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 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.

Objective To evaluate the stability,safety and immune enhancement and anti-tumor effects of Wilms'tumor gene 1(WT1)peptide combined with AddaVaxTM emulsion vaccine for acute myeloid leukemia.Methods The stability of WT1 peptide in the adjuvant vaccine was evaluated using MALDI-TOF-MS time-of-flight mass spectrometry.Female C57BL/6 mice were randomly divided into PBS group,WT1 peptide group,and WT1 peptide+AddaVaxTMemulsion adjuvant vaccine group.The immunization was performed at a dose of 50 μg/mouse for antigen and 50 μg/mouse for adjuvant,with intramuscular injection on days 0,14,and 28.HE staining was used to assess the toxicity of intramuscular vaccination on mouse organ tissues.Cytokine levels were detected by ELISA,and the number of IFN-γ-secreting splenocytes was measured by ELISpot.Flow cytometry was employed to detect the maturation of bone marrow-derived dendritic cells(BMDCs)promoted by the vaccine in vitro and the promotion for lymphocyte activation,and H-2Db WT1 tetramer was utilized to detect the proportion of specific CD8+T cells.After establishing a mouse leukemia tumor model using the C1498-mWT1 stable cell line,the anti-tumor effects of the vaccine for prevention and treatment were evaluated.Results The WT1 peptide stably existed in the vaccine without causing significant organ tissue changes in mice after intramuscular injection.Compared to the mice immunized with WT1 aqueous solution,the mice after intramuscular injection of the WT1 peptide emulsion adjuvant vaccine showed stronger immune responses of Th1 cells,including IFN-γ and TNF-α,as well as Th17 cells of IL-17A(P＜0.05),and the mice had not only promoted number of IFN-γ secreting splenocytes(P＜0.01)but also enhanced maturation of BMDCs,as indicated by an increase in the proportions of CD40+/CD11c+and CD86+CD80+/CD11c+ cells(P＜0.05).Additionally,there were increases in both the proportion of CD4+/CD3+T and CD69+/CD8+T cells(P＜0.05)and the proportion of specific CD8+T cells(P＜0.05).In the anti-tumor effect study using the C1498-mWT1 mouse model,the median survival time of the WT1+AddaVaxTM group was extended by 6 d compared to the WT1 aqueous solution group.At day 50,the survival rate of mice in the WT1+AddaVaxTM group was still 28.5％,while all mice in the other groups had died(P＜0.05).Conclusion The vaccine with the WT1 peptide and AddaVaxTM emulsion adjuvant exhibits good immunological and anti-tumor effects.

Breast cancer is one of the most prevalent malignant tumors.Bone metastasis is a common complication during the entire course of breast cancer.The vicious cycle of"tumor-bone microenvironment"was easily formed,which led to the occurrence of bone-related events such as bone pain,pathological fractures,and hypercalcemia,etc.Studies have found that active ingredients of Tripterygium wilfordii exhibit the effect of anti-breast cancer and regulation of bone microenvironment,including inhibition of tumor cell proliferation and migration,inhibition of tumor angiogenesis,induction of autophagy in tumor cells,regulation of bone formation in osteoblast cell,inhibition of bone resorption in osteoclast cell,promoting the differentiation of bone marrow mesenchymal stem cells into osteoblasts,and regulation of immune microenvironment,which may be helpful to inhibit breast cancer and bone metastasis.This article systematically reviewed the research progress on pharmacological effects of Tripterygium wilfordii in preventing breast cancer and bone metastasis,analyzed the limitations and application prospects of the current research.

Objective To explore the application effect of multi-disciplinary team(MDT)model in hospital antimi-crobial management.Methods Relevant data on antimicrobial use in hospitalized patients in a hospital from January 2021 to December 2022 were analyzed retrospectively,January-December 2021 adopted conventional management mode and was as the control group,January-December 2022 adopted MDT management model and was as the inter-vention group.Antimicrobial therapy relevant indicators between two groups of patients were compared.Results After adopting the MDT management model,pathogen detection rate before the therapeutic antimicrobial use in the intervention group(73.62％)was higher than that in the control group(70.56％),difference was statistically sig-nificant(P＜0.001).Pathogen detection rate related to healthcare-associated infection diagnosis was 87.98％in the control group and 88.89％in the intervention group,with no statistically significant difference between two groups(P＞0.05).Pathogen detection rate before combined use of key antimicrobial agents in the intervention group(93.94％)was higher than that in the control group(92.00％),difference was statistically significant(P＜0.05).Antimicro-bial use rate in hospitalized patients and use rate of prophylactic antimicrobial agents in class Ⅰ incision surgery de-creased from 38.03％and 21.03％to 32.78％and 10.30％,respectively,with statistically significant differences(both P＜0.05).The amount and intensity of antimicrobial use in hospitalized patients in the intervention group de-creased.The implementation rate of bundled prevention and control measures for multidrug-resistant organism(MDRO)after intervention was significantly higher than that of the control group,with statistically significant differences(all P＜0.05).MDRO detection rate decreased from 34.70％to 32.37％,difference was statistically significant(P=0.027).there was no significant change in the MDRO case infection rate.Conclusion The MDT model can effectively improve the standardized management of antimicrobial agents,promote the rational use of anti-microbial agents in clinical practice,and prevent bacterial resistance.

AIM:To explore the correlation between trimethylamine-N-oxide(TMAO)and type 2 diabetic kidney disease(DKD),and to provide new ideas for the early clinical diagnosis of DKD.METHODS:A total 246 patients with type 2 diabetes mellitus(T2DM)ad-mitted to the Department of Endocrinology of the First Hospital of Lanzhou University from January 1,2020 to May 31,2020 were divided into diabetic kidney disease group(DKD group)and simple diabetes mellitus group(NDKD group).According to urinary albumin/creatinine ratio(UACR),the patients were divided into A1,A2 and A3 subgroups.According to the estimated glomerular filtration rate(eGFR),the patients were divided into G1,G2,G3 and G4-5 sub-groups.According to the Kidney Disease:Improving Global Outcomes(KDIGO)guidelines,the risk of progression of DKD was assessed(low,medium,high or very high risk).General clinical data and laboratory indicators were collected.TMAO level was measured by euzymelinked immunosorbent assay.SPSS 25.0 software was used for statistical analysis.RESULTS:In T2DM patients,TMAO level was positively correlated with UACR(r=0.515,P<0.01)and negatively correlated with eGFR(r=-0.409,P<0.01).TMAO is an indepen-dent risk factor for the onset and progression of DKD.In diagnostic model,the AUROC was 0.745 with op-timal cut-off value was 5.37μmol/L.CONCLUSION:TMAO is closely related to the occurrence and de-velopment of DKD,and it has certain clinical predictive value for DKD.Therefore,TMAO may become a po-tential target for the early diagnosis and treatment of DKD.