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 analyze the influence factors on the efficacy of immunosuppression therapy (IST) combined with eltrombopag and IST alone in the treatment of childhood severe aplastic anemia (SAA).Methods:A retrospective cohort study. A total of 124 children with SAA who were initially treated with IST at Beijing Children′s Hospital from March 2017 to May 2020 were enrolled. Clinical characteristics, laboratory examination and prognosis data were collected at the time of enrollment. According to the treatment plan, the children were divided into the eltrombopag combined with IST group (eltrombopag group) and the IST group. Binary Logistic regression model was used to analyze the factors affecting the efficacy of the two groups at 6 months of treatment, and the factors affecting the efficacy of the eltrombopag group at the end of follow-up.Results:There were 75 cases (45 males and 30 females) in the eltrombopag group. The age of diagnosis was 5.9 (3.5, 8.5) years. There were 49 patients in the IST group, including 23 males and 26 females, whose age at diagnosis was 6.2 (4.4, 8.8) years. The absolute lymphocyte count before treatment in the eltrombopag group was significantly lower than that in the IST group (1.1 (0.4, 1.6)×10 9vs. 2.1 (1.4, 2.8)×10 9/L). Absolute reticulocyte count in the eltrombopag group was significantly higher than that of IST group (26.9 (8.7, 54.2)×10 9vs. 9.5 (4.0, 19.0)×10 9/L) (both P<0.05). Influencing factors of 6-month response: a comparison between response and un-response groups in the eltrombopag treated patients showed that, before treatment, hemoglobin (69 (61, 78) vs. 64 (59, 68) g/L), platelet (10 (6, 16)×10 9vs. 6 (3, 8)×10 9/L), absolute reticulocyte count (ARC) (34.0 (15.8, 57.3)×10 9vs. 6.5 (4.6, 16.8)×10 9/L) and the response rate to granulocyte colony stimulating factor (G-CSF) after treatment (82.4% (47/57) vs. 9/18) were significantly different (all P<0.05). Logistic regression model analysis showed that ARC ( OR=1.09, 95% CI 1.02-1.18) and absolute neutrophil count were independent influencing factors of 6-month response rate in the eltrombopag group ( OR=0.00, 95% CI 0.00-0.89). ARC was also the independent influencing factors of the end of follow-up response rate in the eltrombopag group ( OR=1.04, 95% CI 1.01-1.07). Conclusions:Pre-treatment blood count and response to G-CSF were predictors of overall response to eltrombopag combined with IST. The higher the ARC before treatment, the higher the total response rate and complete response.

Objective To develop a portable three-dimensional foot motion analysis system based on low-cost inertial measurement units(IMU)and force sensing resistor(FSR),and to explore the feasibility of assessing three-dimensional motion of internal small joints of foot in barefoot and shod conditions. Methods The system consisted of data sampling,data transmitting and data processing parts.IMUs were employed for data acquisition of small foot joints,and FSRs were utilized to detect heel strike and toe off.All the data were transmitted via wireless local area network.Data processing was accomplished by a self-programmed Excel mac-ro.From January to July,2024,two healthy female subjects wearing the device walked in the corridor at self-se-lected pace,for ten meters.Gait analysis was used to conduct consistency test on subject 2.Dorsiflexion-plan-tarflexion,adduction-abduction and internal rotation-external rotation of the 1st metatarsal relative to the phalan-geal(Met-Ph),the midfoot relative to the 1st metatarsal(Mid-Met)were recorded and analyzed on subject 1 in consecutive barefoot walking and two types of nurse footwear walking conditions. Results The system showed good consistency between tests.Dorsiflexion-plantarflexion,adduction-abduction and inter-nal rotation-external rotation ranges of motion were reduced in both Met-Ph and Mid-Met with shoes compared with those of bare foot,they were the least in arch support. Conclusion A low-cost,portable three-dimensional foot motion analysis system has been developed,which could be used to measure barefoot motion and shod foot motion in consecutive walking.

