Objective:To explore the correlation between intrahepatic cholestasis of pregnancy(ICP)and ad-verse pregnancy outcomes.Methods:A total of 511 singleton pregnant women with ICP treated at The Third Affili-ated Hospital of Guangzhou Medical University from August 2017 to January 2024 were selected as the study sub-jects.Among them,patients were divided into the adverse pregnancy outcome group(n=49)and the control group without adverse pregnancy outcomes(n=462).The general and clinical data of the two groups were com-pared and analyzed.Results:①General situation:The number of pregnancies and deliveries,ICU transfer rate,total hospital stay,and total hospitalization costs were significantly higher in the adverse pregnancy outcome group compared to the control group(P<0.05).The number of prenatal check-ups,diagnostic gestational weeks,and gestational weeks at delivery were significantly lower compared to the control group(P<0.05).②Clinical symp-toms:The incidence of itching in the adverse pregnancy outcome group was lower compared to the control group(10.2%vs.26.6%,P<0.05),while other symptoms such as rash,fatigue,jaundice,and gastrointestinal symp-toms showed no significant difference between the two groups(P>0.05).③Laboratory examinations:Compared with the control group,patients in the adverse pregnancy outcome group had significantly the increased levels of alanine aminotransferase,aspartate aminotransferase,uric acid,urea nitrogen,and triglycerides,and significantly the decreased levels of alkaline phosphatase and fasting blood glucose,with statistical significance(P<0.05).Other biochemical indicators showed no significant difference between the two groups(P>0.05).④ICP grading and complications:The proportion of early-onset ICP,severe and very severe ICP in the adverse pregnancy out-come group was significantly higher compared to the control group(P<0.001);the proportion of adverse preg-nancy outcome group with pregnancy-induced hypertension was significantly higher compared to the control group;the incidence of preterm birth,fetal growth restriction,meconium-stained amniotic fluid,and fetal distress in the adverse pregnancy outcome group was significantly higher compared to the control group(P<0.001).⑤Neo-natal outcomes:The neonatal Apgar scores(1 min,5 min,10 min)and neonatal weight in the adverse pregnancy outcome group were lower compared to the control group(P<0.001),and the incidence of mild neonatal asphyx-ia was significantly higher,with a statistically significant difference(P<0.001).Conclusions:The severity of ICP is closely related to the occurrence of adverse pregnancy outcomes.Therefore,it is clinically necessary to pay at-tention to the grading of ICP,closely monitor the levels of total bile acids and liver enzymes,and try to avoid ad-verse pregnancy outcomes,especially intrauterine fetal death.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective:To explore the correlation between intrahepatic cholestasis of pregnancy(ICP)and ad-verse pregnancy outcomes.Methods:A total of 511 singleton pregnant women with ICP treated at The Third Affili-ated Hospital of Guangzhou Medical University from August 2017 to January 2024 were selected as the study sub-jects.Among them,patients were divided into the adverse pregnancy outcome group(n=49)and the control group without adverse pregnancy outcomes(n=462).The general and clinical data of the two groups were com-pared and analyzed.Results:①General situation:The number of pregnancies and deliveries,ICU transfer rate,total hospital stay,and total hospitalization costs were significantly higher in the adverse pregnancy outcome group compared to the control group(P<0.05).The number of prenatal check-ups,diagnostic gestational weeks,and gestational weeks at delivery were significantly lower compared to the control group(P<0.05).②Clinical symp-toms:The incidence of itching in the adverse pregnancy outcome group was lower compared to the control group(10.2%vs.26.6%,P<0.05),while other symptoms such as rash,fatigue,jaundice,and gastrointestinal symp-toms showed no significant difference between the two groups(P>0.05).③Laboratory examinations:Compared with the control group,patients in the adverse pregnancy outcome group had significantly the increased levels of alanine aminotransferase,aspartate aminotransferase,uric acid,urea nitrogen,and triglycerides,and significantly the decreased levels of alkaline phosphatase and fasting blood glucose,with statistical significance(P<0.05).Other biochemical indicators showed no significant difference between the two groups(P>0.05).