OBJECTIVE: To explore the pain-location interaction between pressure-sensitive points on the body surface and traditional acupoints in patients with chronic non-specific low back pain (CNLBP) under different disease courses, using Euclidean distance and multivariate statistical analysis. METHODS: A pressure-sensitive point detection was performed on 30 CNLBP patients with varying disease courses. A constant pressure was applied using an FDK20 algometer within a designated lumbar area, a total of 50 points were tested, and the tested points were numbered; the visual analogue scale (VAS) pain score was recorded simultaneously. MatlabR2022a9.12. software was used to extract the positions of pressure-sensitive points, and preprocessing and normalization of point location and VAS scores data were conducted. Under constraint conditions (VAS≥8.0 ∩ Euclidean distance to acupoint≤0.5), the proportion of pressure-sensitive points within the Euclidean distance threshold to each acupoint (PVD_acupoint) was calculated, followed by multivariate statistical analysis. RESULTS: ①Constrained analysis of PVD_acupoint showed that PVD_{Qihaishu (BL24)} and PVD_{Dachangshu (BL25)} were positively correlated with disease course (r=0.55, P<0.01). ②Factor analysis and silhouette analysis revealed that PVD_{Shenshu (BL23)} and PVD_{Dachangshu (BL25)} exhibited trends consistent with disease course progression (P>0.05), with different degree (P<0.01). CONCLUSION The PVD_acupoint value based on Euclidean distance can characterize the pressure sensitivity features of traditional acupoints associated with disease. Multivariate statistical analysis of PVD_acupoint confirms that selecting the acupoint combination of Shenshu (BL23) and Dachangshu (BL25) for CNLBP is associated with the distribution of surrounding pressure-sensitive points and the pathological characteristics of the condition.
Humans ; Acupuncture Points ; Low Back Pain/physiopathology* ; Male ; Female ; Middle Aged ; Adult ; Aged ; Acupuncture Therapy ; Young Adult ; Pressure

OBJECTIVES: To study the mechanism mediating the protective effect of asiaticoside (AS) against myocardial ischemia-reperfusion injury (MIRI) in rats. METHODS: Fifty SD rats were randomized into sham-operated group, MIRI model group and AS treatment group. AS treatment was administered at low, moderate and high doses by daily gavage for 2 weeks before MIRI modeling (n=10). Serum levels of lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB), interleukin-18 (IL-18) and IL-1β, the volume of myocardial infarction and ischemia, and myocardial pathologies of the rats were determined or observed. The protein expression levels of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1β and IL-18 in the myocardial tissues were detected using Western blotting. The changes in the expression levels of these proteins were also detected in H9C2 cells with AS pretreatment prior to hypoxia-reoxygenation (H/R) injury. RESULTS: The rats models of MIRI exhibited significant myocardial infarction and ischemia with increased serum levels of LDH and CK-MB and myocardial expressions of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1β and IL-18. AS pretreatment effectively reduced myocardial infarction volume in the rat models and significantly reduced serum LDH and CK-MB levels and the protein levels in the myocardial tissue in a dose-dependent manner. In the H9C2 cell model of H/R injury, AS pretreatment significantly suppressed the elevation of the protein expressions of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1β and IL-18. Molecular docking studies showed that AS had a strong binding affinity with NLRP3. CONCLUSIONS Asiaticoside can alleviate MIRI in rats possibly by inhibiting NLRP3 inflammasome-mediated pyroptosis.
Animals ; Myocardial Reperfusion Injury/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Pyroptosis/drug effects* ; Rats, Sprague-Dawley ; Rats ; Inflammasomes/metabolism* ; Triterpenes/pharmacology* ; Interleukin-18/metabolism* ; Male ; Interleukin-1beta/metabolism* ; Caspase 1/metabolism*

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Objective To evaluate the characteristics of dose distribution of neuronal networks in vitro on microelectrode arrays(MEAs)under 2.6 GHz radiofrequency(RF)exposure.Methods The MEAs were coupled with a real-time RF exposure setup,and electromagnetic simulation software was used to calculate the RF dose absorbed in cultured neuronal networks.A fiber-optic temperature probe was used for experimental validation and monitoring of the cell temperature during RF exposure.The MEAs were used to record the electrical activity of neurons.Results For an input power of 1 W,a specific absorption rate(SAR)level of(15.51±2.48)W/kg was calculated,and the variability of the SAR distribution was 16%.In our experimental system,the temperature elevation of neurons was up to 0.15℃for an SAR of 4 W/kg RF exposure.Conclusion The exposure device can provide high SAR efficiency and uniformity in the 2.6 GHz band,which is suitable for studying the real-time effects of RF fields on the electrical activity of neuronal networks in the 5G network band.