Objective:To investigate the effects of Porphyromonas gingivalis derived outer membrane vesicles (Pg OMV) on osteoclast differentiation of macrophages and its underlying mechanisms. Methods:The morphology and the size distribution of Pg OMV were analyzed by transmission electron microscopy and nanoparticle tracing analysis, respectively. The osteoclast precursors were treated with 1, 3 and 10 mg/L Pg OMV (1, 3 and 10 mg/L OMV treatment group) or phosphate buffer solution (PBS)(control group). The formation of osteoclasts was analyzed by tartrate-resistant acid phosphase (TRAP) staining and F-actin staining and real-time quantitative PCR (RT-qPCR) were used to detect the expression of Fos and matrix metallopeptidase 9 (MMP9). Polymyxin B (PMB) was used to block lipopolysaccharide (LPS) and then Pg OMV was used to treat osteoclast precursor (PMB-OMV treatment group), and OMV treatment group was used as control. TRAP and F-actin staining were used to observe the formation of osteoclasts and actin rings. The effect of Pg OMV on the expression of Toll-like receptor (TLR) 2 and TLR4 in preosteoclasts was detected by Western blotting. The osteoclast precursors were pretreated with 10, 50, 100 and 200 μmol/L C29, an inhibitor of TLR2, and then treated with Pg OMV(OMV+10, 50, 100 and 200 μmol/L C29 treatment group) and OMV treatment group without C29 pretreatment was control. TRAP and F-actin staining were used to observe the formation of osteoclasts and actin rings. The osteoclast precursor cells were treated with OMV (OMV treatment group) and OMV incubated with PMB (PMB-OMV treatment group) and the expression of TLR2 in osteoclast precursor was detected by Western blotting.Results:Pg OMV showed classical vesicular structures, and the average particle size of Pg OMV were 179.2 nm. A large number of actin rings were observed in the 3 and 10 mg/L OMV treatment groups. The percentages of TRAP-positive osteoclast area in 3 mg/L OMV treatment group [(22.6±2.1)%] and 10 mg/L OMV treatment group [(32.0±2.3)%] were significantly increased compared with control group [(4.9±0.5)%] ( P<0.001). Compared with the control group (1.000±0.029), the mRNA relative expression of Fos in 3 mg/L OMV treatment group (1.491±0.114) and 10 mg/L OMV treatment group (1.726±0.254) was significantly increased ( P=0.013, P=0.001). Compared with the control group (1.007±0.148), the mRNA relative expression of MMP9 in the group of 10 mg/L OMV (2.232±0.097) was significantly increased ( P<0.001). Actin ring formation was less in PMB-OMV treatment groups than in OMV treatment groups. The proportion of TRAP-positive osteoclasts area [(14.8±3.8)%] in PMB-OMV treatment group was significantly lower than OMV treatment group [(31.5±6.7) %] ( P=0.004). The relative expression of TLR2 in OMV treatment group (1.359±0.134) was significantly higher than that in the control group (1.000±0.000) ( t=4.62, P=0.044). Compared with the OMV treatment group [(29.4±1.7)%], 50, 100 and 200 μmol/L C29 significantly decreased the formation of osteoclasts [(24.0±1.7)%, (18.5±2.1)%, (9.1±1.3) %] ( P=0.026, P<0.001, P<0.001). TLR2 protein expression in PMB-OMV group (0.780±0.046) was significantly lower than that in OMV group (1.000±0.000)( t=8.32, P=0.001). Conclusions:Pg OMV can promote osteoclast differentiation by carrying LPS, TLR2 plays an important role in Pg OMV mediated osteoclast differentiation.

Animals ; Callithrix ; Sex Factors ; Vocalization, Animal ; Sex Characteristics

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.

Objective To observe the value of anatomical characteristics of femoral intercondylar notch of knee joint for predicting non-contact anterior cruciate ligament tear(NC-ACLT).Methods MRI data of knee joint of 55 patients with NC-ACLT(NC-ACLT group)and 55 controls(control group)were retrospectively analyzed.The parameters of intercondylar notch,including depth,width,depth/width ratio,opening width,opening width index,area and width of the femoral condyle's outer edge at the same level were measured between groups,and the types of intercondylar notch(type A,U and W)were recorded.Univariate and multivariate logistic regression analysis were used to screen the independent impact factors of NC-ACLT.Receiver operating characteristic curves were drawn,and the area under the curves(AUC)were calculated to evaluate the efficacy of each intercondylar notch parameter for predicting NC-ACLT.Results The depth and depth/width ratio of intercondylar notch in NC-ACLT group were both higher,while the opening width and opening width index of intercondylar notch in NC-ACLT group were both lower than those in control group(all P＜0.05).Multivariate logistic regression analysis revealed that the depth of intercondylar notch was an independent impact factors of NC-ACLT(P＜0.05).Taken 29.55 mm in depth of intercondylar notch,1.45 in depth/width ratio of intercondylar notch,21.15 mm in opening width of intercondylar notch and 0.29 in opening width index as the optimal cut-off value,respectively,the sensitivity of the above parameters for predicting NC-ACLT was 74.55％,58.18％,67.27％and 67.27％,the specificity was 69.09％,80.00％,61.82％and 78.18％,and the AUC was 0.720,0.713,0.652 and 0.710,respectively.Conclusion The anatomical characteristics of femoral intercondylar notch of knee joint could be used to predict NC-ACLT.The depth,depth/width ratio,opening width and opening width index of intercondylar notch could be used as predictive indicators.

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.

