Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

OBJECTIVES: To evaluate the inhibitory effect of oridonin against proliferation of pancreatic cancer cells and the mechanism underlying the synergistic effect of low-intensity pulsed ultrasound (LIPUS). METHODS: PANC-1 cells treated with different concentrations of oridonin were examined for changes in cell proliferation using CCK-8 assay and in MDA, GSH and ATP levels using flow cytometry. The protein expressions of GPX4, Nrf2 and HO-1 in the treated cells were detected with Western blotting. The effect of Fer-1, a ferroptosis inhibitor, on proliferation of oridonin-treated cells were assessed, and the effects of oridonin combined with LIPUS on PIEZO1 protein expression was evalauted using Western blotting. A C57BL/6J mouse model bearing pancreatic cancer cell xenograft was established and treated with oridonin, LIPUS, or both, and the histological changes in the tumor tissues and tumor cell proliferation were examined with HE staining and immunohistochemistry for Ki67; the changes in GPX4 expression in the tumor tissues were detected using Western blotting and immunofluorescence staining. RESULTS: In PANC-1 cells, oridonin treatment significantly inhibited cell proliferation, increased intracellular Fe²⁺, ROS, and MDA levels, and decreased GSH and ATP levels. Oridonin also resulted in lowered GPX4 and increased HO-1 and Nrf2 protein expression levels in the cells. The combined treatment with LIPUS signficiantly enhanced the inhibitory effect of oridonin on PANC-1 cell viability in vitro and on xenograft growth in the mouse models, resulting also in more obvious reduction of the intensity of Ki67 staining and GPX4 protein expression and more pronounced increase of PIEZO1 protein expression in the tumor tissues in the mouse models. CONCLUSIONS LIPUS enhances the effect of oridonin to promote ferroptosis of pancreatic cancer cells by activating PIEZO1 through the Nrf2/HO-1/GPX4 pathway.
Ferroptosis/drug effects* ; Animals ; Pancreatic Neoplasms/metabolism* ; NF-E2-Related Factor 2/metabolism* ; Humans ; Cell Line, Tumor ; Mice ; Heme Oxygenase-1/metabolism* ; Diterpenes, Kaurane/pharmacology* ; Cell Proliferation/drug effects* ; Mice, Inbred C57BL ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Ion Channels/metabolism* ; Ultrasonic Waves ; Signal Transduction

Objective To comparatively evaluate the clinical efficacy of liposomal bupivacaine and ropiva-caine in transversus abdominis plane(TAP)block combined with intravenous patient-controlled analgesia(PCA)following cesarean section,and to explore the analgesic advantages of liposomal bupivacaine.Methods Eighty parturients scheduled for elective cesarean section were recruited and randomly allocated into two groups via a random number table:the liposomal bupivacaine group and the ropivacaine group.At the conclusion of the surgical procedure,both groups underwent ultrasound-guided bilateral TAP block.In the ropivacaine group,20 mL of 0.5%ropivacaine was administered per side.In the liposomal bupivacaine group,266 mg of liposomal bupivacaine was dissolved in 0.9%normal saline to a total volume of 40 mL,with 20 mL injected per side.The following parameters were compared between the two groups:Visual Analog Scale(VAS)scores at rest and during movement at various postop-erative time points,the overall scores of the 15-item Quality of Recovery(QoR-15)scale,postoperative opioid consumption,the time to first ambulation,the time to first flatus,and the incidence of adverse drug reactions such as nausea,vomiting,constipation,and pruritus.Results In comparison with the ropivacaine group,the liposomal bupivacaine group exhibited significantly lower Visual Analogue Scale(VAS)scores both at rest and during move-ment at 12 hours,24 hours,and 48 hours postoperatively(P<0.001).Significantly higher Quality of Recovery-15(QoR-15)scores were recorded in the liposomal bupivacaine group at 24 hours and during the 24-48-hour period postoperatively(P<0.001).The postoperative opioid consumption within 48 hours was markedly lower in the liposo-mal bupivacaine group(P<0.001).The time to first flatus was significantly shorter in the liposomal bupivacaine group(P<0.001).No significant differences were detected in the incidence of nausea,vomiting,or constipation between the two groups(P>0.05),and no cases of pruritus or other severe adverse reactions were observed.Conclusion Liposomal bupivacaine used for TAP block following cesarean section offers extended analgesia,reduces the need for opioids,enhances the quality of postoperative recovery,promotes gastrointestinal motility,and demonstrates excellent safety.

