Objective To elucidate the changes in the gut microbiota and molecular mechanism of huaier in enhancing the efficacy of oxaliplatin (OXA) chemotherapy in gastric cancer (GC). Methods The effects of huaier on the gut microbiota structure and intestinal barrier function in MKN45-bearing mice were analyzed by using 16S rRNA sequencing, RT-qPCR, and IHC. UPLC-MS and network pharmacology, as well as in vivo experimental approaches, were employed to investigate the key bioactive constituents of huaier systematically and elucidate the underlying mechanisms by which huaier exerts therapeutic effects against GC. The expression of the PI3K/AKT/SREBP pathway was detected in cancer cells and tissues via Western blot analysis. The safety profile of huaier combined with OXA was verified through serum biochemistry and HE-stained tissue section analyses. Results Huaier inhibited the PI3K/AKT/SREBP pathway by increasing the abundance of Akkermansia muciniphila, reduced lipid droplet deposition, and ultimately enhanced the sensitivity to OXA in the treatment of GC. Conclusion This study demonstrates the value of huaier in gastric cancer treatment by enhancing chemosensitivity and provides novel insights into its systemic therapeutic effects through molecular mechanisms and gut microbiota modulation.

Objective: To explore the efficacy of a novel injectable hydrogel (GelMA/P11/IL4@LIP) loaded with P11 bacteriophages and interleukin-4 (IL-4) liposomes (LIP) in preventing relapse after maxillary expansion in mice, providing experimental evidence for its clinical application. Methods: This study was approved by the experimental animal ethics committee of our hospital. First, 15 7-week-old C57BL/6 mice were used to establish a maxillary expansion model and divided into 5 groups (3 mice in each group): a control group, post expansion day 3 group (PED3 group), post expansion day 7 group (PED7 group), retention for 14 days group (RET group), and relapse for 7 days group (REL group). The mice in each group were sacrificed at their designated time points (day 0, 3, 7, 21, 28), and their maxilla and anterior cranial regions were collected. Bone parameters and the inter-crestal distance (ICD) of maxillary incisor mesial alveolar ridge were measured using micro-computed tomography (micro-CT). Histological staining was performed to evaluate bone formation and resorption, while immunohistochemistry (IHC) was performed for macrophage markers (CD86 and CD206), mesenchymal stem cell markers (glioma-associated oncogene homolog 1 [Gli1]), and osteogenic markers (Runt-related transcription factor 2 [Runx2] and Osterix [OSX]). Next, GelMA/P11/IL4@LIP was synthesized and administered to mouse models of maxillary expansion. A total of 24 7-week-old C57BL/6 mice were divided into 4 groups (6 mice in each group): a blank control group, GelMA group, GelMA/P11 group, and GelMA/P11/IL4@LIP group. All mice underwent palatal expansion. On PED7, the expanders of all 24 mice were cemented with resin to initiate the 14-day retention period. On day 1 of the retention phase, the mice in each group received injections of saline, GelMA, GelMA/P11, or GelMA/P11/IL4@LIP at the midpalatal suture. After the 14-day retention period, three mice in each group were randomly selected and sacrificed, while the other three had their expanders removed and underwent a 7-day relapse before being sacrificed on day 28 (REL). Micro-CT, histological staining, and IHC were performed to evaluate the preventive effect of GelMA/P11/IL4@LIP on post-expansion relapse. Results: The mice maxillary expansion model exhibited a decreased ICD at REL compared to RET in micro-CT analysis (P = 0.008). IHC analysis demonstrated prolonged M1 macrophage infiltration, scarce Gli1+ mesenchymal stem cells, and insufficient expression of osteogenic markers (RUNX2 and OSX) (P < 0.001). Compared to the blank control and GelMA groups, GelMA/P11/IL4@LIP hydrogel injection in the midpalatal suture led to increased ICD at REL, promoted the timely M2 polarization of macrophages, recruited Gli1+ mesenchymal stem cells, and upregulated the expression of RUNX2 and OSX (P < 0.05). Conclusion The mechanism of relapse after maxillary expansion involves the persistent infiltration of M1 macrophages, as well as the inadequate recruitment and insufficient osteogenic differentiation of MSCs in the midpalatal suture. The GelMA/P11/IL4@LIP composite enhanced orofacial mesenchymal stem cell recruitment and promoted the M2 polarization of macrophages, thereby enhancing osteogenesis in the midpalatal suture and preventing post-expansion relapse.

