Objective To investigate the impact of two different algorithms, AAA and AXB, on the dose distribution of postoperative radiotherapy for left-sided breast cancer after breast-conserving surgery. Methods A total of 96 target volumes from patients who underwent breast-conserving surgery for left-sided breast cancer were selected for dose verification using a two-dimensional matrix system. The planned dose distributions were simulated using both AAA and AXB algorithms. Dosimetric differences in organs at risk and the target volumes were then compared to identify the algorithm that could reduce the radiation dose to organs at risk without compromising the dose distribution to the target volume. Dose verification was performed on the plans generated by both algorithms, and the pass rates of plans for each target volume using both algorithms were compared to provide a quantitative basis for the precise selection of subsequent radiotherapy plans. Results Both AAA and AXB plans met the radiotherapy requirements. The AXB algorithm demonstrated significant advantages in the D₉₈, D₂, homogeneity index, and conformity index for the planning target volume, as well as in the V₅ and V₂₀ for the left lung. The AXB algorithm showed advantages in the V₃₀ for the heart and the maximum and mean doses for the skin. With the 2 mm/2% criterion in dose verification, the gamma pass rate was higher for the AXB algorithm. Conclusion Through a comparative analysis of the two algorithms, this study revealed that the AXB algorithm offers certain advantages in the dose distribution of radiotherapy after breast-conserving surgery for left-sided breast cancer. These findings provide an important reference for the rational selection of algorithms in clinical practice and are expected to improve radiotherapy efficacy and patient prognosis.

BACKGROUND:Carnosic acid,a bioactive compound found in rosemary,has been shown to reduce inflammation and reactive oxygen species(ROS).However,its mechanism of action in osteoclast differentiation remains unclear. OBJECTIVE:To investigate the effects of carnosic acid on osteoclast activation,ROS production,and mitochondrial function. METHODS:Primary bone marrow-derived macrophages from mice were extracted and cultured in vitro.Different concentrations of carnosic acid(0,10,15,20,25 and 30 μmol/L)were tested for their effects on bone marrow-derived macrophage proliferation and toxicity using the cell counting kit-8 cell viability assay to determine a safe concentration.Bone marrow-derived macrophages were cultured in graded concentrations and induced by receptor activator of nuclear factor-κB ligand for osteoclast differentiation for 5-7 days.The effects of carnosic acid on osteoclast differentiation and function were then observed through tartrate-resistant acid phosphatase staining,F-actin staining,H2DCFDA probe and mitochondrial ROS,and Mito-Tracker fluorescence detection.Western blot and RT-PCR assays were subsequently conducted to examine the effects of carnosic acid on the upstream and downstream proteins of the receptor activator of nuclear factor-κB ligand-induced MAPK signaling pathway. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining and F-actin staining showed that carnosic acid dose-dependently inhibited in vitro osteoclast differentiation and actin ring formation in the cell cytoskeleton,with the highest inhibitory effect observed in the high concentration group(30 μmol/L).Carnosic acid exhibited the most significant inhibitory effect during the early stages(days 1-3)of osteoclast differentiation compared to other intervention periods.Fluorescence imaging using the H2DCFDA probe,mitochondrial ROS,and Mito-Tracker demonstrated that carnosic acid inhibited cellular and mitochondrial ROS production while reducing mitochondrial membrane potential,thereby influencing mitochondrial function.The results of western blot and RT-PCR revealed that carnosic acid could suppress the expression of NFATc1,CTSK,MMP9,and C-fos proteins associated with osteoclast differentiation,and downregulate the expression of NFATc1,Atp6vod2,ACP5,CTSK,and C-fos genes related to osteoclast differentiation.Furthermore,carnosic acid enhanced the expression of antioxidant enzyme proteins and reduced the generation of ROS during the process of osteoclast differentiation.Overall,carnosic acid exerts its inhibitory effects on osteoclast differentiation by inhibiting the phosphorylation modification of the P38/ERK/JNK protein and activating the MAPK signaling pathway in bone marrow-derived macrophages.

