1.Mechanism of Modified Erxian Decoction Regulating Perimenopausal Syndrome via SIRT1/Kisspeptin/GnRH Signaling Pathway
Ruiyu HUANG ; Fang LEI ; Wuchaonan LIU ; Jingjing YANG ; Qianru ZENG ; Shengping LUO ; Yanling CHEN ; Mengge ZHANG ; Fanshun SHEN ; Yihui DENG ; Dingxiang LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):51-62
ObjectiveTo explore the regulation of hypothalamic-pituitary-gonadal (HPG) axis by modified Erxian decoction in rats with perimenopausal syndrome (PMS) and to further analyze the expression of proteins related to the silent information regulator 1 (SIRT1)/hypothalamic kisspeptin (Kisspeptin)/gonadotropin-releasing hormone (GnRH) signaling pathway in the arcuate nucleus region (ARC) of the hypothalamus, so as to reveal the potential target of action and molecular biological mechanism of modified Erxian decoction for the treatment of perimenopausal syndrome. MethodsAn animal model was established via the incomplete castration method, with successful modeling confirmed by the exfoliated cervical cell smear method. The 48 rats were divided into six groups based on the randomization principle after successful modeling, including a sham operation group, a model group, an estradiol valerate group (0.09 mg∙kg-1∙d-1), high-, medium-, and low-dose modified Erxian decoction groups (7.614, 3.807,1.903 5 g∙kg-1∙d-1), with 8 rats in each group. The estradiol valerate group and the high-, medium- and low-dose modified Erxian decoction groups were continuously administered by gavage for 28 days, and the indicators were detected 24 hours after the last administration. Body weights and uterine indices were measured. The pathological changes of the uterus were observed by hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was performed to measure the levels of estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and gonadotropin-releasing hormone (GnRH). Real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to determine the expression levels of SIRT1, Kisspeptin, kisspeptin receptor (GPR54), and GnRH in the ARC region of the hypothalamus and gonadotropin-releasing hormone receptor (GnRH-R) in pituitary. ResultsCompared with the sham operation group, rats in the model group had a significantly increased body weight (P0.01), reduced wet weight and index of uterus (P0.01), endometrial thinning or atrophy, glandular atrophy, and a decreasing number of glands. Additionally, serum levels of E2 and the expression of SIRT1 in the ARC region of the hypothalamus significantly decreased (P0.01). Serum levels of FSH, LH, and GnRH, the expression of Kisspeptin, GPR54, and GnRH in the ARC region of the hypothalamus, and GnRH-R in pituitary significantly increased (P0.01). Compared with the model group, the estradiol valerate group and the high-, medium-dose modified Erxian decoction groups had significantly reduced body weight, serum levels of FSH, LH, and GnRH, and expression of Kisspeptin, GPR54, and GnRH in the ARC region of the hypothalamus and GnRH-R in pituitary (P0.05, P0.01) and significantly increased wet weight and index of uterus, serum level of E2, and expression of SIRT1 in the ARC region of the hypothalamus (P0.05, P0.01). In addition, they showed thickened endometrium, increased number of endometrial glands, and improved glandular atrophy. ConclusionModified Erxian decoction regulates the function of the HPG axis through multi-targets, and its mechanism of action may be related to the up-regulation of the expression of SIRT1 in the ARC region of the hypothalamus, the inhibition of the over-activation of the Kisspeptin/GnRH signaling pathway, the regulation of the expression of GnRH-R in the pituitary, the restoration of secretion balance of gonadotropins, and the elevation of the estrogen level. This study provides an experimental basis for the interpretation of the scientific connotation of modified Erxian decoction in the treatment of perimenopausal syndrome and a theoretical reference for the development of a novel therapeutic strategy based on the SIRT1/Kisspeptin/GnRH pathway.