Objective: To understand the interrelationships of parental control, peer relationship, and aggressive behavior in junior high school students, in order to provide a theoretical basis for preventing the occurrence of adolescent aggressive behavior. Methods: During June to July, 2022, 2 564 students of grade one to grade three were selected from 6 junior high schools from each of Suzhou and Xuancheng cities in Anhui Province by using convenient cluster random sampling method, and then the questionnaire survey was administered, including the Chinese version of Parent Control Questionnaire, Chinese version of Buss & Perry Aggression Questionnaire and Adolescent Peer Relationship Questionnaire. Results: Boys scored (185.31±27.49, 21.65±7.43, 21.77 ±8.18, 69.50±11.41, 72.39±11.53) higher than girls (178.21±25.13, 20.08±7.09, 20.61±7.62, 66.56± 11.14 , 70.95± 11.84 ) in parental control, father s psychological control, mother s psychological control, father s behavioral control, and mother s behavioral control ( t =8.63, 5.47, 3.70, 6.60, 3.12), while girls scored (48.41±11.26) higher in peer relationship than boys ( 47.13 ± 10.84 ) ( t =-2.95) ( P <0.01). The scores of first grade students in parental control, father s psychological control, mother s psychological control, father s behavior control, peer relationship, and aggressive behavior (184.67±27.18, 21.83± 7.29 , 22.15±8.07, 68.81±10.95, 50.21±9.57, 80.23±17.66) were higher than those of second gradestudents (180.98±25.46, 20.16±7.82, 20.21±7.55, 68.29±11.69, 45.47±11.67, 74.08±17.70) and third grade students (179.21±26.79, 20.53±7.22, 21.17 ± 8.06 , 66.81± 11.39 , 47.54±11.43, 75.75±16.29) ( F =9.44, 12.87, 13.61, 6.84, 42.85, 30.40, P <0.01). The scores of parental control and peer relationship were positively correlated with the scores of aggressive behavior ( r=0.22, 0.47, P <0.01). Peer relationship partially mediate the relationship between parental control and aggressive behavior, with a partial mediation effect value of 0.04, accounting for 26.39% of the total effect of parental control on aggressive behavior. Conclusions High parental control and poor peer relationship are both positively correlated with the level of aggressive behavior. The peer relationship of teenagers should be improved by establishing appropriate parenting style, tackling campus violence, and maintaining good social norms, in order to reduce the occurrence of aggressive behavior among adolescents.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Objective To investigate the status quo and its influencing factors of nurses'organizational silence in 3 Grade A general hospitals.Methods Convenient sampling method was used to investigate clinical nurses in 3 Grade A general hospitals in Xi'an from April to August 2023 by general data questionnaire,nurses'organizational silence questionnaire and hospital magnetic factor scale.Multiple linear regression was used to analyze the influencing factors of organizational silence.Results A total of 855 nurses completed the study.The total silence score of nurses was(56.33±8.55);The total score of hospital magnetic level was(107.63±12.85).There was a negative correlation between nurse tissue silence and hospital magnetic level(r=-0.318,P<0.01).Hospital magnetic level,age,job title and working time were the influential factors of nurses'organizational silence(all P<0.001),which together explained 62.60%of the variation.Conclusions The silence of nurses'tissue and the level of hospital magnetism are in the low-medium level.Nurses are younger in age,lower in professional title,shorter in nursing age and lower in hospital magnetism level,the higher the tissue age level is,the nursing managers can reduce the tissue silence of nurses by improving the hospital magnetism level.