Objective:To assess the efficacy and safety of pain control nursing for burn patients.Methods:Databases including CNKI, Wanfang Data Knowledge Service Platform, Weipu Database, China Biomedical Literature Database, Web of Science and Cochrane Library were searched to collect the literature on pain control nursing of burn patients from their inception to December 31, 2024. Literature screening, data extraction and quality assessment were performed independently by 2 researchers based on inclusion and exclusion criteria. Meta-analysis of the included studies was performed by applying RevMan 5.4 software. The efficacy of pain control care was assessed in terms of improving care satisfaction, alleviating negative emotions, reducing pain, and decreasing infection rate. Publication bias was analyzed on the related studies.Results:A total of 9 papers were included, all of which were randomized controlled trial (RCT) studies, involving 791 burn patients, with 392 in the pain control nursing group and 399 in the conventional care group. Meta-analysis showed that compared with the conventional care, pain control nursing significantly increased satisfaction of care ( OR=0.28, 95% CI 0.22, 0.34), improved negative emotions ( SMD=-3.06, 95% CI -4.65, -1.47), reduced pain ( SMD=-2.49, 95% CI -3.41, -1.58), and effectively reduced the incidence of infection ( OR=0.13, 95% CI 0.05, 0.34). The studies related to negative emotions were at the risk of publication bias. Conclusion:Compared with conventional care, pain control nursing can significantly increase care satisfaction, alleviate negative emotions, reduce pain, and lower infection risk in burn patients.

AIM:To investigate the therapeutic effects and potential mechanism of pachymic acid(PA)on li-popolysaccharide(LPS)-induced acute kidney injury(AKI)in mice.METHODS:(1)Genes related to AKI were screened using the DAVID database.Core genes were identified by intersecting related genes and analyzed using Cyto-scape software.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were performed through the DAVID database for the cross-targets.Molecular docking and activity assays were conducted on the primary core targets.(2)A total of 100 C57BL/6J mice were randomly divided into five groups:normal control(NC),model(LPS),solvent control(LPS+DMSO),and treatment groups(LPS+PA-10 and LPS+PA-20),with 20 mice in each group.The LPS-AKI model was established by intraperitoneal injection of 18 mg/kg LPS.The treatment groups received 10 mg/kg and 20 mg/kg PA,respectively,and the solvent control group was administered an equivalent dose of DMSO.Mice were euthanized 24 h after injection.Serum was collected for biochemical analysis,and Western blot was used to detect neutro-phil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),caspase-3,cleaved caspase-3,interleu-kin-1β(IL-1β),and monocyte chemoattractant protein-1(MCP-1)protein expression.RT-qPCR was employed to detect inflammatory factor mRNA levels.Molecular docking was used to simulate the optimal binding site of PA to caspase-3.En-zyme activity assays were performed to assess caspase protein activity,and renal lesions were observed via hematoxylin and eosin(HE)staining.Apoptosis was detected by TUNEL staining.RESULTS:(1)Thirty-one potential targets of PA against AKI were identified through network pharmacology.GO and KEGG enrichment analyses indicated that these tar-gets were primarily involved in immune response,inflammatory processes,apoptosis and survival,angiogenesis and hemo-dynamics,oxidative stress,and endoplasmic reticulum stress.Key targets included CASP3(caspase-3),PTGS2,BCL2,CCL2,and CYP219.(2)PA treatment improved renal function and reduced tubular epithelial injury.It significantly de-creased NGAL,KIM-1,and cleaved caspase-3 protein levels,as well as inflammatory factors TNF-α,IL-1β,and MCP-1 mRNA and protein expression.PA also reduced apoptosis of renal tubular epithelial cells.Enzyme activity assays and mo-lecular docking revealed that PA exerted its anti-apoptotic effect by directly binding to caspase-3,thereby inhibiting its ac-tivation by caspase-8.CONCLUSION:PA demonstrated a therapeutic effect in LPS-AKI,potentially through the inhibi-tion of inflammatory factor synthesis and release,as well as the inhibition of caspase-3 activation by caspase-8,reducing apoptosis in renal tubular epithelial cells.

