OBJECTIVE To investigate the improvement effect and potential mechanism of Qingxue xiaozhi jiangtang formula on insulin resistance （IR） in type 2 diabetes mellitus （T2DM） rats. METHODS T2DM rat model was established by intraperitoneal injection of 30 mg/kg streptozotocin combined with high-fat and high-sugar diet. The rats were randomly divided into normal control group， model group， Qingxue xiaozhi jiangtang formula low-dose and high-dose groups （6.525， 13.05 g/kg， calculated by raw material） and metformin group （positive control， 0.18 g/kg）， with 8 rats in each group. Administration groups were given relevant medicine intragastrically； normal control group and model group were given constant volume of normal saline intragastrically， once a day， for consecutive 6 weeks. Body mass and fasting blood glucose （FBG） were determined， and oral glucose tolerance test was conducted. Serum fasting insulin （FINS） level was measured to calculate the insulin resistance index （HOMA-IR） and insulin sensitivity index （ISI）. Additionally， the level of serum lipids， liver function， oxidative stress indicators and inflammatory factors were assessed. The phosphorylation levels of kinase R-like endoplasmic reticulum kinase （PERK） and forkhead box O1 （FOXO1） protein in liver tissue of rats were determined. RESULTS Compared with model group， the body weight， ISI， the levels of high-density lipoprotein cholesterol and superoxide dismutase were increased significantly in Qingxue xiaozhi jiangtang formula high-dose group and metformin group （P＜0.05）； FBG， blood glucose level at 120 minutes of glucose loading， area under the curve of glucose， FINS， HOMA-IR， low-density lipoprotein cholesterol， total cholesterol， triglyceride， alanine transaminase， aspartate transaminase， alkaline phosphatase， malondialdehyde， interleukin-6， tumor necrosis factor-α， and C-reactive protein levels were significantly reduced （P＜ Δ0.05）； the pathological damage of liver tissue had significantlyimproved， and the phosphorylation levels of PERK and FOXO1 proteins in liver tissue were significantly decreased （P＜0.05）. CONCLUSIONS Qingxue xiaozhi jiangtang formula can regulate glucose and lipid metabolism， inflammation factor and oxidative stress levels， and alleviate insulin resistance in T2DM rats. Its mechanism of action may be related to the inhibition of the PERK/FOXO1 signaling pathway.

Diabetic cataract, a prevalent ocular complication of diabetes mellitus, arises from a complex interplay of pathological mechanisms, with oxidative stress and glycation stress playing central roles. Autophagy, a critical cellular self-protection mechanism, sustains intracellular homeostasis by selectively degrading damaged organelles and misfolded proteins, thereby counteracting the detrimental effects of oxidative and glycation stress under hyperglycemic conditions. Emerging evidence indicates a synergistic interaction between glycation stress and oxidative stress, which may exacerbate autophagic dysfunction and accelerate the onset and progression of diabetic cataract. However, the precise molecular mechanisms underlying this relationship remain incompletely understood. This review systematically examines the regulatory role of autophagy inthe pathogenesis of diabetic cataract, with a particular focus on how autophagic impairment influences disease progression under the combined effects of glycation and oxidative stress. By elucidating these mechanisms, the paper aims to provide novel insights into molecular diagnostic approaches and targeted therapeutic strategies for diabetic cataract.

COMPERA 2.0 risk stratification has been demonstrated to be useful in patients with precapillary pulmonary hypertension (PH). However, its suitability for patients at risk for post-capillary PH or PH associated with left heart disease (PH-LHD) is unclear. To investigate the use of COMPERA 2.0 in patients with severe aortic stenosis (SAS) undergoing transcatheter aortic valve replacement (TAVR), who are at risk for post-capillary PH, a total of 327 eligible SAS patients undergoing TAVR at our institution between September 2015 and November 2020 were included in the study. Patients were classified into four strata before and after TAVR using the COMPERA 2.0 risk score. The primary endpoint was all-cause mortality. Survival analysis was performed using Kaplan-Meier curves, log-rank test, and Cox proportional hazards regression model. The study cohort had a median (interquartile range) age of 76 (70‒80) years and a pulmonary arterial systolic pressure of 33 (27‒43) mmHg (1 mmHg=0.133 kPa) before TAVR. The overall mortality was 11.9% during 26 (15‒47) months of follow-up. Before TAVR, cumulative mortality was higher with an increase in the risk stratum level (log-rank, both P<0.001); each increase in the risk stratum level resulted in an increased risk of death (hazard ratio (HR) 2.53, 95% confidential interval (CI) 1.54‒4.18, P<0.001), which was independent of age, sex, estimated glomerular filtration rate (eGFR), hemoglobin, albumin, and valve type (HR 1.76, 95% CI 1.01‒3.07, P=0.047). Similar results were observed at 30 d after TAVR. COMPERA 2.0 can serve as a useful tool for risk stratification in patients with SAS undergoing TAVR, indicating its potential application in the management of PH-LHD. Further validation is needed in patients with confirmed post-capillary PH by right heart catheterization.
Humans ; Aortic Valve Stenosis/complications* ; Aged ; Hypertension, Pulmonary/mortality* ; Male ; Female ; Transcatheter Aortic Valve Replacement ; Aged, 80 and over ; Risk Assessment/methods* ; Proportional Hazards Models ; Kaplan-Meier Estimate ; Retrospective Studies