2.Analysis of hotpots and evolution trends in the field of alzheimer's disease care
Yanling FANG ; Jianling YAO ; Xiaoyu LU ; Jiana WEI ; Yushan YIN ; Xingzuan JIANG
Modern Hospital 2024;24(3):469-473,478
Objective To explore the research status and hot highlights in the field of Alzheimer's disease nursing,and provide reference and direction for future research.Methods The high-level articles on Alzheimer's disease nursing during 2012 to 2022 were collected from Web of Science core database,were analyzed and visualized by the CiteSpace 5.8.R3C software.Re-sults 956 articles were included in the Web of Science core database.The demand and focus on AD nursing research increased year by year.United States America had the largest number of articles(175 articles),followed by France(43 articles)and Chi-na(31 articles).Minnesota University and Harvard Medical School had the largest number of articles(11 articles).The authors'analysis shows that BRUNO VELLAS,an academician of the French Academy of Sciences,had the largest number of articles.Keyword co-occurrence analysis shows that the research in the past decade mainly focuses on"nursing home","people"and"quality of life","long-term care"and"exercise therapy"may become the key research directions in the future.Conclusion Domestic scholars should improve the social security system of long-term care,promote"people-oriented"humanistic nursing services and develop appropriate sports training programs in the future.
3.Relationship between serum P-glycoprotein and claudin-5 levels with epilepsy and cognitive impairment in children
Guosheng XIE ; Na ZHANG ; Yanling ZHANG ; Fang WANG ; Xiaojing YAN
Chinese Pediatric Emergency Medicine 2024;31(11):841-845
Objective:To explore the relationship between the levels of serum P-glycoprotein(P-gp)and claudin-5 with epilepsy and cognitive impairment in children.Methods:A total of 120 children with epilepsy admitted to Xingtai People's Hospital from June 2020 to June 2022 were retrospectively selected as the epilepsy group,and divided into the general tonic-clonic seizure group( n=44)and the focal seizure group( n=76)according to the type of epilepsy,and also divided into the cognitive normal group( n=88)and the cognitive impairment group( n=32)according to the cognitive function of the children. Another 100 healthy children in the hospital were selected as the control group. Serum P-gp and claudin-5 levels were detected by enzyme-linked immunosorbent assay and compared between the two groups. Pearson correlation was used to analyze the relationship between serum P-gp,claudin-5 levels and epilepsy condition in children. Receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of serum P-gp and claudin-5 for cognitive impairment in children with epilepsy. Results:The serum P-gp level in the epilepsy group was higher than that in the control group[(3.11±0.34) ng/L vs. (1.33±0.17) ng/L],and the serum claudin-5 level was lower than that in the control group[(0.66±0.12) ng/mL vs. (1.66±0.28) ng/mL] , and the differences were statistically significant (all P<0.05). The serum P-gp level in the generalized tonic-clonic seizure group was higher than that in the focal seizure group [(5.62±1.02) ng/mL vs. (2.55±0.28) ng/mL],and the serum claudin-5 level was lower than that in the focal seizure group[(0.40±0.05) ng/mL vs. (1.10±0. 25) ng/mL] , and the differences were all statistically significant (all P<0.05). Pearson correlation analysis showed that serum P-gp was positively correlated with negatively correlated with national hospital seizure severity scale(NHS3) score in pediatric epilepsy( r=0.447, P<0.05),and serum claudin-5 was NHS3 score in pediatric epilepsy( r=-0.485, P<0.05). The serum P-gp level in the cognitive impairment group was higher than that in the cognitive normal group [(5.87±1.05) ng/L vs. (2.44±0.26) ng/L],and the serum claudin-5 level was lower than that in the cognitive normal group [(0.32±0.03) ng/mL vs. (0.86±0.08) ng/mL], and the differences were all statistically significant (all P<0.05). ROC curve analysis showed that the area under the curve(AUC)of serum P-gp for evaluating cognitive impairment in children with epilepsy was 0.831(95% CI 0.781-0.881),the AUC of serum claudin-5 for evaluating cognitive impairment was 0.854(95% CI 0.804-0.904),and the AUC of the combination was 0.905(95% CI 0.855-0.955). Conclusion:Serum P-gp level is increased and claudin-5 level is decreased in children with epilepsy,and both levels are closely associated with the disease condition and cognitive impairment,with the combination of the two indexes more effective than either indicator in diagnosing cognitive impairment in pediatric epilepsy.
