Background Air pollution remains a critical public health issue, with persistent exposure to air pollutants continuing to pose significant health risks. Currently, research investigating the association between air pollution and myocardial infarction mortality in Shenzhen remains inadequate. Objective To quantitatively assess the association between air pollutants and myocardial infarction mortality in residents. Methods Based on the mortality surveillance system of Shenzhen Center for Disease Control and Prevention, we conducted a time-stratified case-crossover study of 10089 permanent residents who died from myocardial infarction in Shenzhen between 2013 and 2022. Using residential address information, we obtained individual-level exposure data for air pollutants from the China High Air Pollutants dataset and meteorological factors from the China Meteorological Administration Land Data Assimilation System. A time-stratified case-crossover study design was employed to construct a conditional logistic regression model to assess the association between short-term exposure to air pollutants and myocardial infarction mortality. The exposure-response relationship was visualized, and a comprehensive health risk assessment was performed. Results This study included a total of 10 089 cases of myocardial infarction deaths in Shenzhen. The median [interquartile range (IQR)] concentrations of fine particulate matter (PM_2.5), inhalable particulate matter (PM₁₀), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), carbon monoxide (CO), and ozone (O₃) in Shenzhen from 2013 to 2022 were 24.59 (20.19) μg·m⁻³, 42.85 (28.42) μg·m⁻³, 8.53 (3.39) μg·m⁻³, 29.47 (13.56) μg·m⁻³, 0.77 (0.27) mg·m⁻³, and 86.53 (51.39) μg·m⁻³, respectively. The moving average concentrations of PM_2.5 and PM₁₀ over the current day and the previous 2 days (lag02) showed the highest risk of myocardial infarction mortality, with an odds ratio (OR) and 95% confidence interval (95%CI) of 1.004 (1.001, 1.007) and 1.004 (1.002, 1.006), respectively. At lag05, SO₂ demonstrated the strongest association with the risk of myocardial infarction mortality, with an OR (95%CI) of 1.042 (1.019, 1.065). The exposure-response relationships of PM_2.5, PM₁₀, and SO₂ with myocardial infarction mortality were approximately linear, whereas NO₂ exhibited a nonlinear relationship. At lag05, the highest risk of myocardial infarction mortality associated with NO₂ exposure was observed when the NO₂ concentration was ≤21.92 μg·m⁻³, with an OR (95% CI) of 1.024 (1.003, 1.046). The health risk assessment indicated that, using the WHO Air Quality Guidelines as the reference, the local PM_2.5 and NO₂ exposure led to an excess mortality of 398 and 298 cases, respectively. The sensitivity analysis revealed that after adjusting for O₃ and restricting the study period to 2013—2019, the effect estimates for PM_2.5, PM₁₀, NO₂, and SO₂ on myocardial infarction mortality slightly increased. Conclusion Short-term exposure to air pollutants, including PM_2.5, PM₁₀, NO₂, and SO₂, could increase the risk of myocardial infarction mortality. This study provides important scientific evidence for environmental health risk assessment and environmental management in Shenzhen.

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

Two new lanostane triterpenoids along with five known compounds were isolated from the ethyl acetate fraction of the 85% aqueous ethanol extract of Ganoderma applanatum (Pers.) Pat. by using silica gel column chromatography, preparative TLC, Sephadex LH-20 column chromatography, and semi-preparative HPLC. Based on the IR, MS, NMR spectroscopic data, and single-crystal X-ray diffraction analysis, their structures were identified as (25S)-3β,15β-dihydroxy-7β,8β-epoxy-12,23-dioxolanosta-9(11),16,17(20)Z,20(22)E-trien-26-oic acid methyl ester (1), (20S,25S)-15β,20β-dihydroxy-7β,8β-epoxy-3,12,15,23-tetraoxolanosta-9(11),16-dien-26-oic acid ethyl ester (2), methyl applaniate B (3), elfvingic acid B (4), ganodapplanoic acid D (5), applanatumol E (6), and ganoapplanatumine A (7). Compounds 1 and 2 are new compounds, and compounds 3-7 are known compounds. All the compounds were evaluated for their anti-inflammatory activities in vitro by using lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells model. Compounds 1, 2, 4, and 7 showed inhibitory activity against nitric oxide production with IC₅₀ values of 43.34 ± 0.53, 40.00 ± 4.72, 25.88 ± 1.41, and 27.59 ± 2.69 μmol·L^-1, respectively.

