ObjectiveTo evaluate the diagnostic value of cone-beam computed tomography （CBCT） arthrography for temporomandibular joint disc perforation. MethodsA retrospective analysis was conducted on patients who were clinically diagnosed with temporomandibular joint osteoarthrosis （TMJOA） and underwent CBCT arthrography and open surgery between December 2013 and January 2023. The diagnostic results of CBCT arthrography were compared with the gold standard of open surgical exploration to determine the number of true and false positive and negative cases， thereby evaluating the overall accuracy of CBCT arthrography in diagnosing disc perforation. ResultsA total of 90 patients （106 joints） met the inclusion criteria of this study， including 10 males with an average age of 36.4 years and 80 females with an average age of 42.6 years. Among them， 74 joints exhibited unilateral lesions （82.22%）， and 16 joints exhibited bilateral lesions （17.78%）. Among these， 94 joints （88.68%） showed good contrast medium visualization， while 12 joints （11.32%） showed poor contrast medium visualization. CBCT arthrography clearly diagnosed disc perforation in 75 joints （70.75%）， and surgical exploration confirmed perforation in 75 joints. In 5 cases， poor contrast medium visualization was observed， and the imaging diagnosis suggested possible perforation， with surgical exploration confirming perforation in 5 cases； the true positive rate of imaging diagnosis was 100%. CBCT arthrography clearly diagnosed the absence of disc perforation in 19 joints （17.92%）， and surgical exploration confirmed the absence of perforation in 19 joints， with a true negative rate of 73.08%. In 7 cases， poor contrast medium visualization was observed， and the imaging results did not report disc perforation， but surgical exploration revealed perforation in 7 cases， with a false negative rate of 26.92%. ConclusionsCBCT arthrography demonstrates high diagnostic accuracy for temporomandibular joint disc perforation and may provide reliable imaging evidence for clinical decision-making.

ObjectiveTo evaluate the diagnostic value of cone-beam computed tomography （CBCT） arthrography for temporomandibular joint disc perforation. MethodsA retrospective analysis was conducted on patients who were clinically diagnosed with temporomandibular joint osteoarthrosis （TMJOA） and underwent CBCT arthrography and open surgery between December 2013 and January 2023. The diagnostic results of CBCT arthrography were compared with the gold standard of open surgical exploration to determine the number of true and false positive and negative cases， thereby evaluating the overall accuracy of CBCT arthrography in diagnosing disc perforation. ResultsA total of 90 patients （106 joints） met the inclusion criteria of this study， including 10 males with an average age of 36.4 years and 80 females with an average age of 42.6 years. Among them， 74 joints exhibited unilateral lesions （82.22%）， and 16 joints exhibited bilateral lesions （17.78%）. Among these， 94 joints （88.68%） showed good contrast medium visualization， while 12 joints （11.32%） showed poor contrast medium visualization. CBCT arthrography clearly diagnosed disc perforation in 75 joints （70.75%）， and surgical exploration confirmed perforation in 75 joints. In 5 cases， poor contrast medium visualization was observed， and the imaging diagnosis suggested possible perforation， with surgical exploration confirming perforation in 5 cases； the true positive rate of imaging diagnosis was 100%. CBCT arthrography clearly diagnosed the absence of disc perforation in 19 joints （17.92%）， and surgical exploration confirmed the absence of perforation in 19 joints， with a true negative rate of 73.08%. In 7 cases， poor contrast medium visualization was observed， and the imaging results did not report disc perforation， but surgical exploration revealed perforation in 7 cases， with a false negative rate of 26.92%. ConclusionsCBCT arthrography demonstrates high diagnostic accuracy for temporomandibular joint disc perforation and may provide reliable imaging evidence for clinical decision-making.