OBJECTIVES: To investigate the effects of dihydroartemisinin (DHA) combined with doxorubicin (DOX) on proliferation and apoptosis of triple-negative breast cancer cells and explore the underlying molecular mechanism. METHODS: MDA-MB-231 cells were treated with 50, 100 or 150 μmol/L DHA, 0.5 μmol/L DOX, or with 50 μmol/L DHA combined with 0.5 μmol/L DOX. The changes in proliferation and survival of the treated cells were examined with MTT assay and colony-forming assay, and cell apoptosis was analyzed with flow cytometry. Western blotting was performed to detect the changes in protein expression levels of PCNA, cleaved PARP, Bcl-2, Bax, STAT3, p-STAT3, HIF-1α and survivin. RESULTS: The IC₅₀ of DHA was 131.37±29.87 μmol/L in MDA-MB-231 cells. The cells with the combined treatment with DHA and DOX showed significant suppression of cell proliferation. Treatment with DHA alone induced apoptosis of MDA-MB-231 cells in a dose-dependent manner, but the combined treatment produced a much stronger apoptosis-inducing effect than both DHA and DOX alone. DHA at 150 μmol/L significantly inhibited clone formation of MDA-MB-231 cells, markedly reduced cellular expression levels of PCNA, p-STAT3, HIF-1α and survivin proteins, and obviously increased the expression level of cleaved PARP protein and the Bax/Bcl-2 ratio, and the combined treatment further reduced the expression level of p-STAT3 protein and increased the Bax/Bcl-2 ratio. CONCLUSIONS DHA combined with DOX produces significantly enhanced effects for inhibiting cell proliferation and inducing apoptosis in MDA-MB-231 cells possibly as result of DHA-mediated negative regulation of the STAT3/HIF-1α pathway.
Humans ; STAT3 Transcription Factor/metabolism* ; Apoptosis/drug effects* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Doxorubicin/pharmacology* ; Triple Negative Breast Neoplasms/metabolism* ; Cell Line, Tumor ; Artemisinins/pharmacology* ; Female ; Cell Proliferation/drug effects* ; Signal Transduction/drug effects* ; Survivin

Clear aligner treatment is a novel technique in current orthodontic practice. Distinct from traditional fixed orthodontic appliances, clear aligners have different material features and biomechanical characteristics and treatment efficiencies, presenting new clinical challenges. Therefore, a comprehensive and systematic description of the key clinical aspects of clear aligner treatment is essential to enhance treatment efficacy and facilitate the advancement and wide adoption of this new technique. This expert consensus discusses case selection and grading of treatment difficulty, principle of clear aligner therapy, clinical procedures and potential complications, which are crucial to the clinical success of clear aligner treatment.
Humans ; Consensus ; Orthodontic Appliance Design ; Orthodontic Appliances, Removable ; Tooth Movement Techniques/methods* ; Malocclusion/therapy* ; Orthodontics, Corrective/instrumentation*

OBJECTIVE: The investigation of the correlation between ecological factors and the genetic characteristics or metabolites of plants offers valuable insights into the regional causes of genetic and metabolic diversity. Here, Gastrodia elata, a medicinal plant, is employed as a model to explore the environmental factors that influence its genetic characteristics and metabolic accumulations. METHODS: A total of 23 G. elata populations from six cultispecies and 11 cultivated regions were selected based on the predictions of the global geographic information system. The genetic characteristics of these populations were evaluated using highly polymorphic simple sequence repeat markers. Additionally, the metabolic accumulations and antioxidant capacity of mature tubers were measured employing colorimetry and high performance liquid chromatography (HPLC). Ecological data of each region were obtained from the WorldClim-global climate database and harmonized world soil database. To assess the influence of ecological factors on the genetic characteristics and metabolic profiles of G. elata, Pearson's correlation analysis was conducted. RESULTS: Genetic variation among G. elata populations exceeded that within populations. Genetic diverisity, distance and structure manifested regional and species-specific patterns. Metabolic profiling and antioxidant capacity exhibited regional variations. Notably, the Lueyang region demonstrated that a content range of total polysaccharide, total protein, and phenolic glycosides was 9.34%-189.67% higher than the average. Similarly, in the Hubei region, total phenolic content, p-hydroxybenzyl alcohol content, and antioxidant indicators were observed to be higher than the average levels, by 106.57%, 136.47% and 12.50%-91.14%, respectively. Furthermore, ecological factors had a significant comprehensive impact on G. elata genetic characteristics (r > 0.256 and P < 0.05). Multivariate metabolite accumulations in G. elata were influenced by dominant ecological factors. Temperature notably impacted the accumulation of total protein (|r| > 0.528 and P < 0.05). Moisture, encompassing precipitation and soil content, significantly affected the production of phenolic glycosides (|r| > 0.503 and P < 0.05). CONCLUSION The genetic characteristics of G. elata manifested regional and species-specific patterns, with the metabolic accumulations and antioxidant capacity of mature tubers exhibited regional variations. Specifically, multivariate ecological factors comprehensively influenced genetic characteristics. Temperature and moisture played pivotal roles in regulating the accumulations of proteins and phenolic glycosides, respectively. These findings underscore the significant impact of ecological factors on the shaping of G. elata, highlighting their crucial role in enhancing the quality of Chinese medicinal materials.