Immature permanent teeth refer to those that have erupted but have not yet formed and matured in terms of shape and structure. The characteristics of their disease onset and treatment methods are different from those of ordinary permanent teeth. Children with special healthcare needs often lack the capacity to cooperate during routine dental procedures, making treatment under general anesthesia (GA) the preferred option. With social advancements, the demand for pediatric dental GA has considerably increased. This study discuss the treatment strategies for immature permanent teeth under GA, including diagnosis, therapeutic principles, key considerations, and clinical approaches for dental caries, pulpitis periapical periodontitis, etc.
Child ; Humans ; Anesthesia, General ; Dental Caries/diagnosis* ; Dentition, Permanent ; Periapical Periodontitis/therapy* ; Pulpitis/therapy*

Objective:To investigate the synergistic activity and mechanism of vinegar baked radix bupleurum polysaccharides(VBCP)in combination with oxaliplatin(OXA),and to provide new ideas for the clinical treatment of primary hepatocellular carci-noma.Methods:MTT assay was used to detect the cytotoxic effect of VBCP 3-4 and VBCP 3-3 in combination with OXA on Huh7 cells;ICP-MS was used to measure the uptake rate of OXA by Huh7 cells and evaluate the in vitro synergistic pathway of VBCP 3-4 in combination with OXA;Western blotting was used to measure the expression levels of related transporter proteins in Huh7 cells and explore the synergistic mechanism of VBCP 3-4 in combination and MRP1 in Huh7 cells,and the protein expression level of multidrug resistance-associated protein(MRP)2 was upregulated to 18.11%and 25.00%,respectively(P=0.008,P=0.001),while that of MRP1 was upregulated to 28.51%(P>0.05)and 39.70%(P=0.015),respectively.After the combination of VBCP 3-4 and OXA,the protein expression of MRP2,MRP1,and breast cancer resis-tance protein(BCRP)was inhibited;MRP2 was reduced by 47.38%in the high-dose combination group(P=0.000)and 15.18%in the low-dose combination group(P=0.049);MRP1 was reduced by 64.96%in the high-dose combination group(P=0.000)and 34.63%in the low-dose combination group(P=0.000);BCRP was reduced by 29.00%(P=0.020)in the high-dose combination group.Acting on Huh7 cells alone,VBCP 3-4 significantly reduced the protein expression levels of MRP2,MRP1,and BCRP,and in the high-dose VBCP 3-4 group,MRP2 and MRP1 were reduced by 24.91%and 20.79%,respectively(P=0.004,P=0.005).VBCP 3-4 downregu-lated the protein expression level of BCRP by 15.02%in the high-dose group(P=0.003)and 13.92%in the middle-dose group(P=0.030).Conclusion:VBCP 3-4 exerts a synergistic effect by inhibiting the expression of the efflux transporter proteins MRP1,MRP2,and BCRP,promoting the intake of OXA by Huh7 cells,and increasing the intracellular effective concentration.

Objective:To study the results of detection of pulmonary nodules among military flying personnel and analyze the contributors to pulmonary nodules so as to provide data for early prevention and interventions.Methods:The physical examination data of 1 465 military flying personnel was retrospectively analyzed who had received the annual health checkup and undergone chest CT examinations at Lintong Rehabilitation and Recuperation Center. They were grouped by age (<40 years and ≥40 years), flying hour (<1 000 h and ≥1 000 h) and type of personnel [pilots and air support (technical) personnel]. The detection rates of pulmonary nodules among flying personnel were compared across groups, and a multivariate Logistic regression analysis was conducted to analyze the contributing factors to pulmonary nodules.Results:Among the 1 465 military flying personnel, 212 cases (14.47%) with pulmonary nodules were detected. A total of 230 pulmonary nodules were detected, including 35 pulmonary nodules (15.22%) in the left upper lung, 42 pulmonary nodules (18.26%) in the left lower lung, 52 pulmonary nodules (22.61%) in the right upper lung, 47 pulmonary nodules (20.43%) in the right middle lung, and 54 pulmonary nodules (23.48%) in the right lower lung. The detection rate of pulmonary nodules among military flying personnel in the ≥1 000 h group was higher than in the <1 000 h group, and the difference was statistically significant ( χ2=4.14, P=0.042). More pulmonary nodules were detected among military flying personnel who smoked than among those who did not, and the difference was statistically significant ( χ2=9.34, P=0.002). Age, types of personnel, body mass index, and complications with other lung diseases made no significant difference in the detection rate of pulmonary nodules (all P>0.05). Multivariate Logistic regression analysis showed that smoking was a risk factor for pulmonary nodules ( OR=1.692, 95% CI: 1.217-2.351). Conclusions:Among military flying personnel, pulmonary nodules are more likely to occur in the right lung. Smoking is an independent risk factor for pulmonary nodules, suggesting that routine chest CT screening should be carried out during the annual physical examinations of military flying personnel in order to exercise early interventions.