Objective To investigate the relationship between the expression of Osteoglycin(OGN)mRNA and Axis inhibitory protein 1(Axin1)mRNA and Epithelial-mesenchymal transition(EMT)and prognosis in cervical cancer(CC).Methods 142 patients with CC who were treated in Yulin Hospital,the First Affiliated Hospital of Xi'an Jiaotong University from April 2019 to April 2021 were collected.Real time fluorogenic quantitative PCR(RT-qPCR)was used to detect the expression of OGN mRNA,Axin1 mRNA and EMT markers Snail mRNA,N-cadherin(N-cad)mRNA,Vimentin(Vim)mRNA.The expression of OGN and Axin1 protein was detected by immunohistochemistry(IHC).Pearson correlation analysis was used to analyze the correlation between OGN mRNA,Axin1 mRNA and EMT indicators Snail mRNA,N-cad mRNA,Vim mRNA.The effect of OGN and Axin1 protein expression on the survival of CC was analyzed by Kaplan-Meier(K-M)survival curve and COX model.Results Compared with adjacent tissues,the expression of OGN mRNA in CC cancer tissues(0.84±0.22 vs 2.01±0.38)was lower,and the expression of Axin1 mRNA(2.41±0.42 vs 1.02±0.33)was higher,the differences were statistically significant(t=31.752,31.010,all P<0.001).Pearson correlation analysis,the expression of OGN mRNA was negatively correlated with that of Snail mRNA,N-cad mRNA and Vim mRNA(r=-0.765,-0.703,-0.697,all P<0.001).The expression of Axin1 mRNA was positively correlated with that of Snail mRNA,N-cad mRNA and Vim mRNA(r=0.771,0.798,0.690,all P<0.001).Compared with adjacent tissues,the positive rate of OGN protein in CC cancer tissues was lower[28.17%(40/142)vs 88.03%(125/142)],and the positive rate of Axin1 protein was higher[69.01%(98/142)vs 11.27%(16/142)],the differences were statistically significant(χ2=73.185,98.535,all P<0.001).Compared with patients with ⅠA-ⅠB1 and no lymph node metastasis,the positive rate of OGN protein in cancer tissues of patients with International Federation of Gynecology and Obstetrics(FIGO)stage Ⅰ B2-Ⅱ A and lymph node metastasis was lower,and the positive rate of Axin1 protein was higher,and the differences were statistically significant(χ2=4.315～13.252,all P<0.05).The 3-year overall survival rates of OGN positive group and negative group were 90.00%(36/40)and 70.59%(72/102),respectively,and the difference was statistically significant(Log-Rankχ2=7.140,P=0.008).The 3-year overall survival rates of Axin1 positive group and negative group were 69.39%(68/98)and 90.91%(40/44),respectively,and the difference was statistically significant(Log-Rankχ2=9.061,P=0.003).Axin1 positive,FIGO stage IB2～ⅡB,lymph node metastasis were risk factors for poor survival of CC,and OGN positive was a protective factor(Wald χ2=6.250～12.278,all P<0.05).Conclusion OGN is down-regulated and Axin1 is up-regulated in CC,which are related to EMT indicators and adverse survival outcomes of CC patients.

Objective To study the impact of tympanic membrane opening on respiratory-driven middle ear pressure in patients with patulous eustachian tube(PET),using a simplified in vitro model.Methods CT imaging data from a PET patient(with full-length eustachian tube opening observed during a Valsalva maneuver followed by breath-holding)were used to design a simplified eustachian tube model.Two simplified in vitro models of the eusta-chian tube were constructed using silicone-based 3D printing technology and connected to a pressure controller and pressure sensors.The pressure controller was activated to introduce negative-pressure airflow into the nasopharyn-geal model to simulate respiratory-induced middle ear pressure fluctuations.A hemostat was used to alternately open and close the external interface of the middle ear chamber,simulating conditions of an open and intact tympanic membrane,while middle ear pressure was continuously monitored using pressure sensors.Results In the first mod-el,with-800 mbar negative pressure applied at the nasopharynx,the middle ear pressure stabilized between-3.9 mbar and-4.3 mbar with tympanic membrane opening,and between-7.9 mbar and-8.2 mbar with intact tym-panic membrane.In the second model,under the same pressure setting,middle ear pressure stabilized between-2.7 mbar and-3.1 mbar with tympanic membrane opening,and between-5.0 mbar and-7.7 mbar with intact tympanic membrane.Conclusion This study,based on a simplified in vitro model,demonstrates that tympanic membrane opening can effectively reduce respiratory-driven pressure in the middle ear.This phenomenon may partly explain the clinical efficacy of tympanostomy tube insertion in certain PET patients.

Total-body PET/CT, with its long axial field of view and high sensitivity detector, has shown potential for reducing the dose of radiopharmaceuticals. However, pediatric patients are significantly more sensitive to radiation and have a higher long-term cancer risk than adults, posing fundamental challenges for dose management in PET/CT examinations for these patients. In this article, the technical characteristics of total-body PET/CT and its radiation exposure status in children were systematically analyzed. The radiation exposure could be controlled by the following optimization strategies: adjusting the CT exposure parameters, optimizing the scanning mode, adding reconstruction algorithm, and reducing the injected dose of radioactive tracer. By addressing both external and internal radiation during the PET/CT scanning process, the overall radiation dose received by pediatric patients can be reduced within a certain range. In addition, this article also discusses the technical differences between “total-body” and “whole-body” concepts, and emphasizes that the future optimization of radiation dose in pediatric PET/CT should be realized by integration of personalized scanning protocols. Through reasonable management of scanning protocols and processes, low-dose and high-quality PET/CT imaging can be achieved in clinical environments, thus maximizing protection of pediatric patient health while minimizing the risks associated with ionizing radiation exposure.