Vein graft (VG) failure (VGF) is associated with VG intimal hyperplasia, which is characterized by abnormal accumulation of vascular smooth muscle cells (VSMCs). Most neointimal VSMCs are derived from pre-existing VSMCs via a process of VSMC phenotypic transition, also known as dedifferentiation. There is increasing evidence to suggest that ginger or its bioactive ingredients may block VSMC dedifferentiation, exerting vasoprotective functions; however, the precise mechanisms have not been fully characterized. Therefore, we investigated the effect of ginger on VSMC phenotypic transition in VG remodeling after transplantation. Ginger significantly inhibited neointimal hyperplasia and promoted lumen (L) opening in a 3-month VG, which was primarily achieved by reducing ferroptotic stress. Ferroptotic stress is a pro-ferroptotic state. Contractile VSMCs did not die but instead gained a proliferative capacity and switched to the secretory type, forming neointima (NI) after vein transplantation. Ginger and its two main vasoprotective ingredients (6-gingerol and 6-shogaol) inhibit VSMC dedifferentiation by reducing ferroptotic stress. Network pharmacology analysis revealed that 6-gingerol inhibits ferroptotic stress by targeting P53, while 6-shogaol inhibits ferroptotic stress by targeting 5-lipoxygenase (Alox5), both promoting ferroptosis. Furthermore, both ingredients co-target peroxisome proliferator-activated receptor gamma (PPARγ), decreasing PPARγ-mediated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (Nox1) expression. Nox1 promotes intracellular reactive oxygen species (ROS) production and directly induces VSMC dedifferentiation. In addition, Nox1 is a ferroptosis-promoting gene that encourages ferroptotic stress production, indirectly leading to VSMC dedifferentiation. Ginger, a natural multi-targeted ferroptotic stress inhibitor, finely and effectively prevents VSMC phenotypic transition and protects against venous injury remodeling.

ObjectiveTo explore the comprehensive effects of Qingxin Zishen decoction on the symptom score and neuroendocrine indexes and the mechanism of the decoction in regulating KNDy neurons in the patients with menopausal syndrome. MethodA total of 60 patients with menopausal syndrome due to yin deficiency with effulgent fire who attended the menopausal outpatient of Jiangsu Province Hospital of Chinese Medicine were randomized into an experimental （Qingxin Zishen decoction） group （30 cases） and a control （femoston） group （30 cases）. The treatment lasted for 12 weeks in both groups. The two groups were compared in terms of the comprehensive efficacy， frequency and degree of hot flashes and sweating， modified Kupperman score， and the serum levels of hypothalamic peptide kisspeptin， neurokinin B （NKB）， dynorphin （Dyn）， follicle-stimulating hormone （FSH）， and estradiol （E₂）. Result① Comprehensive efficacy： The comprehensive efficacy of the two groups was comparable. ② Frequency and degrees of hot flashes and sweating： After treatment， the frequency and degrees of hot flashes and sweating in the two groups were reduced （P<0.05） and the control group outperformed the experimental group （P<0.05）. ③ Modified Kupperman score and menopausal symptoms： After treatment， the modified Kupperman score decreased in both groups （P<0.05）. After 4 weeks of treatment， the experimental group was superior to the control group in terms of the scores of dizziness and headache （P<0.05）. ④ Serum levels of sex hormones： After treatment， the serum E₂ level elevated and the FSH level lowered in both groups （P<0.05）， and the changes were more obvious in the control group （P<0.05）. ⑤ Neuroendocrine indexes： After treatment， the serum levels of kisspeptin and NKB in the two groups decreased （P<0.05）， and the serum Dyn level in the experimental group increased （P<0.05）. Moreover， the experimental group had higher Dyn level than the control group after treatment （P<0.05）. ConclusionQingxin Zishen decoction can alleviate hot flashes， sweating， and other symptoms in the women with menopausal syndrome by acting on the KNDy neurons to lower the kisspeptin and NKB levels and elevate the Dyn level. The findings provide new ideas for the clinical treatment of hot flashes in menopause.

