1.Effect of Tongmai Kaiqiao Pills on Mitochondrial Biogenesis of Hippocampal Neurons in Rats with Vascular Cognitive Impairment Based on AMPK/PGC-1α Signaling Pathway
Luyao MA ; Yanjie LI ; Haoyuan LIU ; Yanjie BAI ; Ruoxing XING
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):125-134
ObjectiveTo observe the effects of Tongmai Kaiqiao pills on AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) signaling pathway and mitochondrial biogenesis in hippocampal tissue of rats with vascular cognitive impairment (VCI) and to investigate the potential mechanism of Tongmai Kaiqiao pills in improving cognitive impairment in rats with VCI. MethodsTwelve of 72 male SD rats were selected as the sham operation group, and the remaining rats were modelled using the modified 2VO method. The rats that were successfully modelled were divided into the model group, the high-dose group of Tongmai Kaiqiao pills (27.6 g·kg-1), the low-dose group of Tongmai Kaiqiao pills (13.8 g·kg-1), the combination group (27.6 g·kg-1 Tongmai Kaiqiao pills + 25 mg·kg-1 dorsomorphin), and the donepezil hydrochloride group (0.45 g·kg-1) according to the random number table method. After four weeks of continuous intraperitoneal injection of the corresponding drugs, the Morris water maze test was used to test the learning and memory ability of rats. Hematoxylin-eosin (HE) staining and Nissl staining were used to detect pathological changes in the hippocampus of the rats. The content of mitochondrial adenosine triphosphate (ATP) in the brain hippocampus was detected by colorimetry, and reactive oxygen species (ROS) level was detected in rat mitochondria by MitoSOX Red assay. Mitochondrial DNA copy number was detected by real-time fluorescent quantitative PCR (Real-time PCR). Pathological changes in mitochondria were observed by transmission electron microscopy (TEM), and AMPK, PGC-1α, phosphorylated AMP-activated protein kinase (p-AMPK), nuclear respiratory factor 1 (Nrf1), and mitochondrial transcription factor A (TFAM) protein expression in the hippocampus of the rats were detected by Western blot. ResultsCompared with those in the sham operation group, rats in the model group had a reduced number of platform crossings (P<0.01), significantly prolonged evasion latency (P<0.01), disorganized neuronal arrangement in the hippocampal region, widened gaps, and blurred nucleus membrane and nucleolus boundaries. The emergence of necrotic cells was visible. The color of the nissl bodies was light, and the number was reduced with severe loss. Mitochondria were atrophied, and cristae were lost. Severe damage was observed. The content of ROS was increased, and the level of ATP was decreased. mtDNA copy number decreased significantly (P<0.01), and the protein expression of p-AMPK, PGC-1α, Nrf1, and TFAM decreased (P<0.05, P<0.01). Compared with those in the model group, rats in the high-dose group of Tongmai Kaiqiao pills and donepezil hydrochloride group showed a shorter time to find the platform (P<0.01), increased number of platform crossings (P<0.01), restored mitochondrial morphology and structure of the hippocampal neurons, alleviated neuronal death, increased number of nissl bodies, weaken degree of injury, lower content of ROS, and significantly increased levels of ATP and number of copies of mtDNA (P<0.05, P<0.01). In addition, there was increased protein expression of p-AMPK, PGC-1α, Nrf1, and TFAM (P<0.05, P<0.01). Compared with the model group, the evasion latency was shortened in the low-dose group of Tongmai Kaiqiao pills (P<0.01), and the number of platform crossings was increased, but the difference was not statistically significant. The mitochondria were swollen and deformed, and the cristae became shorter and partially disappeared. The degree of damage did not improve significantly, and the number of nissl bodies was increased but not statistically significant. The ROS content decreased (P<0.01), but there was no significant difference in ATP level and mtDNA copy number. The protein expression of PGC-1α was increased (P<0.05), but there was no significant difference in the protein expression of p-AMPK, Nrf1, and TFAM, and the results were not statistically significant. Compared with the donepezil hydrochloride group, there was no significant change in the results of each assay in the high-dose group of Tongmai Kaiqiao pills, and the difference was not statistically significant. Compared with the high-dose group of Tongmai Kaiqiao pills, rats in the combination group had a significantly lower number of platform crossings (P<0.01), a significantly longer evasion latency (P<0.01), a reduced number of neuronal cells, disorganized tissue structure, swollen and blurred cell outlines, a significant reduction in the number of nissl bodies. Moreover, there was an increase in the content of ROS, a decrease in the level of ATP and the number of mtDNA copies (P<0.01), and a decrease in the expression of p-AMPK, PGC-1α, Nrf1, and TFAM (P<0.05). ConclusionTongmai Kaiqiao pills is able to improve cognitive function in rats by activating the AMPK/PGC-1α signaling pathway, promoting mitochondrial biogenesis, and attenuating pathological damage to neurons in the hippocampal region, thereby demonstrating its therapeutic potential.
