1.Efficacy and safety of surgery-assisted transjugular intrahepatic portosystemic shunt in treatment of portal hypertension comorbid with complex portal vein thrombosis
Zhenhua FAN ; Chengbin DONG ; Qimei LI ; Yu ZHANG ; Yifan WU ; Dongfang LIU ; Guangzhong XU ; Dezhong WANG ; Jianfei CHEN ; Zhendong YUE ; Lei WANG
Journal of Clinical Hepatology 2026;42(3):586-592
ObjectiveTo investigate the feasibility, safety, and efficacy of surgery-assisted transjugular intrahepatic portosystemic shunt (SA-TIPS) in the treatment of portal hypertension comorbid with complex portal vein thrombosis, including cavernous transformation of the portal vein (CTPV). MethodsAn analysis was performed for the data of 36 patients with portal hypertension and complex portal vein thrombosis who underwent SA-TIPS in Beijing Shijitan Hospital, Capital Medical University, from November 2023 to January 2025, including general status, technical data of the surgical process (surgical success rate, puncture times, time of operation, the number of stents used, and the length of shunt), perioperative complications, and surgical recovery. The change in portal pressure gradient (PPG) after shunt was compared, and the rate of reaching the standard for PPG reduction was calculated, as well as stent patency rate within 1 week after surgery. The paired samples t-test was used for comparison of continuous data between two groups. ResultsAmong the 36 patients, 34 (94.4%) underwent SA-TIPS successfully. The incidence rate of perioperative complications was 16.7% (6/36), including 3 cases of thoraco-abdominal hemorrhage, 2 cases of intraoperative arrhythmia, and 1 case of incision infection. There was a significant reduction in PPG after SA-TIPS (t=19.85, P<0.01), and the patients achieving a ≥50% reduction in PPG accounted for 76.5% (26/34). Imaging reexamination within 1 week showed a shunt patency rate of 100%. ConclusionSA-TIPS has a high technical success rate, a favorable safety profile, and good efficacy in the treatment of portal hypertension comorbid with complex portal vein thrombosis (including CTPV), and therefore, it holds promise for clinical application.
2.Evaluation of CARIFS Score and Negative Antigen Conversion Rate of Qingxuan Daozhi Formula in Treatment of Influenza in Children (Heat Accumulation in Lung and Stomach Syndrome):A Multi-center Randomized Controlled Clinical Study
Jing WANG ; Liqun WU ; Tiegang LIU ; Yongning CAO ; Jing QIU ; Jing LI ; Huaqing TAN ; Ying ZHANG ; Xulei GOU ; Jia WANG ; Jing LI ; Haipeng CHEN ; Xueying QIN ; Yuanshuo TIAN ; Yang WANG ; Chen BAI ; Zhendong WANG ; Qianqian LI ; He YU ; Xueyan MA ; Fei DONG ; Lin JIANG ; Yingqi XU ; Jianping LIU ; Xiaohong GU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):188-196
ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children (heat accumulation in the lung and stomach syndrome). MethodsThrough a multi-center randomized controlled methodology design,confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals,such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days,and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale (CARIFS) and the incidence of complications,severe cases, and critical cases. Follow-up observation was conducted on the day of enrollment,48 hours after medication,72 hours after medication, and (6+1) d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group (90 cases) or the control group (90 cases). All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was (5.29±1.25) d,and that in the control group was (5.40±1.68) d,without a statistically significant difference. After five days of intervention,52 cases in the experimental group and 51 cases in the control group converted to negative,without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention,there were statistically significant differences between the experimental group and the control group in three dimensions, including headache,muscle soreness, and the need for extra care (P<0.05). On the (6+1) days after the intervention,the differences in both the experimental group and the control group were statistically significant in 10 dimensions, including sore throat,bad sleep,uncomfortable feeling,poor spirit and fatigue,crying more than usual,the need for extra care,symptom,function,influence on parents,and total score (P<0.05). The comparison results within the group in the dimensional scores of symptom, function, and influence on parents,as well as the CARIFS total score showed that with the delay of follow-up time,scores of both groups decreased significantly,with a statistically significant difference (P<0.01). Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention,the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up,the mean score of the experimental group was lower than that of the control group,with no statistically significant difference. In terms of the incidence of complications,severe cases, and critical cases, there were no complications,severe cases, and critical cases in the two groups,without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children (heat accumulation in the lung and stomach syndrome) are not inferior to Oseltamivir Phosphate granules, and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children (heat accumulation in the lung and stomach syndrome).
3.Dysregulated Pathways During Pregnancy Predict Drug Candidates in Neurodevelopmental Disorders.