4.Analysis of arsenic reduction and water improvement projects and arsenic level monitoring results in drinking water type endemic arsenic poisoning areas in Jinzhong City, Shanxi Province
Yanling REN ; Wenjie ZHAI ; Junli CHENG ; Jingzhen LIU ; Fang YANG ; Guangfeng TIAN ; Tiantian WEN
Chinese Journal of Endemiology 2024;43(8):647-651
Objective:To learn about the operation of arsenic reduction and water improvement projects and the present situation of arsenic level in drinking water in drinking water type endemic arsenic poisoning areas in Jinzhong City, Shanxi Province.Methods:From May to August 2023, in accordance with the requirements of the "Investigation Plan for Arsenic Content in Drinking Water of Residents in Arsenic Exposed Areas of Shanxi Province", 29 high arsenic villages in the drinking water type endemic arsenic poisoning historical areas of Pingyao County, Jiexiu City and Qi County in Jinzhong City, Shanxi Province were selected as monitoring villages to investigate the operation of water improvement projects. The drinking water samples of village residents were collected and water arsenic level was measured by hydride atomic fluorescence spectrophotometry. At the same time, monitoring of the operation of water improvement projects and water arsenic level for residents within adjacent local areas were carried out in townships where 29 high arsenic villages located.Results:In 2023, a total of 29 high arsenic villages in 3 counties (cities) of Jinzhong City, Shanxi Province were monitored, all of which had undergone water improvement and all water improvement projects were operating normally. The range of water arsenic level was 0.000 - 0.047 mg/L, with 27 high arsenic villages had water arsenic level < 0.01 mg/L. A total of 81 natural villages within the adjacent local areas of high arsenic villages in Jinzhong City were monitored, all of which had undergone water improvement and the water improvement projects were operating normally. The range of water arsenic level was 0.000 - 0.043 mg/L, and there were 4, 7, and 2 natural villages in Pingyao County, Jiexiu City and Qi County with water arsenic level ranging from 0.01 to 0.05 mg/L.Conclusions:All high arsenic villages in Jinzhong City, Shanxi Province have completed water improvement, and the water improvement projects are operating normally. The water arsenic level in most high arsenic villages meets the national drinking water standard (< 0.01 mg/L).
5.Analysis of the review results of salt iodine monitoring in county-level iodine deficiency disorders laboratories in Jinzhong City form 2021 to 2023
Fang YANG ; Jingzhen LIU ; Junli CHENG ; Yanling REN
Chinese Journal of Endemiology 2024;43(11):928-932
Objective:To analyze the review results of salt iodine monitoring in the county-level laboratories of iodine deficiency disorders in Jinzhong City, and to learn about the quality of the monitoring in the county-level laboratories, so as to provide scientific basis for formulating iodine deficiency disorders prevention and control strategies.Methods:From 2021 to 2023, Jinzhong Center for Disease Control and Prevention used the systematic random sampling method to select 5% (15 samples each) of all edible salt samples (short for salt samples) tested by 11 county-level iodine deficiency disorders laboratories under its jurisdiction for retesting each year. The salt iodine was determined by the redox titration method in accordance with the "General Test Method in Salt Industry-Determination of Iodine" (GB/T 13025.7-2012). Comparisons between groups for count data were analyzed using the χ 2 test, and the comparisons between groups for measurement data were analyzed using a random group design t-test. Results:From 2021 to 2023, the municipal laboratories reviewed and tested 165 salt samples (495 in total over 3 years). The proportion of households using adquately iodized salt tested by county-level laboratories was 92.53% (458/495), with annual rates of 89.70% (148/165), 93.33% (154/165), and 94.55% (156/165), respectively. The proportion of households using adquately iodized salt detected by municipal laboratories was 94.95% (470/495), with annual rates of 90.91% (150/165), 96.36% (159/165), and 97.58% (161/165), respectively. There was no significant difference in the proportion of households using adquately iodized salt detected by the two-level laboratories from 2021 to 2023 (χ 2 = 2.48, P = 0.116). The proportion of salt samples with relative error > 20% in the salt iodine detection results of county-level laboratories reviewed at the municipal laboratory from 2021 to 2023 were 20.00% (33/165), 16.97% (28/165), and 8.48% (14/165), respectively. The differences between different years were statistically significant (χ 2 = 8.49, P = 0.004). Compared with 2023, in 2021 and 2022, the differences were statistically significant ( P < 0.05). The proportion of salt samples with relative error > 30% were 7.88% (13/165), 6.06% (10/165), and 3.64% (6/165), respectively. There was no significant difference among different years (χ 2 = 2.69, P = 0.101). The comparison of laboratory test results between the two-level laboratories showed statistically significant differences ( t = 6.05, P < 0.001). Among the group data reviewed, there were a total of 16 groups with statistical significance, including 4 groups in 2021, 7 groups in 2022, and 5 groups in 2023. Conclusions:The review results indicate that the quality of salt iodine monitoring in county-level laboratories in Jinzhong City continues to improve, and the testing data are authentic and reliable. In the future, training for county-level laboratory inspectors should be increased to enhance their operational skills and minimize testing result errors.