2.Jiawei Chunze Decoction treats urinary retention after spinal cord injury in rats based on the regulation of endoplasmic reticulum stress apoptosis
Bochao ZHU ; Yanjie LI ; Hewei QIN ; Nannan ZHAO ; Haoyuan LIU ; Zhenhua XU ; Yupu WANG
Chinese Journal of Tissue Engineering Research 2025;29(2):371-378
BACKGROUND:Preliminary clinical observations found that Jiawei Chunze Decoction is an effective formula for clinical treatment of urinary retention after spinal cord injury.Animal experiments have found that the phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway is closely related to the degree of bladder dysfunction. OBJECTIVE:To further investigate the effects of Jiawei Chunze Decoction on bladder function and PI3K/Akt signaling pathway in rats with urinary retention. METHODS:Sixty female Sprague-Dawley rats were randomly divided into sham operation group,model group,Jiawei Chunze Decoction low-dose group,Jiawei Chunze Decoction high-dose group and agonist group.In the sham operation group,the spinal cord was exposed but not transected.In the other groups,the modified Hassan Shaker spinal cord transection method was used to prepare the model of sacral medullary injury.At 24 hours after modeling,the sham operation group and model group were intragastrically given equal volume of normal saline,Jiawei Chunze Decoction low-dose and high-dose groups were given Jiawei Chunze Decoction granules containing 14.4 and 28.8 g/kg,respectively,via intragastric administration for 4 weeks,and the agonist group was treated with an intraperitoneal injection of PI3K/Akt signaling pathway agonist 740Y-P at a dose of 0.02 mg/kg.After 4 weeks of treatment,the maximum bladder capacity,leakage point pressure and bladder compliance of rats in each group were detected by urine flow dynamics.The minimum bladder contraction tension and frequency of rats in each group were detected by detrusor pull test.The pathological changes of the rat bladder in each group were observed by hematoxylin-eosin staining.The concentrations of GRP78,CHOP and Caspase-12 in serum were detected by ELISA,and the mRNA and protein expressions of PI3K,Akt,GRP78,CHOP and Caspase-12 in bladder tissues were detected by RT-PCR and western blot,respectively. RESULTS AND CONCLUSION:Compared with the sham operation group,the maximum bladder volume,bladder compliance and minimum systolic tension of rats in the model group were increased(P<0.05),and the leakage point pressure and bladder contraction frequency were decreased(P<0.05);serum GRP78,CHOP,and Caspase-12 levels were also increased(P<0.05).The arrangement of bladder epithelial cells in the model group was disordered,and there was monocyte infiltration between cells,tissue edema,and detrusor tract atrophy.The mRNA and protein expressions of PI3K and Akt in bladder tissues were significantly decreased in the model group compared with the sham operation group,while those of GRP78,CHOP and Caspase-12 were increased(P<0.05).Compared with the model group,the maximum bladder volume,bladder compliance and minimum systolic tension of rats were decreased in the Jiawei Chunze Decoction low-dose,high-dose and agonist groups after 4 weeks of intervention(P<0.05),while the leakage point pressure and bladder contraction frequency were increased(P<0.05);serum GRP78,CHOP,Caspase-12 levels were decreased(P<0.05).The bladder epithelial cells in the three intervention groups were distributed evenly,arranged neatly,with less inflammatory cell infiltration and fuller detrusor muscle bundle.Compared with the model group,the mRNA and protein expressions of PI3K and Akt were increased in the three intervention groups,while those of GRP78,CHOP and Caspase-12 were decreased(P<0.05).The Jiawei Chunze Decoction high-dose group was better than the Jiawei Chunze Decoction low-dose group and shared the similar results with the agonist group.To conclude,Jiawei Chunze Decoction can improve the bladder function of rats with urinary retention after spinal cord injury,and the mechanism may be related to reducing the occurrence of endoplasmic reticulum stress in bladder tissue through the PI3K/Akt signaling pathway,and then alleviating apoptosis.
