1.Assessment of ochratoxin A exposure in the diets of pregnant women in Shanghai
Kailin LI ; Renjie QI ; Hua CAI ; Xia SONG ; Jingjin YANG ; Danping QIU ; Zhenni ZHU ; Yi HE ; Baozhang LUO ; Hong LIU
Shanghai Journal of Preventive Medicine 2026;38(3):181-186
ObjectiveTo investigate the contamination status of ochratoxin A (OTA) in commercially available food products in Shanghai, and to assess OTA exposure levels and the associated non-carcinogenic and carcinogenic risks among pregnant women by integrating dietary consumption data of this population. MethodsThe levels of OTA contamination in 1 520 food samples collected in Shanghai from 2022 to 2023 were determined using liquid chromatography-tandem mass spectrometry. An exposure assessment model was developed based on the dietary consumption levels of pregnant women from the 2016‒2017 Shanghai Pregnant Women Dietary Monitoring Survey to calculate the estimated daily intake (EDI) of OTA, the margin of exposure for non-carcinogenic toxicity (MOE1), and the margin of exposure for carcinogenic toxicity (MOE2). An MOE1 greater than 200 and an MOE2 greater than 10 000 indicate that the non-carcinogenic toxicity and carcinogenic toxicity resulting from exposure are negligible, respectively. For samples with OTA contamination levels below the limit of detection (LOD), which accounted for more than 80% of the samples, the OTA levels were assigned values of 0 and LOD, respectively, for subsequent calculations. ResultsThe detection rates of OTA in cereals, nuts, dried fruits, and alcohol samples collected in 2022 were 2.03%, 0, 0, and 0, respectively. The OTA detection rates in cereals, nuts, dried fruits, beans, and alcohol samples collected in 2023 were 2.50%, 0.39%, 2.47%, 1.67%, and 13.33%, respectively. For pregnant women in Shanghai in 2022, simulation results indicated that when assigning a value of 0 and the LOD, theP50 values of EDI for dietary OTA exposure were 0.05 and 0.72 ng·(kg·d)-1, respectively, and the P95 values of EDI for dietary OTA exposure were 0.25 and 2.40 ng·(kg·d)-1, respectively. For pregnant women in Shanghai in 2023, the P50 values of EDI for dietary OTA exposure were 0.04 and 1.00 ng·(kg·d)-1, respectively, and the P95 values of EDI for dietary OTA exposure were 0.23 and 2.67 ng·(kg·d)-1, respectively, both substantially below the tolerable daily intake (TDI) for OTA [17 ng·(kg·d)-1]. The EDI for dietary OTA exposure in 100.0% of Shanghai pregnant women was lower than the TDI, indicating an overall low level of dietary OTA exposure among this population. For 100.0% of pregnant women, the MOE₁ for dietary OTA exposure exceeded 200. When assigned a value of 0, the MOE₂ for 100.0% of pregnant women in both 2022 and 2023 exceeded10 000. When assigned the LOD value, 72.3% and 81.8% of pregnant women in 2022 and 2023, respectively, had an MOE₂ exceeding 10 000. ConclusionFrom 2022 to 2023, samples of cereals, nuts, dried fruits, beans, and alcohol sold in Shanghai exhibited varying degrees of OTA contamination. The overall EDI of OTA exposure among pregnant women in Shanghai remained at a low level. The non-carcinogenic and carcinogenic risks associated with OTA exposure were generally low and at controllable levels.
