Cancer multidrug resistance (MDR) impairs the therapeutic efficacy of various chemotherapeutics. Novel approaches, particularly the development of MDR reversal agents, are critically needed to address this challenge. This study demonstrates that tenacissoside I (TI), a compound isolated from Marsdenia tenacissima (Roxb.) Wight et Arn, traditionally used in clinical practice as an ethnic medicine for cancer treatment, exhibits significant MDR reversal effects in ABCB1-mediated MDR cancer cells. TI reversed the resistance of SW620/AD300 and KBV200 cells to doxorubicin (DOX) and paclitaxel (PAC) by downregulating ABCB1 expression and reducing ABCB1 drug transport function. Mechanistically, protein arginine methyltransferase 1 (PRMT1), whose expression correlates with poor prognosis and shows positive association with both ABCB1 and EGFR expressions in tumor tissues, was differentially expressed in TI-treated SW620/AD300 cells. SW620/AD300 and KBV200 cells exhibited elevated levels of EGFR asymmetric dimethylarginine (aDMA) and enhanced PRMT1-EGFR interaction compared to their parental cells. Moreover, TI-induced PRMT1 downregulation impaired PRMT1-mediated aDMA of EGFR, PRMT1-EGFR interaction, and EGFR downstream signaling in SW620/AD300 and KBV200 cells. These effects were significantly reversed by PRMT1 overexpression. Additionally, TI demonstrated resistance reversal to PAC in xenograft models without detectable toxicities. This study establishes TI's MDR reversal effect in ABCB1-mediated MDR human cancer cells through inhibition of PRMT1-mediated aDMA of EGFR, suggesting TI's potential as an MDR modulator for improving chemotherapy outcomes.
Humans ; Protein-Arginine N-Methyltransferases/antagonists & inhibitors* ; Drug Resistance, Neoplasm/drug effects* ; ErbB Receptors/genetics* ; Animals ; Cell Line, Tumor ; Drug Resistance, Multiple/drug effects* ; Methylation/drug effects* ; Saponins/administration & dosage* ; Mice ; Mice, Nude ; Mice, Inbred BALB C ; ATP Binding Cassette Transporter, Subfamily B/genetics* ; Doxorubicin/pharmacology* ; Paclitaxel/pharmacology* ; Female ; Repressor Proteins

Objective To explore the mediating effect of community elderly care service on the influence of social isolation on cognitive function of the elderly.Methods Based on the data of China Health and Retirement Longitudinal Study in 2018,mini mental status examination(MMSE)was used to assess the cognitive function of the elderly.Multivariate Logistic regression was used to analyze the influence of individual characteristics and social isolation on cognitive function of the elderly,and the correlation among social isolation,community elderly care service and cognitive function was analyzed through mediating effect.Results A total of 6615 elderly individuals were included,among whom 2906 cases(43.93％)had cognitive impairment.The results of multivariate Logistic regression analysis indicated that social isolation,age,gender,educational level,place of residence,marital status,activities of daily living ability,smoking,sleep duration,loneliness,community elderly care service,social interaction,and less than one contact with children per week were all influencing factors for the occurrence of cognitive impairment in the elderly(P＜0.05).Community elderly care service exerted a partial mediating effect in the impact of social isolation on the cognitive function of the elderly.Conclusion Social isolation is a risk factor for cognitive impairment in the elderly,and community elderly care service is a protective factor for cognitive impairment in the elderly.It is necessary to improve the coverage and utilization rate of community elderly care service support,improve the social isolation of the elderly,and protect the cognitive function of the elderly.