3.Traditional Chinese medicine monomer in treatment of neuroinflammation after spinal cord injury:effects of nuclear transcription factor kappa B signaling pathway
Zhenhua XU ; Yanjie LI ; Hewei QIN ; Haoyuan LIU ; Bochao ZHU ; Yupu WANG
Chinese Journal of Tissue Engineering Research 2025;29(3):590-598
BACKGROUND:Targeted therapy based on nuclear transcription factor kappa B signaling pathway to explore neuroinflammation is increasingly worth exploring,and the advantages of Chinese medicine such as many targets,wide range,rich mechanisms,and few side effects have great potential in the treatment of various diseases. OBJECTIVE:Based on the nuclear transcription factor kappa B signaling pathway,this paper systematically expounded and summarized the research progress of kaempferol,safflower yellow,baicalin,and triptolide in the treatment of neuroinflammation after spinal cord injury. METHODS:Search terms"spinal cord injury,inflammation,anti-inflammatory,traditional Chinese medicine monomer,monomeric compound,NF-κB signaling pathway,flavonoids,glycosides,phenols,esters,alkaloids"were searched in CNKI and PubMed databases.Totally 67 articles were finally included. RESULTS AND CONCLUSION:(1)The role of nuclear transcription factor kappa B signaling pathway in the nervous system is complex and diverse,which can regulate neutrophils,microglia,astrocytes,and macrophages,and mediate the occurrence and development of inflammation after injury.(2)The effects of traditional Chinese medicine monomers such as baicalin on the degradation of nuclear transcription factor kappa B inhibitory protein,the inhibition of phosphorylation process by safflowerin on nuclear transcription factor kappa B signaling pathway,and the inhibition of kaempferol on nuclear transcription factor kappa B signaling pathway p65 nuclear translocation can reduce the impact of inflammatory response on the body,thereby promoting the recovery of neurological function.(3)The nuclear transcription factor kappa B signaling pathway can promote inflammation and immune cell migration and activation in the early stage of injury,and can promote the repair of injury site and the occurrence of fibrosis in the middle and late stages of injury.Appropriate activation of the nuclear transcription factor kappa B signaling pathway can promote the release of inflammatory factors,improve the antioxidant capacity of cells,and promote the activation of immune cells,but the over-activated nuclear transcription factor kappa B signaling pathway can easily lead to the occurrence and continuation of chronic inflammation and the inhibition of apoptosis.(4)Future research can further explore how to accurately regulate the activation level of nuclear transcription factor kappa B signaling pathway,how to achieve precise intervention for nervous system inflammation and injury,and can also focus on the preparation of traditional Chinese medicine monomers and the mechanism of action of traditional Chinese medicine monomers on signaling pathways,in order to provide more effective treatment strategies for the rehabilitation and functional recovery of neurological diseases.