Allergic rhinitis (AR), a globally prevalent immune-mediated inflammatory condition, is still an incurable disease. In the present study, we have validated the impact of the Kelch-like ECH associated protein 1 (Keap1)-related oxidative stress and inflammatory response in clinical AR patient peripheral blood and nasal swab samples, emphasizing the biological relevance of Keap1 and AR. Targeting Keap1 -nuclear factor erythroid 2-related factor 2 (Nrf2) related anti-oxidative stress may be effective for AR intervention. Drawing inspiration from the Keap1 homodimerization and the E3 ligase characteristics, we herein present a design of novel bivalent molecules for chemical knockdown of Keap1. For the first time, we characterized ternary complexes of Keap1 dimer and one molecule of bivalent compounds. The best bivalent molecule 8 encompasses robust capacity to degrade Keap1 as a homoPROTAC^KEAP1. It efficaciously suppresses inflammatory cytokines in extensively different cells, including human nasal epithelial cells. Moreover, in an AR mouse model, we confirmed that the chemical degradation induced by homoPROTAC^KEAP1 led to therapeutic benefits in managing AR symptoms, oxidative stress and inflammation. In summary, our findings underscore the efficacy of targeting the Keap1 system through the homoPROTAC-ing technology as an innovative and promising treatment strategy for the incurable allergic disorders.

Objective:To analyze the clinical and electrophysiological characteristics of patients with sensory neuronopathies (SNN), and to evaluate the significance of electrophysiological markers in the diagnosis and assessment of disease progression.Methods:A retrospective analysis was performed to evaluate the clinical manifestations, electrophysiological characteristics, and spinal cord magnetic resonance imaging (MRI) features of 8 cases diagnosed with SNN at the Third Central Hospital of Tianjin between 2015 and 2023. The neurophysiological examination mainly included limb nerve conduction study (NCS), same core needle electrode electromyography, somatosensory evoked potential (SEP), skin sympathetic reflex (SSR), and contact heat evoked potential (CHEP).Results:Among the 8 cases with SNN, 7 cases exhibited asymmetrical onset and a non-length-dependent pattern. All the 8 cases presented with severe deep sensory ataxia, accompanied by superficial sensory abnormalities and tendon areflexia. Paraneoplastic SNN were the most prevalent etiological subtype (4 cases), all of whom presented peripheral neuropathy as the initial symptom. Among these 4 cases, malignancies were identified in 3 cases and 3 cases presented with anti-Hu antibodies. Among the remaining 4 patients, 2 cases were autoimmune and the other 2 cases were idiopathic. NCS results of the 8 cases revealed decrease or absence of sensory nerve action potential (SNAP) amplitudes, with normal sensory conduction velocities. Six cases showed abnormal SEP, including 2 cases of central damage and 4 cases of peripheral damage, 5 cases had abnormal SSR, and 2 cases exhibited abnormal CHEP. Motor nerve conduction studies were normal in all 8 cases. Six patients underwent spinal MRI, and 4 exhibited abnormal signals in dorsal columns.Conclusions:The hallmark clinical manifestation of SNN is sensory ataxia, characterized by substantial impairment of superficial sensation, typically manifesting in a non-length-dependent distribution. Beyond the widespread and significant reduction in SNAP amplitudes, SNN may also exhibit additional electrophysiological impairments, such as those observed in SEP, SSR and CHEP.SEP combined with spinal cord MRI can improve the detection rate for damages in the central sensory conduction pathway.

