BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

Objective To observe the value of noninvasive right ventricular pressure-strain loop(RVPSL)for quantitative evaluation on right ventricular myocardial function changes in liver cirrhosis patients after TIPS.Methods Totally 26 cases of liver cirrhosis who would undergo TIPS were prospectively recruited as liver cirrhosis group.Echocardiography was performed before and 1 week,1 month after TIPS,and parameters of right ventricular myocardial function,including routine right ventricular echocardiography,right ventricular strain and right ventricular myocardial work were acquired.Meanwhile,30 healthy adults were recruited as control group,and the above parameters were recorded.Then these parameters were compared between groups,also before and after TIPS within liver cirrhosis group,and the changes of right ventricular myocardial function after TIPS were evaluated.Results Right ventricular global work index(RVGWI),right ventricular global constructive work(RVGCW)and right ventricular global wasted work(RVGWW)in liver cirrhosis group were higher than those in control group at all time points(all P＜0.05).One weak and 1 month after TIPS,right ventricular global longitudinal strain(RVGLS)and right ventricular free wall longitudinal strain(RVFWLS)in liver cirrhosis group were all higher than those in control group(all P＜0.05).In liver cirrhosis group,RVGWI,RVGCW and RVGWW 1 week after TIPS were all higher than those before TIPS and 1 month after TIPS(all P＜0.05),while RVGLS 1 weak and RVGWI 1 month after TIPS were both higher than those before TIPS(both P＜0.05).Conclusion Noninvasive RVPSL could be used to sensitively and quantitatively evaluate right ventricular function changes in patients with liver cirrhosis after TIPS.

Objective To explore the multimorbidity pattern and traditional Chinese medicine(TCM)syndrome characteristics of patients with adenomyosis(AM)and to provide insights and data support for medical treatment and comprehensive AM management.Methods By retrospectively analyzing multi-center,large-sample,nationwide cross-sectional survey data,patients were divided into a single AM group or a multimorbidity group based on whether they had other diseases.The prevalence rates of specific multimorbidity or a combination of multimorbidities were calculated respectively.Single-factor analysis was used to explore the influence of age,course of disease,education level,labor nature,monthly income,production history,abortion history,operation history,region,and TCM syndromes on multimorbidity in patients with AM.The multimorbidity patterns of patients with AM were explored using Apriori association rules,and the distribution characteristics of TCM syndromes in different multimorbidity patterns were explored.Results Among 1,814 patients with AM,1,429 were in the multimorbidity group(prevalence of 78.78％).Compared with the single AM group,the patients in the multimorbidity group had a long disease course,high academic qualifications,jobs that mostly involved sitting,a history of surgery,and were primarily concentrated in the north(P＜0.05).The proportion of patients with qi stagnation and blood stasis syndrome decreased,whereas the proportion of patients with kidney deficiency and blood stasis syndrome increased.Ten multimorbidity association rules were sorted according to the confidence level,and the first place of binary association rules was breast nodule to breast hyperplasia,and the first place of ternary association rules was hysteromyoma,breast nodule to breast hyperplasia.Comprehensive support and confidence level,in the binary association rules,the strong association rule was breast nodule to thyroid nodule,and sub-strong association rule was thyroid nodule to breast hyperplasia;In the ternary association rules,the strong association rule was hysteromyoma,breast nodules to breast hyperplasia,and sub-strong association rule was endometriosis,thyroid nodules to breast hyperplasia.There was no significant difference in the distribution of TCM syndromes in AM patients with different binary and ternary multimorbidity patterns.Conclusion Patients with AM have different multimorbidity patterns,and the TCM syndromes of patients with AM under different multimorbidity patterns have different characteristics.The management system of AM multimorbidity should be further developed to ensure more comprehensive and standardized health management for patients with AM.

