Objective: To explore the longitudinal associations between dietary macronutrients and lung function in schoolaged children, so as to provide the nutritional research evidence for promoting children s lung health. Methods: In November 2021, two primary schools located in Chengdu, Sichuan Province were selected from the Southwest China Childhood Nutrition and Growth (SCCNG) cohort by a stratified cluster random sampling method, enrolling a total of 1 112 school aged children aged 8 to 13 years. At baseline, the dietary and sociodemographic characteristics of the children were assessed. One year later, the forced vital capacity (FVC) of the children was measured and converted into Z scores (FVC- Z ), while the vital capacity index (VCI) was also calculated. Generalized linear regression analysis was employed to examine the associations between dietary macronutrients and lung function, considering interactions with gender and age, followed by stratified analysis. Results: After adjusting for confounding factors, the analysis results of the generalized linear regression model showed that the carbohydrate energy ratio was negatively correlated with FVC- Z ( β =-0.02) and VCI ( β =-0.16), while the fat energy ratio showed a positive correlation with FVC- Z ( β =0.03) and VCI ( β =0.23) ( P <0.05). The protein energy ratio was positively correlated with FVC- Z ( β =0.09) and VCI ( β =0.60) specifically in girls ( P <0.05). Additionally, there was an interaction effect of age on the associations between macronutrients and lung function ( P <0.01); in children aged 8-9 and 10-11, the carbohydrate energy supply ratio was negatively correlated with FVC- Z ( β =-0.04, -0.03) and VCI ( β =-0.29, -0.21), and fat energy supply ratio was positively correlated with FVC- Z ( β =0.07, 0.05) and VCI ( β =0.46, 0.32) ( P <0.05). Conclusions There are age and sex differences in the association of dietary macronutrients with lung function, with a low carbohydrate, high fat diet promoting lung function in children. Additionally, protein intake appears to have a positive influence on the lung function of girls. The early school age period may represent a critical window for dietary interventions aimed at promoting lung health.

Objective: To investigate the effects of Erianin on cell proliferation and apoptosis in human oral squamous cell carcinoma (OSCC) cells, providing a research foundation for the clinical treatment of OSCC. Methods: Erianin was applied to OSCC cells (CAL27 and SCC9) at concentrations of 0, 2.5, 5, and 10 μmol/L. The inhibitory effect of Erianin on OSCC cell proliferation was evaluated using CCK-8 and soft agar colony formation assays. Western blotting (WB) was employed to analyze the expression levels of anti-apoptotic proteins B-cell lymphoma-extra large (Bcl-xL), B-cell lymphoma-2 (Bcl-2), myeloid cell leukemia-1 (Mcl-1), and apoptotic protein cleaved-Caspase 3 (c-Caspase 3) in OSCC cells. Caspase 3 activity was further assessed using a caspase 3 activity detection kit to examine the pro-apoptotic effect of Erianin in OSCC cells. Mcl-1 overexpression was induced in CAL27 cells via plasmid transfection, and the influence of Mcl-1 on the effects of Erianin in CAL27 cells was analyzed by WB and caspase 3 activity measurement. All animal experiments were approved by the Ethics Committee of Hunan Cancer Hospital. A CAL27 xenograft mouse model was established and randomly divided into two groups (n = 5): the treatment group received intraperitoneal injection of Erianin (25 mg/kg), while the control group was injected with phosphate-buffered saline (PBS) as the vehicle. Immunohistochemistry (IHC) was used to detect the expression levels of Ki67 and Mcl-1 in the tumor tissues. Results: Erianin inhibited the proliferation of CAL27 and SCC9 cells in a dose-dependent manner and downregulated the protein expression of Mcl-1, with minimal effects on Bcl-2 and Bcl-xL. Furthermore, Erianin induced apoptosis in OSCC cells, as evidenced by increased expression of c-Caspase 3 and enhanced caspase 3 activity (P<0.001). Overexpression of Mcl-1 inhibited the Erianin-induced increase in c-Caspase 3 protein levels and caspase 3 activity. In vivo results were consistent with the in vitro findings. After Erianin treatment, CAL27 cell growth in nude mice was suppressed (P<0.001), and the expression levels of the proliferation marker Ki67 and the anti-apoptotic protein Mcl-1 in the tumor tissues were downregulated (P<0.001). Conclusion Erianin exhibits potent anti-tumor effects, effectively inhibiting the proliferation of OSCC cells and inducing apoptosis. The underlying mechanism may involve the downregulation of the pro-survival protein Mcl-1.