Huamin YIN ; Zhendong WANG ; Wenhang WANG ; Jiaxin LIU ; Yirui XUE ; Li LIU ; Jingling SHEN ; Lian DUAN
Neuroscience Bulletin 2025;41(6):987-1002
Maternal health during pregnancy has a direct impact on the risk and severity of neurodevelopmental disorders (NDDs) in the offspring, especially in the case of drug exposure. However, little progress has been made to assess the risk of drug exposure during pregnancy due to ethical constraints and drug use factors. We collected and manually curated sub-pathways and pathways (sub-/pathways) and drug information to propose an analytical framework for predicting drug candidates. This framework linked sub-/pathway activity and drug response scores derived from gene transcription data and was applied to human fetal brain development and six NDDs. Further, specific and pleiotropic sub-/pathways/drugs were identified using entropy, and sex bias was analyzed in conjunction with logistic regression and random forest models. We identified 19 disorder-associated and 256 regionally pleiotropic and specific candidate drugs that targeted risk sub-/pathways in NDDs, showing temporal or spatial changes across fetal development. Moreover, 5443 differential drug-sub-/pathways exhibited sex-biased differences after filling in the gender labels. A user-friendly NDDP visualization website ( https://ndd-lab.shinyapps.io/NDDP ) was developed to allow researchers and clinicians to access and retrieve data easily. Our framework overcame data gaps and identified numerous pleiotropic and specific candidates across six disorders and fetal developmental trajectories. This could significantly contribute to drug discovery during pregnancy and can be applied to a wide range of traits.
Humans
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Female
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Pregnancy
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Neurodevelopmental Disorders/metabolism*
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Male
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Prenatal Exposure Delayed Effects
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Fetal Development/drug effects*
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Drug Discovery/methods*
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Brain/metabolism*
4.Relationship between bile acid sub components and traditional biochemical indicators and nonalcoholic fatty liver
Jinlong DU ; Haoyu ZHANG ; Zhendong LIU ; Shumei LIU ; Haiyan DU ; Chunyan TANG ; Zhuomin LI ; Yanguo TAN
International Journal of Laboratory Medicine 2025;46(7):786-790
Objective To investigate the changes of 22 bile acid sub components and 17 traditional bio-chemical indicators in serum of patients with non-alcoholic fatty liver disease(NAFLD),and the diagnostic value of detecting the above indicators alone or in combination for NAFLD.Methods A total of 168 NAFLD patients(NAFLD group)and 216 non-NAFLD apparently healthy individuals(non-NAFLD group)were se-lected,bile acid sub components were determined by liquid chromatography tandem mass spectrometry,and traditional biochemical indicators were detected by automatic biochemical analyzer.Results There were sta-tistically significant differences in the levels of 12 bile acid sub components and 12 traditional biochemical indi-cators between NAFLD group and non-NAFLD group(P<0.05).Compared to traditional biochemical indica-tors,bile acid sub components were less affected by body mass index(BMI).The area under the curve for di-agnosing NAFLD by combining three bile acid sub components[taurocholic acid(TCA),sodium taurodeoxy-cholate(TDCA),and tauroursodeoxycholic acid(UDCA)]with three traditional biochemical indicators[ala-nine aminotransferase(ALT),5'Nucleotidase(5'-NT),and small and dense low-density lipoprotein cholester-ol(sd-LDL-C)]was the largest,which was 0.810.Conclusion Twelve kinds of bile acid sub components in the blood of NAFLD patients have changed,and the combined detection of bile acid sub components and tradi-tional biochemical indicators could improve the diagnostic efficacy of NAFLD to a certain extent.
