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

Objective To explore the effect and preliminary mechanism of the plant-derived immunostimulatory molecule,ophiopogonin,on enhancing the immune response of a subunit vaccine with the receptor-binding domain(RBD)of coronavirus spike protein as the antigen.Methods CCK-8 assay was used to determine the cytotoxicity of ophiopogonin D'(OPD')on bone marrow-derived dendritic cells(BMDCs).Female Balb/c mice were randomly divided into RBD,RBD/OPD',RBD/Alum,and control groups.The immunization dose was 5 μg of antigen per mouse and 100 μg of adjuvant per mouse,and immunization was carried out according to the intramuscular injection immunization procedure on days 0,21,and 42.The titers of specific IgG and its subtype antibodies were detected by ELISA.The cytokine levels in the supernatant of splenocytes were detected using ELISA.The number of splenocytes secreting IFN-γ was detected by ELISpot.Laser confocal microscopy was employed to observe the uptake of antigen by BMDCs.The phagocytic ability of BMDCs for antigen was quantitatively analyzed by flow cytometry.The mechanism of its enhanced immune effect was preliminarily explored using transcriptomics technology combined with bioinformatics research.Results When the concentration of OPD'was less than 5 μg/mL,the survival rate of BMDCs was 100%.After a single intramuscular injection in mice,except for a slight decrease in body weight,the other biochemical indicators were within corresponding normal ranges.After intramuscular injection immunization of the vaccine,the titers of serum-specific IgG,IgG1,and IgG2a in the RBD/OPD'group were significantly higher than those in the RBD group(P<0.05).Compared with the RBD group,the RBD/OPD'group induced a high-level Th1 cell immune response of IL-1β,TNF-α,and IFN-γ(P<0.01)and had more lymphocytes secreting IFN-γ(P<0.001).Laser confocal microscopy displayed that BMDCs took up more antigens after OPD'treatment,which was further confirmed with flow cytometry in quantitative analysis on antigen uptake rate(P<0.01).Transcriptomics results indicated that there was more significant enrichment of the PPAR signaling pathway in the RBD/OPD'group than the RBD group,suggesting that OPD'may activate the PPAR signaling pathway to exert its adjuvant effect.Conclusion OPD'effectively enhances the immune response of the RBD subunit vaccine,and its action mechanism may be related to the activation of the PPAR signaling pathway.

Objective To establish a mouse model of infection with the minimum lethal dose of Vibrio vulnificus(V.vulnificus)and to evaluate the protective efficacy of inactivated whole-cell(IWC)vaccine using this model.Methods A mouse model of lethal-dose infection was established by intraperitoneal injection of different doses of V.vulnificus.Bacterial colonization in the organs was detected with tissue homogenate plating,and pathological changes in the organs were observed after tissue section staining.Flow cytometry was used to detect immune cell responses after liver tissues were digested into single-cell suspension.IWC vaccine of V.vulnificus was prepared,and the mice were immunized through different routes to observe the protective efficacy of the vaccine.Results A mouse model of infection with the minimum lethal dose at 1×106 CFU of V.vulnificus was successfully established.After infection,the bacteria were mainly colonized in the liver of mice and caused severe pathological damages.Compared with the uninfected mice,the proportion of neutrophils in the liver was significantly increased in the infected mice,whereas the proportions of B cells and T cells were correspondingly decreased(P<0.05).A single intramuscular or intraperitoneal injection of the IWC vaccine could protect the mice effectively against lethal infection of V.vulnificus in 7 d later(P<0.01),although the level of serum IgG having no significant increase.Conclusion A mouse model of lethal-dose infection with V.vulnificus is successfully established,with histopathological characteristics.The IWC vaccine of V.vulnificus rapidly mediates immune protection in this model probably independent of IgG.

