Nifedipine-induced gingival overgrowth (NIGO) refers to gingival hyperplasia caused by long-term use of the hypertensive drug nifedipine (NIF), and it is a drug adverse reaction. NIGO is characterized by a high incidence rate and a large patient base, and it is one of the most common types of gingival hyperplasia in clinical practice. Previous studies on the etiology of NIGO mainly focused on the pharmacological effects of NIF, while in recent years, it has been proposed that inflammation may also be a major risk factor for NIGO. Plaque is the initiating factor of periodontal inflammation. However, the role and mechanism of bacteria in the pathogenesis of NIGO remain unclear at present. Therefore, this article reviews relevant research and finds that bacteria may be involved in the pathogenesis of NIGO through the following pathways: ① Hypertensive drugs represented by NIF can cause dysbiosis of the oral flora, increasing the relative abundance of periodontal pathogenic bacteria. The inflammatory chemokines released by fibroblasts in the immune response to bacteria can work in synergy with NIF to promote excessive collagen production or recruit immune cells to participate in tissue fibrosis. ② Transforming growth factor-β (TGF-β) plays a significant role in fibrotic diseases. Bacterial infections can significantly increase the level of TGF-β, promoting epithelial-mesenchymal transition or allowing TGF-β and its downstream substances to directly participate in gingival fibrosis. ③ Bacteria can also cause massive proliferation of gingival fibroblasts, increased collagen synthesis and reduced degradation by activating the Wnt/β-catenin pathway, interfering with integrin α2β1 expression, and inhibiting miR-200 to alter the cell cycle, ultimately exacerbating NIGO. In conclusion, bacteria may be an important factor in aggravating NIGO, and oral health management for patients with hypertension should be given due attention. Future research can focus on the interaction between the oral microbiota and immune cells in NIGO patients, providing new strategies for their prevention and treatment.

Objective : To analyze the relationship between tongue volume, tongue position, dental and skeletal parameters in adult patients with different skeletal malocclusions, providing references for the etiology, diagnosis, and treatment of skeletal malocclusions. Methods: This study has been reviewed and approved by the Ethics Committee, and informed consent has been obtained from patients. Cone-beam computed tomography (CBCT) and cephalometric radiographs were collected from 60 adult patients, divided into three groups based on ANB angle values: skeletal Class I (0° < ANB < 4°), II (ANB > 4°), and III (ANB < 0°), with 20 cases in each group. Dental and skeletal parameters were measured using Dolphin software. Mimics software was used for 3D reconstruction of the tongue, oral cavity, and upper airway to measure tongue position, tongue volume, oral cavity volume, and upper airway volume, followed by statistical analysis. Results: The skeletal Class III group had significantly larger tongue and oral cavity volumes than the skeletal Class I and Class II groups (P = 0.02). Tongue length in the skeletal Class III group was also greater than in the skeletal Class I and Class II groups (P = 0.016). There was no significant difference in the ratio of tongue volume/oral cavity capacity among the three skeletal malocclusion groups (P > 0.05). Tongue volume was positively correlated with U1-SN and negatively correlated with overbite and overjet (P < 0.05). Additionally, tongue volume showed a significant positive correlation with Go-Gn and Pg-Np (P < 0.01), as well as with maxillary and mandibular dental arch width and basal bone arch width (P < 0.01). Upper airway volume was positively correlated with TT-VRL and TP-VRL (P < 0.05). Conclusion Patients with skeletal Class III malocclusion have larger tongue volumes and longer tongues. Patients with larger tongue volumes may also have larger, more forward-positioned mandibles. Patients with more posterior tongue positions may have smaller upper airway volumes. When developing orthodontic or orthognathic treatment plans, it is crucial to consider the relationship between tongue position, tongue volume, the jaws, and the airway to ensure optimal outcomes for both dental and orofacial function.