Objective:To investigate the drug resistance of newly diagnosed HIV-1 infected patients in Shanghai and to provide reference value for clinical antiretroviral therapy (ART).Methods:The peripheral venous blood plasma of 196 newly diagnosed HIV-1 infected patients screened according to the inclusion and exclusion criteria at the Shanghai Public Health Clinical Center from April to June 2023 was collected, HIV-1 RNA was extracted, the pol region was amplified by reverse transcription-polymerase chain reaction (RT-PCR) for sequencing, the mutation sites and ART drug resistance were analyzed.Results:The plasma of 196 newly diagnosed HIV-1 infected patients was amplified successfully in 162 cases (amplification success rate was 82.65%). The subtypes consisted of CRF07_BC(51.23%), CRF01_AE (27.78%), and others (6.79%), CRF55_01B (5.56%), B (3.70%), CRF01_AE/B (3.70%) and CRF08_BC (1.23%). The overall transmitted drug resistance rate was 7.41%, the protease inhibitors (PIs), non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs), nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), integrase inhibitors (INSTIs) resistance rates were 3.09%, 3.70%, 0.00% and 0.62%, respectively. The proportion of NNRTIs-related mutation sites in B (66.67%) and CRF55_01B (88.89%) was higher than that in CRF07_BC (13.25%); the proportion of NNRTIs-related mutation sites in CRF55_01B (88.89%) was higher than that in CRF01_AE (22.22%) and other subtypes (18.18%), the difference was statistically significant (all P<0.05). Multivariate logistic regression analysis showed that the probability of PIs-related mutation sites in CRF01_AE/B was 21.71 times that of CRF07_BC[odds ratio ( OR)=21.71, 95% confidence interval ( CI): 3.36-140.27, P=0.001]. Conclusions:The transmitted drug resistance among newly diagnosed HIV-1 infected patients in Shanghai is at the moderate epidemic level, mainly NNRTIs and PIs-related drug resistance, and the INSTIs resistance rate is low, the use of INSTIs in ART regimens should be considered.

Objective·To determine hyaluronan(HA)expression in the endocrine-resistant microenvironment of estrogen receptor-positive(ER+)breast cancer and elucidate its impact on the acquired resistance.Methods·Chemiluminescent immunoassay was used to quantify HA levels in the culture supernatants of fulvestrant-resistant breast cancer cells.An immunofluorescence(IF)assay was performed to visualize the colocalization of CD44 and HA in MCF7/FulR cells.Using an established adaptive endocrine-resistant breast cancer mouse model,HA expression in resistant breast cancer tissues was assessed by immunohistochemistry(IHC)assay.Single-cell RNA sequencing(scRNA-seq)and RNA sequencing(RNA-seq)were conducted to examine transcriptomic profiles and alterations in HA-related genes in resistant breast cancer cells.Flow cytometry(FCM)was utilized to measure the proportion of CD44+CD24-cells in MCF7/FulR.The correlation between HA synthesis genes and cell stemness was investigated in clinical ER+breast cancers from GEO data sets.Hyaluronidase(HAase)treatment was applied to remove the"HA coat",and RT-qPCR and Western blotting analysis were carried out to monitor changes in stemness-related molecules.CCK-8 assays,flow cytometry(FCM),and Hoechst 33258 staining were performed to determine changes in apoptosis and fulvestrant efficiency after HAase treatment.Results·IF results revealed that compared with MCF7 cells,the"HA coat"on the surface of MCF7/FulR cells was significantly thickened.IHC demonstrated markedly increased HA retention in fulvestrant-resistant mouse breast cancer tissues.ScRNA-seq and RNA-seq analyses indicated elevated expression of stemness-related genes and HA synthesis-associated genes in fulvestrant-resistant breast cancer cells.Correlation analysis revealed a positive association between HA synthesis and cancer stemness in ER+breast cancer.IF and RT-qPCR results demonstrated that removing the HA coating from the surface of MCF7/FulR cells led to a significant reduction in the expression of stemness-related molecules;concurrently,CCK-8 assays,FCM analysis,and Hoechst 33258 staining revealed that"HA coat"clearance reduced MCF7/FulR'tolerance to fulvestrant and increased apoptosis.Conclusion·Endocrine-resistant breast cancer cells develop an enriched"HA coat",which promotes stemness in fulvestrant-resistant tumors.Disruption of this HA coat through HAase treatment effectively reduces cell stemness,induces apoptosis,and re-sensitizes breast cancer cells to fulvestrant.