2.Timosaponin BⅡ Combined with Icariin Maintains Osteoclast-osteoblast Coupling by Restoring Yin-Yang Balance
Zaishi ZHU ; Zeling HUANG ; Weiye CAI ; Hua CHEN ; Boen SONG ; Yue LU ; Qing LU ; Xiaofeng SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):48-57
ObjectiveTo explore the effect of timosaponin BⅡ (TBⅡ) combined with icariin (ICA) on osteoclast (OC)-osteoblast (OB) coupling and decipher the mechanism from the cellular level. MethodsThe cell counting kit-8 (CCK-8) was used to assess the effects of different concentrations of TBⅡ and different concentrations of TBⅡ+ICA on the growth of RAW264.7 cells. Soluble receptor activator of nuclear factor-κB ligand (sRANKL) was used to induce the differentiation of RAW264.7 pre-osteoclasts into osteoclasts. The cells were allocated into sRANKL, TBⅡ (1, 5, 10 μmol·L-1), and TBⅡ+ICA groups. Tartrate-resistant acid phosphatase staining was performed to assess the effects of TBⅡ and TBⅡ+ICA on osteoclast differentiation. Real-time quantitative polymerase chain reaction (Real-time PCR) was conducted to examine the effects of TBⅡ+ICA on the expression of key genes involved in osteoclast differentiation and osteoclast-derived coupling factors. The osteogenic differentiation conditioned medium mixed with osteoclast supernatant was used to induce osteogenic differentiation of MC3T3-E1 cells. Alkaline phosphatase staining and alizarin red S staining were employed to determine the effect of TBⅡ+ICA on osteogenic differentiation. Real-time PCR was employed to evaluate the effects of conditioned medium on key genes involved in osteogenic differentiation. ResultsTBⅡ at 1, 5, 10 μmol·L-1 had no significant effect on the cell survival rate. Compared with the sRANKL group, TBⅡ inhibited osteoclast differentiation in a dose-dependent manner and achieved the best effect at 10 μmol·L-1 (P<0.01). Compared with the sRANKL group, different concentrations of TBⅡ down-regulated the mRNA levels of osteoclast differentiation-related genes c-Fos, RANK, and RANKL (P<0.05). None of 10 μmol·L-1 TBⅡ, 10 μmol·L-1 TBⅡ+10-4 μmol·L-1 ICA, or 10 μmol·L-1 TBⅡ+10-3 μmol·L-1 ICA affected the viability of RAW264.7 cells. TBⅡ and/or ICA inhibited osteoclast differentiation (P<0.01), and TBⅡ + ICA had the best effect (P<0.01). Compared with the sRANKL group, TBⅡ and/or ICA down-regulated the mRNA levels of c-Fos, RANK, and RANKL (P<0.05). The single application of TBⅡ and ICA had no significant effect on the mRNA levels of Wnt10b, Cthrc1, and C3a, while TBⅡ+ICA exerted up-regulating effects (P<0.05). Compared with those in the blank group, the bone differentiation and mineralization abilities of the normal osteogenic induction group and each osteogenic induction + osteoclast supernatant group were improved (P<0.01). Compared with the blank group, the normal osteogenic induction group and the osteogenic induction + osteoclast supernatant group showed up-regulated mRNA levels of Runx2 and OCN (P<0.01). ConclusionTBⅡ+ICA can inhibit osteoclast differentiation, maintain the normal osteoclast-osteoblast coupling, and promote osteogenic differentiation.
3.Deoxynivalenol contamination in cereals and bakery products in Shanghai and dietary exposure assessment in pregnant women
Kailin LI ; Baozhang LUO ; Renjie QI ; Hua CAI ; Xia SONG ; Jingjin YANG ; Danping QIU ; Zhenni ZHU ; Yi HE ; Hong LIU
Journal of Environmental and Occupational Medicine 2025;42(10):1170-1176
Background Deoxynivalenol (DON), a priority contaminant for food safety risk monitoring, is produced by Fusarium spp. infesting crops, and its common derivatives are 3-acetyl-DON (3A-DON) and 15-acetyl-DON (15A-DON), which have been shown to possess gastrointestinal toxicity, immunotoxicity, reproductive toxicity, and cytotoxicity. Due to the stable physicochemical properties of the DON family of toxins (DONs), they cannot be effectively removed during food processing, thus following the food chain, entering the human body, and posing health risks. Objective To understand the contamination status of DONs in commercial foods (cereals and bakery products) in Shanghai in 2022–2023, and to assess the exposure risk of DONs in pregnant women by combining their dietary consumption data. Methods Liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to determine the contamination level of DONs in 1 100 food samples (cereals and baked goods) collected in 2022 and 944 samples collected in 2023 from Shanghai. The dietary monitoring data of pregnant women in Shanghai from 2016 to 2017 were adopted. The monitoring employed the food frequency questionnaire distributed among pregnant women through a combination of online telephone enquiry and offline on-site face-to-face survey to estimate their food consumption levels. An exposure assessment model was established to calculate the exposure level to DONs, and the probability distribution of the DONs exposure level in the pregnant women group in Shanghai was obtained by applying @Risk 7.5 software and simulating the calculation according to the Monte Carlo principle. With reference to the tolerable daily intake (TDI) of DONs [1.00 µg·(kg·d)−1] proposed by the Joint FAO/WHO Expert Committee on Food Additives, the risk of exposure to DONs from commercial cereals and bakery products in pregnant women in Shanghai was assessed. Results DONs were detected in cereal and bakery samples collected in 2022 and 2023 with different levels of contamination. The level of DONs in cereal foods in 2023 (mean: 36.33 µg·kg−1) decreased compared to 2022 (mean: 23.64 µg·kg−1). However, the positive rate (71.67%) and level (mean: 51.22 µg·kg−1) of DONs in bakery products increased significantly compared with 2022 (positive rate: 10.00%, mean: 24.39 µg·kg−1). The mean consumption of cereals in 783 pregnant women was 222.48 g·d−1 and the mean consumption of bakery products was 36.07 g·d−1, and there was no statistically significant difference in the intake of all types of cereals and bakery products across the early, middle, and late stages of pregnancy. The modelled intakes of DONs via commercial cereals and bakery products for pregnant women in Shanghai were calculated to be 0.20 and 0.57 µg·(kg·d)−1 in 2022 for the mean level and the 95th percentile level, respectively, and 0.16 µg·(kg·d)−1 and 0.35 µg·(kg·d)−1 in 2023, respectively. The results of the health risk assessment showed that pregnant women in Shanghai had 2.6% and 1.4% probability of exposure to DONs from cereal consumption in 2022 and 2023, respectively. Conclusion The risk of exposure of pregnant women in Shanghai to DONs via commercial cereals and bakery products is relatively low (1.4%-2.6%). However, considering the physical sensitivity of pregnant women, they should avoid consuming moldy grains and appropriately reduce intake of bakery products.
4.Effect of liposome binding antisense oligonucleotide BP1003 on albumin-bound paclitaxel sensitivity in pancreatic cancer cells by inhibiting STAT3
Hua FU ; Guochao ZHOU ; Rongmin CAI ; Xin SONG ; Dinghua YANG
China Oncology 2025;35(5):440-448
Background and purpose:The resistance of pancreatic cancer to albumin-bound paclitaxel affects the therapeutic effect and prognosis.Signal transducer and activator of transcription 3(STAT3)is one of the important molecules regulating the chemotherapy sensitivity of cancer cells.The liposome BP1003 targeting the antisense oligonucleotide of STAT3 mRNA can inhibit the expression of STAT3 and increase the chemotherapy sensitivity.However,the effect of BP1003 on the sensitivity of pancreatic cancer cells to albumin-bound paclitaxel remains unclear.The purpose of this study was to investigate the effects of liposome binding antisense oligonucleotide BP1003 on albumin-bound paclitaxel sensitivity in pancreatic cancer cells by inhibiting STAT3.Methods:Pancreatic cancer cell lines PANC-1 and ASPC-1 were cultured.They were divided into control group(without drugs),BP1003 group(200 μg/mL BP1003 intervention),different concentrations of albumin-bound paclitaxel group(5,10,20 nmol/L albumin-bound paclitaxel intervention),BP1003+different concentrations of albumin-bound paclitaxel group(200 μg/mL BP1003 combined with 5,10,20 nmol/L albumin-bound paclitaxel intervention).The proliferation viability,apoptotic rate and the protein expression levels of STAT3,STAT4,STAT6,Bcl-2,Bax and c-Myc were detected.The transplanted tumor model was established by subcutaneous injection of PANC-1 and ASPC-1 cell