Background The Inner Mongolia Autonomous Region is a vast area with a wide array of ecological environments, resulting in considerable regional variations in air pollution characteristics. Current research is limited by a scarcity of systematic, region-wide studies and risk assessments. Objective To assess the health risks associated with inhalation exposure to nine heavy metal and metalloid elements in atmospheric fine particulate matter (PM_2.5) for the population of the Inner Mongolia Autonomous Region. Methods From the 10th to the 16th of each month throughout 2023, atmospheric PM_2.5 samples were collected at designated monitoring sites in 12 leagues (cities) across the Inner Mongolia Autonomous Region to analyze the characteristics and trends in concentration. The health risk assessment model developed by the United States Environmental Protection Agency was employed to evaluate both the non-carcinogenic and carcinogenic risks associated with the heavy metal elements beryllium (Be), cadmium (Cd), chromium (Cr), hydrargyrum (Hg), plumbum (Pb), manganese (Mn), and nickel (Ni) and the metalloid elements stibium (Sb) and arsenic (As). Results In 2023, a total of 1206 valid PM_2.5 samples were analyzed from the Inner Mongolia Autonomous Region. The annual average PM_2.5 concentrations in Inner Mongolia, as well as in the cities of Ordos, Wuhai, and the Alxa League, all exceeded the national limit of 35 μg·m⁻³. The PM_2.5 concentrations across the leagues (cities) exhibited a clear seasonal variation, peaking in winter, followed by spring, and reaching a minimum in summer and autumn. The median PM_2.5 concentration in Ordos throughout the year was higher than that in the other leagues (cities) of the region. Concerning health risks, the non-carcinogenic risks associated with the 9 elements detected in each league (city) were all below 1, indicating acceptable levels. However, the non-carcinogenic risk values for Mn, Cr, and As were relatively high; specifically, Ordos City displayed the highest non-carcinogenic risk values for Mn (7.74×10⁻¹) and Cr (2.97×10⁻²), while Chifeng City recorded the highest value for As (2.34×10⁻³). The carcinogenic risk values for As, Cd, Cr, and Ni fell within the range of 1×10⁻⁹ to 1×10⁻⁵, representing an acceptable level. The health risks varied with age, and the elderly residents faced the highest non-carcinogenic and carcinogenic health risks. Conclusion While the carcinogenic and non-carcinogenic risks from heavy metals and metalloids within atmospheric PM_2.5 in the Inner Mongolia Autonomous Region are generally within acceptable limits, the potential risks that Mn, As, and Cr pose to the health of elderly people warrants particular attention, and Ordos and Chifeng cities exhibit notably higher health risks among other areas. It is recommended that regular, long-term monitoring be conducted, taking into account the specific conditions at monitoring sites across each league (city), and that targeted air quality management strategies be implemented to protect public health.

Human carboxylesterase 2A (hCES2A) plays pivotal roles in prodrug activation and hydrolytic metabolism of ester-bearing chemicals. Targeted inhibition of intestinal hCES2A represents a feasible strategy to mitigate irinotecan-triggered gut toxicity (ITGT), but the orally active, selective, and efficacious hCES2A inhibitors are rarely reported. Here, a novel drug-like hCES2A inhibitor was developed via three rounds of structure-based drug design (SBDD) and structural optimization. Initially, donepezil was identified as a moderate hCES2A inhibitor from 2000 US Food and Drug Administration (FDA)-approved drugs. Following two rounds of SBDD and structural optimization, a donepezil derivative (B7) was identified as a strong reversible hCES2A inhibitor. Subsequently, nine B7 carbamates were rationally designed, synthesized and biologically assayed. Among all synthesized carbamates, C3 showed the most potent time-dependent inhibition on hCES2A (IC₅₀ = 0.56 nmol/L), excellent specificity and favorable drug-like properties. C3 could covalently modify the catalytic serine of hCES2A with high selectivity, while this agent also showed favorable safety profiles, high intestinal exposure, and impressive effects for ameliorating ITGT in both human intestinal organoids and tumor-bearing mice. Collectively, this study showcases a rational strategy for developing drug-like and serine-targeting covalent inhibitors against target serine hydrolase(s), while C3 emerges as a promising orally active drug candidate for ameliorating ITGT.