4.Effect of Modified Chunzetang on Bladder Fibrosis and Detrusor Function in Rats with Neurogenic Bladder Urinary Retention Induced by Spinal Cord Injury via Regulating NF-κB/TGF-β1 Signaling Pathway
Zhenhua XU ; Yanjie LI ; Yafeng REN ; Haoyuan LIU ; Bochao ZHU ; Juan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):95-103
ObjectiveTo investigate the therapeutic effect and mechanism of modified Chunzetang on bladder fibrosis and detrusor function in rats with neurogenic bladder urinary retention induced by spinal cord injury. MethodsIn this study, an improved Hassan Shaker spinal cord transection method was used to establish a model of neurogenic bladder urinary retention induced by spinal cord injury, and rats with a spinal cord injury behavior score of 0 were selected for follow-up experiments. The selected rats were randomly divided into a model group (normal saline gavage), low-dose traditional Chinese medicine (TCM) group (gavage of 14.4 g·kg-1 modified Chunzetang), high-dose TCM group (gavage of 28.8 g·kg-1 modified Chunzetang), positive drug group [intraperitoneal injection of 0.05 g·kg-1 nuclear transcription factor-κB (NF-κB) inhibitor pyrrolidine dithiocarbamate (PDTC)], and combination group (intraperitoneal injection of 0.05 g·kg-1 PDTC + gavage of 28.8 g·kg-1 modified Chunzetang). The rats in these groups were administrated with corresponding drugs once a day for four weeks. The BL-420s biofunction acquisition system was used in the experiment to calculate the urodynamic indexes, and the isolated bladder was quickly weighed. The detrusor traction experiment was used to record the minimum bladder contraction tension and frequency in each group. The pathological morphology and tissue fibrosis of detrusor in each group observed by Hematoxycin-eosin (HE) staining and Masson staining were compared. The expression level of α-smooth muscle actin (α-SMA) was detected by immunohistochemistry. Western blot was used to detect the protein expression of NF-κB p65, nuclear transcription factor-κB suppressor protein α (IκBα), transforming growth factor-β1 (TGF-β1), type Ⅰ collagen (ColⅠ), and type Ⅲ collagen (ColⅢ) in bladder tissue of rats in each group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the changes in serum levels of IL-6, IL-1β, and TNF-α. ResultsCompared with that in the sham operation group, the pressure at the urinary leakage point in the model group decreased (P<0.01), and the bladder mass, bladder contractile tension, maximum bladder capacity, and bladder compliance increased (P<0.05,P<0.01). HE staining showed that the arrangement of bladder epithelial cells was disordered, and the pathological manifestations such as mucosa and myometria neutrophil infiltration were obvious. The lamina propria structure was destroyed, and the muscle fiber arrangement was disordered. The interstitial widening and tissue edema were obvious. Masson staining showed that the bladder wall of the model group had more collagen fiber deposition, and the degree of detrusor fibrosis was more severe. The content of detrusor in the visual field was reduced. At the same time, the protein expressions of NF-κB p65, TGF-β1, IκBα, ColⅠ, and ColⅢ in bladder tissue of rats in the model group were significantly increased (P<0.01), and the serum levels of IL-6, IL-1β, and TNF-α were significantly increased (P<0.05). Compared with that in the model group, the pressure at the urinary leakage point in the modified Chunzetang and positive drug groups was increased (P<0.05), and the wet bladder weight, minimum bladder contractile tension, maximum bladder capacity, and bladder compliance were restored (P<0.05, P<0.01). HE and Masson showed that the bladder epithelial cells were relatively neatly arranged, and the structure of the bladder lamina propria was relatively stable. The detrusor bundles were arranged in an orderly manner, and the interstitium was narrow. The degree of tissue edema was relatively low, and the degree of bladder detrusor fibrosis in the modified Chunzetang and positive drug groups was reduced, while the degree of bladder detrusor fibrosis in the positive drug group and combination groups was not obvious. The results of Western blot showed that the expression of NF-κB p65, IκBα, TGF-β1, ColⅠ, and ColⅢ in bladder tissue, as well as the serum levels of IL-6, IL-1β, and TNF-α in modified Chunzetang and positive drug groups were significantly lower, and the expression of bladder tissue-related proteins and the serum levels of IL-6, IL-1β, and TNF-α in the TCM groups decreased significantly with the increase in dose (P<0.05). The results of immunohistochemistry suggested that modified Chunzetang could fully affect the expression of α-SMA in bladder tissue. ConclusionModified Chunzetang can inhibit collagen deposition in bladder tissue of rats with urinary retention induced by spinal cord injury, delay the occurrence and development of bladder fibrosis, and protect the normal contractile function of bladder detrusor, and its mechanism may be related to inhibiting the NF-κB/TGF-β1 signaling pathway, reducing the production of NF-κB p65, IκBα, TGF-β1, ColⅠ, ColⅢ, and other related proteins, and protecting the muscle strength of detrusor.