④ICP grading and complications:The proportion of early-onset ICP,severe and very severe ICP in the adverse pregnancy out-come group was significantly higher compared to the control group(P<0.001);the proportion of adverse preg-nancy outcome group with pregnancy-induced hypertension was significantly higher compared to the control group;the incidence of preterm birth,fetal growth restriction,meconium-stained amniotic fluid,and fetal distress in the adverse pregnancy outcome group was significantly higher compared to the control group(P<0.001).⑤Neo-natal outcomes:The neonatal Apgar scores(1 min,5 min,10 min)and neonatal weight in the adverse pregnancy outcome group were lower compared to the control group(P<0.001),and the incidence of mild neonatal asphyx-ia was significantly higher,with a statistically significant difference(P<0.001).Conclusions:The severity of ICP is closely related to the occurrence of adverse pregnancy outcomes.Therefore,it is clinically necessary to pay at-tention to the grading of ICP,closely monitor the levels of total bile acids and liver enzymes,and try to avoid ad-verse pregnancy outcomes,especially intrauterine fetal death.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective:To investigate the effect of biological maternal sounds on blood gas analysis index, mechanical ventilation time, oxygen therapy time and hospital stay in mechanically ventilated children with severe pneumonia.Methods:This study was a randomized controlled trial. From June 2020 to November 2020, 128 mechanically ventilated children with severe pneumonia in Hunan Children′s Hospital were selected by convenient sampling method and divided into four groups with 32 cases in each group by random number table method. Group A was given routine nursing care, group B was given mother sounds, group C was given mother cardiotone, group D was given biological maternal sounds. Data of blood gas analysis index, mechanical ventilation duration, oxygen therapy duration, hospital stays were collected for comparative analysis.Results:Finally, group A, B, C, and D included 28, 30, 28 and 28 cases, respectively. There was no statistically significant difference in PaO 2 among the four groups on the 1st to 2nd day after intervention ( P>0.05), but PaO 2 on the 3rd to 7th day after intervention were (75.57 ± 12.88), (77.71 ± 15.81), (78.21 ± 14.51), (78.64 ± 17.71), (79.04 ± 11.57) mmHg (1 mmHg=0.133 kPa), (81.71 ± 17.89), (82.93 ± 18.36), (82.68 ± 15.47), (83.25 ± 14.24), (83.77 ± 13.90) mmHg, (80.89 ± 18.78) (82.11 ± 13.34), (82.96 ± 14.20), (83.43 ± 14.37), (83.68 ± 12.64) mmHg, (84.54 ± 18.77), (86.29 ± 10.94), (86.96 ± 10.53), (87.46 ± 12.64), (89.08 ± 12.21) mmHg, with statistically significant differences ( F values were 41.17 - 332.68, all P<0.01). Further pairwise comparison revealed that PaO 2 in group B and group C were higher than those in group A on the 3rd to 7th day after intervention, while those in group D were higher on the 3rd to 7th day after intervention than those in group A, B, and C, with statistically significant differences( t values were 3.35- 4.75, all P<0.01). There was no statistically significant difference in PaCO 2 among the four groups on the 1st to 4th day after intervention ( P>0.05), but PaCO 2 on the 5th to 7th day after intervention was (47.31 ± 2.89), (46.18 ± 2.06), (41.94 ± 2.09) mmHg, (44.73 ± 1.76), (41.38 ± 1.30), (38.33 ± 1.16) mmHg, (44.81 ± 1.24), (41.23 ± 1.89), (38.73 ± 2.55) mmHg, (40.83 ± 1.78), (37.87 ± 1.43), (34.78 ± 2.05) mmHg, with statistically significant differences ( F=29.48, 36.12, 34.52, all P<0.05). Further pairwise comparison revealed that PaCO 2 in group B and group C were lower than those in group A on the 5th to 7th day after intervention, while PaCO 2 in group D were lower than those in groups A, B, and C, with statistically significant differences ( t values were 3.37-4.85, all P<0.01). During the analysis of PaO 2 and PaCO 2 in the four groups at different time points, the interaction effects were not statistically significant ( P>0.05). There was no significant difference in invasive mechanical ventilation duration, non-invasive mechanical ventilation duration and hospital stay among the four groups after intervention ( P>0.05). The oxygen therapy time of the four groups were (8.61 ± 6.40), (6.17 ± 4.80), (6.23 ± 2.75), and (3.75 ± 2.10) days, with statistically significant differences ( F=17.27, P<0.01). Further pairwise comparison revealed that the oxygen therapy time in group B and group C was shorter than that in group A, while group D was significantly shorter than that in groups A, B, and C, with statistically significant differences ( t values were 4.02-4.74, all P<0.01). Conclusions:Biological maternal sounds is superior to maternal sound and mother cardiotone in improve the blood gas analysis index, shorten the oxygen treatment time, which is worthy of clinical promotion in neonatal unaccompanied ward.