BACKGROUND:Mesenchymal stem cells can regulate the tumor microenvironment by secreting extracellular vesicles containing cytokines,growth factors and exosomes for the precise regulation of biological behavior of tumor cells. OBJECTIVE:To investigate the effects of human umbilical cord-derived mesenchymal stem cell conditioned medium and their released exosomes on the biological properties of hepatocellular carcinoma cells. METHODS:Human umbilical cord mesenchymal stem cell supernatant was collected,centrifuged and filtered at high speed to obtain human umbilical cord mesenchymal stem cell conditioned medium.Human umbilical cord mesenchymal stem cell supernatant was collected and human umbilical cord mesenchymal stem cell exosomes were extracted by ultra-high speed gradient centrifugation.Human umbilical cord mesenchymal stem cell exosomes were labeled with PKH26 and co-cultured with hepatocellular carcinoma cell MHCC97-H.The uptake of exosomes by MHCC97-H cells was observed by fluorescence microscopy.The effects of human umbilical cord mesenchymal stem cell conditioned medium and human umbilical cord mesenchymal stem cell exosomes on biological functions of hepatocellular carcinoma cells were assessed by the CCK-8 proliferation assay,Transwell migration and invasion assay,and the apoptosis assay. RESULTS AND CONCLUSION:(1)Human umbilical cord mesenchymal stem cell exosomes could be uptaken by MHCC97-H cells and was mainly distributed in the cytoplasm.(2)After treatment with human umbilical cord mesenchymal stem cell conditioned medium,MHCC97-H cells showed a significant increase in proliferation,migration,and invasion(P<0.001,P<0.05,P<0.01),and a significant decrease in apoptosis(P<0.001),while after treatment with human umbilical cord mesenchymal stem cell exosomes,MHCC97-H cells showed a decrease in proliferation(P<0.001)and migration,invasion,and apoptosis were significantly enhanced(P<0.001).(3)The results indicated that human umbilical cord mesenchymal stem cell conditioned medium had the ability to promote the proliferation,migration,invasion,and inhibit apoptosis of MHCC97-H cells,while human umbilical cord mesenchymal stem cell exosomes had the properties of promoting the migration,invasion and apoptosis of MHCC97-H cells,inhibiting the proliferation.

Central nervous system diseases (CNSDs) refer to a range of disorders resulting from structural or functional impairments of the brain and spinal cord, including stroke, Alzheimer’s disease (AD), Parkinson’s disease, spinal cord injury (SCI), and brain tumors. As a leading cause of disability and the second leading cause of death worldwide, CNSDs involve complex pathological mechanisms that profoundly affect patients’ physical and mental health as well as their quality of life. Therefore, identifying potential therapeutic targets and developing targeted intervention strategies for the prevention and treatment of CNSDs is of great significance. Recent studies have revealed that lactate can transmit energy between cells via the “lactate shuttle” mechanism and act as an endogenous signaling molecule, exerting diverse biological functions in CNSDs. Lactylation, a novel type of post-translational modification that uses lactate and lysine residues as substrates, plays a critical role in regulating gene transcription, immune responses, and cellular metabolism under both physiological and pathological conditions. Studies have confirmed that lactate participates in the onset and progression of CNSDs through both lactate metabolism and lactylation. In AD, lactate promotes Aβ plaque formation and impairs synaptic plasticity and cognitive function. Lactylation contributes to AD pathogenesis by regulating Aβ accumulation, Tau protein phosphorylation, neuroinflammation, pyroptosis, and ferroptosis. In ischemic stroke (IS), lactate suppresses neuroinflammation and alleviates ischemic injury. Lactylation is involved in the regulation of neuroinflammation, endothelial cell apoptosis, and neuronal ferroptosis, contributing to IS progression. In SCI, lactate promotes the phenotypic transition of astrocytes from the A1 to the A2 type, thereby mitigating neural injury. Lactylation alleviates neurological dysfunction by modulating neuroinflammation, axonal regeneration, mitochondrial function, and microglial proliferation. In glioblastoma (GBM), lactate promotes M2 polarization of microglia, facilitating tumor cell growth and dissemination. Lactylation further accelerates GBM progression by enhancing tumor cell migration, proliferation, immune evasion, and drug resistance. These findings suggest that lactate may serve as a potential therapeutic target for the prevention and treatment of CNSDs. However, its precise role in CNSDs remains unclear, and the specific mechanisms by which lactate metabolism and lactylation influence disease progression warrant further investigation. Moreover, studies have confirmed that exercise, as a key non-pharmacological intervention, holds great promise in the prevention, treatment, and rehabilitation of CNSDs. Specifically, exercise can regulate lactate metabolism and lactylation, which in turn suppresses neuroinflammation, enhances synaptic plasticity, promotes neurogenesis and angiogenesis, improves mitochondrial function in the hippocampus, and facilitates the release of neuroprotective factors, ultimately contributing to the improvement of CNSDs. This review summarizes the roles of lactate metabolism and lactylation in CNSDs, as well as the potential mechanisms by which exercise regulates lactate metabolism and lactylation to improve CNSDs, providing a theoretical basis for the benefits of exercise on brain health.