ObjectiveTo investigate the mechanism of kidney-tonifying and liver-regulating cyclical therapy and its formula in regulating endometrial receptivity during the "implantation window" in rats with polycystic ovary syndrome （PCOS）. MethodsSix rats were randomly selected from 36 SPF SD female rats as the normal group， and the remaining rats were administered letrozole to induce a PCOS model. By using a random number method， the rats were divided into the following groups： normal group， model group， Xiaoyaosan group （11.97 g·kg^-1）， Sanzi Yangmo decoction group （28.35 g·kg^-1）， cyclical therapy group （11.97/28.35 g·kg^-1）， and aspirin group （8 × 10^-3 mg·kg^-1）. After 12 days of continuous administration by gavage （equivalent to three estrous cycles）， female and male rats were co-housed. On the fifth day of pregnancy， the number of blastocyst implantation in each group was counted. Hematoxylin-eosin （HE） staining was used to observe the pathological morphology of rat endometrial tissue. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of estradiol （E₂） and progesterone （P） in rat serum. Western blot was used to detect the protein expression of vascular endothelial growth factor （VEGF）， progesterone receptor （PR）， estrogen receptor （ER）， androgen receptor （AR）， and integrin（ITG） αvβ3 in rat endometrial blood vessels. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of miR-140-5 P， VEGF， vascular endothelial growth factor receptor 2 （VEGFR2）， PR， ER， AR， and ITGαvβ3 in rat endometrium. ResultsCompared with normal group， the estrous cycle of the rats in model group continued to be in the estrus interval and the estrous cycle lost regular changes. The endometrium was significantly thinner， the number of uterine glands and blood vessels were significantly reduced （P<0.01）， and the pregnancy rate was significantly reduced. Compared with the model group， each drug group restored the regular estrous cycle to varying degrees， and the endometrial thickness and the number of blood vessels were significantly improved （P<0.01）. The pregnancy rate of each drug group increased， and the effect of the cycle therapy group could reach the normal level. The results of molecular biology experiments showed that compared with the normal group， the levels of serum E₂ and P in the model group were significantly decreased （P<0.01）， the expression of VEGF， ER， PR and ITGαvβ3 protein was significantly decreased （P<0.05，P<0.01）， the expression of AR protein was significantly increased （P<0.01）， the expression of miR-140-5P and AR mRNA was significantly increased （P<0.01）， and the expression of VEGF， VEGFR2， ER， PR and ITGαvβ3 mRNA was significantly decreased （P<0.01）. Compared with model group， the serum E₂ level in the Xiaoyaosan group was significantly increased （P<0.01）.The levels of E₂ and P in serum of rats in Sanzi Yangmo decoction group， cycle therapy group and aspirin group were significantly increased （P<0.01）. The expression of AR protein in each drug group was significantly decreased （P<0.01）. The expression of VEGF and ITGαvβ3 protein in Xiaoyaosan group was significantly increased （P<0.01）. The expression of VEGF， ER and PR protein in Sanzi Yangmo decoction group was increased to varying degrees （P<0.05，P<0.01）. The expression of VEGF， PR， ER and ITGαvβ3 protein in the cycle therapy group and the aspirin group increased to varying degrees （P<0.05，P<0.01）. The expression of miR-140-5P and AR mRNA in each drug group was significantly decreased （P<0.01）. The expression of VEGF， VEGFR2， ER， PR and ITGαvβ3 mRNA in each drug group increased to varying degrees （P<0.05，P<0.01）. Compared with Xiaoyaosan group and Sanzi Yangmo decoction group， the expression of miR-140-5P， VEGFR2， ER， PR， AR and ITGαvβ3 mRNA in the cycle therapy group were significantly different （P<0.05，P<0.01）. ConclusionThe kidney-tonifying and liver-regulating cyclical therapy may reduce the activity of miR-140-5P， target the upregulation of VEGF expression， mediate angiogenesis， and promote endometrial angiogenesis， thereby playing a synergistic role in improving endometrial receptivity in PCOS-induced infertility. Its efficacy in increasing pregnancy rates surpasses that of Xiaoyaosan or Sanzi Yangmo decoction used alone.