suspension in nude mice,which were divided into control group(normal saline intervention),BP1003 group(25 mg/kg BP1003 intervention,once every 2 weeks)and albumin-bound paclitaxel group(10 mg/kg albumin-bound paclitaxel,once a week),BP1003+albumin-bound paclitaxel group(25 mg/kg BP1003 intervention,once every 2 weeks combined with 10 mg/kg albumin-bound paclitaxel,once a week).Four weeks later,the graft volume and mass were measured,and the protein expression levels of STAT3,Bcl-2,Bax and c-Myc were detected.Results:The apoptotic rate and the protein expression levels of Bax of PANC-1 and ASPC-1 cells in BP1003 group and albumin-bound paclitaxel group were higher than those in the control group,while the proliferation viability and protein expression levels of STAT3,Bcl-2 and c-Myc were lower than those in control group(P<0.05).There was no significant difference in the expression levels of STAT4 and STAT6 in PANC-1 and ASPC-1 cells between BP1003 group and the control group(P>0.05).The apoptotic rate and the protein expression levels of Bax of PANC-1 and ASPC-1 cells in BP1003+different concentrations of albumin-bound paclitaxel groups were higher than those in different concentrations of albumin-bound paclitaxel groups,and the proliferation viability and protein expression levels of STAT3,Bcl-2 and c-Myc were lower than those in different concentrations of albumin-bound paclitaxel groups(P<0.05).The volume and mass of transplanted tumor and the protein expression levels of STAT3,Bcl-2 and c-Myc of nude mice in BP1003 group,albumin-bound paclitaxel group and BP1003+albumin-bound paclitaxel group were all lower compared with the control group,the protein expression level of Bax was higher compared with the control group(P<0.05),and the above changes in BP1003+albumin-bound paclitaxel group were more significant compared with BP1003 and albumin-bound paclitaxel group.Conclusion:BP1003 increases the sensitivity of pancreatic cancer cells to albumin-bound paclitaxel by inhibiting the expression of STAT3.
5.Research on the mechanism of Sini Powder regulating the HPA axis and inflammatory levels to ameliorate depression-like behaviors and inhibiting tumor proliferation in liver cancer
Xiaojun CAI ; Yuwei SONG ; Renyi YANG ; Chengjing HU ; Hua LIU ; Chong ZHONG ; Jing LI
Journal of Beijing University of Traditional Chinese Medicine 2025;48(11):1507-1518
Objective To investigate the effects of Sini Powder on serum hypothalamic-pituitary-adrenal(HPA)axis-related hormones and inflammatory factors in liver cancer mice with comorbid depression,and to evaluate its effect on depressive behavior and tumor proliferation activity.Methods Forty-eight specific pathogen-free female C57BL/6 mice were randomly assigned to either a blank(n=8)or model group(n=40).The modeling group was subjected to chronic unpredictable mild stress(CUMS)for six weeks.Both groups underwent orthotopically transplanted liver tumor surgery at the end of the fourth week of CUMS treatment.At the end of the sixth week of CUMS treatment,color Doppler ultrasonography was used to observe tumor formation in the orthotopic transplantation liver tumors,and the tail suspension test was used to assess depressive behavior.Non-tumor-bearing and deceased mice were excluded.The remaining model group mice were stratified by tail suspension immobility time and randomly assigned to the following groups:model group(distilled water),Fluoxetine group(5.0 mg/kg),and Sini Powder low-dose,medium-dose,and high-dose groups(5.2,10.4,and 20.8 g/kg,respectively),with six mice per group.The treatments were administered once daily for 21 consecutive days.After treatment,depressive behaviors were assessed using the open field,tail suspension,and forced swimming tests.The proliferation status of the orthotopic liver transplantation tumor was evaluated by measuring the size of the tumor,observing pathological changes in the tumor tissue through hematoxylin and eosin staining,and detecting the positive cell rate of proliferating cell nuclear antigen(Ki-67)in the tumor tissue using immunohistochemistry.The levels of HPA axis-related hormones in serum,such as corticotropin-releasing hormone(CRH),adrenocorticotropic