Objective To address the bottlenecks in the application of wastewater biological treatment technology under space conditions,an experimental system for the biological treatment of space wastewater was constructed and its biochemical performance examined.The findings of this study will provide technical support for the biological treatment of space wastewater.Methods Based on the Membrane Aerated Biofilm Reactor(MABR)process,a biological treatment experimental system for space wastewater was constructed and conducted the continuous flow test for 77 days to investigate the performance of PVDF and PP membrane modules in the treatment of simulated air condensate.Results The results demonstrated that both membrane modules exhibited an average TOC removal rate of 90%,indicative of their effective organic matter removal capacity.In the air supply mode,the ammonia oxidation capacity was observed to be comparatively lower,whereas in the oxygen source without bubbling mode,the nitrogen oxidation rate and total nitrogen removal rate could be attained above 90%,indicating a notable degree of simultaneous nitrification and denitrification.The results demonstrated that the mode of gas supply had a significant impact on the nitrogen conversion performance.The abundance of nitrogen-converting bacteria in PP membrane module is higher than that in PVDF membrane module,indicating a better nitrogen-converting performance in PP membrane module.Conclusion The constructed wastewater biological treatment system is optimally suited for the treatment of air condensate,thereby offering a novel technical approach for space wastewater treatment.

Objective:To explore the clinical and pathological features and survival outcomes of patients with early-onset intrahepatic cholangiocarcinoma (EOICC).Methods:This is a multicenter, retrospective cohort study. Data of 1 160 intrahepatic cholangiocarcinoma patients undergoing radical resection in 14 tertiary Grade A hospitals in China from January 2010 to November 2021 were retrospectively collected. The cohort included 632 males and 528 females, aged( M (IQR)) 61 (14) years (range: 22 to 93 years). ICC aged ≤50 years at the time of diagnosis was defined as EOICC and >50 years as late-onset intrahepatic cholangiocarcinoma (LOICC). Of these, there were 247 cases in the EOICC group and 913 cases in the LOICC. The clinical and pathological characteristics of both groups were analyzed and compared using the independent sample t-test, Mann-Whitney U test or Kaplan-Meier method. Univariate and multivariate Cox regression models for patient outcomes were constructed and forest graphed. Results:Compared with the patients in the LOICC group, patients in the EOICC group had lower carcinoembryonic antigen levels (2.5(4.0) μg/L vs. 3.1(5.2)μg/L, U=124 899, P=0.009) and CA19-9 level (63.4(524.7)U/ml vs. 77.9(611.3)U/ml, U=120 320, P=0.013), higher levels of ALT (29(35)U/L vs. 24(26)U/L, U=101 214, P=0.013), a lower score of the Eastern US Cooperative Oncology Group (0 score patients: 54.7% vs. 44.1%, χ2=12.472, P=0.014), higher TNM stage ( χ2=11.807, P=0.038), and proportion of lymph node dissection (62.3% vs. 54.1%, χ2=5.355, P=0.021). Patients in the two groups in sex, first diagnosis symptoms, intrahepatic bile duct stone history, nail protein, albumin, total bilirubin, transaminase, liver function Child-Pugh grade, T stage, stage, N stage, preoperative laparoscopic exploration proportion, tumor diameter, vascular invasion proportion, differentiation, margin, intraoperative bleeding, postoperative complications, postoperative hospital days were no statistical significance (all P>0.05). Patients in the EOICC group had better outcomes than the LOICC group (median survival time: 29.7 months vs. 25.0 months, 3-year overall survival: 45.1% vs. 37.8%, P=0.027). Conclusion:EOICC patients are better than LOICC patients in carcinoembryonic antigen, CA19-9, ALT, physical strength status and TNM stage, and the long-term prognosis is also better than LOICC patients.

Objective:To explore the relationship between the dark triad, fear of missing out and smartphone addiction, as well as the mediating role of fear of missing out between the dark triad and smartphone addiction.Methods:A total of 408 college students were assessed using dirty dozen, fear of missing out scale, and mobile phone addiction index. SPSS 24.0 software was used for common method bias tests, descriptive statistical analysis, and correlation analysis. Mplus 8.3 software was employed to construct a structural equation model, and the Bootstrap method was used for mediation effect analysis.Results:The dark triad (36.14±9.06) was positively correlated with fear of missing out (22.55±6.60) and smartphone addiction (46.77±13.62) ( r=0.48, 0.45, both P<0.01). Fear of missing out was also positively correlated with smartphone addiction ( r=0.54, P<0.01). Fear of missing out played a partial mediating role in the relationship between the dark triad and smartphone addiction, with a total effect value of 0.495 and a mediating effect value of 0.217. Conclusion:Fear of missing out partially mediates the relationship between the dark triad and smartphone addiction. The dark triad not only directly predicts smartphone addiction but also indirectly influences smartphone addiction through fear of missing out.