5.Effect of Wulao Qisun Prescription on Proliferation and Osteogenic Differentiation of AS Fibroblasts by Regulating Wnt/β-catenin Signaling Pathway
Juanjuan YANG ; Ping CHEN ; Haidong WANG ; Zhendong WANG ; Haolin LI ; Zhimin ZHANG ; Yuping YANG ; Weigang CHENG ; Jin SU ; Jingjing SONG ; Dongsheng LU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):67-73
ObjectiveTo investigate the effect and underlying mechanism of the Wulao Qisun prescription on pathological new bone formation in ankylosing spondylitis (AS). MethodsSynovial fibroblasts were isolated from the hip joints of AS patients and observed under a microscope to assess cell morphology. The cells were identified using immunofluorescence staining. The isolated AS fibroblasts were divided into blank group, low drug-containing serum group, medium drug-containing serum group, high drug-containing serum group, and positive drug group. After drug intervention, cell proliferation was measured using the cell counting kit-8 (CCK-8) assay to observe fibroblast growth and determine the optimal intervention time. Alkaline phosphatase (ALP) activity was measured using the alkaline phosphatase assay. Protein expression of osteocalcin (OCN), osteopontin (OPN), and runt-related transcription factor 2 (Runx2) was detected by Western blot. The mRNA expression levels of Wnt5a, β-catenin, and Dickkopf-1 (DKK-1) were measured by real-time quantitative polymerase chain reaction (Real-time PCR). ResultsCompared with the blank group, each drug-containing serum group of Wulao Qisun prescription and the positive drug group inhibited the proliferation of AS fibroblasts and reduced ALP expression (P<0.01). Compared with the blank group, the low drug-containing serum group of Wulao Qisun prescription downregulated β-catenin mRNA expression (P<0.05). The medium and high drug-containing serum groups and the positive drug group significantly downregulated Wnt5a and β-catenin mRNA expression (P<0.05, P<0.01), with the positive drug group showing the most pronounced effect (P<0.01). The high drug-containing serum group and the positive drug group significantly upregulated DKK-1 mRNA expression (P<0.01). Compared with the blank group, the low drug-containing serum group of Wulao Qisun prescription inhibited the expression of OPN and Runx2 proteins (P<0.05, P<0.01), while the medium and high drug-containing serum groups and the positive drug group inhibited the expression of OCN, OPN, and Runx2 proteins (P<0.05, P<0.01). ConclusionThe Wulao Qisun prescription can inhibit the proliferation and osteogenic differentiation of AS fibroblasts, thereby delaying the formation of pathological new bone in AS. The possible mechanism involves the regulation of Wnt/β-catenin-related gene expression, further inhibiting the transcription of downstream target genes.
6.Clinical Efficacy of Xiaoji Hufei Formula in Protecting Children with Close Contact Exposure to Influenza: A Multicenter,Prospective, Non-randomized, Parallel, Controlled Trial
Jing WANG ; Jianping LIU ; Tiegang LIU ; Hong WANG ; Yingxin FU ; Jing LI ; Huaqing TAN ; Yingqi XU ; Yanan MA ; Wei WANG ; Jia WANG ; Haipeng CHEN ; Yuanshuo TIAN ; Yang WANG ; Chen BAI ; Zhendong WANG ; Qianqian LI ; He YU ; Xueyan MA ; Fei DONG ; Liqun WU ; Xiaohong GU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):223-230
ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza, and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter, prospective, non-randomized, parallel, controlled trial was conducted from October 2021 to May 2022 in five hospitals, including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness (ILI) cases were collected, and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention, they were assigned to the observation group (108 cases) or the control group (108 cases). Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine (TCM) symptom score scale for influenza, influenza-related emergency (outpatient) visit rate, influenza hospitalization rate, and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled, with 108 in the observation group and 108 in the control group. Primary outcomes: (1) Incidence of ILI: The incidence was 12.0% (13/108) in the observation group and 23.1% (25/108) in the control group, with the observation group showing a significantly lower incidence (χ2=4.6, P<0.05). (2) Influenza confirmation rate: 3.7% (4/108) in the observation group and 4.6% (5/108) in the control group, with no statistically significant difference. Secondary outcomes: (1) TCM symptom score scale: after onset, nasal congestion and runny nose scores differed significantly between the two groups (P<0.05), while other symptoms such as fever, sore throat, and cough showed no significant differences. (2) Influenza-related emergency (outpatient) visit rate: 84.6% (11 cases) in the observation group and 96.0% (24 cases) in the control group, with no significant difference. (3) Time to onset after exposure: The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group, with a statistically significant difference (P<0.05). ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions, Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.
7.Clinical Efficacy of Xiaoji Hufei Formula in Protecting Children with Close Contact Exposure to Influenza: A Multicenter,Prospective, Non-randomized, Parallel, Controlled Trial
Jing WANG ; Jianping LIU ; Tiegang LIU ; Hong WANG ; Yingxin FU ; Jing LI ; Huaqing TAN ; Yingqi XU ; Yanan MA ; Wei WANG ; Jia WANG ; Haipeng CHEN ; Yuanshuo TIAN ; Yang WANG ; Chen BAI ; Zhendong WANG ; Qianqian LI ; He YU ; Xueyan MA ; Fei DONG ; Liqun WU ; Xiaohong GU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):223-230
ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza, and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter, prospective, non-randomized, parallel, controlled trial was conducted from October 2021 to May 2022 in five hospitals, including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness (ILI) cases were collected, and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention, they were assigned to the observation group (108 cases) or the control group (108 cases). Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine (TCM) symptom score scale for influenza, influenza-related emergency (outpatient) visit rate, influenza hospitalization rate, and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled, with 108 in the observation group and 108 in the control group. Primary outcomes: (1) Incidence of ILI: The incidence was 12.0% (13/108) in the observation group and 23.1% (25/108) in the control group, with the observation group showing a significantly lower incidence (χ2=4.6, P<0.05). (2) Influenza confirmation rate: 3.7% (4/108) in the observation group and 4.6% (5/108) in the control group, with no statistically significant difference. Secondary outcomes: (1) TCM symptom score scale: after onset, nasal congestion and runny nose scores differed significantly between the two groups (P<0.05), while other symptoms such as fever, sore throat, and cough showed no significant differences. (2) Influenza-related emergency (outpatient) visit rate: 84.6% (11 cases) in the observation group and 96.0% (24 cases) in the control group, with no significant difference. (3) Time to onset after exposure: The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group, with a statistically significant difference (P<0.05). ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions, Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.