Objective To investigate the changes in interleukin-34 (IL-34)levels in serum and bronchoalveolar lavage fluid (BALF) of patients with severe pneumonia and their prognostic value. Methods A total of 66 patients with severe pneumonia (severe pneumonia group), 35 patients with non-severe pneumonia (non-severe pneumonia group), and 27 healthy adults (control group) were enrolled. The severe pneumonia group was further divided into survival group of 38 patients and non-survival group of 28 patients based on 28-day survival. Clinical data of all subjects were analyzed. Receiver operating characteristic (ROC) curves were plotted to assess the predictive power of serum IL-34 and relative IL-34 gene expression in BALF for 28-day mortality in patients with severe pneumonia, as well as the predictive power of serum IL-34 for severe pneumonia. Kaplan-Meier survival curves were plotted, and the Log-rank test was used to compare cumulative survival rates. Cox regression analysis was conducted to explore risk factors for 28-day mortality in patients with severe pneumonia. Pearson correlation analysis was used to assess the correlation between serum IL-34 levels and relative IL-34 gene expression in BALF of patients with severe pneumonia. Results Serum IL-34 levels were higher in the severe pneumonia group than those in the non-severe pneumonia group, and were higher in the non-severe pneumonia group than in the control group (P < 0.05). Serum IL-34 levels and relative IL-34 gene expression in BALF were higher in the non-survival group than in the survival group (P < 0.05). ROC curve analysis showed that the areas under the curve for predicting 28-day mortality in patients with severe pneumonia were 0.908 for serum IL-34 levels and 0.878 for relative IL-34 gene expression in BALF. The optimal cutoff value for serum IL-34 levels in predicting severe pneumonia was 129.9 pg/mL. Multivariate Cox regression analysis showed that increased serum IL-34 levels and increased relative IL-34 gene expression in BALF were independent risk factors for 28-day mortality in patients with severe pneumonia (P < 0.05). The Kaplan-Meier survival analysis results indicate that, with a cutoff value of 129.9 pg/mL, patients with severe pneumonia who had high serum levels of IL-34 exhibited a lower cumulative survival rate compared to those with low IL-34 level(Log-rank P < 0.001). Conclusion Serum IL-34 levels are significantly increased in patients with severe pneumonia, and relative IL-34 gene expression in BALF is positively correlated with serum IL-34 levels. Both can be used as indicators for predicting the prognosis of 28-day mortality in patients with severe pneumonia.

Objective To develop a self-care scale for patients with lymphedema after breast cancer surgery and verify its reliability and validity.Methods Based on the model of knowledge,belief and practice,a questionnaire item pool was constructed after literature reviews and qualitative interviews.A questionnaire-based scale was drafted based on the established item pool by carrying out two rounds of consultation with 15 clinical nursing specialists,nursing administrators and nursing educators from 8 provinces or cities in China.Reliability and validity of the scale were tested using convenience sampling,involving 444 patients with breast cancer surgery related lymphedema from 7 general hospitals in Hubei and Henan provinces,China,between May and July 2023.Results The response rates for the two rounds of expert consultation were 93.75%and 93.33%,respectively.The authority coefficients of the two rounds were 0.86 and 0.89,respectively,and the coordination coefficients for the 2 rounds were 0.130 and 0.379,respectively.In the first round,the average importance rating was from 4.33 to 4.93 with the coefficient of variation from 0.05 to 0.19,and the full score ratio from 53.33%to 93.33%.In the second round,the average importance rating ranged from 2.86 to 4.93 with the coefficient of variation from 0.05 to 0.36,and the full score ratios from 7.14%to 92.86%.A total of 421 patients completed the survey.The overall Cronbach's α coefficient of the scale was 0.943,the overall split-half reliability was 0.824,the scale-level content validity index(S-CVI)was 0.912,and the item-level content validity index(I-CVI)of the total scale ranged from 0.857 to 1.000.The KMO value of exploratory factor analysis was 0.919,the Bartrett spherical test value was 4671.724(P<0.001),and the cumulative variance contribution rate was 64.155%.Confirmatory factor analysis showed a good model fit.After the reliability and validity tests,the scale was finalised and determined to consist of three dimensions with 33 items:knowledge(9 items),attitude(6 items)and behaviour(18 items).Conclusion The self-care scale for the patients with lymphedema after breast cancer surgery has demonstrated good reliability and validity,and makes it an effective assessment tool for the patients with lymphedema after breast cancer surgery.