups(P<0.05).Conclusion:The synergistic application of point catgut-embedding therapy and cupping therapy can improve TCM symptoms,obesity-related indicators,and blood lipid parameters of patients with simple obesity due to stomach heat and dampness obstruction;compared to the use of either point catgut-embedding therapy or cupping therapy alone,the combined application of the two therapies shows a more significant therapeutic effect.

Objective:To investigate the effect of luteinizing hormone (LH) levels on the clinical outcome and cumulative live birth rate of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) fresh embryo transfer in patients with normal ovarian reserve function after application of a flexible protocol of gonadotropin-releasing hormone antagonist (GnRH-A) to promote ovulation with the addition of GnRH-A. Methods:A retrospective cohort study was conducted to analyze the data of 685 patients with normal ovarian reserve function who underwent IVF/ICSI after ovulation induction with antagonist flexible regimen between January 2016 and June 2021 at the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University. The quartile method was used to group patients after the addition of the antagonist by the mean value of serum LH each time they were monitored (usually twice, depending on the rate of follicular growth and patients' need) until the day of the trigger, and were divided into group A (smaller than the 25th percentile of the mean LH level of the included population, LH<1.25 U/L, n=166), group B (in the 25th to 50th percentile of the mean LH level of the included population, 1.25 U/L≤LH<1.91 U/L, n=174), group C (in the 50th to 75th percentile of the mean LH level of the included population, 1.91 U/L≤LH<2.85 U/L, n=171), and group D (greater than the 75th percentile of the mean LH level of the included population, 2.85 U/L≤LH≤7.55 U/L, n=174). The general condition, clinical data, embryo laboratory indices, clinical outcome indices of fresh embryo transfer cycle and cumulative live birth rate were compared among the 4 groups. Results:After correcting for confounding factors by multifactorial linear regression, the number of high-quality embryos and the rate of blastocyst formation of patients in group C were significantly higher than those in group A, and the differences were statistically significant ( B=0.600, 95% CI: 0.086-1.114, P=0.022; B=0.134, 95% CI: 0.052-0.216, P=0.001). The number of high-quality embryos, the number of available embryos, and the rate of blastocyst formation of patients in group D were significantly higher than those in group A, and the differences were statistically significant ( B=0.771, 95% CI: 0.259-1.284, P=0.003; B=0.730, 95% CI: 0.205-1.255, P=0.007; B=0.085, 95% CI: 0.003-0.167, P=0.042).After multifactorial logistic regression, there was no statistically significant difference in live birth rate between group A and groups B, C and D ( P>0.05). The cumulative live birth rate of patients in group D was significantly higher than that in group A, and the difference was statistically significant ( aOR=2.439, 95% CI: 1.169-4.974, P=0.014). Conclusion:In patients with normal ovarian reserve function, a flexible protocol of antagonists was applied to promote ovulation, and the addition of antagonists had no significant effect on the clinical outcome of the fresh embryo transfer cycle in terms of mean LH levels, but the quality of the embryos was significantly reduced when the mean LH level was <1.25 U/L, and this may consequently reduce the developmental potential of the embryos and the cumulative live birth rate.

Objective:To investigate the effect of luteinizing hormone (LH) levels on the clinical outcome and cumulative live birth rate of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) fresh embryo transfer in patients with normal ovarian reserve function after application of a flexible protocol of gonadotropin-releasing hormone antagonist (GnRH-A) to promote ovulation with the addition of GnRH-A. Methods:A retrospective cohort study was conducted to analyze the data of 685 patients with normal ovarian reserve function who underwent IVF/ICSI after ovulation induction with antagonist flexible regimen between January 2016 and June 2021 at the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University. The quartile method was used to group patients after the addition of the antagonist by the mean value of serum LH each time they were monitored (usually twice, depending on the rate of follicular growth and patients' need) until the day of the trigger, and were divided into group A (smaller than the 25th percentile of the mean LH level of the included population, LH<1.25 U/L, n=166), group B (in the 25th to 50th percentile of the mean LH level of the included population, 1.25 U/L≤LH<1.91 U/L, n=174), group C (in the 50th to 75th percentile of the mean LH level of the included population, 1.91 U/L≤LH<2.85 U/L, n=171), and group D (greater than the 75th percentile of the mean LH level of the included population, 2.85 U/L≤LH≤7.55 U/L, n=174). The general condition, clinical data, embryo laboratory indices, clinical outcome indices of fresh embryo transfer cycle and cumulative live birth rate were compared among the 4 groups. Results:After correcting for confounding factors by multifactorial linear regression, the number of high-quality embryos and the rate of blastocyst formation of patients in group C were significantly higher than those in group A, and the differences were statistically significant ( B=0.600, 95% CI: 0.086-1.114, P=0.022; B=0.134, 95% CI: 0.052-0.216, P=0.001). The number of high-quality embryos, the number of available embryos, and the rate of blastocyst formation of patients in group D were significantly higher than those in group A, and the differences were statistically significant ( B=0.771, 95% CI: 0.259-1.284, P=0.003; B=0.730, 95% CI: 0.205-1.255, P=0.007; B=0.085, 95% CI: 0.003-0.167, P=0.042).After multifactorial logistic regression, there was no statistically significant difference in live birth rate between group A and groups B, C and D ( P>0.05). The cumulative live birth rate of patients in group D was significantly higher than that in group A, and the difference was statistically significant ( aOR=2.439, 95% CI: 1.169-4.974, P=0.014). Conclusion:In patients with normal ovarian reserve function, a flexible protocol of antagonists was applied to promote ovulation, and the addition of antagonists had no significant effect on the clinical outcome of the fresh embryo transfer cycle in terms of mean LH levels, but the quality of the embryos was significantly reduced when the mean LH level was <1.25 U/L, and this may consequently reduce the developmental potential of the embryos and the cumulative live birth rate.