6.QL1604 plus paclitaxel-cisplatin/ carboplatin in patients with recurrent or metastatic cervical cancer:an open-label, single-arm, phase II trial
Cheng FANG ; Yun ZHOU ; Yanling FENG ; Liping HE ; Jinjin YU ; Yuzhi LI ; Mei FENG ; Mei PAN ; Lina ZHAO ; Dihong TANG ; Xiumin LI ; Buzhen TAN ; Ruifang AN ; Xiaohui ZHENG ; Meimei SI ; Baihui ZHANG ; Lingyan LI ; Xiaoyan KANG ; Qi ZHOU ; Jihong LIU
Journal of Gynecologic Oncology 2024;35(6):e77-
Objective:
QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer.
Methods:
This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment.
Results:
Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%).
Conclusion
QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.
7.QL1604 plus paclitaxel-cisplatin/ carboplatin in patients with recurrent or metastatic cervical cancer:an open-label, single-arm, phase II trial
Cheng FANG ; Yun ZHOU ; Yanling FENG ; Liping HE ; Jinjin YU ; Yuzhi LI ; Mei FENG ; Mei PAN ; Lina ZHAO ; Dihong TANG ; Xiumin LI ; Buzhen TAN ; Ruifang AN ; Xiaohui ZHENG ; Meimei SI ; Baihui ZHANG ; Lingyan LI ; Xiaoyan KANG ; Qi ZHOU ; Jihong LIU
Journal of Gynecologic Oncology 2024;35(6):e77-
Objective:
QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer.
Methods:
This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment.
Results:
Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%).
Conclusion
QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.
8.QL1604 plus paclitaxel-cisplatin/ carboplatin in patients with recurrent or metastatic cervical cancer:an open-label, single-arm, phase II trial
Cheng FANG ; Yun ZHOU ; Yanling FENG ; Liping HE ; Jinjin YU ; Yuzhi LI ; Mei FENG ; Mei PAN ; Lina ZHAO ; Dihong TANG ; Xiumin LI ; Buzhen TAN ; Ruifang AN ; Xiaohui ZHENG ; Meimei SI ; Baihui ZHANG ; Lingyan LI ; Xiaoyan KANG ; Qi ZHOU ; Jihong LIU
Journal of Gynecologic Oncology 2024;35(6):e77-
Objective:
QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer.
Methods:
This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment.
Results:
Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%).
Conclusion
QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.