AIM:To explore the potential of Huangqi sanqi mixture(AP)in improving renal fi-brosis by performing transcriptome sequencing of the kidneys of the unilateral ureteral ligation mouse group and the Huangqi sanqi mixture inter-vention group,and using bioinformatics to verify the signitficantly different lncRNAs mechanism.METHODS:Twenty-four C57 mice were divided in-to sham operation group,renal fibrosis group,Huangqi sanqi mixture intervention group(3.944 g/kg)and irbesartan positive control intervention group,with 6 mice in each group.A mouse model of renal fibrosis was established by unilateral ure-teral ligation(UUO).The animals were given intra-gastric administration after operation,and the ani-mals were sacrificed and the specimens were col-lected after seven consecutive days of administra-tion.The changes of Huangqi sanqi mixture on re-nal fibrosis pathological damage were analyzed by HE and Masson staining,and the protein levels of Fn and α-SMA in renal tissue of each group were detected by Western blot and immunohistochemis-try to evaluate the alleviating effect of Huangqi san-qi mixture on renal fibrosis.Subsequently,lncRNA expression information was obtained by transcrip-tome sequencing,and Quantitative Real-time PCR(qPCR)was performed after data quality,GO en-richment and differential lncRNA were analyzed.According to the differential lncRNA and target analysis results obtained by sequencing,lncRNA Gm51500/Adam12 was overexpressed in vitro,and its mechanism in the protection of renal fibrosis by Huangqi sanqi mixture was studied by immunohis-tochemistry,immunofluorescence staining and qP-CR verification.RESULTS:Compared with the mod-el group,the renal fibrosis of the mice in the Huangqi sanqi mixture intervention group was sig-nificantly reduced,and the protein levels of α-SMA and Fn and the expression of lncRNA in the renal tis-sue were significantly down-regulated(P＜0.000 1).Three lncRNAs were screened and verified to in-crease in the model group and significantly de-crease after AP intervention,namely lncRNA Gm29994,Gm51500 and Gm35391.Target analysis showed that lncRNA Gm51500 had the most signifi-cant relationship with Adam12.The results of ani-mal experiments showed that Adam12 was highly expressed in the kidney of UUO mice and was sig-nificantly inhibited after AP intervention.Subse-quent cell experiments confirmed that overexpres-sion of lncRNA Gm51500 could up-regulate TGF-β-induced renal tubular cell fibrosis and Adam12 ex-pression.Cell recovery experiments confirmed that Adam12 overexpression reversed the inhibitory ef-fect of AP on renal tubular cell injury and fibrosis.CONCLUSION:Huangqi sanqi mixture can improve renal fibrosis.Based on transcriptomic sequencing,lncRNA Gm51500/Adam12 axis may be a potential target for Huangqi sanqi mixture to improve renal fibrosis.

OBJECTIVE To investigate the acute lung injury effects of pulmonary phospholipids and their phospholipase A2(PLA2)decomposition products-lysophospholipids and fatty acids-on mice.METHODS Mice were randomly assigned to the following groups:① solvent control(PBS)and PLA2;② solvent control and glycerol phospholipid groups:1,2-dioleoyl-sn-glycero-3-phosphoserine(DOPS),1,2-dipalmitoyl-sn-glycero-3-phosphoserine(DPPS),1,2-dioleoyl-sn-glycero-3-phosphoethanol-amine(DOPE),1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine(DPPE),1,2-dipalmitoyl-sn-glycero-3-phosphocholine(DPPC),and 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine(SOPC);③ solvent con-trol and fatty acid groups:palmitic acid(PA),oleic acid;④ solvent control and lysophospholipid groups:1-oleoyl-2-hydroxy-sn-glycero-3-phosphoserine(18∶1 LysoPS),1-stearoyl-sn-glycero-3-phosphoserine(18∶0 LysoPS),1-palmitoyl-sn-glycero-3-phosphoserine(16∶0 LysoPS),1-palmitoyl-sn-glycero-3-phos-phoethanolamine(16∶0 LysoPE),1-palmitoyl-sn-glycero-3-phosphocholine(16∶0 LysoPC);⑤ solvent control,PLA2,DPPC,PA,16∶0 LysoPC,16∶0 LysoPS,and 18∶1 LysoPS.Following anesthesia,mice were administered nebulized PBS in the solvent control group,2.1 ug·kg-1 PLA2 in PBS in the PLA2 group and 2.5 mg·kg-1 of the corresponding substance in PBS in other experimental groups.For group①,survival times were recorded and survival curves were plotted.At 1 h post-treatment,lung tissues from groups ①②③④ were collected,photographed to obtain white light images,and subjected to HE staining to assess histopathological changes and pathological scoring.At 2 h post-treatment,pulmonary blood flow in group ⑤ was assessed using laser speckle contrast imaging,arterial blood gas was analyzed with a blood gas analyzer,and lung function was evaluated using whole-body pleth-ysmography.At 6 hours post-treatment,blood cells from group ⑤ were analyzed using an automated hematology analyzer.RESULTS Compared with the solvent control group,severe pathological changes were observed in lung tissues of the PLA2 group,accompanied by extensive inflammatory infiltration and interstitial thickening,with all mice succumbing within 240 min.In mice treated with glyc-erol phospholipids,alveolar structures remained clear,alveolar walls were intact and continuous,and alveolar spaces were translucent,with only occasional minor inflammatory cell infiltration in the septa.No significant pathological alterations were detected in the fatty acid groups.Minor inflammatory cell infiltration was seen in the 16∶0 LysoPE and 16∶0 LysoPC groups.However,such pathological changes as patchy hemorrhage,alveolar interstitial edema,increased alveolar wall thickness,and elevated neutrophil counts were observed in the 18∶1 LysoPS,18∶0 LysoPS,and 16∶0 LysoPS groups.Pathological scores based on HE staining were significantly increased in the 16∶0 LysoPS and 18∶1 LysoPS groups com-pared with the solvent control.The percentage of the lung tissue injury area was also markedly higher in the 16∶0 LysoPS group.A significant decrease in the mean fluorescence intensity of blood flow was observed in the 16∶0 LysoPS group.Arterial partial pressure of oxygen(pO2)was significantly reduced in the PLA2 group,while arterial partial pressure of carbon dioxide(pCO2)was markedly elevated in the 16∶0 LysoPS and 18∶1 LysoPS groups.Lung function tests revealed that the 16∶0 LysoPS group exhibited significant increases in expiratory time,end-expiratory pressure,and enhanced pause,in contrast to significant decreases in tidal volume,expired volume,and minute volume.The 18∶1 LysoPS group also exhibited a significant decline in minute volume.No significant changes in inflammatory cell concentrations were detected in blood,with the exception of neutrophils in the 16∶0 LysoPS group,which showed a significant but physiologically normal increase.CONCLUSION Pulmonary phospholipids and their PLA2-derived fatty acid metabolites do not induce severe lung injury in mice while the lyso-phospholipid metabolites,particularly lysophosphatidylserine,are found to cause significant lung injury.