5.Comparison of efficacy and influential factors between tislelizumab and sintilimab in the treatment of advanced NSCLC
Yan PAN ; Shengxi YANG ; Jiaxin LIU ; Haoyuan QIAN ; Wenlian TU
China Pharmacy 2025;36(24):3096-3101
OBJECTIVE To compare the efficacy and safety of chemotherapy combined with tislelizumab or sintilimab in patients with advanced non-small cell lung cancer (NSCLC), and to analyze the influential factors of prognostic. METHODS A retrospective study was conducted on 163 patients with advanced NSCLC who received chemotherapy combined with tislelizumab or sintilimab at the First People’s Hospital of Yunnan Province from September 1, 2021 to November 30, 2024. Among them, there were 90 patients in the tislelizumab group and 73 patients in the sintilimab group. The objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), and overall survival (OS) of two groups were observed, and the occurrence of adverse drug reactions in patients was evaluated. Kaplan-Meier method was used to plot PFS and OS survival curves, Log-rank test was applied for univariate analysis, and Cox regression model was used to evaluate the independent prognostic factors of PFS and OS. RESULTS The median PFS of patients in the tislelizumab group and the sintilimab group were 14.14 months (95%CI of 10.95-17.33) and 10.95 months (95%CI of 8.75-13.15), respectively. The median OS was 25.89 months (95%CI of 22.67-29.11) and 24.25 months (95%CI of 19.34-29.16), with ORR of 45.56% and 49.32%, DCR of 94.44% and 90.41%, and the incidence of adverse drug reactions of 84.44% and 79.45%, respectively, the differences were not statistically significant (P>0.05). Age ≥60 years (HR=1.542, 95%CI of 1.044-2.278, P=0.029) and systemic immune inflammatory nutritional index (SIINI)> 116.58 (HR=1.541, 95%CI of 1.058-2.245, P=0.024) were risk factors for PFS in NSCLC patients receiving immune checkpoint inhibitor therapy; the use of antibiotics may affect the overall survival of patients (P=0.001). CONCLUSIONS The efficacy and safety of chemotherapy combined with tislelizumab or sintilimab for advanced NSCLC are comparable; age≥60 years and SIINI >116.58 are risk factors for PFS in NSCLC patients, and the use of antibiotics may affect the patients’ OS.
6.Application of tourniquet in amputation for lower limb gangrene
Gang TIAN ; Haoyuan ZHANG ; Jiajia SONG ; Peng TANG ; Hongwei MIN ; Rui GU ; Kemin LIU
Chinese Journal of Rehabilitation Theory and Practice 2024;30(5):560-564
Objective To explore the efficacy and safety of using a tourniquet in amputation for lower limb gangrene. Methods All patients underwent amputation for lower limb gangrene from January,2009 to June,2023 in Beijing Bo'ai Hospital were reviewed,involving 41 patients with a total of 44 limbs,and they were divided into non-tourniquet group(n=28)and tourniquet group(n=16)according to whether a tourniquet was used during surgery.The am-putation field clearness,surgical bleeding,incision healing,reoperation rate within 30 days post-operation,intra-operative blood pressure and heart rate,and operation time were compared. Results The amputation field was clearer in the tourniquet group(χ2=42.385,P<0.001),with less bleeding(Z=-2.082,P<0.05).No tourniquet-related local damages,such as nerve damage and skin injuries,was observed in the limbs using tourniquets.The incidence of grade A of incision healing was not significantly different(χ2=0.028,P=0.624). Conclusion Application of tourniquet can improve the amputation field clearness and reduce bleeding during amputation for lower limb gangrene,without affecting incision healing.