hormone(ACTH),corticosterone(CORT),as well as inflammatory factors such as tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)were measured using an enzyme-linked immunosorbent assay.Western blotting was used to assess mitogen-activated protein kinase(MAPKs)phosphorylation and the expression of nuclear factor-κB(NF-κB),NOD-like receptor family pyrin domain-containing receptor 3(NLRP3),and cysteine aspartic protease-1(Caspase-1)in orthotopic tumors.Results Compared with the blank group,the model group showed reduced total distance traveled in open field test,prolonged immobility times in the tail suspension and forced swimming tests(P<0.05,P<0.01),indicating successful establishment of the liver cancer with comorbid depression mice model.Also,the model group showed increased orthotopic tumor volume(P<0.01),and elevated serum CRH,ACTH,CORT,TNF-α,IL-1β,and IL-6 levels(P<0.01).The phosphorylation of MAPKs in tumor tissues was suppressed(P<0.01),while NF-κB,NLRP3,and Caspase-1 expression levels were downregulated(P<0.01).Compared with the model group,Sini Powder medium-and high-dose groups exhibited increased total distance traveled in the open field test(P<0.05),reduced forced swimming test and prolonged total distance traveled in open field test(P<0.01),while Sini Powder high-dose group showed reduced immobility times in the tail suspension test(P<0.05).Also,Sini Powder low-dose,medium-dose,and high-dose groups showed slower tumor growth,histological changes,including vacuolization and necrosis,decreased Ki-67 positive cell rate(P<0.01),and reduced serum CRH,ACTH,CORT,TNF-α,IL-1β,and IL-6 levels(P<0.05).Additionally,the phosphorylation of MAPKs in tumor tissues was suppressed(P<0.01),and NF-κB,NLRP3,and caspase-1 expression levels were downregulated(P<0.01).Conclusion Sini Powder may alleviate depressive behaviors and suppress tumor proliferation activity in liver cancer mice with comorbid depression by modulating MAPKs activation,inhibiting NF-κB,NLRP3,and Caspase-1 expressions,and reducing serum inflammatory factors and HPA axis-related hormones levels.
6.Association of higher serum follicle-stimulating hormone levels with successful microdissection testicular sperm extraction outcomes in nonobstructive azoospermic men with reduced testicular volumes.
Ming-Zhe SONG ; Li-Jun YE ; Wei-Qiang XIAO ; Wen-Si HUANG ; Wu-Biao WEN ; Shun DAI ; Li-Yun LAI ; Yue-Qin PENG ; Tong-Hua WU ; Qing SUN ; Yong ZENG ; Jing CAI
Asian Journal of Andrology 2025;27(3):440-446
To investigate the impact of preoperative serum follicle-stimulating hormone (FSH) levels on the probability of testicular sperm retrieval, we conducted a study of nonobstructive azoospermic (NOA) men with different testicular volumes (TVs) who underwent microdissection testicular sperm extraction (micro-TESE). A total of 177 NOA patients undergoing micro-TESE for the first time from April 2019 to November 2022 in Shenzhen Zhongshan Obstetrics and Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital, Shenzhen, China) were retrospectively reviewed. The subjects were divided into four groups based on average TV quartiles. Serum hormone levels in each TV group were compared between positive and negative sperm retrieval subgroups. Overall sperm retrieval rate was 57.6%. FSH levels (median [interquartile range]) were higher in the positive sperm retrieval subgroup compared with the negative outcome subgroup when average TV was <5 ml (first quartile [Q1: TV <3 ml]: 43.32 [17.92] IU l -1 vs 32.95 [18.56] IU l -1 , P = 0.048; second quartile [Q2: 3 ml ≤ TV <5 ml]: 31.31 [15.37] IU l -1 vs 25.59 [18.40] IU l -1 , P = 0.042). Elevated serum FSH levels were associated with successful micro-TESE sperm retrieval in NOA men whose average TVs were <5 ml (adjusted odds ratio [OR]: 1.06 per unit increase; 95% confidence interval [CI]: 1.01-1.11; P = 0.011). In men with TVs ≥5 ml, larger TVs were associated with lower odds of sperm retrieval (adjusted OR: 0.84 per 1 ml increase; 95% CI: 0.71-0.98; P = 0.029). In conclusion, elevated serum FSH levels were associated with positive sperm retrieval in micro-TESE in NOA men with TVs <5 ml. In men with TV ≥5 ml, increases in average TVs were associated with lower odds of sperm retrieval.