Objective:To deeply understand the real emotional experience and needs of the parents of dying newborns, so as to provide a reference for future neonatal palliative care.Methods:From February to October 2021, purposeful sampling was used to select 15 parents of dying newborns in the Department of Neonatology of Hunan Children's Hospital as the research object. A qualitative research design was conducted, and the semi-structured interview method was used to conduct in-depth interviews with the research subjects, and NVivo 10.0 software was used for data analysis.Results:A total of 3 themes were extracted, namely, the ambivalence when giving up treatment, negative life effects after giving up, needs and expectations.Conclusions:Parents of dying newborns generally have ambivalence when they give up treatment. After giving up, they will show emotions such as sadness and helplessness, self-blame and regret, and depression. Understanding the real emotions and inner needs of the parents of dying newborns helps medical and nursing staff to pay attention to parents' negative psychology and understand their needs, and provide parents with targeted psychological support and other care, so as to help the parents of dying newborns and their families through a special period.

Objective:To explore the association between genetic polymorphism of APP gene and bipolar disorder(BD) in children and adolescents for seeking suitable single nucleotide loci(SNP), and provide reference for early diagnosis and intervention of children and adolescent BD.Methods:The genomic DNA of peripheral blood was extracted from 178 BD cases(case group) and 178 normal controls(control group) of Han children and adolescents.Four SNP loci of APP gene were selected and were analyzed by LDR-PCR SNP genotyping.Genotypes and allele differences were compared between the cases and control group by SPSS22.0 software.The software SHEsis was also used to make linkage disequilibrium and haplotype analysis.Results:The genotype frequency and allele frequency of the 4 SNP loci of APP gene were statistically significant different between the case group and the control group ( P<0.05). The association of s2040273, rs466433, rs463946, rs364048 with BD in the APP gene was statistically significant( P<0.05). The construction of 4 SNP haplotypes indicated that AACT, AGGC, and GACT accounted for more than 80% of the total.The percentage of haplotype AGGC in the case group(11.9%)was significantly higher than that in the control group(4.7%)( P<0.05), and the odds ratio of AGGC haploid was 2.727. Conclusion:Four SNP loci s2040273, rs466433, rs463946, rs364048 in the APP gene and haplotype AGGC are associated with BD in Han children and adolescents.These results confirmed that the APP gene is one of BD susceptible gene.

Objective To explore the influence of vagus nerve stimulation (VNS) on inflammatory factors in serum and nucleus of the solitary tract,and hippocampal apoptosis in rats with depression induced by chronic unpredictable stress ( CUS). Methods Totally 32 male Sprague Dawley ( SD) rats aged 8-9 weeks were selected. Eight rats were chosen as control group,and the other 24 rats were treated as the de-pression model with CUS. The rats were randomly divided into CUS,fluoxetine and VNS group,with 8 rats in each group after successful modeling. The control group and CUS group were induced by normal saline. Flu-oxetine group and VNS group were implanted with VNS stimulation electrode. The VNS stimulation lasted for 28 d. On the time points of before experiment,after modeling and after treatment,the sucrose consumption test and open-field test (OFT) were performed to observe the behavioral changes of rats. Elisa was used to detect the levels of TNF-α,IL-6 and IL-1β in serum and nucleus of the solitary tract. Cell apoptosis was ob-served with TUNEL staining in hippocampal CA1 region. Results ( 1) Sucrose consumption experiment and OFT showed that,compared with the CUS group,the consumption of sucrose,percentage of sucrose con-sumption,scores of vertical and horizontal movement increased significantly in the VNS group ( consumption of sucrose: (11. 