OBJECTIVE To evaluate the quality of total flavonoids of Lamiophlomis rotata from different producing areas. METHODS Total flavonoids of S1-S15 batches of L. rotata from different producing areas were extracted by percolation and purified by polyamide column. The content of total flavonoids was determined by UV spectrophotometry， and its purity was calculated. HPLC fingerprint chromatograms and control fingerprint of total flavonoids from 15 batches of L. rotata were established with Similarity Evaluation System of Chromatographic Fingerprint of TCM （2012 version）. Their similarities were analyzed. Cluster analysis， principal component analysis and orthogonal partial least squares-discriminant analysis were used to evaluate the quality of total flavonoids from 15 batches of L. rotata， and the main components which affected the quality of total flavonoids were analyzed. RESULTS The purities of total flavonoids from 15 batches of L. rotata were 55.82%-94.12%， with an average value of 77.72%； a total of five common peaks were identified in the fingerprint， and No. 3 peak was luteolin； the similarities between the fingerprint of each batch of samples and the control fingerprint were 0.925-1.000. By cluster analysis， S1 and S3-S9 were clustered into the first class， which were samples from Qinghai Province and Tibet Autonomous Region. S14 and S15 were clustered into the second class， which were samples from Yunnan Province. S10-S13 were clustered into the third class， which were all samples from Sichuan Province. S2 was clustered into the fourth class. The principal component analysis showed that the qualities of samples from the first and fourth classes were better； peaks 2， 3 and 5 were identified as the main components that caused the differences among different batches of samples by orthogonal partial least squares-discriminant analysis. CONCLUSIONS The qualities of total flavonoids of L. rotata from Qinghai Province and Tibet Autonomous Region are better.

Objective:To investigate the efficacy of shoulder arthroscopic balance point compaction with cross suture-bridge technique inr the treatment of avulsion fracture of the greater tuberosity of the humerus.Methods:A retrospective case series study was conducted on 14 patients with avulsion fracture of the greater tuberosity of the humerus treated in Affiliated Xinhua Hospital of Dalian University from March 2021 to March 2022, including 8 males and 6 females; aged 30-58 years [(40.2±10.5)years]. Among them, 5 patients had fracture in the left shoulder and 9 in the right shoulder. The fracture was classified as the avulsion type according to Mutch classification. All the patients were treated with shoulder arthroscopic balance point compaction with cross suture-bridge technique. The anteroposterior X-ray of the shoulder joint was taken at 1 week, 3 months, and 6 months after surgery to evaluate fracture reduction and fixation. The operative time and intraoperative blood loss were recorded. Fracture healing was evaluated by shoulder MRI at 6 months after surgery. The visual analog score (VAS), Constant shoulder joint score, American Shoulder and Elbow Surgeons (ASES) score, and shoulder range of motion (active abduction angle, active lateral external rotation angle, and active lateral internal rotation) preoperatively, at 3, 6 months after surgery and at the last follow-up were compared. The postoperative complications were observed.Results:All the patients were followed up for 12-15 months [(12.5±0.8)months]. The operative time and intraoperative blood loss were (67.0±10.5)minutes and (20.0±3.8)ml. The anteroposterior X-ray of the shoulder joint showed good reduction and fixation at 1 week, 3 months and 6 months after surgery. MRI T1 image at 6 months after surgery showed locally evenly distributed high signal, suggesting that the fracture was healed well. The values of VAS were (3.2±0.4)points, (2.5±0.5)points, and (0.7±0.3)points at 3, 6 months after surgery and at the last follow-up, which were lower than (7.2±0.6)points preoperatively; the values of Constant joint shoulder score were (53.2±5.3)points, (81.1±4.4)points, and (92.8±5.3)points, which were higher than (42.3±7.6)points preoperatively; the values of ASES score were (55.6±3.6)points, (77.1±3.2)points, and (90.8±3.5)points, which were higher than (45.8±4.2)points preoperatively; the active abduction angles were (60.5±2.5)°, (107.8±6.6)°, and (168.5±3.5)°, which were higher than (18.3±3.3)°preoperatively; the active lateral external rotation angles were (25.8±2.5)°, (30.8±2.2)°, and (63.8±2.8)°, which were higher than (15.6±3.2)°preoperatively ( P<0.05 or 0.01). The level of active internal rotation was L 5, L 1, and T 10, which was better than S 3 before surgery. The VAS, Constant shoulder joint score, ASES score, active abduction and active external rotation were significantly improved at the last follow-up compared with those at 3, 6 months after surgery (all P<0.05), with markedly improved level of active internal rotation. No major complications such as infection, instability of the shoulder joint or acromial impingement were found after surgery. Conclusion:Shoulder arthroscopic balance point compaction with cross suture-bridge technique for the treatment of avulsion fracture of the greater tuberosity of the humerus has advantages of decreased intraoperative blood loss, good reduction and healing, shoulder pain relief, early restoration of shoulder function and mobility, and few complications.