Humans
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Male
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Azoospermia/surgery*
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Sperm Retrieval/statistics & numerical data*
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Adult
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Follicle Stimulating Hormone/blood*
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Retrospective Studies
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Testis/pathology*
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Microdissection
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Organ Size
7.Clinical efficacy of 3 surgical methods for spontaneous supratentorial intracerebral hemorrhage
Ping SONG ; Zhiyang LI ; Pan LEI ; Qiuwei HUA ; Lun GAO ; Hongxiang JIANG ; Long ZHOU ; Hui YE ; Qianxue CHEN ; Qiang CAI
Chinese Journal of Neuromedicine 2025;24(2):154-162
Objective:To investigate the clinical efficacy and major complications (postoperative hemorrhage and cerebral edema) of 3 surgical methods in spontaneous supratentorial intracerebral hemorrhage (SSICH).Methods:A retrospective analysis was performed; 294 patients with SSICH admitted to Department of Neurosurgery, Renmin Hospital of Wuhan University from December 2018 to October 2021 were selected. According to different surgical methods, these patients were divided into neuroendoscopic hematoma removal group ( n=126), stereotactic drilling and drainage group ( n=98), and craniotomy hematoma removal group ( n=70). The surgical efficacy and complications in the 3 groups were analyzed, and the postoperative residual hematoma and edema volumes were quantitatively calculated based on 3D Slicer software. Results:The hematoma evacuation rate in the neuroendoscopic hematoma removal group, stereotactic drilling and drainage group, and craniotomy hematoma removal group was 86.25%±2.27%, 44.45%±3.61%, and 75.45%±2.89%, respectively; Glasgow coma Scale scores at discharge were 13.51±1.28, 11.24±2.17 and 10.25±2.56, respectively; postoperative hemorrhage incidence was 16.1%, 26.0% and 22.9%, respectively; postoperative residual hematoma volume was (18.90±12.33) mL, (25.75±11.43) mL and (22.91±7.93) mL, and postoperative peak edema volume was (37.43±11.07) mL, (39.54±9.43) mL, and (42.26±10.94) mL, respectively; percentage of patients with peak edema on 3-5 days after surgery was 31.0%, 65.3% and 68.6%; the diameter of edema zone was (20.04±2.98) mm, (24.12±5.85) mm and (23.59±3.81) mm, respectively, on 7 days after surgery; percentage of patients with edema resolution was 45.2%, 24.5%, 42.9% and 76.2%, 57.1%, 62.9%, respectively, on 9-11 days and 12-14 days after surgery; these indexes in the neuroendoscopic hematoma removal group were significantly different compared with those in the other two groups ( P<0.05). Conclusion:Compared with stereotactic drilling and drainage or craniotomy hematoma removal, neuroendoscopic surgery can effectively remove the hematoma and reduce the occurrences of postoperative hemorrhage and brain edema.
8.Research on the mechanism of Sini Powder regulating the HPA axis and inflammatory levels to ameliorate depression-like behaviors and inhibiting tumor proliferation in liver cancer
Xiaojun CAI ; Yuwei SONG ; Renyi YANG ; Chengjing HU ; Hua LIU ; Chong ZHONG ; Jing LI
Journal of Beijing University of Traditional Chinese Medicine 2025;48(11):1507-1518
Objective To investigate the effects of Sini Powder on serum hypothalamic-pituitary-adrenal(HPA)axis-related hormones and inflammatory factors in liver cancer mice with comorbid depression,and to evaluate its effect on depressive behavior and tumor proliferation activity.Methods Forty-eight specific pathogen-free female C57BL/6 mice were randomly assigned to either a blank(n=8)or model group(n=40).The modeling group was subjected to chronic unpredictable mild stress(CUMS)for six weeks.Both groups underwent orthotopically transplanted liver tumor surgery at the end of the fourth week of CUMS treatment.At the end of the sixth week of CUMS treatment,color Doppler ultrasonography was used to observe tumor formation in the orthotopic transplantation liver tumors,and the tail suspension test was used to assess depressive behavior.Non-tumor-bearing and deceased mice were excluded.The remaining model group mice were stratified by tail suspension immobility time and randomly assigned to the following groups:model group(distilled