7.Influence of clinical and rehabilitation characteristics on prognosis of diabetic foot amputees:a systematic review
Haoyuan ZHANG ; Gang TIAN ; Xuefeng LI ; Hongjiang LI ; Hongwei MIN ; Peng TANG ; Rui ZHANG ; Rui GU ; Kemin LIU
Chinese Journal of Rehabilitation Theory and Practice 2024;30(11):1281-1290
Objective To analyze the impact of different clinical and rehabilitation characteristics on the prognosis of diabetic foot amputees. Methods Related literatures were searched in CNKI,Wanfang Data,PubMed,Cochrane Library and Google Scholar from establishment to August,2024.The literatures were screened and extracted by two researchers independent-ly,the Newcastle-Ottawa Scale(NOS)and the evaluation criteria recommended by Agency for Healthcare Re-search and Quality(US)were used for quality evaluation,and literatures with above medium quality were includ-ed,and a systematic review was conducted. Results A total of 17 articles involving 9 239 subjects were included,in which three were Chinese,and 14 were English.The study designs were case-control study,cohort study and cross-sectional study.They mainly came from the fields of rehabilitation medicine,orthopedics,sports medicine and disability studies,and were published between 1998 to 2023.Clinical and rehabilitation characteristics related to the prognosis of diabetic foot amputees includ-ed amputation level,socioeconomic determinants(educational attainment,economic status,social participation,etc.),psychological states(anxiety,depression,etc.)and physiological factors(age,gender,pain,prosthetic limb usage,and ambulatory capacity,etc.).These different characteristics could affect the quality of life of diabetic foot amputees,and even lead to re-amputation or death. Conclusion Factors of amputation level,socioeconomic status,psychological status and physiological status are impor-tant for poor prognosis in diabetic foot amputees.Controlling the above factors can effectively reduce the re-am-putation rate and mortality,and improve the quality of life in diabetic foot amputees,thus improving their progno-sis,and promoting functional rehabilitation.
8.Establishment of Risk-Prediction Model for Axillary Lymph-Node Metastasis in Microinvasive Breast Cancer Based on SEER Database
Chenghao LIU ; Ting LU ; Fang QIAN ; Yuanbing XU ; Chaohua HU ; Haoyuan SHEN
Cancer Research on Prevention and Treatment 2024;51(9):750-755
Objective To analyze the factors influencing axillary lymph-node metastasis(ALNM)in microinvasive breast cancer(MIBC)patients,as well as to establish the risk-prediction model of ipsilateral ALNM in MIBC patients.Methods A total of 4475 primary female MIBC diagnosed by pathology from 2010 to 2015 were searched and screened from the SEER database.The obtained data were used to establish a prediction model for ALNM of MIBC.A total of 2266 primary female MIBC patients diagnosed by pathology from 2018 to 2020 in the SEER database were screened as the external validation cohort.The clinicopathological data of the enrolled MIBC patients were collected.Univariate analysis was used to screen out the factors affecting ALNM in MIBC patients.Statistically significant variables in univariate analysis were included in multivariate logistic regression analysis.The independent factors influencing ALNM in MIBC patients were screened out,and a nomogram was established.The area under the curve(AUC)was calculated by plotting the ROC curve.After plotting the calibration curve,the model was evaluated by Hosmer-Lemeshow goodness-of-fit test.Results A total of 309 patients were diagnosed with ipsilateral ALNM among the 6741 MIBC patients,accounting for about 4.58%.Univariate analysis of the modeling group showed that age,ethnicity,histological grade,pathological type,molecular subtype,and lateral side were associated with ALNM in MIBC patients(P<0.05).Results of multivariate analysis showed that the risk of ALNM was higher in MIBC patients≤40 years old,black people,histological grade Ⅱand Ⅲ,and primary right side(P<0.05).Subtype is an independent factor influencing ALNM in MIBC patients.However,the difference in ALNM risk was not statistically significant between the subtype of HR+HER2+,HR-HER2+,HR-HER2-and HR+HER2-subtypes.The AUC of the modeling group was 0.716(95%CI:0.682-0.750),the best cut-off value was 0.045,the sensitivity was 0.733,and the specificity was 0.608.The newly established nomogram model was used for the validation cohort,and its AUC was 0.722(95%CI:0.667-0.777).The P values of the Hosmer-Lemeshow goodness-of-fit test of the calibration curves in the modeling and validation groups exceeded 0.05.Conclusion The risk-prediction model of ALNM in MIBC patients established by the SEER database has good predictive ability and can thus be expected to serve as a reference for clinical practice.