ObjectiveTo investigate the mechanism of kidney-tonifying and liver-regulating cyclical therapy and its formula in regulating endometrial receptivity during the "implantation window" in rats with polycystic ovary syndrome （PCOS）. MethodsSix rats were randomly selected from 36 SPF SD female rats as the normal group， and the remaining rats were administered letrozole to induce a PCOS model. By using a random number method， the rats were divided into the following groups： normal group， model group， Xiaoyaosan group （11.97 g·kg^-1）， Sanzi Yangmo decoction group （28.35 g·kg^-1）， cyclical therapy group （11.97/28.35 g·kg^-1）， and aspirin group （8 × 10^-3 mg·kg^-1）. After 12 days of continuous administration by gavage （equivalent to three estrous cycles）， female and male rats were co-housed. On the fifth day of pregnancy， the number of blastocyst implantation in each group was counted. Hematoxylin-eosin （HE） staining was used to observe the pathological morphology of rat endometrial tissue. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of estradiol （E₂） and progesterone （P） in rat serum. Western blot was used to detect the protein expression of vascular endothelial growth factor （VEGF）， progesterone receptor （PR）， estrogen receptor （ER）， androgen receptor （AR）， and integrin（ITG） αvβ3 in rat endometrial blood vessels. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of miR-140-5 P， VEGF， vascular endothelial growth factor receptor 2 （VEGFR2）， PR， ER， AR， and ITGαvβ3 in rat endometrium. ResultsCompared with normal group， the estrous cycle of the rats in model group continued to be in the estrus interval and the estrous cycle lost regular changes. The endometrium was significantly thinner， the number of uterine glands and blood vessels were significantly reduced （P<0.01）， and the pregnancy rate was significantly reduced. Compared with the model group， each drug group restored the regular estrous cycle to varying degrees， and the endometrial thickness and the number of blood vessels were significantly improved （P<0.01）. The pregnancy rate of each drug group increased， and the effect of the cycle therapy group could reach the normal level. The results of molecular biology experiments showed that compared with the normal group， the levels of serum E₂ and P in the model group were significantly decreased （P<0.01）， the expression of VEGF， ER， PR and ITGαvβ3 protein was significantly decreased （P<0.05，P<0.01）， the expression of AR protein was significantly increased （P<0.01）， the expression of miR-140-5P and AR mRNA was significantly increased （P<0.01）， and the expression of VEGF， VEGFR2， ER， PR and ITGαvβ3 mRNA was significantly decreased （P<0.01）. Compared with model group， the serum E₂ level in the Xiaoyaosan group was significantly increased （P<0.01）.The levels of E₂ and P in serum of rats in Sanzi Yangmo decoction group， cycle therapy group and aspirin group were significantly increased （P<0.01）. The expression of AR protein in each drug group was significantly decreased （P<0.01）. The expression of VEGF and ITGαvβ3 protein in Xiaoyaosan group was significantly increased （P<0.01）. The expression of VEGF， ER and PR protein in Sanzi Yangmo decoction group was increased to varying degrees （P<0.05，P<0.01）. The expression of VEGF， PR， ER and ITGαvβ3 protein in the cycle therapy group and the aspirin group increased to varying degrees （P<0.05，P<0.01）. The expression of miR-140-5P and AR mRNA in each drug group was significantly decreased （P<0.01）. The expression of VEGF， VEGFR2， ER， PR and ITGαvβ3 mRNA in each drug group increased to varying degrees （P<0.05，P<0.01）. Compared with Xiaoyaosan group and Sanzi Yangmo decoction group， the expression of miR-140-5P， VEGFR2， ER， PR， AR and ITGαvβ3 mRNA in the cycle therapy group were significantly different （P<0.05，P<0.01）. ConclusionThe kidney-tonifying and liver-regulating cyclical therapy may reduce the activity of miR-140-5P， target the upregulation of VEGF expression， mediate angiogenesis， and promote endometrial angiogenesis， thereby playing a synergistic role in improving endometrial receptivity in PCOS-induced infertility. Its efficacy in increasing pregnancy rates surpasses that of Xiaoyaosan or Sanzi Yangmo decoction used alone.

