This study adopted a three-dimensional "effect-dose-mechanism" evaluation system to screen the optimal regimen of Yuxuebi Tablets(YXB) combined with ibuprofen(IBU) for chronic musculoskeletal pain(CMP) intervention and elucidate its pharmacological mechanism, so as to provide a scientific basis for the clinical application of the regimen. The experiments were conducted using 8-week-old ICR mice, which were randomly divided into sham operation(sham) group, model(CFA) group, IBU group, YXB group, stasis paralysis tablets combined with ibuprofen low-dose group(IBU-L-YXB), stasis paralysis combined with ibuprofen high-dose group(IBU-H-YXB), stasis paralysis tablets combined with ibuprofen high-dose with ibuprofen discontinuation on the 10th day of administration(IBU-10-YXB), and stasis paralysis tablets combined with ibuprofen high-dose with ibuprofen halving on the 10th day of administration(IBU-1/2-YXB) group. An animal model was established using the CFA plantar injection method. On D0(the second day post-modeling), the success of model establishment was assessed, followed by continuous drug administration for 18 consecutive days from D1 to D18. During this period, mechanical pain threshold was measured by the Von Frey test; thermal hyperalgesia was detected by the hot plate test, and depression-like behavior was observed by the tail suspension test. After treatment, peripheral blood was collected from all groups for complete blood biochemical analysis, and the injected feet of the sham, CFA, IBU, YXB, IBU-YXB, and IBU-10-YXB groups were subjected to oxylipin metabolomics analysis. Immunofluorescence double staining was further performed to detect the co-expression of key oxylipin metabolic enzymes(COX2, LTA4H, and 5/12/15-LOX) and macrophage marker CD68 in the sham, CFA, IBU, and YXB-L/M/H groups. Subsequently, confirmatory analysis of positive indicators was conducted in the sham, CFA, IBU, YXB, IBU-YXB, and IBU-10-YXB groups. On D6(acute phase), mechanical pain sensitivity data showed that compared with the CFA group, only the three combination groups(IBU-YXB, IBU-10-YXB, and IBU-1/2-YXB) exhibited significantly increased paw withdrawal thresholds. On D17(chronic phase), only the IBU-10-YXB group showed a mechanical pain threshold significantly higher than all other monotherapy and combination groups. On D17, thermal pain data showed that compared with the CFA group, all groups except IBU-1/2-YXB had significantly prolonged paw withdrawal latency. On D18, tail suspension data showed that compared with the CFA group, the YXB, IBU-YXB, and IBU-10-YXB groups had significantly reduced immobility time. In summary, IBU-10-YXB stably improved the core symptoms of acute and chronic inflammatory pain. Complete blood count data showed that compared with the sham group, the CFA group had significantly increased mean platelet volume(MPV), while compared with the CFA group, the IBU-YXB and IBU-10-YXB groups had significantly reduced MPV. Moreover, the platelet distribution width(PDW) of the IBU-10-YXB group was further reduced compared with the CFA group. These data suggest that the IBU-10-YXB combination regimen has superior effects on inflammation and blood circulation improvement compared with other treatment groups. At the mechanistic level, each treatment group differentially regulated pro-inflammatory and pro-resolving oxylipin(SPM). Specifically, compared with the CFA group, the IBU and IBU-YXB groups significantly inhibited the synthesis of the prostaglandin family downstream of COX2, reducing pro-inflammatory oxylipins PGD2 and 6-keto-PGF1α but inhibiting PGE1 and PGE2, which played positive roles in peripheral circulation, vasodilation, and inflammation resolution. Compared with the CFA group, the YXB group tended to inhibit the pro-inflammatory oxylipin LTB4 downstream of LTA4H and increase SPMs such as LXA4. The IBU-10-YXB group bidirectionally regulated pro-inflammatory oxylipins and SPMs. Compared with IBU, IBU-10-YXB significantly inhibited the pro-inflammatory mediator 5-HETE. Meanwhile, IBU-10-YXB broadly upregulated SPMs, as evidenced by significant upregulation of LXA4 compared with the CFA group, significant upregulation of LXA5 compared with the IBU and IBU-YXB groups, significant upregulation of RvD1 compared with the CFA group and all other treatment groups, and significant upregulation of RvD5 compared with the sham group. Immunofluorescence double staining results were as follows: compared with the CFA group, the IBU group specifically inhibited the oxylipin metabolic enzyme COX2. In the YXB group, COX2, LTA4H, and 5/12-LOX were significantly inhibited. Within the optimal analgesic dose range, YXB's inhibitory effects on COX2 and LTA4H were dose-dependent, while its inhibitory effects on 5/12-LOX were inversely dose-dependent. The two combination groups(IBU-YXB and IBU-10-YXB) inhibited COX2 and LTA4H without significantly affecting 5-LOX, while IBU-10-YXB further significantly inhibited 12-LOX. These results suggest that the IBU-10-YXB combination regimen effectively maintains stable inhibition of COX2, LTA4H, and 12-LOX while enhancing 5-LOX expression. This combinatorial strategy effectively suppresses pro-inflammatory oxylipins and promotes SPM biosynthesis, overcoming IBU's analgesic ceiling effect and its blockade of pain resolution pathways while compensating for YXB's inability to effectively intervene in acute pain and inflammation. Therefore, it achieves more stable anti-inflammatory, analgesic, and antidepressant effects.
Animals ; Ibuprofen/administration & dosage* ; Mice ; Mice, Inbred ICR ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Musculoskeletal Pain/immunology* ; Tablets ; Humans ; Chronic Pain/metabolism* ; Drug Therapy, Combination ; Disease Models, Animal

