Objective:To evaluate the effect of remimazolam tosilate on postoperative delirium (POD) in elderly patients undergoing urological surgery.Methods:In this randomized controlled trial, 220 American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ elderly patients of either sex, aged≥65 yr, with body mass index of 18-28 kg/m 2, scheduled for elective urological surgery under general anesthesia, were divided into 2 groups ( n=110 each) using a random number table method: propofol group (group P) and remimazolam tosilate group (group R). Group P received propofol 1.0-1.5 mg/kg for induction and propofol 2-6 mg·kg -1·h -1 for maintenance, while group R received remimazolam tosilate 0.2-0.3 mg/kg for induction and remimazolam tosilate 0.5-1.2 mg·kg -1·h -1 for maintenance. The other drugs for induction and maintenance were the same in the two groups. POD was assessed using the Chinese version of the 3-minute diagnostic interview for Confusion Assessment Method within 3 days after surgery in the two groups. The intraoperative consumption of remifentanil and usage of vasoactive drugs, extubation time, 15-item Quality-of-Recovery scale scores at 24 h after operation, requirement for rescue analgesia within 24 h after operation, and postoperative adverse effects were recorded. Results:There were no significant differences in the incidence of POD within 3 days after operation, 15-item Quality-of-Recovery scale scores at 24 h after operation, or rate of rescue analgesia within 24 h after operation between two groups ( P>0.05). Compared with group P, the requirement for intraoperative vasoactive drugs was significantly reduced, the extubation time was shortened, and the incidence of hypoxemia was decreased within 24 h after operation in group R ( P<0.05 or 0.001). Conclusions:Remimazolam tosilate has no marked effect on the occurrence of POD in elderly patients undergoing urological surgery.

Objective To explore the associations of dietary patterns with bone mineral density(BMD)and osteoporosis(OP)in patients with knee osteoarthritis(KOA)in south China,identify the dietary patterns that could reduce the risk of OP,and provide a reference for prevention of OP.Methods Data from 600 KOA patients who were enrolled in the Pearl River Osteoarthritis Cohort(PROC)between April 2020 and April 2024 were extracted,including general characteristics,dietary questionnaire and BMD test.Factor analysis was employed to identify dietary patterns.Scores of dietary pattern were treated as continuous or categorical variables(quartile-based groups).Multivariable linear regression was used to assess associations between scores of dietary pattern and BMD,while the relationships with OP were analysed by binary logistic regression.Results The prevalence of OP in KOA patients was 19.8%.Factor analysis extracted eight dietary patterns:seafood-nuts,livestock-poultry meats,coarse grains-fruits,wheat-eggs,fish-dairy-vegetables,legumes-fruits,rice-wheat flour,and soy-dairy.After adjusting for confounders,it was found that the pattern of coarse grains-fruits was positively correlated with the BMD of left femoral neck and lumbar spine(P<0.01)and the fish-dairy-vegetables pattern was positively correlated with the BMD of lumbar spine(P<0.01).When pattern scores were discretized into quartiles,the legumes-fruits pattern(Q3 vs.Q1)was found in association with a 68.2%reduction in the risk of OP(P<0.05).Conclusion This study has identified that the pattern of legumes-fruits may lower a risk of OP,while the patterns of coarse grains-fruits and fish-dairy-vegetables correlate with higher BMD.The diet patterns are potentially beneficial to prevention of OP.For bone health,a balanced diet rich in legumes,fruits,vegetables,coarse grains,fish,nuts and dairy is recommended.