ObjectiveTo monitor the real-time changes in ammonia concentration in the laboratory animal facility environment before, during, and after the air conditioning system stops supplying air, so as to provide a basis and reference for developing emergency plans for the shutdown of the air conditioning system. MethodsThe laboratory animal facilities of the Wuhan Institute of Biological Products were used as the research object. Ammonia concentration detectors were used to monitor ammonia concentration continuously in the environment of conventional rabbit production facility, SPF hamster production facility, and SPF guinea pig experimental facility before and after the passive shutdown due to repairs and active maintenance shutdown of the air conditioning system, as well as the time for the ammonia concentration to return to daily levels after resuming air supply. ResultsUnder both shutdown modes of the air conditioning system, the trend of ammonia concentration changes in different laboratory animal facilities was consistent, showing a rapid increase after shutdown and a rapid decrease after resuming air supply. Under active maintenance shutdown, the maximum ammonia concentrations in the conventional rabbit production facilities, SPF hamster production facilities, and SPF guinea pig experimental facilities were 9.81 mg/m³, 14.27 mg/m³, and 6.98 mg/m³, respectively. Within 12 minutes after resuming air supply, ammonia concentration could return to normal daily levels. Under passive long-term shutdown, ammonia concentration value was positively correlated with the duration of air supply suspension. As the shutdown duration increased, ammonia concentration continued to increase. The maximum ammonia concentration values in the three facilities occurred at 88 minutes (38.06 mg/m³), 40 minutes (18.43 mg/m³), and 34 minutes (15.61 mg/m³) after air supply suspension, respectively.Within 11 minutes after resuming air supply, ammonia concentration could return to normal daily levels. ConclusionShutdown of the air conditioning system causes a rapid increase in ammonia concentration in laboratory animal facilities, and the rise in ammonia concentration is positively correlated with the duration of air supply suspension. Therefore, when an emergency shutdown of the air-conditioning system is required due to maintenance or other reasons, backup fans should be provided in accordance with the requirements of GB 50447-2008 "Architectural and Technical Code for Laboratory Animal Facilities". Older facilities should make adequate preparations and develop a scientifically sound emergency plan.

OBJECTIVE To investigate the induction of apoptosis in hepatocellular carcinoma cells by polyphyllin 9 （PP9） through the regulation of the Fas/Fas ligand （FasL） signaling pathway， and its inhibitory effect on the growth of transplanted tumor in nude mice. METHODS Based on the screening of cell lines and intervention conditions， HepG2 cells were selected as the experimental subject to investigate the effects of 2 μmol/L and 4 μmol/L PP9 treatment on cell colony formation activity， apoptosis rate， as well as the protein expressions of Fas， FasL， cleaved caspase-8 and cleaved caspase-3. Additionally， Fas inhibitor KR- 33493 was introduced to investigate the underlying mechanism of PP9’s anti-hepatocellular carcinoma activity. Using HepG2 cell tumor-bearing nude mice model as the object， and 5-fluorouracil （20 mg/kg） as the positive control， the effects of 10 mg/kg PP9 on tumor volume， tumor mass， and the protein expressions of the nuclear proliferation-associated antigen Ki-67 and cleaved caspase-3 in tumor-bearing nude mice were investigated. RESULTS Compared with the control group， 2， 4 μmol/L PP9 significantly decreased the number of clones and the clone formation rate of cells， but significantly increased the apoptosis rate， the protein expressions of Fas， FasL， cleaved caspase-8 and cleaved caspase-3 （P＜0.05 or P＜0.01）. However， the combination of Fas inhibitor KR-33493 could significantly reverse the effect of PP9 on the up-regulation of proteins related to the Fas/FasL signaling pathway （P＜0.01）. Compared with the control group， the tumor volume （on day 27）， mass and protein expression of Ki- 67 in nude mice of the PP9 group were significantly decreased， while the protein expression of cleaved caspase-3 was significantly increased （P＜0.01）. CONCLUSIONS PP9 can induce apoptosis of HepG2 cells by activating the Fas/FasL signaling pathway. Meanwhile， PP9 can also effectively inhibit the growth of transplanted tumors in nude mice.