OBJECTIVE: To observe the effects of "olfactory three needles" on cognition, learning and memory abilities, as well as hippocampal microglia (MG) phagocytic activity in vascular dementia (VD) rats, and explore the mechanisms of acupuncture in regulating MG activation and improving remyelination, so as to ameliorate VD. METHODS: Among 38 SD rats meeting experimental requirements, 9 rats were randomly assigned to a sham-operation group, and the remaining rats underwent permanent bilateral common carotid artery ligation to establish VD model. Eighteen successfully modeled rats were randomly divided into a model group and an electroacupuncture (EA) group, with 9 rats in each one. In the EA group, EA was performed at "olfactory three needles" ("Yintang" [GV24⁺] and bilateral "Yingxiang" [LI20]), at disperse-dense wave, the frequency of 2 Hz/15 Hz and the current intensity of 1 mA, for 15 min per intervention, once daily. One course was composed of 7 days, and 2 courses were required, with the interval of 2 days. The novel object recognition test was employed to assess the cognition of rats, and the Morris water maze was adopted to observe learning and memory abilities. Luxol fast blue (LFB) staining was performed to evaluate myelin sheath loss in the hippocampus, the Western blot was used to detect the protein expression of triggering receptor expressed on myeloid cells-2 (TREM2) and proteolipid protein (PLP) in the hippocampus; and the immunofluorescence staining was used to detect the positive expression of PLP, sex determining region Y-box 10 (SOX10), ionized calcium binding adaptor molecule 1 (Iba1)⁺ TREM2⁺ and Iba1⁺ lysosome-associated membrane protein 1 (LAMP1)⁺ in the hippocampus. RESULTS: Compared with the sham-operation group, the rats in the model group exhibited the prolonged escape latency on day 3 and 4 (P<0.05, P<0.01), the increase of the total distance traveling (P<0.01) and the decrease of the recognition index (RI) and platform crossing frequency (P<0.01). Compared with the model group, the rats in the EA group showed the shortened escape latency on day 3 and 4 (P<0.05), the decrease of total distance traveling (P<0.01) and the increase of RI and platform crossing frequency (P<0.05, P<0.01). When compared with the sham-operation group, the rats of the model group presented uneven staining, sparse arrangement of myelin sheath fibers, unclear contours, and prominent vacuole-like changes in the hippocampal CA1 region. When compared with the model group, the EA group showed more dense staining, the increase of myelin sheath fibers with more orderly alignment, and fewer vacuolar changes in the hippocampal CA1 region. Compared with the sham-operation group, the model group exhibited the increase of TREM2 protein expression and the decrease of PLP protein expression in the hippocampus (P<0.01), whereas the EA group showed the up-regulation of TREM2 and PLP protein expression when compared with the model group (P<0.01, P<0.05). The positive expression of the hippocampal PLP, SOX10, and Iba1⁺LAMP1⁺ in the model group was reduced in comparison with the sham-operation group (P<0.05, P<0.01), and the positive expression of Iba1⁺ TREM2⁺ was elevated (P<0.05). In the EA group, the positive expression of PLP, SOX10, Iba1⁺TREM2⁺, and Iba1⁺ LAMP1⁺ was higher compared with that in the model group (P<0.05, P<0.01). CONCLUSION "Olfactory three needles" can improve the learning and memory, and cognitive functions of VD rats, and its mechanism may be associated with the up-regulation of TREM2 and LAMP1 to adjust MG phagocytic activity and intracellular degradation, and promote remyelination.
Animals ; Dementia, Vascular/metabolism* ; Rats ; Rats, Sprague-Dawley ; Microglia/metabolism* ; Male ; Acupuncture Therapy/instrumentation* ; Acupuncture Points ; Humans ; Remyelination ; Memory ; Hippocampus/cytology* ; Cognition ; Electroacupuncture ; Needles

Invasive fungal infections (IFIs) have become prominent global health threats, escalating the burden on public health systems. The increasing occurrence of invasive fungal infections is due primarily to the extensive application of chemotherapy, immunosuppressive therapies, and broad-spectrum antifungal agents. At present, therapeutic practices utilize multiple categories of antifungal agents, such as azoles, polyenes, echinocandins, and pyrimidine analogs. Nevertheless, the clinical effectiveness of these treatments is progressively weakened by the emergence of drug resistance, thereby substantially restricting their therapeutic utility. Consequently, there is an imperative need to expedite the discovery of novel antifungal agents. This review seeks to present an exhaustive synthesis of novel antifungal drugs and candidate agents that are either under current clinical investigation or anticipated to progress into clinical evaluation. These emerging compounds exhibit unique benefits concerning their modes of action, antimicrobial spectra, and pharmacokinetic characteristics, potentially leading to improved therapeutic outcomes relative to conventional antifungal regimens. It is anticipated that these novel therapeutic agents will furnish innovative treatment modalities and enhance clinical outcomes in managing invasive fungal infections.