Objective:To evaluate the effect of remimazolam tosilate on postoperative delirium (POD) in elderly patients undergoing urological surgery.Methods:In this randomized controlled trial, 220 American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ elderly patients of either sex, aged≥65 yr, with body mass index of 18-28 kg/m 2, scheduled for elective urological surgery under general anesthesia, were divided into 2 groups ( n=110 each) using a random number table method: propofol group (group P) and remimazolam tosilate group (group R). Group P received propofol 1.0-1.5 mg/kg for induction and propofol 2-6 mg·kg -1·h -1 for maintenance, while group R received remimazolam tosilate 0.2-0.3 mg/kg for induction and remimazolam tosilate 0.5-1.2 mg·kg -1·h -1 for maintenance. The other drugs for induction and maintenance were the same in the two groups. POD was assessed using the Chinese version of the 3-minute diagnostic interview for Confusion Assessment Method within 3 days after surgery in the two groups. The intraoperative consumption of remifentanil and usage of vasoactive drugs, extubation time, 15-item Quality-of-Recovery scale scores at 24 h after operation, requirement for rescue analgesia within 24 h after operation, and postoperative adverse effects were recorded. Results:There were no significant differences in the incidence of POD within 3 days after operation, 15-item Quality-of-Recovery scale scores at 24 h after operation, or rate of rescue analgesia within 24 h after operation between two groups ( P>0.05). Compared with group P, the requirement for intraoperative vasoactive drugs was significantly reduced, the extubation time was shortened, and the incidence of hypoxemia was decreased within 24 h after operation in group R ( P<0.05 or 0.001). Conclusions:Remimazolam tosilate has no marked effect on the occurrence of POD in elderly patients undergoing urological surgery.

Objective To explore the associations of dietary patterns with bone mineral density(BMD)and osteoporosis(OP)in patients with knee osteoarthritis(KOA)in south China,identify the dietary patterns that could reduce the risk of OP,and provide a reference for prevention of OP.Methods Data from 600 KOA patients who were enrolled in the Pearl River Osteoarthritis Cohort(PROC)between April 2020 and April 2024 were extracted,including general characteristics,dietary questionnaire and BMD test.Factor analysis was employed to identify dietary patterns.Scores of dietary pattern were treated as continuous or categorical variables(quartile-based groups).Multivariable linear regression was used to assess associations between scores of dietary pattern and BMD,while the relationships with OP were analysed by binary logistic regression.Results The prevalence of OP in KOA patients was 19.8%.Factor analysis extracted eight dietary patterns:seafood-nuts,livestock-poultry meats,coarse grains-fruits,wheat-eggs,fish-dairy-vegetables,legumes-fruits,rice-wheat flour,and soy-dairy.After adjusting for confounders,it was found that the pattern of coarse grains-fruits was positively correlated with the BMD of left femoral neck and lumbar spine(P<0.01)and the fish-dairy-vegetables pattern was positively correlated with the BMD of lumbar spine(P<0.01).When pattern scores were discretized into quartiles,the legumes-fruits pattern(Q3 vs.Q1)was found in association with a 68.2%reduction in the risk of OP(P<0.05).Conclusion This study has identified that the pattern of legumes-fruits may lower a risk of OP,while the patterns of coarse grains-fruits and fish-dairy-vegetables correlate with higher BMD.The diet patterns are potentially beneficial to prevention of OP.For bone health,a balanced diet rich in legumes,fruits,vegetables,coarse grains,fish,nuts and dairy is recommended.

Objective To investigate the protective effect of 5-hydroxy-6,7-dimethoxyflavone(5-HDF),a compound extracted from Elsholtzia blanda Benth.,against lung injury induced by H1N1 influenza virus and explore its possible mechanism of action.Methods 5-HDF was extracted from Elsholtzia blanda Benth.using ethanol reflux extraction and silica gel chromatography and characterized using NMR and MS analyses.In an A549 cell model of H1N1 influenza virus infection(MOI=0.1),the cytotoxicity of 5-HDF was assessed using MTT assay,and its effect on TRAIL and IL-8 expressions was examined using flow cytometry;Western blotting was used to detect the expression levels of inflammatory,apoptosis,and ferroptosis-related proteins.In a mouse model of H1N1 influenza virus infection established by nasal instillation of 50 μL H1N1 virus at the median lethal dose,the effects of 30 and 60 mg/kg 5-HDF by gavage on body weight,lung index,gross lung anatomy and lung histopathology were observed.Results 5-HDF exhibited no significant cytotoxicity in A549 cells within the concentration range of 0-200 μg/mL.In H1N1-infected A549 cells,treatment with 5-HDF effectively inhibited the activation of phospho-p38 MAPK and phospho-NF-κB p65,lowered the expressions of IL-8,enhanced the expression of anti-ferroptosis proteins(SLC7A11 and GPX4),and inhibited the expressions of apoptosis markers PARP and caspase-3 and the apoptotic factor TRAIL.In H1N1-infected mice,treatment with 5-HDF for 7 days significantly suppressed body weight loss and increment of lung index and obviously alleviated lung tissue pathologies.Conclusion 5-HDF offers protection against H1N1 influenza virus infection in mice possibly by suppressing H1N1-induced ferroptosis,inflammatory responses,and apoptosis via upregulating SLC7A11 and GPX4,inhibiting the activation of phospho-NF-κB p65 and phospho-p38 MAPK,and decreasing the expression of cleaved caspase3 and cleaved PARP.