Background Injury poses a serious threat to human health. As global warming continues to intensify, there is an urgent need to explore the impact of temperature changes on injury deaths. However limited research has focused on this issue. Objective To investigate the relationship between daily mean temperature change (Tm) and injury death, as well as to estimate the associated future death burden in Hunan Province. Methods We employed an individual-level, time-stratified case-crossing design to establish a conditional logistic regression model to analyze the exposure-response relationship between daily mean temperature change and injury death in Hunan Province from 2013 to 2018. Consequently, we conducted subgroup analysis of gender, age group, and injury type. Finally, we estimated the excess burden of injury death attributable to temperature changes under a sustainable development path [low emission scenario (SSP1-2.6)], regional competition path [high emission scenario (SSP3-7.0)], or fossil fuel development path [very high emission scenario (SSP5-8.5)]. Results The study collected 155577 injury deaths in Hunan Province. The results indicated that for each 1 ℃ increment in daily mean temperature, the cumulative excess risk (CER) of injury mortality among Hunan residents increased by 0.71% (95%CI: 0.53%, 0.90%). Notably, the CER for intentional injuries (1.06%, 95%CI: 0.51%, 1.61%) was higher than that for unintentional injuries (0.66%, 95%CI: 0.46%, 0.87%). Warmer temperatures were positively associated with CER of mortality due to drowning, falls, transport injuries, assaults, and suicides, while they were negatively associated with mortality due to poisoning. Compared with 2010–2019, for 2090–2099, the excess mortality rate (EMR) due to ambient temperature increase in Hunan Province under the SSP5-8.5 scenario (14.62/100000, 95%CI: 10.81/100000, 18.40/100000) would be higher than that of the SSP3-7.0 scenario (10.28/100000, 95%CI: 7.58/100000, 12.97/100000) and the SSP1-2.6 scenario (3.35/100000, 95%CI: 2.46/100000, 4.23/100000); the EMR would be around 2.5 times among men (20.64/100000, 95%CI: 14.44/100000, 26.8/100000) than that among women (8.33/100000, 95%CI: 3.98/100000, 12.6/100000). Among unintentional injuries, the leading contributors to EMR would be drowning (4.46/100000), falls (3.96/100000), and transport injuries (2.96/100000). And among intentional injuries, the EMR for suicide (2.08/100000) would be higher than that for assault (0.47/100000). Conclusion Climate warming will increase the total burden of injury-related deaths among residents in Hunan Province, especially in the absence of effective mitigation strategies and measures. It is necessary to strengthen the prevention and control of severe injuries closely related to temperature changes, such as drowning, falls, traffic, and suicides injuries, in order to reduce injury deaths associated with climate change.