In order to investigate whether the effect of Yuxuebi Tablets on the peripheral and central inflammation resolution of mice with inflammatory pain is related to their regulation of G protein-coupled receptor 37(GPR37), an inflammatory pain model was established by injecting complete Freund's adjuvant(CFA) into the paws of mice, with a sham-operated group receiving a similar volume of normal saline. The mice were assigned randomly to the sham-operated group, model group, ibuprofen group(91 mg·kg~(-1)), and low-, medium-, and high-dose groups of Yuxuebi Tablets(60, 120, and 240 mg·kg~(-1)). The drug was administered orally from days 1 to 19 after modeling. Von Frey method and the hot plate test were used to detect mechanical pain thresholds and heat hyperalgesia. The levels of interleukin-10(IL-10) and transforming growth factor-beta(TGF-β) in the spinal cord were quantified using enzyme-linked immunosorbent assay(ELISA), and the mRNA and protein expression of GPR37 in the spinal cord was measured by real-time quantitative reverse transcription PCR(qRT-PCR) and Western blot. Additionally, immunofluorescence was used to detect the expression of macrosialin antigen(CD68), mannose receptor(MRC1 or CD206), and GPR37 in dorsal root ganglia, as well as the expression of calcium-binding adapter molecule 1(IBA1), CD206, and GPR37 in the dorsal horn of the spinal cord. The results showed that compared with those of the sham-operated group, the mechanical pain thresholds and hot withdrawal latency of the model group significantly declined, and the expression of CD68 in the dorsal root ganglia and the expression of IBA1 in the dorsal horn of the spinal cord significantly increased. The expression of CD206 and GPR37 significantly decreased in the dorsal root ganglion and dorsal horn of the spinal cord, and IL-10 and TGF-β levels in the spinal cord were significantly decreased. Compared with those of the model group, the mechanical pain thresholds and hot withdrawal latency of the high-dose group of Yuxuebi Tablets significantly increased, and the expression of CD68 in the dorsal root ganglion and IBA1 in the dorsal horn of the spinal cord significantly decreased. The expression of CD206 and GPR37 in the dorsal root ganglion and dorsal horn of the spinal cord significantly increased, as well as IL-10 and TGF-β levels in the spinal cord. These findings indicated that Yuxuebi Tablets may reduce macrophage(microglial) infiltration and foster M2 macrophage polarization by enhancing GPR37 expression in the dorsal root ganglia and dorsal horn of the spinal cord of CFA-induced mice, so as to improve IL-10 and TGF-β levels, promote resolution of both peripheral and central inflammation, and play analgesic effects.
Inflammation/genetics* ; Pain/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Mice ; Freund's Adjuvant/pharmacology* ; Ibuprofen ; Pain Threshold/drug effects* ; Hyperalgesia/genetics* ; Ganglia, Spinal ; Interleukin-10/genetics* ; Transforming Growth Factor beta/genetics* ; Reverse Transcriptase Polymerase Chain Reaction ; Tablets ; Receptors, G-Protein-Coupled