Objective To analyze the clinical efficacy and safety of Huoxue Xiaoyi decoction combined with exercise in the treatment of ovarian endometriosis.Methods 36 patients with ovarian endometriosis treated in Guang'anmen Hospital,China Academy of Chinese Medical Sciences from May 2022 to November 2022 were selected and treated with Huoxue Xiaoyi decoction combined with exercise for 3 months.The size of ovarian ectopic cyst,dysmenorrhea VAS score,PBAC score,female hormones,serum CA125 and CA199,catecholamines and cytokines levels were observed to evaluate the clinical efficacy and safety.Results After treatment,the maximum diameter of ovarian ectopic cyst,dysmenorrhea VAS score,PBAC score,cytokines(serum IL-1β,IL-2,IL-4,IL-6,IL-8,IL-10)levels were significantly lower than those before treatment(P<0.05).The levels of SHBG and adrenaline were significantly higher than those before treatment(P<0.05).During the treatment,the patient had no adverse drug reactions,vital signs,liver,and kidney function indexes were normal.Conclusion Huoxue Xiaoyi decoction combined with exercise therapy can reduce the size of ovarian ectopic cyst,relieve dysmenorrhea,regulate menstrual volume,increase the level of adrenaline,increase the level of sex hormone binding globulin,reduce the level of cytokines,and has fewer adverse reactions and good safety.

Objective To analyze the clinical efficacy and safety of Huoxue Xiaoyi decoction combined with exercise in the treatment of ovarian endometriosis.Methods 36 patients with ovarian endometriosis treated in Guang'anmen Hospital,China Academy of Chinese Medical Sciences from May 2022 to November 2022 were selected and treated with Huoxue Xiaoyi decoction combined with exercise for 3 months.The size of ovarian ectopic cyst,dysmenorrhea VAS score,PBAC score,female hormones,serum CA125 and CA199,catecholamines and cytokines levels were observed to evaluate the clinical efficacy and safety.Results After treatment,the maximum diameter of ovarian ectopic cyst,dysmenorrhea VAS score,PBAC score,cytokines(serum IL-1β,IL-2,IL-4,IL-6,IL-8,IL-10)levels were significantly lower than those before treatment(P<0.05).The levels of SHBG and adrenaline were significantly higher than those before treatment(P<0.05).During the treatment,the patient had no adverse drug reactions,vital signs,liver,and kidney function indexes were normal.Conclusion Huoxue Xiaoyi decoction combined with exercise therapy can reduce the size of ovarian ectopic cyst,relieve dysmenorrhea,regulate menstrual volume,increase the level of adrenaline,increase the level of sex hormone binding globulin,reduce the level of cytokines,and has fewer adverse reactions and good safety.