Objective: To construct an evaluation index system of cervical cancer prevention and control literacy, so as to provide an assessment tool for cervical cancer prevention and control literacy. Methods: The preliminary framework for cervical cancer prevention and control literacy was designed based on literature review. Twenty-one experts with both theoretical and practical experience in cervical cancer prevention and control were invited to participate in two rounds of Delphi consultation. The weights of indicators were determined by the percentage weighting method and product method, and the response rate, authority level, opinion concentration degree, and coordination degree of experts were evaluated. Results: Twenty-one experts participated in the consultation, including 3 males and 18 females. There were 11 experts with a doctor's degree, 7 with a master's degree and 3 with a bachelor's degree. All of them had senior professional titles and had more than 10 years of working experience. The recovery rates of the two rounds of consultations were 100.00% and 95.24%, the authority coefficients were 0.963 and 0.948, and Kendall's coefficients of concordance were 0.175 and 0.148 (both P<0.05), respectively. The final cervical cancer prevention and control literacy evaluation index system included 3 primary indicators (basic knowledge and concepts: 0.334; healthy lifestyle and behaviors: 0.338; basic skills: 0.328), 12 secondary indicators, with "capability to accurately acquire, comprehend, evaluate and apply health information" having the highest weight (0.166), and 51 tertiary indicators, with "HPV vaccination" (0.086), "consulting on relevant issues" (0.082), and "expressing personal perspectives" (0.080) having relatively higher weights. Conclusion The evaluation index system of cervical cancer prevention and control literacy serves as a valid assessment tool for women of appropriate age, providing the reference for developing targeted health education to enhance cervical cancer prevention and control literacy.

BACKGROUND: Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China. METHODS: This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion. RESULTS: The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon. CONCLUSIONS: Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings. REGISTRATION Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans ; Male ; Female ; Anemia/etiology* ; Middle Aged ; Renal Insufficiency, Chronic/complications* ; Glycine/adverse effects* ; Isoquinolines/adverse effects* ; Aged ; Prospective Studies ; Adult ; Hemoglobins/metabolism* ; Treatment Outcome ; China ; Registries ; East Asian People

Objective·To determine hyaluronan(HA)expression in the endocrine-resistant microenvironment of estrogen receptor-positive(ER+)breast cancer and elucidate its impact on the acquired resistance.Methods·Chemiluminescent immunoassay was used to quantify HA levels in the culture supernatants of fulvestrant-resistant breast cancer cells.An immunofluorescence(IF)assay was performed to visualize the colocalization of CD44 and HA in MCF7/FulR cells.Using an established adaptive endocrine-resistant breast cancer mouse model,HA expression in resistant breast cancer tissues was assessed by immunohistochemistry(IHC)assay.Single-cell RNA sequencing(scRNA-seq)and RNA sequencing(RNA-seq)were conducted to examine transcriptomic profiles and alterations in HA-related genes in resistant breast cancer cells.Flow cytometry(FCM)was utilized to measure the proportion of CD44+CD24-cells in MCF7/FulR.The correlation between HA synthesis genes and cell stemness was investigated in clinical ER+breast cancers from GEO data sets.Hyaluronidase(HAase)treatment was applied to remove the"HA coat",and RT-qPCR and Western blotting analysis were carried out to monitor changes in stemness-related molecules.CCK-8 assays,flow cytometry(FCM),and Hoechst 33258 staining were performed to determine changes in apoptosis and fulvestrant efficiency after HAase treatment.Results·IF results revealed that compared with MCF7 cells,the"HA coat"on the surface of MCF7/FulR cells was significantly thickened.IHC demonstrated markedly increased HA retention in fulvestrant-resistant mouse breast cancer tissues.ScRNA-seq and RNA-seq analyses indicated elevated expression of stemness-related genes and HA synthesis-associated genes in fulvestrant-resistant breast cancer cells.Correlation analysis revealed a positive association between HA synthesis and cancer stemness in ER+breast cancer.IF and RT-qPCR results demonstrated that removing the HA coating from the surface of MCF7/FulR cells led to a significant reduction in the expression of stemness-related molecules;concurrently,CCK-8 assays,FCM analysis,and Hoechst 33258 staining revealed that"HA coat"clearance reduced MCF7/FulR'tolerance to fulvestrant and increased apoptosis.Conclusion·Endocrine-resistant breast cancer cells develop an enriched"HA coat",which promotes stemness in fulvestrant-resistant tumors.Disruption of this HA coat through HAase treatment effectively reduces cell stemness,induces apoptosis,and re-sensitizes breast cancer cells to fulvestrant.