9.Effects of clinical treatment decisions on long-term survival outcomes of locally advanced breast cancer with different molecular subtypes based on the SEER database
Fang QIAN ; Haoyuan SHEN ; Chunyan DENG ; Tingting SU ; Chaohua HU ; Chenghao LIU ; Yuanbing XU ; Qingqing YANG
Journal of Clinical Surgery 2024;32(10):1044-1049
Objective To explore the impact of clinical treatment decisions on the long-term survival of different molecular subtypes of locally advanced breast cancer(LABC),and to promote the development of more effective and individualized treatment regimens for LABC.Methods The cases of LABC diagnosed by pathology from 2010 to 2015 were searched in the database.Breast cancer-specific survival(BCSS)and overall survival(OS)were estimated by plotting Kaplan-Meier curves.The log rank test(Mantel-Cox)was used to analyze the difference between the groups,and the benefit population of LABC was determined after for age,TNM stage,grade,treatment methods.Results The 5-year OS and BCSS were 77.43%and 84.34%in breast-conserving,and 68.03%and 76.90%in mastectomy,respectively.The 5-year OS and BCSS of Luminal A LABC were 79.91%and 87.23%in breast-conserving,and 71.78%and 81.16%in mastectomy,respectively.The 5-year OS and BCSS of Luminal B LABC were 79.30%and 83.14%in breast-conserving,and were 70.37%and 76.92%in mastectomy,respectively.The 5-year OS and BCSS of triple-negative LABC were 60.77%and 68.13%in breast-conserving,and those of mastectomy were 47.13%and 55.94%,respectively.The 5-year OS and BCSS of HER2 positive were 75.42%,82.05%in breast-conserving,and were 67.05%and 75.01%in mastectomy,respectively;The 5-year OS and BCSS of triple-positive LABC were 86.12%and 91.63%in breast-conserving,and 74.54%and 82.56%in mastectomy,respectively.The 5-year OS and BCSS of well differentiated and N0 triple-positive LABC patients with chemotherapy were 88.24%and 76.91%,and those of patients without chmotherapy were 88.24%and 90.91%,respectively(BCSS:P=0.812;OS:P=0.311).Conclusion In the selective population,OS and BCSS of patients with LABC undergoing breast conserving surgery were significantly better than those of mastectomy.When OS and BCSS were compared for different molecular types and stages of LABC,breast-conserving surgery was still superior to total mastectomy.LABC could be considered for highly differentiated,N0 stage Triple positive without chemotherapy.
10.Protease inhibitor DUBs-IN-1 suppresses proliferation of Marek's disease virus in chicken cells
Xin AI ; Jiacui XU ; Jialiang XIE ; Haoyuan MA ; Kai YU ; Mingcheng LIU ; Xinyue WANG ; Junyan LIN ; Xu GAO
Chinese Journal of Veterinary Science 2024;44(8):1622-1628
Vaccination is a main measure for protecting chickens against Marek's disease,while it is not able to suppress the infection,proliferation,transmission,and virulence enhancement on Marek's disease virus.Inhibiting the proliferation of Marek's disease virus in chicken is therefore an im-portant option for enhancing defense effectiveness.In this study,a compound,DUBs-IN-1,was found to inhibit the activity of MDV049,a protease encoded by Marek's disease virus,via screening a protease inhibitor library using MDV049 as target and ubiquitin probe.Molecular docking re-vealed that DUBs-IN-1 can interact with the residues which formed the catalytic pocket of MDV049,blocking the interaction between Ub substrate and the catalytic center of MDV049,then suppress the activity of MDV049 with competitive inhibition.Using the CPE model,it was found that DUBs-IN-1 at the concentration of 0.35 and 0.70 μmol/L significantly inhibited the CPE in-duced by Marek's disease virus in CEF cells.Quantitative analysis revealed that DUBs-IN-1 inhibi-ted the proliferation of Marek's disease virus in CEF cells(P<0.01).Furthermore,it was found that the administration of 80 and 150 pg/(kg·d)of DUBs-IN-1 in chicken infected by Marek's disease virus significantly inhibited the proliferation of MDV in T cells(P<0.01).In summary,this study demonstrated that the compound DUBs-IN-1 is able to inhibit the proliferation of Marek's disease virus in chicken cells,laying a theoretical and practical foundation for further de-velopment of the drugs against Marek's disease virus.

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