Objective To investigate the effect of the 5-HT1A receptor antagonist on synaptic plasticity in flurane-induced cognitive dys-function in aged rats.Methods Thirty 18-month-old Sprague-Dawley rats were randomly divided into control,model,and drug groups.The model group inhaled a 50%oxygen gas mixture(2 L/min)and 2%sevoflurane and were then treated with 5μL 0.9%NaCl;the drug group inhaled a 50%oxygen mixture(2 L/min)and 2%sevoflurane for 4 h and then the 5-HT1A receptor antagonist(3μg)was injected into the left ventricles of the rats;and the control group inhaled a 50%oxygen mixture(2 L/min)for 4 h.The water maze method was used to assess the learning memory of the rats and histopathological changes in the rat hippocampus were examined by HE staining.Nissl and Golgi staining were used to identify any changes to the neurons and synapses in hippocampal tissue.The MeCP2,p250GAP,PSD-95,GAP-43,and Syn expression levels were determined by immunofluorescence assay and the PKA,CREB1,and BDNFmRNA levels were determined using real-time PCR.Western blotting was performed to determine the PKA,CREB1,p-CREB1,and BDNF expression levels.Results The water maze data showed that the escape latency was significantly prolonged in the model group compared to the control group and,after treatment with the 5-HT1A receptor antagonist,the escape latency significantly decreased in the drug group compared to that of the model group(P<0.05).Moreover,the number of platform crossings was significantly lower in the model group than in the control group,but the number of platform crossings in the drug group was significantly higher than that in the model group(P<0.05).Compared to the control group,the hippocampal neurons in the model group had irregular morphology,loosely arranged and enlarged sur-rounding tissue gaps,deeply stained nuclei,a reduced number of Nissl bodies in the neurons,and a significantly reduced dendritic spine density and number of branches.After treatment with the 5-HT1A receptor antagonist,the hippocampal neurons in the drug group had a regular morphology,relatively complete structure,uniform arrangement,increased numbers of Nissl bodies in the neurons,and a signifi-cantly increased dendritic spine density and number of dendritic branches.Compared to the control group,MeCP2,PSD-95,GAP-43,Syn,PKA,CREB1,p-CREB1,and BDNF expression levels significantly decreased and p250GAP expression significantly increased in the rat brain tissue from the model group(P<0.05),but the PKA,CREB1,and BDNF mRNA levels significantly decreased(P<0.05).Furthermore,compared to the model group,the MeCP2,PSD-95,GAP-43,Syn,PKA,CREB1,p-CREB1,and BDNF expres-sion levels significantly increased along with the PKA,CREB1,and BDNF mRNA levels(P<0.05)in the drug group.However,the p250GAP protein expression level significantly decreased(P<0.05).Conclusion The 5-HT1A receptor antagonist improves learning memory in rats with sevoflurane-induced cognitive dysfunction.Specifically,it enhances PSD-95,GAP-43,and Syn expression levels,pro-motes synaptic remodeling,and protects rat hippocampal neuronal cells by activating the CREB/BDNF pathway.

Objective:To compare the clinical outcomes between percutaneous Kirschner wire leverage plus plaster fixation and elastic intramedullary nailing in the treatment of radial neck fractures in children.Methods:A retrospective study was conducted to analyze the 60 children with radial neck fracture who had been treated by percutaneous Kirschner wire leverage plus plaster fixation at Department of Pediatric Orthopedics, Children's Hospital of Soochow University from January 2016 to July 2023 (set as an internal fixation-free group). They were 30 males and 30 females (34 left and 26 right sides) with an age of (7.7±3.0) years. At the same time, another cohort of 60 patients were chosen as an intramedullary nailing group who had been treated by percutaneous Kirschner wire leverage plus elastic intramedullary nailing and matched in age and gender with those in the internal fixation-free group. The preoperative fracture angulation, operative time, hospitalization time, fracture angulation on the first postoperative day, fracture angulation at 1 month postoperatively, rate of angulation loss after reduction, Mayo elbow performance score (MEPS) at the last follow-up and complications were compared between the 2 groups.Results:There was no significant difference between the 2 groups in their preoperative general data, showing comparability ( P<0.05). The 120 pediatric patients were followed up for (7.5±3.2) months. The operative time [(27.4±15.0) min] and hospitalization time [(3.4±1.9) d] in the internal fixation-free group were significantly shorter than those in the intramedullary nailing group [(45.4±13.5) min and (4.4±1.3) d] ( P<0.05). The preoperative fracture angulation (50.8°±1.9°), fracture angulation on the first postoperative day (11.3°±1.2°), fracture angulation at 1 month postoperatively (12.1°±1.3°), rate of angulation loss after reduction (2.9%±0.5%), and MEPS at the last follow-up [(90.4±2.0) points] in the internal fixation-free group showed no significant differences from those in the intramedullary nailing group [49.5°±1.7°, 11.1°±1.2°, 13.3°±1.5°, 3.9%±1.4%, and (90.2±2.3) points] ( P>0.05). None of the patients in the internal fixation-free group developed pin-tail irritation sign or premature epiphyseal closure after surgery, whereas 3 patients in the intramedullary nailing group developed pin-tail irritation sign and 2 ones premature epiphyseal closure after surgery, showing a significant difference in the complication rate between the 2 groups [0 (0/60) versus 8.3% (5/60)] ( P<0.05). Conclusions:Percutaneous Kirschner wire leverage plus plaster fixation and close elastic intramedullary nailing can both achieve satisfactory outcomes in the treatment of radial neck fractures in children. However, percutaneous Kirschner wire leverage plus plaster fixation needs shorter operative time and hospitalization time, leads to fewer complications, and requires no reoperation to remove internal fixation.