water),Fluoxetine group(5.0 mg/kg),and Sini Powder low-dose,medium-dose,and high-dose groups(5.2,10.4,and 20.8 g/kg,respectively),with six mice per group.The treatments were administered once daily for 21 consecutive days.After treatment,depressive behaviors were assessed using the open field,tail suspension,and forced swimming tests.The proliferation status of the orthotopic liver transplantation tumor was evaluated by measuring the size of the tumor,observing pathological changes in the tumor tissue through hematoxylin and eosin staining,and detecting the positive cell rate of proliferating cell nuclear antigen(Ki-67)in the tumor tissue using immunohistochemistry.The levels of HPA axis-related hormones in serum,such as corticotropin-releasing hormone(CRH),adrenocorticotropic hormone(ACTH),corticosterone(CORT),as well as inflammatory factors such as tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)were measured using an enzyme-linked immunosorbent assay.Western blotting was used to assess mitogen-activated protein kinase(MAPKs)phosphorylation and the expression of nuclear factor-κB(NF-κB),NOD-like receptor family pyrin domain-containing receptor 3(NLRP3),and cysteine aspartic protease-1(Caspase-1)in orthotopic tumors.Results Compared with the blank group,the model group showed reduced total distance traveled in open field test,prolonged immobility times in the tail suspension and forced swimming tests(P<0.05,P<0.01),indicating successful establishment of the liver cancer with comorbid depression mice model.Also,the model group showed increased orthotopic tumor volume(P<0.01),and elevated serum CRH,ACTH,CORT,TNF-α,IL-1β,and IL-6 levels(P<0.01).The phosphorylation of MAPKs in tumor tissues was suppressed(P<0.01),while NF-κB,NLRP3,and Caspase-1 expression levels were downregulated(P<0.01).Compared with the model group,Sini Powder medium-and high-dose groups exhibited increased total distance traveled in the open field test(P<0.05),reduced forced swimming test and prolonged total distance traveled in open field test(P<0.01),while Sini Powder high-dose group showed reduced immobility times in the tail suspension test(P<0.05).Also,Sini Powder low-dose,medium-dose,and high-dose groups showed slower tumor growth,histological changes,including vacuolization and necrosis,decreased Ki-67 positive cell rate(P<0.01),and reduced serum CRH,ACTH,CORT,TNF-α,IL-1β,and IL-6 levels(P<0.05).Additionally,the phosphorylation of MAPKs in tumor tissues was suppressed(P<0.01),and NF-κB,NLRP3,and caspase-1 expression levels were downregulated(P<0.01).Conclusion Sini Powder may alleviate depressive behaviors and suppress tumor proliferation activity in liver cancer mice with comorbid depression by modulating MAPKs activation,inhibiting NF-κB,NLRP3,and Caspase-1 expressions,and reducing serum inflammatory factors and HPA axis-related hormones levels.
9.Effect of liposome binding antisense oligonucleotide BP1003 on albumin-bound paclitaxel sensitivity in pancreatic cancer cells by inhibiting STAT3
Hua FU ; Guochao ZHOU ; Rongmin CAI ; Xin SONG ; Dinghua YANG
China Oncology 2025;35(5):440-448
Background and purpose:The resistance of pancreatic cancer to albumin-bound paclitaxel affects the therapeutic effect and prognosis.Signal transducer and activator of transcription 3(STAT3)is one of the important molecules regulating the chemotherapy sensitivity of cancer cells.The liposome BP1003 targeting the antisense oligonucleotide of STAT3 mRNA can inhibit the expression of STAT3 and increase the chemotherapy sensitivity.However,the effect of BP1003 on the sensitivity of pancreatic cancer cells to albumin-bound paclitaxel remains unclear.The purpose of this study was to investigate the effects of liposome binding antisense oligonucleotide BP1003 on albumin-bound paclitaxel sensitivity in pancreatic cancer cells by inhibiting STAT3.Methods:Pancreatic cancer cell lines PANC-1 and ASPC-1 were cultured.They were divided into control group(without drugs),BP1003 group(200 μg/mL BP1003 intervention),different concentrations of albumin-bound paclitaxel group(5,10,20 nmol/L albumin-bound paclitaxel intervention),BP1003+different concentrations of albumin-bound paclitaxel group(200 μg/mL BP1003 combined with 5,10,20 nmol/L albumin-bound paclitaxel intervention).The proliferation viability,apoptotic rate and the protein expression levels of STAT3,STAT4,STAT6,Bcl-2,Bax and c-Myc were detected.The transplanted tumor model was