OBJECTIVE: To investigate the effect of innovative perioperative pain management on prostate cancer patients with hematuria undergoing prostatic artery embolization (PAE). METHODS: A total of 60 patients undergoing PAE in the Interventional Therapy Department of General Hospital of Eastern Theater Command from May 2024 to January 2025 were selected by convenience sampling method and randomly divided into the intervention group and the control group, with 30 patients in each group. The control group received traditional pain management of nursing. An innovative perioperative pain management was performed in intervention group including preoperative "body-mind-pain" holistic assessment and preparation, intraoperative humanistic care and real-time support, postoperative multimodal analgesia and rehabilitation, dynamic monitoring and closed-loop feedback. The pain degree after 6 hours, 1 day, 3 days and 1 week of the operation, and the quality of life after 1 week of operation, as well as nursing satisfaction at discharge were compared between the two groups. RESULTS: The VAS scores of the intervention group were significantly lower than those of the control group after 6 hours, 1 day, 3 days and 1 week of operation (P<0.05). One week after the operation, the quality of life in the observation group was higher than that of the control group significantly (P<0.05). The nursing satisfaction of the observation group was significantly higher than that of the control group at discharge(P<0.05). CONCLUSION The application of innovative perioperative pain management can alleviate pain of patients with PAE, which improves the quality of life and nursing satisfaction of patients, and is conducive to the rehabilitation of patients.
Humans ; Male ; Embolization, Therapeutic ; Hematuria/therapy* ; Prostatic Neoplasms/surgery* ; Pain Management/methods* ; Quality of Life ; Prostate/blood supply* ; Perioperative Care ; Pain, Postoperative ; Middle Aged ; Aged ; Pain Measurement

Objective : To explore the expression profile of core 1 β1,3-galactosyltransferase 1(C1GALT1) in glioblastoma(GBM) and to elucidate its impact on the initiation and progression of GBM. Methods : The expression levels and prognostic significance of C1GALT1 in GBM were analyzed using the GEPIA and CGGA databases. Two representative glioblastoma cells(U251 and LN18) were selected to construct C1GALT1-knockdown cell lines and performed in vitro experiments. The Cell Counting Kit-8(CCK-8) and Transwell assays were employed to evaluate the impact of C1GALT1 on proliferation, migration and invasion of GBM cells. Transcriptome data were analyzed to identify potential signaling pathways. Senescence β-Galactosidase Staining Kit was used to detect β-galactosidase activity. Results : nalysis of GEPIA and CGGA databases revealed that C1GALT1 was significantly upregulated in GBM tissues compared to adjacent non-cancerous tissues (P < 0. 05) , and its high expression was associated with poor prognosis of patients (P < 0. 000 1) . The CCK-8 experiment demonstrated a significant reduction in prolifera- tion rate following C1GALT1 knockdown (P < 0. 05) . Transwell assay showed that cell migration and invasion de- creased after C1GALT1 was knocked down ( P < 0. 001) . Transcriptome sequencing and senescence β-galactosi- dase staining showed that C1GALT1 was involved in the cellular senescence signaling pathway , and the activity of β-galactosidase associated with cellular senescence significantly increased after C1GALT1 was knocked down(P < 0. 05) . Conclusion C1GALT1 is overexpressed in GBM tissues and may promote the proliferation , migration and invasion of GBM cells by inhibiting cellular senescence .