78±2. 67) ml,(8. 06±2. 85) ml; percentage of sucrose consumption: (72. 31±9. 98)%, (63. 67±8. 95)%; score of vertical movement: (16. 61±3. 98),(10. 31±3. 86); score of horizontal move-ment: (44. 25±9. 59),(36. 21±7. 21)) (t=4. 87,7. 98,5. 87,9. 12,all P<0. 05). There was no signifi-cant difference between VNS and fluoxetine groups (consumption of sucrose: (11. 32±2. 66) ml; percentage of sucrose consumption: (71. 31±9. 03)%; score of vertical movement: (15. 63±4. 11); score of horizontal movement: (45. 61±8. 54)) (t=-0. 32,-1. 83,0. 98,-1. 13,all P>0. 05). (2) Compared with the CUS group,levels of TNF-α,IL-6 and IL-1β in serum decreased in the VNS group ( serum TNF-α: ( 46. 72 ± 11. 63) pg/ml,(125. 47±15. 18) pg/ml; serum IL-6: (243. 65±38. 90) pg/ml,(441. 39±83. 31) pg/ml;serum IL-1β: (209. 31±32. 45) pg/ml,(339. 21±76. 37) pg/ml) (t=-70. 38,-196. 25,-131. 13,all P<0. 05). The results in the VNS group were lower than those in the fluoxetine group (serum TNF-α: (58. 76 ±12. 64) pg/ml; serum IL-6: (308. 83± 64. 31) pg /ml,serum IL-1β: ( 249. 18 ± 43. 6) pg/ml) ( t=-15. 38,-64. 25,-18. 83,both P<0. 05). The levels of TNF-α,IL-6 and IL-1β in nucleus of the solitary tract in the VNS group were lower than those in the CUS ( TNF-α: (53. 52± 12. 31) pg/ml,(135. 51± 20. 64)pg/ml; IL-6: (265. 31±45. 63) pg/ml,(465. 32±60. 21) pg/ml; IL-1β: (212. 66±43. 32)pg/ml, (365. 96±76. 32) pg/ml) (t=-79. 38,-189. 13,-127. 50,all P<0. 05) and fluoxetine groups (TNF-α:(63. 42±10. 64) pg/ml; IL-6: (315. 62±53. 21) pg/ml; IL-1β: (278. 32±65. 38) pg/ml ) (t=-10. 25,-39. 00,-83. 00,all P<0. 05). (3) The apoptotic rate of hippocampal CA1 region in VNS group ((21. 41± 5. 86)%) was lower than that in the CUS group ((32. 78±8. 32)%) (t=-10. 75,P<0. 05); and there was no difference between VNS group and fluoxetine group ((22. 54±6. 31)%) (t=-1. 75,P>0. 05). Conclu-sion VNS can improve the depression behavior in rats with depression induced by CUS and the mechanism maybe related to inhibiting the expression of TNF-α,IL-6 and IL-1β in serum and nucleus of the solitary tract and cell apoptosis in hippocampal CA1 region.

AIM: To investigate the effects of astragalus injection combined with puerarin injection on endo-plasmic reticulum stress through PERK pathway in diabetic nephropathy mice .METHODS: Male KKAy mice were ran-domly divided into model group ( injected with normal saline ) and treatment group ( injected with astragalus and puerarin ) . The male C57BL/6J mice served as normal group .The mice were sacrificed 4 weeks after treatments for observing morpho-logical changes under electron microscope .The renal tissues were collected to determine the expression of protein kinase R-like endoplasmic reticulum kinase ( PERK ) , eukaryotic initiation factor 2α( eIF2α) and glucose-regulated protein 78 (GRP78) at mRNA and protein levels by real-time PCR and Western blot.RESULTS: Under electron microscope, the renal tubular epithelial cells in model group and treatment group showed the swelling of the nucleus , endoplasmic reticulum and mitochondria .The results of real-time PCR and Western blot showed that the expression of PERK , eIF2αand GRP78 at mRNA and protein levels in model group was higher than that in normal group (P<0.05), while that in treatment group was lower than that in model group .CONCLUSION: Astragalus injection combined with puerarin injection reduces the mRNA and protein expression of PERK , eIF2αand GRP78, thus inhibiting the endoplasmic reticulum stress in type 2 dia-betic mice to protect the kidney function .