Abstract Ring finger protein 183(RNF183) is an E3 ubiquitin ligase that catalyzes the covalent attachment of ubiquitin molecules to substrate proteins. RNF183 is expressed in tissues such as kidney and testis, and it is mainly localized to the endoplasmic reticulum, Golgi apparatus, and lysosomes in cells. As one of the components of the endoplasmic reticulum membrane, it participates in the endoplasmic reticulum stress-responsive pathway that affects cellular and protein ubiquitination. In recent years, the study of E3 ubiquitin ligase member-RNF183 with various diseases such as colorectal cancer, endometrial cancer and bladder cancer has gradually increased. In this review, the role of RNF183 in colorectal cancer, inflammatory bowel disease and other diseases, as well as biological functions such as endoplasmic reticulum stress are summarized, aiming to provide reference ideas for the study of related diseases.

ObjectiveTo study the effect of Xihuangwan extract on mitochondrial energy metabolism in ovarian cancer SKOV3 and HEY cells and to explore the underlying mechanism. MethodSKOV3 and HEY cells were cultured in vitro and treated with different concentrations （0， 5， 10， 15， 20 g·L^-1） of Xihuangwan extract. Methyl thiazolyl tetrazolium （MTT） was used to examine the viability of SKOV3 and HEY cells treated with Xihuangwan extract. The adenosine-triphosphate （ATP） levels in SKOV3 and HEY cells were measured by kit. Flow cytometry was employed to measure the content of reactive oxygen species （ROS） in cells. Western blot was employed to determine the protein levels of peroxisome proliferator-activated receptor-γ co-activator 1α （PGC1α）， transcription factor A， mitochondrial （TFAM）， translocase of outer mitochondrial membrane 20 （TOMM20）， and aplasia Ras homologue member Ⅰ （ARHⅠ） in SKOV3 and HEY cells. Mito-Tracker Green staining was used to observe the morphological changes of mitochondria in SKOV3 and HEY cells. ResultCompared with blank group， Xihuangwan extract treatment for 24， 48 h inhibited the viability of SKOV3 and HEY cells in a concentration-dependent manner （P<0.05， P<0.01）. Compared with blank group， Xihuangwan extract （10， 15， 20 g·L^-1） groups presented lowered ATP levels （P<0.05， P<0.01）， and the 20 g·L^-1 Xihuangwan extract group had lower ATP level than the 10 and 15 g·L^-1 Xihuangwan extract groups （P<0.05）. Compared with blank group， Xihuangwan extract increased the content of ROS in SKOV3 and HEY cells in a concentration-dependent manner （P<0.05， P<0.01）， and the 20 g·L^-1 Xihuangwan extract group had higher ROS content than the 10 g·L^-1 Xihuangwan extract group （P<0.05）. Compared with blank group， Xihuangwan extract up-regulated the expression level of ARHⅠ protein in SKOV3 and HEY cells in a concentration-dependent manner （P<0.01）， and the expression levels of ARHⅠ protein was higher in the 20 g·L^-1 Xihuangwan extract group than in the 10 and 15 g·L^-1 Xihuangwan extract groups （P<0.05）. Compared with the blank group， Xihuangwan extract down-regulated the protein levels of PGC1α， TFAM， and TOMM20 in SKOV3 and HEY cells in a concentration-dependent manner （P<0.05， P<0.01）， and the protein levels of TFAM and TOMM20 in the HEY cells treated with 20 g·L^-1 Xihuangwan extract were lower than those in the HEY cells treated with 10， 15 g·L^-1 Xihuangwan extract （P<0.05）. Compared with the blank group， 20 g·L^-1 Xihuangwan extract decreased the Mito-Tracker fluorescence intensity of SKOV3 and HEY cells （P<0.05）. ConclusionXihuangwan can compromise the mitochondrial function of ovarian cancer SKOV3 and HEY cells and reduce cell energy metabolism to inhibit the proliferation of SKOV3 and HEY cells by up-regulating ARHⅠ and inhibiting PGC1α/TFAM signaling axis.