8.Analysis and forecast of the disease burden of schistosomiasis in China from 1992 to 2030
Kai LIN ; Chenhuan ZHANG ; Zhendong XU ; Xuemei LI ; Renzhan HUANG ; Yawen LIU ; Haihang YU ; Lisi GU
Chinese Journal of Schistosomiasis Control 2025;37(1):24-34
Objective To analyze the trends in the disease burden of schistosomiasis in China from 1992 to 2021, and to project the disease burden of schistosomiasis in China from 2022 to 2030, so as to provide insights into the elimination of schistosomiasis in China. Methods The prevalence, age-standardized prevalence, disability-adjusted life year (DALYs) rate and age-standardized DALYs rate of schistosomiasis, as well as the years lost due to disability (YLDs) rate and age-standardized YLDs rate of anemia attributable to Schistosoma infections in China, the world and different socio-demographic index (SDI) regions were captured from the Global Burden of Disease Study 2021 (GBD 2021) data resources, and the trends in the disease burden due to schistosomiasis were evaluated with estimated annual percentage change (EAPC) and its 95% confidence interval (CI). In addition, the age, period and cohort effects on the prevalence of schistosomiasis were examined in China using an age-period-cohort (APC) model, and the disease burden of schistosomiasis was predicted in China from 2022 to 2030 using a Bayesian age-period-cohort (BAPC) model. Results The age-standardized prevalence and DALYs rate of schistosomiasis, and the age-standardized YLDs rate of anemia attributable to Schistosoma infections were 761.32/105, 5.55/105 and 0.38/105 in China in 2021. These rates were all lower than the global levels (1 914.30/105, 21.90/105 and 3.36/105, respectively), as well as those in the medium SDI regions (1 413.61/105, 12.10/105 and 1.93/105, respectively), low-medium SDI regions (2 461.03/105, 26.81/105 and 4.48/105, respectively), and low SDI regions (5 832.77/105, 94.48/105 and 10.65/105, respectively), but higher than those in the high SDI regions (59.47/105, 0.49/105 and 0.05/105, respectively) and high-medium SDI regions (123.11/105, 1.20/105 and 0.12/105, respectively). The prevalence and DALYs rate of schistosomiasis were higher among men (820.79/105 and 5.86/105, respectively) than among women (697.96/105 and 5.23/105, respectively) in China in 2021, while the YLDs rate of anemia attributable to Schistosoma infections was higher among women (0.66/105) than among men (0.12/105). The prevalence of schistosomiasis peaked at ages of 30 to 34 years among both men and women, while the DALYs rate of schistosomiasis peaked among men at ages of 15 to 19 years and among women at ages of 20 to 24 years. The age-standardized prevalence of schistosomiasis showed a moderate decline in China from 1992 to 2021 relative to different SDI regions [EAPC = -1.51%, 95% CI: (-1.65%, -1.38%)], while the age-standardized DALYs rate [EAPC = -3.61%, 95% CI: (-3.90%, -3.33%)] and age-standardized YLDs rate of anemia attributable to Schistosoma infections [EAPC = -4.16%, 95% CI: (-4.38%, -3.94%)] appeared the fastest decline in China from1992 to 2021 relative to different SDI regions. APC modeling showed age, period, and cohort effects on the trends in the prevalence of schistosomiasis in China from 1992 to 2021, and the prevalence of schistosomiasis appeared a rise followed by decline with age, and reduced with period and cohort. BAPC modeling revealed that the age-standardized prevalence and age-standardized DALYs rate of schistosomiasis, and age-standardized YLDs rate of anemia attributable to Schistosoma infections all appeared a tendency towards a decline in China from 2022 to 2030, which reduced to 722.72/105 [95% CI: (538.74/105, 906.68/105)], 5.19/105 [95% CI: (3.54/105, 6.84/105)] and 0.30/105 [95% CI: (0.21/105, 0.39/105)] in 2030, respectively. Conclusions The disease burden of schistosomiasis appeared a tendency towards a decline in China from 1992 to 2021, and is projected to appear a tendency towards a decline from 2022 to 2030. There are age, period and cohort effects on the prevalence of schistosomiasis in China. Precision schistosomiasis control is required with adaptations to current prevalence and elimination needs.