9.The relationship between hypertriglyceridemic-waist phenotype and muscle mass loss in the 18-65 year-old adults
Xiaohui ZHANG ; Fang LIU ; Yingfei DIAO ; Yueying LI ; Yanling LI
Chinese Journal of Endocrinology and Metabolism 2023;39(12):1045-1049
Objective:To detect the incidence of muscle mass loss in the adults and explore its relevant influencing factors.Methods:A total of 1 503 participants aged between 18 and 65 years old were collected from the Department of Preventive Treatment of Disease and Health Management Center of First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from March 2019 to October 2021. All subjects completed physical and laboratory examination and bioelectrical impedance analysis. According to the cutpoint of plasma triglycerides concentration≥1.7 mmol/L, waist circumference≥85 cm in men or≥80 cm in women, 1 503 subjects were divided into four groups: normal triglycerides and waist circumference group, normal waist circumference and hypertriglyceridemia group, abdominal obesity and normal triglycerides group, and hypertriglyceridemic-waist phenotype(HTWC) group. Subjects were also divided into 4 groups according to age. Skeletal muscle mass index(ASMI) was calculated according to the skeletal muscle mass of the limbs. Differences of the ASMI and other relevant indicators among the above four groups were analyzed, and body composition was compared among four age groups. Then explore whether HTWC phenotype was an independent risk factor for the occurrence of sarcopenia in different age groups of different gender.Results:The level of triglycerides, fasting blood glucose, systolic blood pressure, and diastolic blood pressure in HTWC group were higher than those in the normal group(all P<0.001). But the incidence of the muscle mass loss in the HTWC group was much lower than that in the other three groups( P<0.001). The incidence of muscle mass loss in overall subjects was 9.2%, in which man was 2.05 times higher than women(12.9% vs 6.3%). There is no statistically significant difference in the incidence of muscle mass loss between the 18-35 age group and the 56-65 age group. Multivariate logistic regression analysis revealed that body mass index, body fat percentage, bone mineral content were independent factors affecting muscle loss in 18-45 year-old adults. After adjustment for other risk factors, HTWC phenotype was still not an independent influencing factor of sarcopenia( OR=1.679, 95% CI 0.523-5.386, P=0.384). Conclusion:HTWC phenotype was not an independent influencing factor of sarcopenia. To prevent the occurrence of sarcopenia in middle-aged and young adults, in addition to assessing the muscle mass, attention should also be given to the measurement of body mass index, bone mineral content, and body fat percentage.
10.Application and evaluation of evidence-based practice nursing program for severe patients with physical constraints based on guidelines
Jing BAO ; Shasha WANG ; Yue LI ; Xinxin LI ; Hua FAN ; Can LI ; Fang LIN ; Jian WANG ; Yanling SHEN ; Yuhong SUN
Chinese Journal of Modern Nursing 2023;29(22):2969-2973
Objective:To explore the effect of the evidence-based practice nursing program for severe patients with physical constraints based on the guideline in Intensive Care Unit (ICU) patients.Methods:From February 2019 to July 2020, 4 663 patients in the Surgical Intensive Care Unit (SICU), Medicine Intensive Care Unit (MICU), Coronary Care Unit (CCU), and Emergency Intensive Care Unit (EICU) of the China-Japan Friendship Hospital were selected as the research object by purposive sampling. The evidence-based practice nursing program for severe patients with physical constraints based on the guideline of Promoting Safety: Alternative Approaches to the Use of Restraints was applied in clinical practice. We recorded the constraint duration, constraint rate, and substitution constraint rate of severe patients after the implementation of the program, and compared the differences in ICU nurses' scores on physical constraint knowledge, attitude, and practice before and after the implementation of the program. Results:Out of 4 663 patients, 871 received restraint, with a restraint rate of 18.68% and a restraint duration of (102.35±82.67) hours. The number of substitution constraint cases was 421, and the substitution constraint rate was 9.03%. The constraint rates in SICU, MICU, CCU and EICU were 23.68% (475/2 006), 28.26% (219/775), 7.29% (97/1 331) and 14.52% (80/551), respectively, and the differences in constraint rates among different departments were statistically significant ( P<0.05). Before and after the implementation of the program, there were statistically significant differences in the scores of ICU nurses on physical constraint knowledge, attitude, and practice dimensions and total scores ( P<0.05) . Conclusions:The evidence-based practice nursing plan program for severe patients with physical constraints based the guideline effectively reduces the rate and duration of physical constraint of ICU patients, improves the substitution constraint rate, standardizes the practice of physical constraint of ICU patients, and ensures patient safety.

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