Objective To investigate the protective effect of 5-hydroxy-6,7-dimethoxyflavone(5-HDF),a compound extracted from Elsholtzia blanda Benth.,against lung injury induced by H1N1 influenza virus and explore its possible mechanism of action.Methods 5-HDF was extracted from Elsholtzia blanda Benth.using ethanol reflux extraction and silica gel chromatography and characterized using NMR and MS analyses.In an A549 cell model of H1N1 influenza virus infection(MOI=0.1),the cytotoxicity of 5-HDF was assessed using MTT assay,and its effect on TRAIL and IL-8 expressions was examined using flow cytometry;Western blotting was used to detect the expression levels of inflammatory,apoptosis,and ferroptosis-related proteins.In a mouse model of H1N1 influenza virus infection established by nasal instillation of 50 μL H1N1 virus at the median lethal dose,the effects of 30 and 60 mg/kg 5-HDF by gavage on body weight,lung index,gross lung anatomy and lung histopathology were observed.Results 5-HDF exhibited no significant cytotoxicity in A549 cells within the concentration range of 0-200 μg/mL.In H1N1-infected A549 cells,treatment with 5-HDF effectively inhibited the activation of phospho-p38 MAPK and phospho-NF-κB p65,lowered the expressions of IL-8,enhanced the expression of anti-ferroptosis proteins(SLC7A11 and GPX4),and inhibited the expressions of apoptosis markers PARP and caspase-3 and the apoptotic factor TRAIL.In H1N1-infected mice,treatment with 5-HDF for 7 days significantly suppressed body weight loss and increment of lung index and obviously alleviated lung tissue pathologies.Conclusion 5-HDF offers protection against H1N1 influenza virus infection in mice possibly by suppressing H1N1-induced ferroptosis,inflammatory responses,and apoptosis via upregulating SLC7A11 and GPX4,inhibiting the activation of phospho-NF-κB p65 and phospho-p38 MAPK,and decreasing the expression of cleaved caspase3 and cleaved PARP.

Zirconia crown has been widely used in the field of prosthodontics.Traditional zirconia exhibits excellent mechanical properties but lacks translucency.The introduction of transparent zirconia significantly enhances its aesthetic performance.In clinical applications,factors affecting the aesthetic results of full zirconia crown should be comprehen-sively considered,and the most suitable restoration should be chosen.Additionally,clinicians need to design appropriate tooth preparation dimensions and methods based on an individual patient's actual situation.During the clinical bonding process of zirconia,proper surface treatment of the tooth and restoration is essential.The selection of suitable adhesives is crucial for achieving optimal bonding strength and aesthetics.

