Objective: To investigate the association between monocyte to high-density lipoprotein cholesterol ratio (MHR) and periodontitis and to provide new epidemiologic evidence on the factors affecting periodontitis. Methods: Data on MHR, periodontitis, and other covariates were selected from the NHANES(National Health and Nutrition Examination) database for 3 cycles of subjects in 2009-2010, 2011-2012, and 2013-2014, and a total of 8 456 study subjects were included. The study participants were grouped according to the prevalence of periodontitis (presence or absence), and three regression models (unadjusted covariates, partially adjusted covariates, and fully adjusted covariates) were constructed to analyze the relationship between MHR and periodontitis by using a weighted logistic regression method with stepwise adjustment for confounders. MHR was divided into four groups from Q1 to Q4 according to quartiles from small to large for weighted trend analysis, and the nonlinear relationship between MHR (continuous) and periodontitis was analyzed using a restricted cubic spline with subgroup analysis and sensitivity analysis. Results: All three logistic regression models showed a positive association between MHR and periodontitis (OR = 2.92, 95%CI: 2.14-3.99, P<0.001 (not adjusted); OR = 1.97, 95%CI: 1.39-2.78, P<0.001 (partially adjusted); OR = 1.62, 95%CI: 1.10-2.39, P = 0.017 (fully adjusted)). Trend analysis showed a significantly higher risk of developing periodontitis in the Q4 group compared with the Q1 group in both single (OR = 1.92, 95% CI: 1.58-2.33, P<0.001) and multifactorial analyses (OR = 1.30, 95% CI: 1.03-1.64, P = 0.029). Restricted cubic spline results did not support a nonlinear relationship between MHR and periodontitis (P for nonlinear>0.05), subgroup analysis showed no significant interaction between the covariates and MHR (P>0.05), and sensitivity analysis also showed a positive correlation between MHR and periodontitis (OR = 1.67, 95%CI: 1.31-2.14, P<0.001). Conclusion MHR is positively associated with the risk of developing periodontitis.

OBJECTIVE To summarize the current status of position training for clinical pharmacists in China and provide references for the continuous optimization of such training programs. METHODS SinoMed， CNKI，VIP and Wanfang Data were electronically searched to collect position training of clinical pharmacists studies from the inception until November 5th 2024. After data extraction and quality evaluation， descriptive analysis was performed on the results of the included studies. RESULTS & A total of 68 pieces of relevant literature were included in the study. Among them， 50 studies reported on training content， 49 involved the allocation of teaching resources in the bases， 48 addressed training methods， and 39 focused on training evaluation； only 2 studies mentioned faculty development. There were notable variations in the clinical pharmacist training programs across different bases， particularly in the allocation of teaching resources， such as the composition of the teaching team and the utilization of auxiliary teaching tools. Additionally， differences existed in training approaches， such as those employing a single method versus a blended approach. Conversely， the core training content of each base generally revolved around clinical pharmacy practice， demonstrating a degree of consistency. Moreover， the overall emphasis on teacher training and assessment tended to be obviously insufficient. Each base can focus on enhancing the competence of clinical pharmacists by allocating teaching resources， selecting training methods， improving training content， and using evaluation tools， to further enhance the quality of clinical pharmacist training.

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

Lysosomes represent a promising target for cancer therapy and reducing drug resistance. However, the short treatment time and low efficiency of lysosomal targeting have limited the application in lysosome-targeting anticancer drugs. In this study, we proposed an adhesive-bandage approach and synthesized a new lysosomal targeting drug, namely long-term lysosome-targeting anticancer drug (LLAD). It contains a SLC38A9-targeting covalently bound moiety and an alkaline component both to prolong the inhibition of SLC38A9 in lysosomes and alkalinize lysosomes. Upon short term and low-dose treatment of HeLa cells, at passage 0, with LLAD, it rapidly alkalinized lysosomes and also can be detected in lysosomes even at passage 15. LLAD induced apoptosis in HeLa cells through long-term lysosomal damage, and showed better long-term anticancer effect than cisplatin in vivo. Overall, our study paves the way for developing long-term lysosomal targeting drugs to treat cancer and overcome the drug resistance of cancer cells, and also provides a candidate drug, LLAD, for treating cancer.

OBJECTIVES: To explore the expression profile of circular RNAs (circRNAs) and their potential roles in prognosis and progression of Wilms' tumor (WT). METHODS: Four pairs of WT and adjacent tissues were collected for high-throughput circRNA sequencing to identify the differentially expressed circular RNAs. RT-qPCR was used to verify the expression levels of the top 6 candidate circRNAs in the clinical samples. hsa_circ_0001900 was selected for analysis of its correlation with clinicopathological features and prognosis in 34 patients with WT. Sanger sequencing and RNase R digestion experiments were used to verify the cycling site and structural stability of hsa_circ_0001900 molecule. RESULTS: A total of 23 978 circular RNA molecules were identified in WT tissues by high-throughput circular RNA sequencing, and among them 614 were differentially expressed in WT. hsa_circ_0001900 showed the highest expression level among the differentially expressed circRNAs, which was consistent with the findings in clinical tumor samples and the sequencing results. Correlation analysis showed that hsa_circ_0001900 expression level was positively correlated with WT volume, and the children with high hsa_circ_0001900 expression had a lowered recurrence-free survival rate. The results of Sanger sequencing verified the circular splice site sequence of the molecule, and Rnase R digestion assay confirmed its stable covalent structure. CONCLUSIONS This study presents a comprehensive expression profile of circular RNAs in WT, and the expression level of hsa_circ_0001900 is related to the size of WT and the patients' prognosis, suggesting its possible role as a key driving gene in WT progression.
Humans ; RNA, Circular ; Wilms Tumor/pathology* ; Prognosis ; High-Throughput Nucleotide Sequencing ; Kidney Neoplasms/genetics* ; Sequence Analysis, RNA ; Male ; Female