OBJECTIVES: To investigate the mechanism through which salidroside inhibits proliferation of gastric cancer (GC) cells focusing on glucose metabolic reprogramming pathways. METHODS: High-throughput sequencing combined with bioinformatics analysis was employed to identify the potential targets of salidroside in human GC MGC-803 cells. Liposome-mediated transfection experiments were carried out to validate the functional and mechanistic roles of these targets. CCK-8 and colony formation assays were used to assess the effects of salidroside on GC cell viability and clonogenic ability. qRT-PCR, Western blotting, and biochemical assay kits were used to analyze the regulatory effects of salidroside on the miR-1343-3p-OGDHL/PDHB enzyme complex-pyruvate metabolic pathway in GC cells. RESULTS: Bioinformatics analysis suggested that the tumor-suppressive factor miR-1343-3p negatively regulated the key glycolytic enzyme gene oxoglutarate dehydrogenase-like (OGDHL) in GC cells, and OGDHL and pyruvate dehydrogenase E1 subunit beta (PDHB) were both significantly upregulated in GC tissues, which was close by correlated with reduced survival rates of GC patients. In MGC-803 cells, salidroside treatment significantly enhanced the expression level of miR-1343-3p and downregulated OGDHL expression, resulting in disruption of the stability of PDHB, reduced pyruvate oxidative decarboxylation, and consequently decreased production of acetyl-CoA and ATP. CONCLUSIONS Salidroside inhibits GC cell proliferation possibly by regulating the miR-1343-3p-OGDHL/PDHB enzyme complex-pyruvate metabolic pathway, which provides new insights into its anti-tumor mechanisms and suggests new strategies for targeted therapy for GC.
Humans ; Stomach Neoplasms/pathology* ; MicroRNAs/genetics* ; Cell Proliferation/drug effects* ; Glucosides/pharmacology* ; Phenols/pharmacology* ; Cell Line, Tumor ; Glucose/metabolism* ; Pyruvate Dehydrogenase (Lipoamide)/metabolism*

Diabetic cognitive dysfunction （DCD） is one of the complications of diabetes， which is characterized by impaired brain structure and progressively decreased learning and memory ability. With the increasing incidence of diabetes worldwide， DCD has become a serious medical and social problem. However， its pathophysiological mechanisms are not well understood. The occurrence and development of DCD involve multiple pathological links and mechanisms， and the prevention and treatment require multi-link and multi-target therapeutic measures. At present， there is no specific drug to prevent or improve DCD. Hypoglycemic drugs such as metformin and vigagliptin or anti-dementia drug including Donepezil are commonly used in clinical treatment to delay the occurrence and progression of cognitive dysfunction， but these drugs have a single target and obvious side effects. Traditional Chinese medicine has a long history in the prevention and treatment of diabetes and central cognitive diseases， and it has many unique advantages such as multiple components， multiple targets， side effects， and low price. A large number of studies have confirmed that traditional Chinese medicine has a significant prevention and treatment effect on DCD， which can improve insulin resistance， synaptic dysfunction， inflammation， oxidative stress， endoplasmic reticulum stress， and neuronal apoptosis by regulating phosphatidylin-ositol 3-kinase （PI3K）/protein kinase B （Akt）， advanced glycation end products （AGEs）/advanced glycation end products receptor （RAGE）/nuclear transcription factor-κB （NF-κB）， NOD-like receptor thermal protein domain associated protein 3 （NLRP3） inflammasome， and endoplasmic reticulum stress and nuclear factor E₂ related factor 2 （Nrf2）/antioxidant response element （ARE） signaling pathways. This article reviewed the effects and related mechanisms of traditional Chinese medicine on DCD in recent years， so as to provide a reference for the prevention and treatment of DCD by traditional Chinese medicine.