OBJECTIVE: Based on the PTEN-induced hypothetical kinase 1 (PINK1)/Parkin pathway, the effect of acupuncture pretreatment on the expression of mitochondrial autophagy-related proteins in gastrocnemius muscle tissue of rats with exercise-induced muscle damage (EIMD) was observed, and the underlying mechanism of acupuncture pretreatment for the prevention and treatment of EIMD was explored. METHODS: Of 88 SD male rats, aged 6 weeks, 8 rats were randomly selected as a blank group, and the remaining 80 rats were randomized into a model group and an acupuncture pretreatment group, with 40 rats in each group. Either the model group or the acupuncture pretreatment group was subdivided randomly into 5 subgroups with 8 rats in each one according to the time points of sample collection, 0 h, 12 h, 24 h, 48 h and 72 h after modeling. An intermittent downhill running centrifugal exercise was carried out on an animal experimental treadmill to establish the EIMD model in the model group and the acupuncture pretreatment group. The rats in the acupuncture pretreatment group received acupuncture at "Guanyuan" (CV6) and bilateral "Zusanli" (ST36), once a day for 20 min each time, for 7 consecutive days before EIMD model preparation. Transmission electron microscopy was used to observe the ultrastructure of gastrocnemius muscle tissue in each group. The contents of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in serum were detected by ELISA. Western blot was used to detect the protein expression of PINK1, Parkin, sequestosome 1 (p62) and microtubule-associated protein light chain 3B (LC3B) in rat gastrocnemius muscle tissue. Real-time PCR was adopted to detect the mRNA expression of PINK1, Parkin, p62 and LC3B in rat gastrocnemius muscle tissue. RESULTS: Compared with the blank group, the mitochondria of gastrocnemius muscles showed obvious swelling in the 0 h, 12 h, 24 h, and 48 h model subgroups , autophagosomes were formed in the 12 h and 24 h model subgroups, and the mitochondrial morphology returned to normal gradually in the 72 h model subgroup. The serum MDA contents of rats in 5 model subgroups increased (P<0.01, P<0.05). The contents of SOD and CAT in the subgroups of 0 h, 12 h, 24 h and 48 h decreased (P<0.05, P<0.01). The protein and mRNA expression levels of PINK1, Parkin and LC3B in gastrocnemius muscle tissue of rats in 0 h, 12 h and 24 h subgroups were elevated (P<0.01); and the protein and mRNA expression levels of p62 in the 0 h, 12 h, 24 h and 48 h subgroups were reduced (P<0.01, P<0.05). Compared with the model subgroup at the same time point, the myofibril damage and the degree of mitochondrial swelling were mild in each acupuncture pretreatment subgroup, and the numbers of autophagosomes were fewer. The contents of MDA in the acupuncture pretreatment subgroups decreased at 0 h, 12 h, 24 h, and 48 h (P<0.05, P<0.01). The contents of SOD and CAT in the 12 h acupuncture pretreatment subgroup increased (P<0.05, P<0.01). The protein and mRNA expression levels of PINK1 and Parkin in the 0 h, 12 h, and 24 h acupuncture pretreatment subgroups decreased (P<0.01, P<0.05). The protein and mRNA expression levels of LC3B in the 12 h acupuncture pretreatment subgroup decreased (P<0.01), and that of p62 in the 0 h and 24 h acupuncture pretreatment subgroups increased (P<0.01, P<0.05). CONCLUSION The intermittent downhill running centrifugal exercise induces the excessive mitochondrial autophagy. Acupuncture pretreatment may attenuate EIMD, and the underlying mechanism is related to the regulation of PINK1/Parkin signaling pathway expression, reducing oxidative stress damage in skeletal muscle cells, and inhibiting mitochondrial autophagy overactivation.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Male ; Rats ; Acupuncture Therapy ; Protein Kinases/genetics* ; Rats, Sprague-Dawley ; Mitophagy ; Humans ; Muscle, Skeletal/metabolism* ; Physical Conditioning, Animal ; Muscular Diseases/physiopathology* ; Signal Transduction