5-Hydroxytryptamine(5-HT)type 3 receptor(5-HT3R)is the only type of ligand-gated ion channel in the 5-HT receptor family.Through the high permeability of Na+,K+,and Ca2+ and activation of subsequent voltage-gated calcium channels(VGCCs),5-HT3R induces a rapid increase of neuronal excitability or the release of neurotransmitters from axon terminals in the central nervous system(CNS).5-HT3Rs are widely expressed in the medial prefrontal cortex(mPFC),amygdala(AMYG),hippocampus(HIP),periaqueductal gray(PAG),and other brain regions closely associated with anxiety reactions.They have a bidirectional regulatory effect on anxiety reactions by acting on different types of cells in different brain regions.5-HT3Rs mediate the activation of the cholecystokinin(CCK)system in the AMYG,and the γ-aminobutyric acid(GABA)"disinhibition"mechanism in the prelimbic area of the mPFC promotes anxiety by the activation of GABAergic intermediate inhibitory neurons(IINs).In contrast,a 5-HT3R-induced GABA"disinhibition"mechanism in the infralimbic area of the mPFC and the ventral HIP produces anxiolytic effects.5-HT2R-mediated regulation of anxiety reactions are also activated by 5-HT3R-activated 5-HT release in the HIP and PAG.This provides a theoretical basis for the treatment of anxiety disorders or the production of anxiolytic drugs by targeting 5-HT3Rs.However,given the circuit specific modulation of 5-HT3Rs on emotion,systemic use of 5-HT3R agonism or antagonism alone seems unlikely to remedy anxiety,which deeply hinders the current clinical application of 5-HT3R drugs.Therefore,the exploitation of circuit targeting methods or a combined drug strategy might be a useful developmental approach in the future.

Objective:To analyze the disease characteristics, diagnosis and treatment methods of venous pulsatile tinnitus treated by intervention of sigmoid sinus.Methods:Fifty patients (from Shandong Provincial ENT Hospital, Shandong University between February 2014 and July 2020) with venous pulsatile tinnitus treated by sigmoid sinus surgery were analyzed retrospectively. The tinnitus characteristics, imaging findings, surgical methods, intraoperative findings and postoperative tinnitus changes were recorded. The patients were followed up for 6-12 months. The sign rank sum test was used to analyze the difference in tinnitus grading before and after surgery. There were 50 patients with unilateral venous pulsatile tinnitus, including 49 females and 1 male. The age ranged from 17 to 67 years, with a median age of 44 years. There were 45 cases of right tinnitus and 5 cases of left tinnitus. The degree of tinnitus before operation was grade Ⅱ or above, including 4 cases of gradeⅡ, 11 cases of grade Ⅲ, 22 cases of grade Ⅳ and 13 cases of grade Ⅴ.Results:Thirty-seven cases were cured, 8 cases were ineffective (no change in tinnitus), 3 cases were markedly effective (tinnitus grade decreased by 3 in 2 cases, 4 in 1 case), and 2 cases were effective (tinnitus grade decreased by 1). The difference of tinnitus grade before and after operation was statistically significant ( Z=-5.70, P<0.05). Temporal bone CT showed 36 cases of sigmoid diverticulum (including 17 cases with sigmoid sinus dehiscence), 12 cases of sigmoid sinus dehiscence and 2 cases of absence of the temporal bone cortex abutting to sigmoid sinus. Thirty-five cases were performed with closure of sigmoid sinus diverticulum, 4 cases were performed with resurfacing of the sigmoid plate, 5 cases were performed with narrowing of sigmoid sinus, 4 cases were performed with simple opening of pre sigmoid mastoid air chamber, 1 case of opening was performed with pre sigmoid mastoid air chamber combined with narrowing of sigmoid sinus, and 1 case was performed with opening of pre sigmoid mastoid air chamber combined with closure of sigmoid sinus diverticulum. Conclusions:Venous pulsatile tinnitus is common in women. The common causes may be sigmoid sinus wall abnormalities such as sigmoid sinus diverticulum and perisigmoid bone defect. Imaging examinations are helpful for diagnosis. Venous pulsatile tinnitus can be treated with surgery.

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG^@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

Malignant tumors are a prominent societal and public health challenges. Occupational tumors, as a subset of malignant tumors, have drawn considerable attention, particularly those caused by carcinogenic heavy metals and metalloids. The International Labor Organization has classified malignant tumors caused by hexavalent chromium compounds, arsenic and its inorganic compounds, cadmium and its compounds, and nickel compounds as occupational diseases, while China only classified lung cancer caused by hexavalent chromium compounds and lung and skin cancers caused by arsenic and its inorganic compounds as occupational diseases. In term of prevention and treatment of occupational tumors caused by carcinogenic heavy metals and metalloids, the principles of tertiary prevention should be followed, and the focus should be paid to combation of carcinogen exposure assessments and tertiary prevention strategies to set up a comprehensive system of prevention and treatment. Multiple effort on its source control, etiology diagnosis, biomarker research, and high-risk population screening can effectively reduce the risk of occupational tumors and improve patients′ quality of life. Advancing research on the mechanisms of occupational tumors caused by carcinogenic heavy metals and metalloids and improving study on the occupational health surveillance are crucial for early screening, diagnosis, and treatment of occupational tumors. Future study on occupational tumors caused by carcinogenic heavy metals and metalloids should combine the etiology, pathogenesis, and tertiary prevention strategies with active application of artificial intelligence. Therefore, developing a preventive model that encompasses the entire occupational population and life cycle will offer support for the prevention and treatment of occupational tumors.