Background Occupational stress is an important public health problem in the military. At present, there are few studies about occupational stress of officers and soldiers of the armed forces in China, especially the effects of plateau related environmental factors on occupational stress. Objective To understand current status and identify influencing factors of occupational stress among officers and soldiers stationed in plateaus, and provide a scientific basis for managing occupational stress. Methods In April 2023, stratified cluster sampling was used to recruit troops by deployed altitudes ranging from 500 to 3000 m into two strata of low altitude (＜2500 m) and high altitude (≥2500 m) based on the medical definition of plateau. Two regimental units were randomly selected from each stratum respectively, and one battalion unit was randomly selected from each regimental unit with all the officers and soldiers. Four selected battalion units were surveyed with a total of 2284 officers and soldiers. We designed a general questionnaire to collect their basic information, and distributed effort-reward imbalance questionnaires to evaluate occupational stress. We used logistic regression to identify potential influencing factors of occupational stress. Results Positive occupational stress was reported in 508 plateau-stationed officers and soldiers, with a prevalence rate of 22.2%. The total effort-reward imbalance score and the dimensional scores of effort, reward, and overcommitment in M (P₂₅, P₇₅) were 0.9 (0.7, 1.0), 16.0 (13.0, 19.0), 36.0 (33.0, 39.0), and 18.0 (15.0, 19.0), respectively. There were significant differences in the positive rate of occupational stress by gender, age, military service length, marital status, only child or not, physical fitness condition, reporting underlying diseases or not, exercise frequency before conscription, psychological changes after entering the plateaus, and having altitude sickness or not (P <0.05). The results of logistic regression showed that being female (OR=1.532, 95%CI: 1.061, 2.213), only child (OR=1.281, 95%CI: 1.038, 1.581), and with underlying diseases (OR=1.950, 95%CI: 1.340, 2.839) were associated with a higher risk of occupational stress. While setting 0 to <3 years of military service as the control group, the risk of occupational stress was higher in subgroups of 3 to 9 years (OR=1.380, 95%CI: 1.113, 1.710) and ≥9 years (OR=2.141, 95%CI: 1.461, 3.137). The participants reporting nervousness or fear (OR=1.728, 95%CI: 1.133, 2.635) and agitation or euphoria (OR=1.380, 95%CI: 1.113, 1.710) had a higher risk of reporting occupational stress than those with no psychological changes after entering the plateaus. Meanwhile, those who had regular exercise (OR=0.670, 95%CI: 0.492, 0.913) before enlistment, good physical fitness condition (OR=0.572, 95%CI: 0.426, 0.767) and excellent physical fitness condition (OR=0.502, 95%CI: 0.366, 0.688) had a lower risk of occupational stress. Conclusion Officers and soldiers in plateaus generally report a high rate of occupational stress. Female, military service length ≥3 years, being only child, with underlying diseases, nervousness/ fear or agitation/ euphoria after entering plateaus are risk factors for elevated occupational stress in this group; while good or excellent physical fitness condition and frequent exercise before enlistment are protective factors for occupational stress. Therefore, it is necessary to pay attention to the occupational stress problems in officers and soldiers stationed in plateaus and provide targeted intervention measures.