Objective To explore the distribution and characteristics of traditional Chinese medicine(TCM)syndromes in patients with adenomyosis.Methods A retrospective analysis was conducted on the data collected from patients with adenomyosis between December 2019 and April 2022 based on a cross-sectional survey.Variables included age,body mass index(BMI),disease duration,geographical region,dysmenorrhea,menstrual flow,diagnosis and treatment goals,history of adenomyosis-related surgery,postoperative recurrence,and carbohydrate antigen 125(CA125)and carbohydrate antigen 199(CA199)levels.The distribution pattern of TCM syndromes,including general information of patients with different syndromes,CA125 and CA199 levels,were analyzed.The relationship between syndromes and age,BMI,duration of disease,geographic region,and history of adenomyosis-related surgery were analyzed using the multinomial logistic regression.Results A total of 1,816 patients with adenomyosis were included.The most common TCM syndrome was syndrome of cold coagulation and blood stasis(36.84%).The other four TCM syndromes,ranked by frequency,were syndrome of qi stagnation and blood stasis(25.39%),syndrome of blood stasis due to qi deficiency(17.35%),syndrome of kidney deficiency and blood stasis(15.97%),and syndrome of intermin-gled phlegm and blood stasis(4.46%).Significant differences in age,disease duration,and BMI were observed among patients with different TCM syndromes(P<0.05).Patients with syndrome of cold congelation and blood stasis,syndrome of kidney deficiency and blood stasis,were younger than those with syndrome of qi stagnation and blood stasis.Patients with syndrome of cold congelation and blood stasis had a longer disease duration than those with syndrome of blood stasis due to qi deficiency.Patients with syndrome of blood stasis due to qi deficiency had lower BMI(P<0.05)than those with syndrome of intermin-gled phlegm and blood stasis.The most common symptom in North China,East China,Southwest China,Northwest China,and Northeast China was syndrome of cold congelation and blood stasis,accounting for 45.39%,35.98%,30.33%,41.38%,and 50.00%,respectively.The most common syndrome in Southern and Central China was syndrome of qi stagnation and blood stasis,accounting for 31.34%and 36.23%respectively.Differences in syndrome distribution were observed between patients in East,Southwest,South,and Central China and those in North China(P<0.05).Syndrome distribution also varied significantly across different diagnosis and treatment goals,as well as menstrual conditions(P<0.05).For treatment goals such as pain relief,lesion control,menstrual flow reduction,and recurrence prevention,the dominant syndromes were syndrome of cold congelation and blood stasis(40.67%,37.13%,36.95%,and 43.35%,respectively)and syndrome of qi stagnation and blood stasis(29.35%,26.39%,26.10%,and 25.75%,respectively).Among patients seeking assisted pregnancy,the primary syndromes were syndrome of cold congelation and blood stasis(41.12%)and syndrome of kidney deficiency and blood stasis(18.69%).Patients with dysmenorrhea were mostly diagnosed with syndrome of cold congelation and blood stasis(39.95%)and syndrome of qi stagnation and blood stasis(28.52%).Differences in syndrome distribution were observed between patients with small and large menstrual volume,with a higher proportion of syndrome of kidney deficiency and blood stasis in patients with small menstrual volume(P<0.05).However,no significant difference was noted in the distribution of TCM syndromes in different treatment stages.Additionally,no statistical significance was observed in the CA125 and CA199 levels among patients with various TCM syndromes.Multinomial logistic regression analysis revealed that compared with syndrome of cold congelation and blood stasis,the course of disease was the influencing factor of syndrome of blood stasis due to qi deficiency,BMI was the influencing factor of syndrome of qi stagnation and blood stasis and syndrome of intermin-gled phlegm and blood stasis,and geography was the influencing factor of syndrome of blood stasis due to qi deficiency,syndrome of qi stagnation and blood stasis,syndrome of kidney deficiency and blood stasis,and syndrome of intermin-gled phlegm and blood stasis.Conclusion Syndrome of cold coagulation and blood stasis is the most prevalent TCM syndrome among patients with adenomyosis,and the distribution of TCM syndromes has a specific regularity.The syndromes are independently correlated with region,disease duration,and BMI.

Objective To observe the value of noninvasive right ventricular pressure-strain loop(RVPSL)for quantitative evaluation on right ventricular myocardial function changes in liver cirrhosis patients after TIPS.Methods Totally 26 cases of liver cirrhosis who would undergo TIPS were prospectively recruited as liver cirrhosis group.Echocardiography was performed before and 1 week,1 month after TIPS,and parameters of right ventricular myocardial function,including routine right ventricular echocardiography,right ventricular strain and right ventricular myocardial work were acquired.Meanwhile,30 healthy adults were recruited as control group,and the above parameters were recorded.Then these parameters were compared between groups,also before and after TIPS within liver cirrhosis group,and the changes of right ventricular myocardial function after TIPS were evaluated.Results Right ventricular global work index(RVGWI),right ventricular global constructive work(RVGCW)and right ventricular global wasted work(RVGWW)in liver cirrhosis group were higher than those in control group at all time points(all P＜0.05).One weak and 1 month after TIPS,right ventricular global longitudinal strain(RVGLS)and right ventricular free wall longitudinal strain(RVFWLS)in liver cirrhosis group were all higher than those in control group(all P＜0.05).In liver cirrhosis group,RVGWI,RVGCW and RVGWW 1 week after TIPS were all higher than those before TIPS and 1 month after TIPS(all P＜0.05),while RVGLS 1 weak and RVGWI 1 month after TIPS were both higher than those before TIPS(both P＜0.05).Conclusion Noninvasive RVPSL could be used to sensitively and quantitatively evaluate right ventricular function changes in patients with liver cirrhosis after TIPS.