Objective To analyze the incidence and mortality of gastric cancer in countries and territories with different human development index(HDI)levels in 2022,and to understand the burden of gastric cancer globally and in China.Methods Data on gastric cancer incidence and mortality were collected from GLOBOCAN 2022 and HDI data for all countries were obtained from the Human development report 2022.Spearman correlation was applied to examine the associations between the age-standardized incidence rate(ASIR),age-standardized mortality rate(ASMR),mortality-to-incidence ratio(M/I),and HDI for gastric cancer.The Wilcoxon rank-sum test was used to assess the differences in ASIR and ASMR between males and females.Results In 2022,gastric cancer ranked the 5th in both incidence and mortality among all cancer types globally.In China,gastric cancer ranked the 5th in incidence and the 3rd in mortality among all cancer types.The ASIR and ASMR of gastric cancer showed a descending trend from high,very high,medium to low HDI countries and territories.The ASIR of gastric cancer was positively correlated with HDI(rs=0.256,P=0.001),while ASMR showed no significant correlation with HDI(rs=-0.008,P=0.918).The M/I was negatively correlated with HDI(rs=-0.831,P＜0.001).The ASIR and ASMR of gastric cancer in males were significantly higher than those in females globally,in China,and across all HDI groups(all P＜0.05).Globally,both ASIR and ASMR of gastric cancer remained relatively stable before the age of 45,but showed a consistently rising trend after the age of 45.In China,the ASIR and ASMR of gastric cancer exceeded global average level across all age groups.Conclusion The burden of gastric cancer incidence and mortality is higher in very high and high HDI countries and territories compared to medium and low HDI countries and territories.In China,the burden of gastric cancer incidence and mortality is above the global average,highlighting the need for targeted prevention and control measures.

Objective To compare the incidence and mortality of brain and central nervous system(CNS)tumors in countries and territories with different human development index(HDI)in 2022,to make a comparison with the current epidemiological situation in China,and to assess the association between HDI and the incidence and mortality of brain and CNS tumors.Methods The data on brain and CNS tumors from GLOBOCAN 2022 were collected,and HDI data were organized based on the Human development report 2022.Generalized additive model(GAM)was used to analyze the relationships between standardized incidence ratio(SIR),standardized mortality ratio(SMR),mortality-to-incidence ratio(M/I),and HDI.Results The incidence and mortality of brain and CNS tumors increased with age in 2022,with a significant increasing trend in countries and territories with very high HDI.Countries and territories with high and very high HDI had more cases and more deaths,and countries and territories with very high HDI had the highest SIR and SMR.SIR for brain and CNS tumors in China was higher than the global average,while China's SMR was lower.M/I varied among countries and territories with different HDI,with lower M/I in countries and territories with high and very high HDI.HDI had a significant nonlinear effect on SIR(edf=1.740,P＜0.000 1)and M/I(edf=1.809,P＜0.000 1),and a significant linear effect on SMR(edf=1,P＜0.000 1).As HDI increased,SIR and SMR generally showed an increasing trend,while M/I showed a decreasing trend.Conclusion There are significant global differences in incidence and mortality of brain and CNS tumors in patients with different HDI in 2022;increasing HDI can reduce the risk of brain and CNS tumors and improve treatment outcomes,and prevention and control strategies should be made for different age groups and HDI.