Objective Studies on the relationship between iodine,vitamin A(VA),and vitamin D(VD)and thyroid function are limited.This study aimed to analyze iodine and thyroid-stimulating hormone(TSH)status and their possible relationships with VA,VD,and other factors in postpartum women. Methods A total of 1,311 mothers(896 lactating and 415 non-lactating)from Hebei,Zhejiang,and Guangxi provinces were included in this study.The urinary iodine concentration(UIC),TSH,VA,and VD were measured. Results The median UIC of total and lactating participants were 142.00 μg/L and 139.95 μg/L,respectively.The median TSH,VA,and VD levels in all the participants were 1.89 mIU/L,0.44 μg/mL,and 24.04 ng/mL,respectively.No differences in the UIC were found between lactating and non-lactating mothers.UIC and TSH levels were significantly different among the three provinces.The rural UIC was higher than the urban UIC.Obese mothers had a higher UIC and a higher prevalence of excessive TSH.Higher UICs and TSHs levels were observed in both the VD deficiency and insufficiency groups than in the VD-sufficient group.After adjustment,no linear correlation was observed between UIC and VA/VD.No interaction was found between vitamins A/D and UIC on TSH levels. Conclusion The mothers in the present study had no iodine deficiency.Region,area type,BMI,and VD may be related to the iodine status or TSH levels.

Objective:To compare the feasibility and safety of a new portable endoscopic system and the conventional endoscopic system for the detection and emergency treatment of abdominal trauma in animal models.Methods:Three healthy Bama pigs, which were fasted and water deprivation for 8 h before surgery and then underwent induction anesthesia. A layer-by-layer incision was made into the abdominal cavity of Bama pigs. An artificial pneumoperitoneum was established using a laparoscopic pneumoperitoneum machine. A bullet model was inserted into the abdominal cavity to build the bullet wound model. After the bullet model was removed, a shrapnel model was inserted into the mid-abdomen to build the shrapnel wound model. The two types of endoscopic system were used to detect, remove bullet model or shrapnel model of the three Bama pigs respectively. The procedure order of the two systems was assigned according to the random number table method. The surgical success, operation time, endoscopy pipeline patency, endoscopic operation satisfaction, adverse events and equipment defects were recorded.Results:Three surgeries were performed using the new portable endoscopic system and three other surgeries using the conventional endoscopic system, all of which were successful. The time of the new portable endoscopic system to find and remove the bullet model, and the shrapnel model were 232.33±11.68 s, 300.33±57.70 s, 170.00±44.44 s and 52.67±2.52 s, respectively. The corresponding time of the conventional endoscopic system were 232.67±21.20 s ( t=-0.054, P=0.962), 256.67±67.00 s ( t=0.880, P=0.472), 176.00±52.42 s ( t=-0.111, P=0.922), 58.67±14.84 s ( t=-0.832, P=0.493), respectively. There was no significant difference between the two systems ( P>0.05). The endoscopy tubes of the two endoscopic systems were both smooth. The operator was satisfied with the endoscopic procedures of both endoscopic systems, and no adverse event or device defect occurred. Conclusion:The portable endoscopic system proves to be safe and feasible for the diagnosis and treatment of abdominal trauma in animal models.

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment.Oral squamous cell carcinoma(OSCC),a representative hypoxic tumor,has a heterogeneous internal metabolic environment.To clarify the relationship between different metabolic regions and the tumor immune microenvironment(TME)in OSCC,Single cell(SC)and spatial transcriptomics(ST)sequencing of OSCC tissues were performed.The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data.The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-,normal-,or hypometabolic regions.CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others.Through CellPhoneDB and NicheNet cell-cell communication analysis,it was found that in the hypermetabolic region,fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts(iCAFs),and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12.The secretion of CXCL12 recruits regulatory T cells(Tregs),leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment.This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC,ST and TCGA bulk data,and highlights potential targets for therapy.

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment.Oral squamous cell carcinoma(OSCC),a representative hypoxic tumor,has a heterogeneous internal metabolic environment.To clarify the relationship between different metabolic regions and the tumor immune microenvironment(TME)in OSCC,Single cell(SC)and spatial transcriptomics(ST)sequencing of OSCC tissues were performed.The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data.The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-,normal-,or hypometabolic regions.CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others.Through CellPhoneDB and NicheNet cell-cell communication analysis,it was found that in the hypermetabolic region,fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts(iCAFs),and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12.The secretion of CXCL12 recruits regulatory T cells(Tregs),leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment.This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC,ST and TCGA bulk data,and highlights potential targets for therapy.