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.

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 conduct scoping review of researches on application of traditional Chinese medicine exercises in exercise rehabilitation of patients with heart failure, so as to provide reference for effective clinical intervention of traditional Chinese medicine exercises.Methods:Chinese and English literature published in PubMed, Web of Science, Cochrane Library, Embase, CNKI, VIP, Wanfang Database and China Biology Medicine disc were searched by computer, and the search deadline was from database establishment to May 28, 2023. The Joanna Briggs Institute Scoping Review Guide was used as a methodological framework to summarize and analyze the included literature.Results:A total of 19 literatures were included, including 17 randomized controlled trials and 2 quasi-randomized controlled trials. The subjects of the intervention were heart failure patients with New York Heart Association heart function gradeⅠ toⅢ. The types of exercises mainly included Eight Pieces of Brocade and Tai Chi. The intervention duration was mostly 30 min each time, and the frequency was mostly 3 to 5 times a week. The intervention intensity was mostly based on The Borg Rating of Perceived Exertion (RPE), and the intervention duration was mostly 3 months. Most of the implementation scenarios were "hospital-home" or home. Traditional Chinese medicine exercises had a positive effect on the clinical symptoms, psychological state and quality of life of patients with heart failure, and were safe and feasible.Conclusions:Traditional Chinese medicine exercises have a positive effect on the exercise rehabilitation of patients with heart failure, and are safe and feasible.

OBJECTIVE: To estimate the social and economic burden of Downs syndrome for patients and their families residing in Changsha, China. METHODS: An 160-item self-administered questionnaire was designed and distributed to the primary caregivers of the patients in March 2020. A total of 81 eligible participants had completed the questionnaire, among which 20 were excluded for incomplete data. A patient perspective was taken to estimate the economic burden of the disease. The social impact of the disease on the patient's family was evaluated through questions adapted from the Stanford Psychological Wellbeing (PWB) Scale. RESULTS: The estimated life-course cost of a Downs syndrome patient in Changsha is 4 985 659 RMB, with the patient and caregiver's loss of income taking the greater proportion. In addition, as the majority of the patients' primary caregivers, female caregivers experienced not only considerable financial hardship caused by the care provision, but also a significant amount of psychological pressure and social discrimination. CONCLUSION Increased level of social welfare for the patients and social support for their female caregivers are essential for reducing economic burden and improving their quality of life in the area. In addition, prenatal screening and diagnosis for Downs syndrome are important for reducing both the social and economic burden of the disease by preventing its occurrence.
Caregivers ; China ; Down Syndrome ; Female ; Financial Stress ; Humans ; Quality of Life ; Social Discrimination ; Surveys and Questionnaires

Objective:To explore the clinical characteristics of hand-foot syndrome (HFS) induced by apatinib.Methods:Case reports of HFS induced by apatinib were collected through searching PubMed, VIP, CNKI, and Wanfang databases (up to March 20, 2019). The clinical characteristics of HFS induced by apatinib were analyzed according to the literature above and the information from 2 related patients admitted to Kailuan General Hospital.Results:A total of 16 patients were enrolled in the study, including 9 males and 7 females, aged (62±16) years. Apatinib was applied for gastric cardia cancer in 4 patients, lung cancer in 4 patients, ovarian cancer in 2 patients, thyroid cancer in 2 patients, and other malignant tumors in 4 patients. And it was used alone in 11 patients and in combination with other antineoplastic agents in 5 patients. Dosages of apatinib included 850 mg/d in 3 patients, 500 mg/d in 6 patients, 425 mg/d in 1 patient, and 250 mg/d in 6 patients (the dose was increased to 500 mg/d in 2 patients after 1 and 2 weeks of administration, respectively). According to the severity, HFS was classified as grade 1 in 2 patients (12.5%), grade 2 in 6 patients (37.5%), and grade 3 in 8 patients (50.0%). Except that the time from application of apatinib to HFS occurrence was not known in 1 patient, the median time from medication to HFS occurrence was 3 (1-11) weeks in other 15 patients, and 10 (66.7%) of them developed HFS within 3 weeks of administration. In addition to the skin lesions of HFS, the skin/mucous membrane damage also appeared on perianal area, genital, axillary fossa, groin, and mouth in 5 patients. Among the 16 patients, 13 had other adverse events, including hypertension in 10 patients (62.5%). The symptoms of 8 patients with HFS of grade 1-2 mostly improved or were tolerable after symptomatic treatments. And in detail, 3 patients′ symptoms had no effect on the treatment of apatinib, 4 patients could tolerate a reduced dose or re-medication after a pause, and 1 patient stopped medication. Symptomatic treatment effects were poor in 8 patients with grade 3 HFS, 4 of whom stopped apatinib because of the serious HFS and 3 of whom died.Conclusions:The HFS induced by apatinib usually occurs within 3 weeks after administration, which can involve many parts of the body except for the skin of hands and feet, and are accompanied with hypertension mostly. HFS symptoms can be relieved by symptomatic treatments, reasonable dose reduction, or drug withdrawal in most patients.