Objective:To evaluate the efficacy of Tongdu Tiaoshen acupuncture combined with low-frequency electrical pulse in the treatment of neurogenic bladder (NB) caused by spinal cord injury (SCI); To explore its effects on urodynamics.Methods:A randomized controlled trial study was conducted. A total of 116 patients with NB caused by SCI in the First Affiliated Hospital of Hunan University of Chinese Medicine from January 2022 to June 2024 were selected as the observation objects and divided into 2 groups with random number table method, with 58 cases in each group. On the basis of conventional bladder function training, the control group was given low-frequency electronic pulse therapy, while the observation group was treated with the Tongdu Tiaoshen method on the basis of the control group. Both groups were treated continuously for 3 months. The urination conditions of the patients were observed before and after the treatment respectively, and the residual urine volume, single urine volume within 24 hours, the number of urine leaks within 24 hours, and the number of urinations within 24 hours were recorded; urodynamic parameters such as bladder volume, urine flow rate, detrusor pressure, bladder compliance, and detrusor contractility were measured using a urodynamic analyzer; the severity of NB symptoms was evaluated using the Chinese version of the Neurogenic Bladder Symptom Scale (NBSS), and the quality of life was evaluated using the Chinese version of the Short Form Health Assessment Scale (SF-Qualiveen). The levels of IL-1β, IL-6 and TNF-α were detected by ELISA. Adverse reactions were recorded during the treatment period and the clinical efficacy was evaluated.Results:The total effective rate was 91.38% (53/58) in the observation group and 75.86% (44/58) in the control group. There was a statistically significant difference between the two groups ( χ2=5.10, P=0.024). After treatment, the residual urine volume, single urine volume within 24 hours, frequency of urine leakage within 24 hours, and frequency of urination within 24 hours in the observation group were lower than those in the control group ( t values were -15.68, 3.75, -3.81, and -7.54 respectively, P<0.01). The bladder capacity, urine flow rate, detrusor pressure, bladder compliance and detrusor contractility were higher than those of the control group ( t values were 11.04, 7.49, 9.76, 5.65 and 4.36 respectively, P<0.01), while the NBSS score and SF-Qualiveen score were lower than those of the control group ( t values were -10.82 and -9.83 respectively, P<0.01). No obvious adverse reactions occurred in either group during the treatment period. Conclusion:Tongdu Tiaoshen acupuncture combined with low-frequency electrical pulses can improve the bladder function of NB caused by SCI, restore urodynamics, and improve the quality of life. Its mechanism may be related to the inhibition of inflammatory responses.

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.
Humans ; Carcinoma, Squamous Cell/metabolism* ; Squamous Cell Carcinoma of Head and Neck ; Mouth Neoplasms/metabolism* ; Immunosuppression Therapy ; Transforming Growth Factor beta ; Head and Neck Neoplasms ; Gene Expression Profiling ; Tumor Microenvironment

Objective:To explore the feasibility of using self-made visual throat forceps to remove hypopharyngeal foreign bodies. Methods:The throat forceps were combined with the endoscope and connected to a monitor via a data cable resulting in a visual throat forceps apparatus. This device was utilized to examine and treat the hypopharyngeal foreign bodies. Results:Among 53 patients, foreign bodies were detected in 51,with 48 cases involving hypopharyngeal foreign bodies. All were successfully extracted using the visual throat forceps. Three cases, diagnosed as esophageal foreign bodies by electronic gastroscopy, were treated using the same method. Conclusion:Visual throat forceps can be used to examine the hypopharynx and remove foreign bodies. It has the advantages of simple operation, rapid operation, and high success rate of foreign body removal from the hypopharynx. It is worthy of clinical application.
Humans ; Hypopharynx/surgery* ; Pharynx/surgery* ; Endoscopes ; Surgical Instruments ; Foreign Bodies/diagnosis*

Humans ; Vascular Stiffness ; Coal Mining ; Occupational Diseases/epidemiology* ; Risk Factors ; Coal ; Miners

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.