Objective:To explore the relationship between the dark triad, fear of missing out and smartphone addiction, as well as the mediating role of fear of missing out between the dark triad and smartphone addiction.Methods:A total of 408 college students were assessed using dirty dozen, fear of missing out scale, and mobile phone addiction index. SPSS 24.0 software was used for common method bias tests, descriptive statistical analysis, and correlation analysis. Mplus 8.3 software was employed to construct a structural equation model, and the Bootstrap method was used for mediation effect analysis.Results:The dark triad (36.14±9.06) was positively correlated with fear of missing out (22.55±6.60) and smartphone addiction (46.77±13.62) ( r=0.48, 0.45, both P<0.01). Fear of missing out was also positively correlated with smartphone addiction ( r=0.54, P<0.01). Fear of missing out played a partial mediating role in the relationship between the dark triad and smartphone addiction, with a total effect value of 0.495 and a mediating effect value of 0.217. Conclusion:Fear of missing out partially mediates the relationship between the dark triad and smartphone addiction. The dark triad not only directly predicts smartphone addiction but also indirectly influences smartphone addiction through fear of missing out.

Objective To explore the mediating effect of community elderly care service on the influence of social isolation on cognitive function of the elderly.Methods Based on the data of China Health and Retirement Longitudinal Study in 2018,mini mental status examination(MMSE)was used to assess the cognitive function of the elderly.Multivariate Logistic regression was used to analyze the influence of individual characteristics and social isolation on cognitive function of the elderly,and the correlation among social isolation,community elderly care service and cognitive function was analyzed through mediating effect.Results A total of 6615 elderly individuals were included,among whom 2906 cases(43.93％)had cognitive impairment.The results of multivariate Logistic regression analysis indicated that social isolation,age,gender,educational level,place of residence,marital status,activities of daily living ability,smoking,sleep duration,loneliness,community elderly care service,social interaction,and less than one contact with children per week were all influencing factors for the occurrence of cognitive impairment in the elderly(P＜0.05).Community elderly care service exerted a partial mediating effect in the impact of social isolation on the cognitive function of the elderly.Conclusion Social isolation is a risk factor for cognitive impairment in the elderly,and community elderly care service is a protective factor for cognitive impairment in the elderly.It is necessary to improve the coverage and utilization rate of community elderly care service support,improve the social isolation of the elderly,and protect the cognitive function of the elderly.

Objective:To explore the clinical and pathological features and survival outcomes of patients with early-onset intrahepatic cholangiocarcinoma (EOICC).Methods:This is a multicenter, retrospective cohort study. Data of 1 160 intrahepatic cholangiocarcinoma patients undergoing radical resection in 14 tertiary Grade A hospitals in China from January 2010 to November 2021 were retrospectively collected. The cohort included 632 males and 528 females, aged( M (IQR)) 61 (14) years (range: 22 to 93 years). ICC aged ≤50 years at the time of diagnosis was defined as EOICC and >50 years as late-onset intrahepatic cholangiocarcinoma (LOICC). Of these, there were 247 cases in the EOICC group and 913 cases in the LOICC. The clinical and pathological characteristics of both groups were analyzed and compared using the independent sample t-test, Mann-Whitney U test or Kaplan-Meier method. Univariate and multivariate Cox regression models for patient outcomes were constructed and forest graphed. Results:Compared with the patients in the LOICC group, patients in the EOICC group had lower carcinoembryonic antigen levels (2.5(4.0) μg/L vs. 3.1(5.2)μg/L, U=124 899, P=0.009) and CA19-9 level (63.4(524.7)U/ml vs. 77.9(611.3)U/ml, U=120 320, P=0.013), higher levels of ALT (29(35)U/L vs. 24(26)U/L, U=101 214, P=0.013), a lower score of the Eastern US Cooperative Oncology Group (0 score patients: 54.7% vs. 44.1%, χ2=12.472, P=0.014), higher TNM stage ( χ2=11.807, P=0.038), and proportion of lymph node dissection (62.3% vs. 54.1%, χ2=5.355, P=0.021). Patients in the two groups in sex, first diagnosis symptoms, intrahepatic bile duct stone history, nail protein, albumin, total bilirubin, transaminase, liver function Child-Pugh grade, T stage, stage, N stage, preoperative laparoscopic exploration proportion, tumor diameter, vascular invasion proportion, differentiation, margin, intraoperative bleeding, postoperative complications, postoperative hospital days were no statistical significance (all P>0.05). Patients in the EOICC group had better outcomes than the LOICC group (median survival time: 29.7 months vs. 25.0 months, 3-year overall survival: 45.1% vs. 37.8%, P=0.027). Conclusion:EOICC patients are better than LOICC patients in carcinoembryonic antigen, CA19-9, ALT, physical strength status and TNM stage, and the long-term prognosis is also better than LOICC patients.