Objective:To analyze the electroencephalogram(EEG) average relative power spectrum in patients with unipolar and bipolar depression under the eyes-open and eyes-closed resting states.Methods:A total of 38 patients with unipolar depression (UD group), 48 patients with bipolar depression (BD group), and 43 healthy controls (HC group) were recruited from August 2022 to December 2023.The 64-channel EEG was recorded under eyes-open (EO) and eyes-closed (EC) resting states which alternated twice. The Mann-Whitney U test and Kruskal-Wallis H test were performed by SPSS 25.0 software. Results:There were no significant differences in the average relative power of delta and beta bands among the UD, BD and HC groups in all EO and EC states (all P>0.05). The average relative power of theta band in the three groups showed statistically significant differences in all EO and EC states ( H=7.852-12.583, all P<0.05). Further pairwise comparisons showed that in the first EO and EC stage, the average relative power of theta band of the UD and BD groups were significantly higher than that of the HC group (EO1: 0.18(0.17, 0.21), 0.19(0.16, 0.21), 0.16(0.14, 0.18), EC1: 0.15(0.13, 0.21), 0.15(0.13, 0.20), 0.13(0.10, 0.16); all P<0.05).In the second EO and EC stage, the average relative power of theta band of the BD group was significantly higher than that of the HC group (EO2: 0.18(0.15, 0.22), 0.16(0.14, 0.18), EC2: 0.15(0.13, 0.19), 0.13(0.11, 0.16); both P<0.05).There were statistically significant differences in the average relative power of alpha band among the three groups in the first EO and EC stage, as well as the second EC stage ( H=5.027-10.668, all P<0.05). Further pairwise comparisons showed that in the first EO stage, the average relative power of alpha band in the BD group was significantly higher than that in the UD group (0.20(0.16, 0.25), 0.14(0.11, 0.22), P=0.003), and in the following EC stages, the average relative power of alpha band in the UD group was significantly lower than that in the HC group (EC1: 0.40(0.33, 0.46), 0.51(0.40, 0.58), EC2: 0.41(0.35, 0.50), 0.48(0.43, 0.58); both P<0.05). Conclusion:At the initial stage of the resting state, both unipolar and bipolar depression patients demonstrate abnormal theta band activity under the eyes-open and eyes-closed states, while the alpha band activity under the eyes-open condition differs between the two groups of patients. These findings may provide potentially objective biomarkers to assist the diagnosis of unipolar and bipolar depression patients in clinical settings.