Objective:To assess the efficacy of neoadjuvant treatment with PD-1 (programmed cell death protein 1) inhibitors combined with paclitaxel (albumin-conjugated) and cisplatin (TP regimen) for locally advanced hypopharyngeal squamous cell carcinoma and laryngeal organ function preservation.Methods:Data of 53 patients, including 51 males and 2 females, aged 38-70 years old, who were diagnosed with locally advanced hypopharyngeal squamous carcinoma confirmed by histology and enhanced CT at the Cancer Prevention and Control Center of Sun Yat-sen University during the initial treatment from January 1, 2019 to January 15, 2023, were retrospectively analyzed. All patients received neoadjuvant therapy with PD-1 inhibitors combined with albumin-bound paclitaxel (260 mg/m 2) and cisplatin (60 mg/m 2) for 3 to 4 cycles. The main outcome measures were larynx dysfunction-free survival (LDFS), overall survival (OS), and progression-free survival (PFS). Survival curves were plotted using the Kaplan-Meier method, and Cox multifactorial analysis was further performed if Cox univariate analysis was statistically significant. Results:The overall efficiency was 90.6% (48/53). The 1-year and 2-year LDFS rates were 83.8% (95% CI: 74.0% to 94.8%) and 50.3% (95% CI: 22.1% to 91.6%), the 1-year and 2-year OS rates were 95.2% (95% CI: 88.9% to 100.0%) and 58.2% (95% CI: 25.6% to 81.8%), and the 1-year and 2-year PFS rates were 83.9% (95% CI: 74.2% to 94.9%) and 53.5% (95% CI: 32.1% to 89.1%). Adverse events associated with the neoadjuvant therapy were mainly myelosuppression (45.3%), gastrointestinal reactions (37.7%) and hypothyroidism (20.8%). Conclusion:The neoadjuvant treatment of locally advanced hypopharyngeal squamous cell carcinoma using PD-1 inhibitors combined with paclitaxel and cisplatin can provide with a higher survival rate with a improved laryngeal organ function preservation rate.

Objective It aims to construct a quality evaluation index system for cancer multidisciplinary diagnosis and treatment(MDT)model in China from a full process perspective,providing guidance for practical application and model optimization.Methods Based on the number of MDT publications and practical situations,20 provincial-level hospitals nationwide were selected as typical cases.Rooted theory was used to extract evaluation indicators from the original text of the cases through three-level coding.A cancer MDT quality evaluation index system was constructed under the Input-Process-Output framework.Results Through three-level coding,27 initial categories,8 subcategories,and 3 main categories were sorted out,and a cancer MDT quality evaluation index system was constructed with input,process,and output as the primary evaluation indicators,and top-level design,management system,object resources,meeting preparation,meeting progress,plan implementation,patient outcomes,and hospital outcomes as the secondary evaluation indicators.Conclusion The quality evaluation index system of cancer MDT mode based on the perspective of the entire process can effectively guide practical optimization,but there is still a need for the improvement of supporting policies and information systems to assist in quality evaluation.

Background and objective The incidence rate of lung cancer in Xuanwei has been continuously in-creasing in recent years,and it also features high incidence across all age groups and high mortality rates among female lung cancer patients.Therefore,the search for more stable biomarkers for the diagnosis of Xuanwei lung cancer holds tremendous clinical application prospects.This study aims to explore the clinical application value of these four microRNAs(miRNAs)in-dividually and in combination with traditional lung cancer tumor markers in the detection and diagnosis of Xuanwei lung can-cer.Methods By detecting the expression levels of four miRNAs and five traditional lung cancer tumor markers in the serum of 45 Xuanwei lung cancer patients and healthy physical examination participants,the Logistic regression model was employed to comprehensively evaluate the sensitivity,specificity,diagnostic efficacy,and other relevant statistical indicators of the four miR-NAs in the diagnosis of Xuanwei lung cancer.Results Among the individual miRNAs,miR-4646-5p and miR-3654 showed significant differences in expression levels between the Xuanwei lung cancer group and the control group(P＜0.05).miR-3654 demonstrated the best diagnostic performance with a sensitivity of 86.7％ ,specificity of 82.2％ ,and an area under the curve of 0.847.Combining miR-3654 with miR-4646-5p and carcinoembryonic antigen(CEA)resulted in the highest diagnostic ef-ficacy for Xuanwei lung cancer,with a sensitivity of 73.3％ ,specificity of 93.3％ ,area under the curve of 0.901,and a positive predictive value of 91.7％ .Conclusion Among the four miRNAs,serum miR-3654 exhibits the best diagnostic efficacy for Xuanwei lung cancer.Combined with miR-4646-5p and CEA,its diagnostic value for Xuanwei lung cancer can be effectively enhanced,making it a promising screening indicator for Xuanwei lung cancer.