OBJECTIVE To investigate the clinical effect of Budigafol combined with Staphylococcus and neisseria tablets in maintenance treatment of patients with stable moderate to severe chronic obstructive pulmonary disease （COPD）. METHODS A total of 122 patients with stable moderate to severe COPD who were admitted to the infections diseases ward of the department of respiratory and critical care medicine in our hospital from October 1， 2021 to January 31， 2023 were divided into control group （n＝61） and observation group （n＝61） according to the random number table method. Patients in the control group were treated with Budigafol inhalation aerosol alone （2 presses each time， twice a day）， and patients in the observation group were treated with Staphylococcus and neisseria tablets （1.2 mg each time， 3 times a day） on the basis of the control group. The treatment course of both groups was 3 months. The quality of life， exercise tolerance， lung function， inflammatory indexes， immune function， as well as the number of acute attacks of COPD and the occurrence of adverse reactions were compared between the two groups before and after treatment. RESULTS Control group and observation group shed 12 and 9 patients， respectively. After treatment， the 6 minute walking distance of the two groups of patients was significantly prolonged compared with that before treatment （P＜0.05）. The COPD assessment test questionnaire score， St George’s respiratory questionnaire score， the ratio of residual volume to total lung capacity， the fractional exhaled nitric oxide， the serum levels of C-reactive protein and interleukin-6 were significantly E-mail：13956685295@163.com decreased compared with those before treatment （P＜0.05）. The forced expiratory volume in one second （FEV1）， the ratio E-mail：13966580920@163.com of FEV1 to forced vital capacity， the percentage of the measured value of carbon monoxide diffusion capacity to the predicted value， and the percentage of the measured value of FEV1 to the predicted value were significantly increased compared with those before treatment （P＜0.05）. The improvement of the above indicators in the observation group was significantly better than that in the control group （P＜0.05）. Compared with before treatment， there was no statistical significance in the immune function indexes of the control group or the serum levels of immunoglobulin A （IgA） and IgM in the observation group after treatment （P＞0.05）. The percentages of CD3+ ， CD4+ ， B lymphocytes and natural killer cells， the levels of CD4+/CD8+ and IgG were significantly increased in the observation group （P＜ 0.05）， the percentage of CD8+ cells was significantly decreased （P＜0.05）， and the improvement degree of the observation group was significantly better than that of the control group （P＜0.05）. There was no significant difference in the number of acute exacerbations of COPD during the follow-up period and the incidence of adverse events during treatment between the two groups （P＞0.05）. CONCLUSIONS Budigafol combined with Staphylococcus and neisseria tablets can effectively improve the immune function of patients with stable moderate to severe COPD， further reduce the level of inflammation， and improve their exercise tolerance and their quality of life with good safety.

The angiogenic microenvironment is a new blood vessel with different molecular and functional characteristics that sprouts on the original blood vessels through different mechanisms,which directly affects the process of tumor cell growth,proliferation,and migration and has an important impact on the occurrence and development of precancerous lesions of gastric cancer.Correa mode has shown that precancerous lesions of gastric cancer is the key pathological stage before the occurrence of gastric cancer,and it is of great significance to advance the prevention and treatment strategy to this stage.TCM believes that qi deficiency and blood stasis is the key pathogenesis of precancerous lesions of gastric cancer,and its basic treatment is to replenish qi and remove blood stasis,and based on the syndrome differentiation,drugs with the efficacy of nourishing yin and tonifying stomach,soothing the liver and regulating qi,resolving phlegm and dispersing lumps,and clearing heat and dampness for treatment.This article discussed the correlation between precancerous lesions of gastric cancer and angiogenic microenvironment and its regulatory pathways,and summarized the methods and mechanisms of TCM in the treatment of precancerous lesions of gastric cancer from the perspective of regulating angiogenic microenvironment-related pathways,in order to provide a reference for the treatment of precancerous lesions of gastric cancer with TCM.