Objective:To explore the clinical characteristics of hand-foot syndrome (HFS) induced by apatinib.Methods:Case reports of HFS induced by apatinib were collected through searching PubMed, VIP, CNKI, and Wanfang databases (up to March 20, 2019). The clinical characteristics of HFS induced by apatinib were analyzed according to the literature above and the information from 2 related patients admitted to Kailuan General Hospital.Results:A total of 16 patients were enrolled in the study, including 9 males and 7 females, aged (62±16) years. Apatinib was applied for gastric cardia cancer in 4 patients, lung cancer in 4 patients, ovarian cancer in 2 patients, thyroid cancer in 2 patients, and other malignant tumors in 4 patients. And it was used alone in 11 patients and in combination with other antineoplastic agents in 5 patients. Dosages of apatinib included 850 mg/d in 3 patients, 500 mg/d in 6 patients, 425 mg/d in 1 patient, and 250 mg/d in 6 patients (the dose was increased to 500 mg/d in 2 patients after 1 and 2 weeks of administration, respectively). According to the severity, HFS was classified as grade 1 in 2 patients (12.5%), grade 2 in 6 patients (37.5%), and grade 3 in 8 patients (50.0%). Except that the time from application of apatinib to HFS occurrence was not known in 1 patient, the median time from medication to HFS occurrence was 3 (1-11) weeks in other 15 patients, and 10 (66.7%) of them developed HFS within 3 weeks of administration. In addition to the skin lesions of HFS, the skin/mucous membrane damage also appeared on perianal area, genital, axillary fossa, groin, and mouth in 5 patients. Among the 16 patients, 13 had other adverse events, including hypertension in 10 patients (62.5%). The symptoms of 8 patients with HFS of grade 1-2 mostly improved or were tolerable after symptomatic treatments. And in detail, 3 patients′ symptoms had no effect on the treatment of apatinib, 4 patients could tolerate a reduced dose or re-medication after a pause, and 1 patient stopped medication. Symptomatic treatment effects were poor in 8 patients with grade 3 HFS, 4 of whom stopped apatinib because of the serious HFS and 3 of whom died.Conclusions:The HFS induced by apatinib usually occurs within 3 weeks after administration, which can involve many parts of the body except for the skin of hands and feet, and are accompanied with hypertension mostly. HFS symptoms can be relieved by symptomatic treatments, reasonable dose reduction, or drug withdrawal in most patients.

Objective: To study the median effective dose of ketorolac tromethamine combined with different doses of sufentanil. Methods: From February 2016 to June 2017, 60 cases of cesarean section were selected.According to the random number table method, they were divided into two groups, with 30 cases in each group.Group I was treated with sufentanil 0.75μg/kg+ dexmedetomidine 200μg, while sufentanil 1μg/kg+ dexmedetomidine 200μg was used in group II.The first two groups were added to pump 150 mg ketorolac tromethamine, gradually increased or decreased in accordance with 30mg effect according to satisfaction or dissatisfaction.The median effective dose of ketorolac tromethamine in the two groups was analyzed. Results: After operation, the systolic blood pressure[(112.5±9.6)mmHg vs.(122.5±8.4)mmHg, (114.2±9.9)mmHg vs.(124.1±8.2)mmHg]and heart rate[(80.6±13.5)times/min vs.(90.5±16.5)times/min, (77.6±15.5)times/min vs.(88.2±18.8)times/min]in the two groups were significantly lower than those before operation (t=4.587, 5.248, 4.214, 3.983, all P<0.05). The VSA scores of the two groups decreased significantly[(6.8±2.4)points, (3.4±1.4)points, (2.1±0.9)points, (6.9±3.1)points, (3.5±1.7)points, (2.2±0.7)points], the difference was statistically significant at different time points (F=4.977, P<0.05). ED50 and 95% confidence interval of ketorolac tromethamine in the group I was 91.75mg, 78.69-106.98mg, which in the group II was 72.44mg, 60.40-86.90mg. Conclusion Ketorolac tromethamine combined with sufentanil has good analgesia effect, less adverse reaction.When sufentanil was given at 0.75 and 1μg/kg, the ED50 of ketorolac tromethamine were 91.75mg and 72.44mg.

Objective:To explore the effects of norepinephrine combined with dobutamine on the hemodynamics,blood lactic acid,creatinine clearance rate (CCr),fractional excretion ofH2O (FEH2O) and fractional excretion of sodium (FENa) of patients with septic shock.Methods:120 cases of patients with septic shock from January 2016 to December 2016 were selected as the research objectives and randomly divided into two groups with 60 cases in each group.Dobutamine was given to both groups,then norepinephrine was additionally given to the observation group,dopamine was additionally given to the control group.The clinical effect,changes of hemodynamics,blood lactic acid,CCr,FEH2O and FENa levels before and after treatment were compared between two groups.Results:The blood lactic acid and FENa levels of both groups were gradually decreased at 6,12,24 and 48 hours after treatment and were significantly lower than those before treatment;the CCr and FEH2O levels were gradually increased and significantly higher than those before treatment (P＜0.01).The blood lactic acid and FENa levels were gradually decreased at 6,12,24 and 48 hours after treatment and were significantly lower than those of the control group at same time (P＜0.01),the FEH2O level was significantly higher than that of the control group at the same time (P＜0.01).The MAP,SVRI of both groups at 6,12,24 and 48 hours after treatment were significantly higher than those before treatment,but the CI at 24,48 hours after treatment were significantly higher than those before treatment (P＜0.01),the MAP of observation group at 6,12,24 and 48 hours after treatment were significantly lower than those before treatment (P＜0.01),the MAP at 6,12 hours after treatment were significantly higher than those before treatment (P＜0.01),the HR of observation group at 6,12,24 and 48 hours after treatment were significantly lower than those of the control group,but SVRI was significantly higher than those of the control group (P＜0.01).The mortality of observation group was 18.33％ at 28th days after treatment,which was 35.00％ in the control group and significantly higher than that of the observation group (P＜0.05).Conclusion:Norepinephrine combined with dobutamine could improve the hemodynamics,reduce the blood lactate level,improve the renal perfusion and prognosis of patients with septic shock.