Objective This study aimed to explore the expression trends of innate immune cells and immune-checkpoint molecules validated by data calculation in the process of oral mucosal carcinogenesis,as well as to explore methods of suppressing oral mucosal carcinogenesis based on immunotherapy by predicting their interactions.Me-thods 1)The cancer genome atlas(TCGA)database comprehensively scores immune cells and immune-checkpoint molecules in the process of oral mucosal carcinogenesis and screens out intrinsic immune cells and immune-check-point molecules that interfere with tumor immune escape.2)Clinical patient blood routine data were collected for the statistical analysis of peripheral blood immune cells during the progression of oral mucosal carcinogenesis.Immune cells in peripheral blood that may affect the progression of oral mucosal carcinogenesis were screened.3)Immunohis-tochemical staining was performed on intrinsic immune cells and immune-checkpoint molecules validated based on da-ta calculation in various stages of oral mucosal carcinogenesis.4)Special staining was used to identify innate immune cells in various stages of oral mucosal carcinogenesis based on data-calculation verification.5)Survival analysis was conducted on intrinsic immune cells and immune-checkpoint molecules validated based on data calculation during the process of oral mucosal carcinogenesis.The association of intrinsic immune cells and immune-checkpoint molecules with the prognosis of oral squamous cell carcinoma was verified.Results The expression of monocytes and neutro-phils increased during the process of oral mucosal carcinogenesis.The expression of eosinophils showed a single peak trend of up and down.The expression of mast cells decreased.In the process of oral mucosal carcinogenesis,the ex-pression of the immune-checkpoint molecules cytotoxic T-lymphocyte-associated protein 4(CTLA4)and programmed cell death-ligand(PD-L1)increased.The expression trends of monocytes,neutrophils,and eosinophils were positively correlated with those of CTLA4 and PD-L1 immune-checkpoint molecules.The expression trend of mast cells was negatively correlated with the expression of CTLA4 and PD-L1.Monocytes,neutrophils,and eosinophils may pro-mote tumor immune escape mediated by CTLA4 and/or PD-L1,thereby accelerating the progression of oral mucosal carcinogenesis.Mast cells may inhibit tumor immune escape mediated by CTLA4 and/or PD-L1,delaying the progres-sion of oral mucosal carcinogenesis.Conclusion Therefore,interference with specific immune cells in innate immu-nity can regulate the expression of CTLA4 and/or PD-L1 to a certain extent,inhibit tumor immune escape,and delay the progression of oral mucosal carcinogenesis.

Objective:To detect gene mutations in a pedigree with dominant dystrophic epidermolysis bullosa (DDEB) .Methods:A 20-year-old male proband presented with repeated blisters, ulceration, pigmentation, scars on the limbs, and deformation of the nails/toenails after birth. There were 5 patients in the 3-generation family, and they all presented with typical skin lesions. Peripheral blood samples were obtained from 14 members of the pedigree (including the 5 patients) and 100 unrelated healthy controls. Whole-exome sequencing was performed in the proband to identify relevant mutation sites, which were then confirmed in the family by Sanger sequencing.Results:Genetic testing indicated that the proband and the other 4 patients all carried a missense mutation (c.7885G>A) in exon 107 of the COL7A1 gene, resulting in the substitution of glycine by arginine at amino acid position 2629 (p.G2629R). The mutation was identified neither in the 9 healthy relatives nor in the 100 unrelated healthy controls. The mutation co-segregated with DDEB in the family, and was not included in databases such as Pubmed, HGMD or ClinVar, suggesting it was a novel missense mutation. The amino acid encoded by this mutation may alter the structure of type Ⅶ collagen, thereby affecting its function.Conclusion:A novel missense mutation was identified in exon 107 of the COL7A1 gene in the family with DDEB, expanding the spectrum of mutations in the COL7A1 gene.

As an important part of tumor microenvironment, neutrophils are poorly understood due to their spatiotemporal heterogeneity in tumorigenesis. Here we defined, at single-cell resolution, CD44-CXCR2- neutrophils as tumor-specific neutrophils (tsNeus) in both mouse and human gastric cancer (GC). We uncovered a Hippo regulon in neutrophils with unique YAP signature genes (e.g., ICAM1, CD14, EGR1) distinct from those identified in epithelial and/or cancer cells. Importantly, knockout of YAP/TAZ in neutrophils impaired their differentiation into CD54+ tsNeus and reduced their antitumor activity, leading to accelerated GC progression. Moreover, the relative amounts of CD54+ tsNeus were found to be negatively associated with GC progression and positively associated with patient survival. Interestingly, GC patients receiving neoadjuvant chemotherapy had increased numbers of CD54+ tsNeus. Furthermore, pharmacologically enhancing YAP activity selectively activated neutrophils to suppress refractory GC, with no significant inflammation-related side effects. Thus, our work characterized tumor-specific neutrophils in GC and revealed an essential role of YAP/TAZ-CD54 axis in tsNeus, opening a new possibility to develop neutrophil-based antitumor therapeutics.
Humans ; Animals ; Mice ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Stomach Neoplasms/pathology* ; Neutrophils/pathology* ; Signal Transduction/genetics* ; YAP-Signaling Proteins ; Tumor Microenvironment ; Hyaluronan Receptors/genetics*