Objective:To investigate the clinical efficacy of over-the-top reconstruction combined with the modified Lemaire technique in the treatment of anterior cruciate ligament (ACL) injuries with pivot-shift positive.Methods:From March 2020 to October 2021, a total of 46 patients with ACL injury and pivot-shift test grade II or above were admitted to Xinhua Hospital Affiliated to Dalian University. There were 28 males and 18 females, aged 28.0±10.5 years (range, 15-45 years). All cases were unilateral, including 17 cases of left knee and 29 cases of right knee. The pivot-shift test showed that 30 cases were grade II and 16 cases were grade III, and the cause of injury was sports injury. The semitendinosus muscle and gracilis muscle were harvested, and the ACL was reconstructed with the over-the-top combined modified Lemaire technique. The International Knee Documentation Committee (IKDC) score, Lysholm score and KT-2000 side-to-side difference before and after operation were compared.Results:All patients successfully completed the operation and were followed up for 26.6±2.3 months (range, 24-28 months). The Lysholm scores of the patients at 3 months and 24 months after operation were 73.6±4.3 and 91.6±2.8, which were higher than those before operation (58.5±4.6), and the difference was statistically significant ( F=18.351, P<0.001). The IKDC scores of patients at 3 months and 24 months after operation were 59.0±2.0 and 91.8±3.2, respectively, which were higher than those before operation 50.3±2.8, and the difference was statistically significant ( F=17.290, P<0.001). The side-to-side difference of KT-2000 was 1.7±0.8 mm and 1.5±0.4 mm at 3 and 24 months after operation, respectively, which was lower than that before operation (5.9±1.1 mm), and the difference was statistically significant ( F=14.192, P<0.001). At 24 months after operation, 3 patients had pivot shift test grade I and 4 patients had Lachman test grade I, but they complained of good knee stability and did not receive further treatment. At the last follow-up, there were no complications such as incision and intra-articular infection, deep vein thrombosis, knee stiffness, quadriceps musculus ossificans myositis, and reconstruction ligament rupture. All patients returned to sports with an average time of 15.7±2.6 months (range, 12-24 months). Conclusion:Over-the-top reconstruction combined with the modified Lemaire technique for the treatment of ACL injury with positive pivot shift test effectively improves knee function and promotes the patient's return to sports, with a low incidence of surgical complications.

To promote the development of the prescription-based processing of Chinese herbal pieces,the China Association of Chinese Medicine published the social organization standard of the Standard for Prescription-based Processing of Chinese Herbal Pieces(T/CACM 1367-2021)in June 2021.The standard was led by the First Affiliated Hospital of Henan University of Chinese Medicine and Jiangsu Province Hospital of Chinese Medicine.It was jointly drafted by 28 Traditional Chinese medical institutions across the country.This paper introduced the standards in detail to promote the implementation and propel the inheritance and innovation of the processing of Chinese herbal pieces.