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Postoperative nausea and vomiting (PONV) are common complications that mainly occur within 24 h after orthognathic surgery. The incidence of nausea and vomiting after orthognathic surgery remains high and is a difficult problem for patients and surgeons. These complications not only affect wound healing and increase the risk of postoperative bleeding. Vomit and blood may also cause nausea and vomiting, which results in a vicious cycle. Frequent nausea and vomiting are a painful experience and more serious than postoperative pain. They are one of the main reasons for postoperative infection, delayed discharge, and increased hospitalization costs and affect patient satisfaction. In this review, the author combined literature review and clinical experience and summarized and analyzed the causes of orthognathic nausea and vomiting and prevention and treatment strategies to improving the related clinical process.
Humans ; Postoperative Nausea and Vomiting/etiology* ; Orthognathic Surgical Procedures/adverse effects*

Objective: To elucidate the potential mechanisms by which Chinese herbal medicine (CHM) regulates gut microbiota (GM) to influence the development of primary open-angle glaucoma (POAG). Methods: Data mining, network pharmacology, and Mendelian randomization (MR) analyses (two-sample design) were conducted in integration to systematically explore the CHM-GM-POAG axis. Literature-based data mining method was applied to identify frequently used herbs and herb pairs for POAG, and the properties and meridian tropism of the herbs were analyzed as well. Target prediction and pathway enrichment analyses were performed to identify shared molecular pathways among CHM components, GM, and POAG. MR analysis was performed to assess the genetically predicted causal associations between specific microbial taxa and POAG risk. Results: Our data mining work indicated that commonly used CHMs were mainly bitter and sweet in flavors and cold in property, with meridian tropism toward the liver, lung, and kidney. The predominant therapeutic effects of the CHMs included soothing the liver and regulating Qi, promoting blood circulation, and reducing fluid retention. Representative herb pairs were Shudihuang (Rehmanniae Radix Praeparata)-Gouqi (Lycii Fructus) with Zexie (Alismatis Rhizoma), Gouqi (Lycii Fructus)-Fuling (Poria) with Shudihuang (Rehmanniae Radix), and Juhua (Chrysanthemi Flos)-Gouqi (Lycii Fructus) with Zexie (Alismatis Rhizoma). Network pharmacology revealed overlapping targets involving antioxidative, anti-inflammatory, and metabolic regulation pathways. MR analysis demonstrated that higher abundances of Ruminiclostridium 6 [odds ratio (OR) = 0.73, 95% confidence interval (CI): 0.58 – 0.92, P = 0.007], Ruminococcaceae UCG-002 (OR = 0.77, 95% CI: 0.63 – 0.96, P = 0.018), Ruminococcus torques group (OR = 0.71, 95% CI: 0.57 – 0.90, P = 0.004), and Victivallis (OR = 0.82, 95% CI: 0.70 – 0.96, P = 0.016) were causally associated with reduced POAG risk, whereas Actinomyces (OR = 1.34, 95% CI: 1.06 – 1.68, P = 0.013) and Blautia (OR = 1.39, 95% CI: 1.01 – 1.90, P = 0.042) showed positive associations. Conclusion This study revealed potential causal links between GM and POAG and provided integrative evidence that CHM may modulate the microbiota to exert neuroprotective effects. These findings offer new integrative insights into the gut-eye axis and a theoretical basis for developing microbiota-targeted CHM strategies in glaucoma management.

Objective:To investigate the effect of DExH-box helicase 9(DHX9)O-linked N-acetylglucosamine(O-GlcNAc)modifi-cation(O-GlcNAcylation)on the proliferation of hepatitis B virus(HBV)-associated hepatoma cells.Methods:The pAdTrack-TO4-DHX9-3Flag recombinant adenovirus plasmid was constructed by molecular cloning and transfected into HEK293 cells for packaging and amplification of the recombinant adenovirus AdDHX9.The interaction between DHX9 and O-GlcNAc transferase(OGT)was con-firmed using co-immunoprecipitation.The co-localization between DHX9 and OGT was measured by immunofluorescence.The level of DHX9 O-GlcNAcylation was determined using succinylated wheat germ agglutinin(sWGA)and glycosylated immunoprecipitation(IP).The effect of DHX9 O-GlcNAcylation on the proliferation of HBV-associated hepatoma cells was assessed using the colony-forming assay and cell growth curves.Results:The recombinant adenovirus AdDHX9 was successfully obtained,and DHX9 expression was confirmed by Western blot.DHX9 interacted with OGT,and the two proteins were co-localized on the nucleus.The sWGA and gly-cosylated IP experiments showed that DHX9 underwent O-GlcNAcylation,which was further enhanced by HBV infection.The colony-forming assay demonstrated that the number of cell clones was increased in the AdDHX9 group(386.667±15.630)compared with the AdGFP control group(142.667±7.572,P<0.001).Moreover,cell growth curves demonstrated that the overall cell growth rate was en-hanced in the AdDHX9 group(22.860±0.770)compared with the AdGFP control group(13.670±0.517,P<0.001).Conclusion:HBV infection promotes DHX9 O-GlcNAcylation,which enhances the proliferation of HBV-associated hepatoma cells.