Objective:To observe the effect of early elevation of luteinizing hormone (LH) with flexible gonadotropin-releasing hormone antagonist (GnRH-A) protocol on pregnancy outcomes of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) fresh embryo transfer. Methods:A retrospective cohort study was conducted to analyze patients with normal ovarian reserve function who underwent IVF/ICSI with flexible GnRH-A protocol at the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University from January 2016 to September 2021. According to the level of LH before antagonist addition, the patients were divided into two groups, group A: early elevation of LH (LH >10 U/L before the addition of antagonist, n=65), group B: the patients whose LH≤10 U/L before the addition of antagonist ( n=193), which was matched with group A using the 1∶3 propensity score matching by age, duration of infertility, anti-Müllerian hormone, body mass index and antral follicle count. The general conditions, clinical data, embryonic laboratory indicators and clinical outcomes were compared between the two groups. Results:There were no significant differences in the baseline characteristics between the two groups (all P>0.05). There were no significant differences in basic LH levels, gonadotropin (Gn) initiation dosage, total dosage and duration of Gn used, duration of Gn used when adding antagonists and estradiol (E 2) level on the trigger day between group A and group B (all P>0.05). The LH level [12.2 (11.1, 17.5) U/L], E 2 level [3 301.0 (2 708.0, 4 275.0) pmol/L] and follicle diameter [14.0 (12.6, 15.5) mm] were significantly higher in group A than in group B [3.5 (2.2, 5.2) U/L, 2 178.5 (1 208.0, 3 218.0) pmol/L, 13.0 (12.0, 14.0) mm] when adding antagonist (all P<0.001). The level of LH in group A decreased rapidly after adding antagonist, LH level in group A after antagonist application [3.4 (2.0, 5.2) U/L] and the LH level on the trigger day [3.0 (1.7, 4.7) U/L] were still higher than those in group B [2.1 (1.5, 3.3) U/L, P<0.001; 2.1 (1.4, 3.3) U /L, P=0.004], the level of progesterone on the trigger day was not significantly higher than that in group B ( P>0.05). There were no statistically significant differences in the number of oocytes retrieved, two pronuclei fertilization rate, the rate of high-quality embryo, the rate of blastocyst formation, endometrial thickness on the day of transplantation, the number of transferred embryos, the proportion of transferred blastocysts and the implantation rate between the two groups (all P>0.05). The clinical pregnancy rate, the early abortion rate, and the live birth rate were not statistically different between the two groups (all P>0.05). Conclusion:In patients with normal ovarian reserve, LH level was elevated early with antagonist flexible protocol, and decreased rapidly after the timely addition of antagonist, which did not lead to an increase of progesterone on the trigger day, and ultimately did not affect the clinical outcomes of IVF/ICSI fresh embryo transfer.

Objective:To observe the effect of early elevation of luteinizing hormone (LH) with flexible gonadotropin-releasing hormone antagonist (GnRH-A) protocol on pregnancy outcomes of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) fresh embryo transfer. Methods:A retrospective cohort study was conducted to analyze patients with normal ovarian reserve function who underwent IVF/ICSI with flexible GnRH-A protocol at the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University from January 2016 to September 2021. According to the level of LH before antagonist addition, the patients were divided into two groups, group A: early elevation of LH (LH >10 U/L before the addition of antagonist, n=65), group B: the patients whose LH≤10 U/L before the addition of antagonist ( n=193), which was matched with group A using the 1∶3 propensity score matching by age, duration of infertility, anti-Müllerian hormone, body mass index and antral follicle count. The general conditions, clinical data, embryonic laboratory indicators and clinical outcomes were compared between the two groups. Results:There were no significant differences in the baseline characteristics between the two groups (all P>0.05). There were no significant differences in basic LH levels, gonadotropin (Gn) initiation dosage, total dosage and duration of Gn used, duration of Gn used when adding antagonists and estradiol (E 2) level on the trigger day between group A and group B (all P>0.05). The LH level [12.2 (11.1, 17.5) U/L], E 2 level [3 301.0 (2 708.0, 4 275.0) pmol/L] and follicle diameter [14.0 (12.6, 15.5) mm] were significantly higher in group A than in group B [3.5 (2.2, 5.2) U/L, 2 178.5 (1 208.0, 3 218.0) pmol/L, 13.0 (12.0, 14.0) mm] when adding antagonist (all P<0.001). The level of LH in group A decreased rapidly after adding antagonist, LH level in group A after antagonist application [3.4 (2.0, 5.2) U/L] and the LH level on the trigger day [3.0 (1.7, 4.7) U/L] were still higher than those in group B [2.1 (1.5, 3.3) U/L, P<0.001; 2.1 (1.4, 3.3) U /L, P=0.004], the level of progesterone on the trigger day was not significantly higher than that in group B ( P>0.05). There were no statistically significant differences in the number of oocytes retrieved, two pronuclei fertilization rate, the rate of high-quality embryo, the rate of blastocyst formation, endometrial thickness on the day of transplantation, the number of transferred embryos, the proportion of transferred blastocysts and the implantation rate between the two groups (all P>0.05). The clinical pregnancy rate, the early abortion rate, and the live birth rate were not statistically different between the two groups (all P>0.05). Conclusion:In patients with normal ovarian reserve, LH level was elevated early with antagonist flexible protocol, and decreased rapidly after the timely addition of antagonist, which did not lead to an increase of progesterone on the trigger day, and ultimately did not affect the clinical outcomes of IVF/ICSI fresh embryo transfer.