Objective:To investigate the expression levels and clinical significance of serum microRNA (miR) -155 and miR-135b-5p in patients with peptic ulcer complicated with Helicobacter pylori ( Hp) infection. Methods:A prospective study was conducted, and 263 patients with peptic ulcer were selected consecutively from July 2021 to February 2023 at the Affiliated Hospital of Jining Medical College. Among them, 146 cases were confirmed as Hp infection ( Hp infection group) and 117 cases were not complicated with Hp infection (non Hp infection group) by 14C breath test; type Ⅰ Hp infection was in 110 cases, and type Ⅱ Hp infection was in 36 cases by immunoblotting method. The serum expression levels of miR-155 and miR-135b-5p were detected by real-time fluorescence quantitative polymerase chain reaction, serum gastrin level was detected by radioimmunoassay method, and the serum pepsinogen (PG) Ⅰ and PG Ⅱ were detected by enzyme linked immunosorbent assay. The clinical data were recorded. Multivariate Logistic regression analysis was used to analyze the independent risk factors of Hp infection in patients with peptic ulcer; receiver operating characteristic (ROC) curve was used to analyze the efficacy of serum miR-155 and miR-135b-5p in diagnosis the Hp infection in patients with peptic ulcer. Results:The gastrin, PG Ⅰ, PG Ⅱ, ulcer bleeding rate and recurrence rate in Hp infection group were significantly higher than those in non Hp infection group: (108.47 ± 15.35) ng/L vs. (79.63 ± 10.58) ng/L, (295.41 ± 37.26) pg/L vs. (236.75 ± 29.17) pg/L, (44.08 ± 8.52) pg/L vs. (39.29 ± 6.74) pg/L, 25.34% (37/146) vs. 15.38% (18/117) and 21.92% (32/146) vs. 11.97% (14/117), and there were statistical differences ( P<0.01 or <0.05). The serum miR-155 and miR-135b-5p in Hp infection group were significantly higher than those in non Hp infection group (1.94 ± 0.63 vs. 0.95 ± 0.29 and 1.86 ± 0.57 vs. 1.03 ± 0.31), and there were statistical differences ( P<0.01). The serum miR-155 and miR-135b-5p in patients with typeⅠ Hp infection were significantly higher than those in patients with type Ⅱ Hp infection (2.05 ± 0.66 vs. 1.60 ± 0.54 and 1.97 ± 0.61 vs. 1.52 ± 0.45), and there were statistical differences ( P<0.01). Multivariate Logistic regression analysis result showed that serum miR-155, miR-135b-5p, gastrin and PG Ⅰwere independent risk factors of Hp infection in patients with peptic ulcer ( OR = 1.443, 1.436, 1.452 and 1.438; 95% CI 1.165 to 1.787, 1.146 to 1.799, 1.187 to 1.777 and 1.150 to 1.798; P<0.01). ROC curve analysis result showed that the area under the curve of serum miR-155 combined with miR-135b-5p in the diagnosis of Hp infection in patients with peptic ulcer was significantly greater than that of serum miR-155 and miR-135b-5p alone (0.907 vs. 0.839 and 0.836, Z = 2.57 and 2.81, P = 0.010 and 0.005). Conclusions:The serum levels of miR-155 and miR-135b-5p are high in patients with peptic ulcer complicated with Hp infection, and the combination of the two has high diagnostic value for Hp infection in patients with peptic ulcer.

Objective To investigate the associations between thyroid hormone sensitivity indices in euthyroid patients with hypertension and the risk of ischemic stroke,as well as gender difference in this association.Methods We selected 760 hypertensive patients admitted to the Geriatric Neurology Department and outpatient clinic in The Second Affiliated Hospital of Xi'an Jiaotong University between April 2021 and May 2022.We collected their basic characteristics,blood biochemical parameters,thyroid indices,and brain magnetic resonance imaging information.All the patients were divided into two groups based on the clinical manifestations and brain magnetic resonance imaging:hypertension combined with ischemic stroke(n=526)and control(n=234)groups.Independent sample t-tests or non-parametric tests were used to compare the differences in thyroid hormone sensitivity indicators between the two groups.Spearman correlation analysis was used to analyze the correlation between serum thyroid indices and ischemic stroke.Multivariate conditional Logistic regression analysis was made to estimate odds ratios(ORs)and 95％confidence intervals(CIs)for thyroid indices and ischemic stroke.Results There were statistically significant differences between the two groups in terms of age,gender,TC,LDL-c,HDL-c,systolic blood pressure,FT3/FT4,TFQI,and PTFQI(all P＜0.05).However,there was no statistically significant difference between the two groups in weight,smoking,drinking,history of diabetes,TG,FBG,diastolic blood pressure,TSHI,or TT4RI(all P＞0.05).The results of Spearman correlation analysis showed a negative correlation between FT3/FT4 and ischemic stroke(P＜0.05),but a positive correlation of TFQI and PTFQI with ischemic stroke(P＜0.05)in euthyroid patients with hypertension.Logistic regression analysis showed that FT3/FT4 was significantly associated with ischemic stroke in euthyroid patients with hypertension(P=0.001),with OR(95％CI)of 0.001(0.000,0.058).After stratifying by gender,Logistic regression analysis found that FT3/FT4,TFQI,and PTFQI were associated with an increased risk of ischemic stroke in female patients,with OR(95％CI)of 0.000(0.000,0.001),3.132(1.415,6.930),and 3.010(1.406,6.445),respectively.Conclusion Lower serum FT3/FT4 ratio is associated with an increased risk of ischemic stroke in euthyroid patients with hypertension,and the significant association of TFQI and PTFQI with the risk of ischemic stroke is found in females.