Objective To evaluate the short-term clinical effect(including curative efficacy,pain relief,and quality of life)of CT-assisted 3D printing template-guided implantation of 125I particles in treating head and neck malignancies.Methods A total of 12 patients with head and neck malignant tumors complicated by moderate to severe cancerous pain,who were admitted to Yichang Municipal second People's Hospital to receive treatment from September 2019 to July 2024,were enrolled in this study.All patients received CT-assisted 3D individualized template-guided implantation of 125I particles therapy.The short-term curative efficacy,pain relief,and quality of life of patients were evaluated.Results Three months after implantation of 125I particles,complete response(CR)was obtained in 3 patients,partial remission(PR)in 5 patients,and stable disease(SD)in 4 patients,with an objective response rate(ORR)of 66.67％and a disease control rate(DCR)of 100％.The preoperative mean NRS score was(5.58±0.79)points,and the postoperative 3-month mean NRS score was(2.08±0.67)points.The postoperative 3-month physiological well-being(PWB),emotional well-being(EWB),functional well-being(FWB),and the total score were significantly better than their preoperative values,the differences were statistically significant(P＜0.05).No statistically significant difference in social/family well-being(SWB)existed between its postoperative 3-month value and its preoperative value.Adverse reactions occurred in 2 patients,including local mucosal ulceration(n=1)and skin redness with swelling(n=1),which were improved after treatment.No serious complications occurred.Conclusion For the treatment of patients with head and neck malignant tumors complicated by moderate to severe cancerous pain,radioactive 125I particle implantation has a significant short-term effect,it can effectively relieve cancerous pain and improve quality of life of patients with reliable clinical safety.

The purpose of this study was to investigate the intervention effect and mechanism of Lycium barbarum leaves on letrozole-induced polycystic ovary syndrome (PCOS) mice. The PCOS model was prepared by letrozole combined with high-fat diet. After successful modeling, 40 mice were randomly divided into PCOS group, positive drug metformin group, low-dose Lycium barbarum leaves group, and high-dose Lycium barbarum leaves group. The corresponding drugs were given by gavage for 29 days. At the end of the experiment, the eyeballs were removed for blood collection and ovarian tissue was collected. The ovarian mass, fasting blood glucose (FBG), fasting insulin (FINS), testosterone (T), anti-Mullerian hormone (AMH), luteinizing hormone (LH), follicle stimulating hormone (FSH), and estradiol (E₂) levels were measured in each group. The morphology of ovarian tissue was observed by hematoxylin-eosin staining, and the oocytes, cystic follicles and corpus luteum were counted. Cecal contents of mice were collected for analysis of intestinal flora composition and differential flora. The animal experiment process was approved by the Animal Ethics Committee of Nanjing University of Traditional Chinese Medicine. The results showed that the estrous cycle of PCOS mice was disordered. Compared with the PCOS group, the Lycium barbarum leaves group can significantly reduce the ovarian damage of mice, reduce the number of cystic dilated follicles, and normalize the estrous cycle. After the intervention of Lycium barbarum leaves, the levels of FBG, FINS, T, AMH, LH, FSH and LH/FSH were significantly decreased (P < 0.05), while the level of E₂ was significantly increased (P < 0.001). In addition, Lycium barbarum leaves can regulate the disorder of intestinal flora diversity in PCOS mice, increase the abundance of Bacteroidetes, and reduce the abundance of Firmicutes, Ileibacterium, Romboutsia and Faecalibaculum. In summary, Lycium barbarum leaves can play a therapeutic role in PCOS mice by improving insulin resistance, regulating reproductive hormone disorders and gut microbiota imbalance. It provides scientific basis and useful reference for the rational utilization and development of Lycium barbarum leaves.

As a novel iron-dependent form of cell death, ferroptosis is characterized by the excessive accumulation of phospholipids containing polyunsaturated fatty acids (PUFA) on the cell membrane and peroxidation. Lipid droplets are always in the dynamic transition of generation and decomposition, play a central role in regulating lipid metabolism, and are always in the dynamic transition of generation and decomposition. Lipid droplet metabolism is closely related to the occurrence of ferroptosis and plays an important role in the disease caused by ferroptosis. This review firstly focuses on the lipid droplet metabolism process and its effects on the storage and release of PUFA, and further elucidates the regulatory mechanism and key regulatory proteins of lipid drop metabolism on ferroptosis, in order to reveal the intrinsic relationship between lipid droplets and ferroptosis, and provide a new strategy for disease prevention and treatment.

Aim To investigate whether salvianolic acid B ( Sal B) has inhibitory effect on hepatoma HuH- 7 cells and explore whether it works via Hippo/YAP signaling pathway. Methods HuH-7 cells were induced by TGF-β1 (9 pmol · L