9.Phase Ⅲ, multicenter, randomized comparative study of LY01005 and Zoladex ? for patients with premenopausal breast cancer
Xiying SHAO ; Qingyuan ZHANG ; Zhaofeng NIU ; Man LI ; Jingfen WANG ; Zhanhong CHEN ; Ruizhen LUO ; Guangdong QIAO ; Jianguo WANG ; Liyuan QIAN ; Ronghua YANG ; Zhendong CHEN ; Jian WANG ; Yumin YAO ; Jianghua OU ; Tao SUN ; Qiao CHENG ; Yongsheng WANG ; Jian HUANG ; Hongying ZHAO ; Wuyun SU ; Zhong OUYANG ; Yu DING ; Lilin CHEN ; Sumei YANG ; Mengsheng CUI ; Aimin ZANG ; Enxiang ZHOU ; Peizhi FAN ; Jing ZHANG ; Qiang LIU ; Yuee TENG ; Hui LI ; Jianyun NIE ; Jin YANG ; Xiaojia WANG ; Zefei JIANG
Chinese Journal of Oncology 2025;47(4):340-348
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.
10.Effect of in situ hypoxia-inducing hydrogel on extracellular matrix secretion in the nucleus pulposus
Xingdie ZHOU ; Zehao CHEN ; Zhendong LÜ ; Yuhui ZHANG ; Li LIU
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(8):990-1000
Objective·To construct an interpenetrating network hydrogel(HMGL)that can induce hypoxia in situ,investigate its effects on promoting the secretion of extracellular matrix in nucleus pulposus cells(NPCs),and evaluate its potential in the treatment of intervertebral disc degeneration.Methods·HMGLs capable of long-term in situ hypoxia induction were prepared by a two-step polymerization method.Hypoxic hydrogels with laccase concentrations of 5 U/mL and 10 U/mL,namely HMGL-5 and HMGL-10,were constructed,whereas a hyaluronic acid methacryloyl(HAMA)hydrogel served as the control.The molecular structures of HAMA and gelatin grafted with vanillin(GelVA)were verified by 1H nuclear magnetic resonance spectra(1H NMR)and Fourier transform infrared spectroscopy(FTIR).The microstructures of the hydrogels were observed by scanning electron microscope(SEM),and the mechanical properties of the hydrogels were tested by a rotational rheometer and a dynamic mechanical analyzer(DMA).The induced hypoxic behaviors of the hydrogels were detected by an oxygen consumption fluorescent probe.The biocompatibility of the hydrogels was tested by live/dead staining and the cell counting kit 8(CCK-8)assay,and the expression of hypoxia-inducible factor-1α(HIF-1α)and type Ⅱ collagen(Col Ⅱ)in NPCs was detected by immunofluorescence staining.A rat model of intervertebral disc degeneration was established,and hydrogels loaded with NPCs were injected into degenerated intervertebral discs to evaluate their repair effects.Disc height and disc water content changes were detected by X-ray imaging and magnetic resonance imaging(MRI),and the integrity of disc structure and proteoglycan levels were detected by histological staining.Results·Structural characterization demonstrated that the materials had been successfully prepared.SEM showed that the three hydrogels all had a loose and porous structure,and their elastic moduli increased with the decrease of pore size.Hypoxia test results indicated that the hypoxia-inducing ability of HMGL-10 hydrogel was the strongest.In vitro experimental results showed that the three hydrogels all had good biocompatibility.Compared with the HAMA hydrogel,the HIF-1α of NPCs was significantly activated in the HMGL-10 hydrogel.The expression levels of HIF-1α and Col Ⅱ in the HMGL-10 hydrogel group were 3.38 and 4.15 times higher than those in the HAMA hydrogel group.In vivo experimental results showed that the integrity,height,and water content of the intervertebral discs in the hypoxia hydrogel group were all superior to those in the other treatment groups.Conclusion·The in situ hypoxia-inducing hydrogel effectively activates HIF-1α,promotes extracellular matrix secretion,and demonstrates superior regenerative potential for intervertebral disc repair.

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