established by subcutaneous injection of PANC-1 and ASPC-1 cell suspension in nude mice,which were divided into control group(normal saline intervention),BP1003 group(25 mg/kg BP1003 intervention,once every 2 weeks)and albumin-bound paclitaxel group(10 mg/kg albumin-bound paclitaxel,once a week),BP1003+albumin-bound paclitaxel group(25 mg/kg BP1003 intervention,once every 2 weeks combined with 10 mg/kg albumin-bound paclitaxel,once a week).Four weeks later,the graft volume and mass were measured,and the protein expression levels of STAT3,Bcl-2,Bax and c-Myc were detected.Results:The apoptotic rate and the protein expression levels of Bax of PANC-1 and ASPC-1 cells in BP1003 group and albumin-bound paclitaxel group were higher than those in the control group,while the proliferation viability and protein expression levels of STAT3,Bcl-2 and c-Myc were lower than those in control group(P<0.05).There was no significant difference in the expression levels of STAT4 and STAT6 in PANC-1 and ASPC-1 cells between BP1003 group and the control group(P>0.05).The apoptotic rate and the protein expression levels of Bax of PANC-1 and ASPC-1 cells in BP1003+different concentrations of albumin-bound paclitaxel groups were higher than those in different concentrations of albumin-bound paclitaxel groups,and the proliferation viability and protein expression levels of STAT3,Bcl-2 and c-Myc were lower than those in different concentrations of albumin-bound paclitaxel groups(P<0.05).The volume and mass of transplanted tumor and the protein expression levels of STAT3,Bcl-2 and c-Myc of nude mice in BP1003 group,albumin-bound paclitaxel group and BP1003+albumin-bound paclitaxel group were all lower compared with the control group,the protein expression level of Bax was higher compared with the control group(P<0.05),and the above changes in BP1003+albumin-bound paclitaxel group were more significant compared with BP1003 and albumin-bound paclitaxel group.Conclusion:BP1003 increases the sensitivity of pancreatic cancer cells to albumin-bound paclitaxel by inhibiting the expression of STAT3.
10.Clinical effect of Huotujiji prescription on patients with asthenospermia of spleen-kidney yang-deficiency type
Yi-li CAI ; Hong-ping SHEN ; Li WANG ; Jia-yi SONG ; Ya-hua LIU ; Yi YU ; Xue-qin CHEN
National Journal of Andrology 2025;31(9):827-831
Objective:To observe the effectiveness and safety of Huotujiji prescription for patients with asthenospermia of spleen-kid-ney yang-deficiency.Methods:Patients with spleen-kidney-yang deficiency type of asthenospermia were divided into two groups by ran-domized control method.The patients in the control group were treated with L-carnitine oral solution alone.And the patients in experimental group were treated with Huotujiji prescription.Semen volume,sperm concentration,PR,TCM symptom score and spouse pregnancy were compared between the two groups before and after treatment.Results:A total of 115 patients were included in the study,with 55 in the ex-perimental group and 60 in the control group.In the experimental group,the sperm concentration before and after treatment were(160.71±53.7)× 106/mL,(187.19±41.89)× 106/mL,and PR were(20.37±9.42)%,(26.7±6.92)%,respectively.PR+NP were(32.06±8.49)%and(34.89±7.25)%.After the treatment,the sperm motility of both groups significantly improved compared to pre-treatment lev-els(P<0.05).And the experimental group's sperm concentration also showed a significant increase after the treatment(P<0.05).The pregnancy rate of spouses in the control group was 11.67%,which was 29.09%in the experimental group.The pregnancy rate of the spouses in the two groups showed a statistically significant difference(P<0.05).After 12weeks of treatment,the Traditional Chinese Medicine(TCM)symptom scores in the control group did not decrease significantly compared to those before treatment(P>0.05).In contrast,the TCM symptom scores in the experimental group decreased significantly after treatment(P<0.05).Moreover,compared with the control group,the TCM symptom scores of the experimental group decreased significantly after treatment(P<0.05).Conclusion:Huotujiji pre-scription can safely and effectively improve the sperm quality and vitality of patients with spleen-kidney-yang deficiency type of asthenosper-mia,improve the symptoms of patients,and increase the pregnancy rate of their spouses,which is worthy of clinical promotion.

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