Objective To explore the multimorbidity pattern and traditional Chinese medicine(TCM)syndrome characteristics of patients with adenomyosis(AM)and to provide insights and data support for medical treatment and comprehensive AM management.Methods By retrospectively analyzing multi-center,large-sample,nationwide cross-sectional survey data,patients were divided into a single AM group or a multimorbidity group based on whether they had other diseases.The prevalence rates of specific multimorbidity or a combination of multimorbidities were calculated respectively.Single-factor analysis was used to explore the influence of age,course of disease,education level,labor nature,monthly income,production history,abortion history,operation history,region,and TCM syndromes on multimorbidity in patients with AM.The multimorbidity patterns of patients with AM were explored using Apriori association rules,and the distribution characteristics of TCM syndromes in different multimorbidity patterns were explored.Results Among 1,814 patients with AM,1,429 were in the multimorbidity group(prevalence of 78.78％).Compared with the single AM group,the patients in the multimorbidity group had a long disease course,high academic qualifications,jobs that mostly involved sitting,a history of surgery,and were primarily concentrated in the north(P＜0.05).The proportion of patients with qi stagnation and blood stasis syndrome decreased,whereas the proportion of patients with kidney deficiency and blood stasis syndrome increased.Ten multimorbidity association rules were sorted according to the confidence level,and the first place of binary association rules was breast nodule to breast hyperplasia,and the first place of ternary association rules was hysteromyoma,breast nodule to breast hyperplasia.Comprehensive support and confidence level,in the binary association rules,the strong association rule was breast nodule to thyroid nodule,and sub-strong association rule was thyroid nodule to breast hyperplasia;In the ternary association rules,the strong association rule was hysteromyoma,breast nodules to breast hyperplasia,and sub-strong association rule was endometriosis,thyroid nodules to breast hyperplasia.There was no significant difference in the distribution of TCM syndromes in AM patients with different binary and ternary multimorbidity patterns.Conclusion Patients with AM have different multimorbidity patterns,and the TCM syndromes of patients with AM under different multimorbidity patterns have different characteristics.The management system of AM multimorbidity should be further developed to ensure more comprehensive and standardized health management for patients with AM.

Objective To explore the distribution and characteristics of traditional Chinese medicine(TCM)syndromes in patients with adenomyosis.Methods A retrospective analysis was conducted on the data collected from patients with adenomyosis between December 2019 and April 2022 based on a cross-sectional survey.Variables included age,body mass index(BMI),disease duration,geographical region,dysmenorrhea,menstrual flow,diagnosis and treatment goals,history of adenomyosis-related surgery,postoperative recurrence,and carbohydrate antigen 125(CA125)and carbohydrate antigen 199(CA199)levels.The distribution pattern of TCM syndromes,including general information of patients with different syndromes,CA125 and CA199 levels,were analyzed.The relationship between syndromes and age,BMI,duration of disease,geographic region,and history of adenomyosis-related surgery were analyzed using the multinomial logistic regression.Results A total of 1,816 patients with adenomyosis were included.The most common TCM syndrome was syndrome of cold coagulation and blood stasis(36.84%).The other four TCM syndromes,ranked by frequency,were syndrome of qi stagnation and blood stasis(25.39%),syndrome of blood stasis due to qi deficiency(17.35%),syndrome of kidney deficiency and blood stasis(15.97%),and syndrome of intermin-gled phlegm and blood stasis(4.46%).Significant differences in age,disease duration,and BMI were observed among patients with different TCM syndromes(P<0.05).Patients with syndrome of cold congelation and blood stasis,syndrome of kidney deficiency and blood stasis,were younger than those with syndrome of qi stagnation and blood stasis.Patients with syndrome of cold congelation and blood stasis had a longer disease duration than those with syndrome of blood stasis due to qi deficiency.Patients with syndrome of blood stasis due to qi deficiency had lower BMI(P<0.05)than those with syndrome of intermin-gled phlegm and blood stasis.The most common symptom in North China,East China,Southwest China,Northwest China,and Northeast China was syndrome of cold congelation and blood stasis,accounting for 45.39%,35.98%,30.33%,41.38%,and 50.00%,respectively.The most common syndrome in Southern and Central China was syndrome of qi stagnation and blood stasis,accounting for 31.34%and 36.23%respectively.Differences in syndrome distribution were observed between patients in East,Southwest,South,and Central China and those in North China(P<0.05).Syndrome distribution also varied significantly across different diagnosis and treatment goals,as well as menstrual conditions(P<0.05).For treatment goals such as pain relief,lesion control,menstrual flow reduction,and recurrence prevention,the dominant syndromes were syndrome of cold congelation and blood stasis(40.67%,37.13%,36.95%,and 43.35%,respectively)and syndrome of qi stagnation and blood stasis(29.35%,26.39%,26.10%,and 25.75%,respectively).Among patients seeking assisted pregnancy,the primary syndromes were syndrome of cold congelation and blood stasis(41.12%)and syndrome of kidney deficiency and blood stasis(18.69%).Patients with dysmenorrhea were mostly diagnosed with syndrome of cold congelation and blood stasis(39.95%)and syndrome of qi stagnation and blood stasis(28.52%).Differences in syndrome distribution were observed between patients with small and large menstrual volume,with a higher proportion of syndrome of kidney deficiency and blood stasis in patients with small menstrual volume(P<0.05).However,no significant difference was noted in the distribution of TCM syndromes in different treatment stages.Additionally,no statistical significance was observed in the CA125 and CA199 levels among patients with various TCM syndromes.Multinomial logistic regression analysis revealed that compared with syndrome of cold congelation and blood stasis,the course of disease was the influencing factor of syndrome of blood stasis due to qi deficiency,BMI was the influencing factor of syndrome of qi stagnation and blood stasis and syndrome of intermin-gled phlegm and blood stasis,and geography was the influencing factor of syndrome of blood stasis due to qi deficiency,syndrome of qi stagnation and blood stasis,syndrome of kidney deficiency and blood stasis,and syndrome of intermin-gled phlegm and blood stasis.Conclusion Syndrome of cold coagulation and blood stasis is the most prevalent TCM syndrome among patients with adenomyosis,and the distribution of TCM syndromes has a specific regularity.The syndromes are independently correlated with region,disease duration,and BMI.

Objective To understand cognition level and treatment intention of patients with endometriosis(EMs);To evaluate the effects of TCM chronic disease management on EMs patients.Methods The disease cognition level and treatment intention of 1 895 EMs patients from October 2020 to December 2021 in 19 provinces,autonomous regions and municipalities were analyzed through cross-sectional investigation.The cognitive effect of chronic disease management of TCM on 801 patients with EMs from 6 Grade A hospitals in Beijing was evaluated by self-control study.Results The cognition level of EMs patients for the disease was improved with the increase of educational background.Patients generally believed that EMs was a chronic disease,requiring regular review and long-term management.The proportion of patients with high school education or below,junior college education,bachelor degree or above who knew the possibility of malignant changes in EMs was less,only 32.3%,41.6%and 47.7%,respectively.The awareness rate of patients with high school education or below for recurrence after EMs conservative surgery was 46.9%,lower than that of those with junior college education(66.8%)and bachelor degree or above(72.7%).Among the patients with dietary contraindications,the proportion of patients with high school education or below,junior college education,bachelor degree or above who knew the contraindication of the forest frog oil was less,only 20.7%,30.3%and 32.9%,respectively.In the aspect of life adjustment,the awareness of patients was generally high.EMs patients mainly recognized the disease through face-to-face communication with gynecologists.Only 34.4%of patients with high school education or below learned about EMs through WeChat public accounts,APPs and other new media,which was lower than those with junior college education(48.6%)and bachelor degree or above(55.4%).EMs patients generally tend to be treated in comprehensive hospitals,with high acceptance of TCM treatment,mainly TCM decoction,and low acceptance of TCM appropriate technology.After 1 year of TCM chronic disease management,the disease awareness of EMs patients was significantly improved compared with before management,with statistical significance(P<0.05).Conclusion EMs patients with different educational backgrounds have different cognition of the disease,and each has different emphasis.Education and popularization should be carried out according to their knowledge blind spots.Chronic disease management of TCM can improve the disease cognition level of EMs patients.