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.

OBJECTIVE To optimize the simmering technology of Rheum palmatum from Menghe Medical School and compare the difference of chemical components before and after processing. METHODS Using appearance score， the contents of gallic acid， 5-hydroxymethylfurfural （5-HMF）， sennoside A+sennoside B， combined anthraquinone and free anthraquinone as indexes， analytic hierarchy process （AHP）-entropy weight method was used to calculate the comprehensive score of evaluation indicators； the orthogonal experiment was designed to optimize the processing technology of simmering R. palmatum with fire temperature， simmering time， paper layer number and paper wrapping time as factors； validation test was conducted. The changes in the contents of five anthraquinones （aloe-emodin， rhein， emodin， chrysophanol， physcion）， five anthraquinone glycosides （barbaloin， rheinoside， rhubarb glycoside， emodin glycoside， and emodin methyl ether glycoside）， two sennosides （sennoside A， sennoside B）， gallic acid and 5-HMF were compared between simmered R. palmatum prepared by optimized technology and R. palmatum. RESULTS The optimal processing conditions of R. palmatum was as follows: each 80 g R. palmatum was wrapped with a layer of wet paper for 0.5 h， simmered on high heat for 20 min and then simmered at 140 ℃， the total simmering time was 2.5 h. The average comprehensive score of 3 validation tests was 94.10 （RSD＜1.0%）. After simmering， the contents of five anthraquinones and two sennosides were decreased significantly， while those of 5 free anthraquinones and gallic acid were increased to different extents； a new component 5-HMF was formed. CONCLUSIONS This study successfully optimizes the simmering technology of R. palmatum. There is a significant difference in the chemical components before and after processing， which can explain that simmering technology slows down the relase of R. palmatum and beneficiate it.

ObjectiveTo explore the effects of astragalin （AST） on autophagy and apoptosis of astrocytes in the L_4-5 dorsal horn of the spinal cord in mice with inflammatory pain induced by complete Freund's adjuvant （CFA）. MethodsTwenty-four male C57BL/6 mice， aged six months， were randomly assigned to four groups： control group， saline group， CFA model group， and CFA+AST group， six mice in each group. The inflammatory pain model was established by injection of 10 µL CFA into the right lateral malleolus fossa. The saline group were injected with an equal amount of normal saline at the same site. The inflammatory pain mice in CFA+AST group were further treated with AST （60 mg/kg） intraperitoneally once a day for 21 consecutive days. Multiplex immunofluorescence staining was used to detect the coexpression of autophagy-related factors including ATG 12 and Beclin-1， apoptosis-related factors including Cleaved-Caspase3 and Caspase9， and the astrocyte marker such as GFAP in the L_4-5 spinal dorsal horn of the mice in each group. Western blot was used to examine the protein expression levels of autophagy-related proteins（ATG12， Beclin-1） and apoptosis-related proteins（Caspase 3， Caspase 9） in the L_4-5 spinal dorsal horn of mice. ResultsImmunofluorescent staining showed that in the L_4-5 dorsal horn of the spinal cord， the fluorescence intensity of ATG12 （P<0.000 1） and Beclin-1 （P<0.000 1） was significantly increased， while that of Cleaved-Caspase 3 （P<0.001） and Caspase 9 （P<0.000 1） was decreased in the CFA+AST group when compared to the CFA model group. Furthermore， AST could inhibit the activation of astrocytes. Western blot further confirmed that AST significantly upregulated the expression of ATG12 （P<0.000 1） and Beclin-1 （P<0.000 1） in the L_4-5 spinal cord of CFA mice， and downregulated the expression of Caspase 3 （P<0.01） and Caspase 9 （P<0.001）. ConclusionsAST promotes autophagy of astrocytes and inhibits their apoptosis in the L_4-5 spinal dorsal horn of CFA mice.

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes. "Internal heat leading to zheng" is the core pathogenesis of DKD, while "glucose toxicity" is transformed from subtle substances through "internal heat" and the cementation of various pathological products, which is pivotal to the transformation of diabetes to DKD. "Glucose toxicity" is characterized by deep and widespread heat, caused by various pathological factors, and its sticky nature makes it difficult to resolve, which can cause severe damage to the kidney collaterals. In the early stage of "glucose toxicity", it is yang pathogen, which can be transformed into yin pathogen in the later stage with disease progression. In clinical practice, treatment should be based on disease staging, with attention on grasping the pathogenesis of "internal heat leading to zheng" and identifying the nature of "glucose toxicity". During the diabetic period, clearing heat is the primary method, often using modified Yueju Pill and Dachaihu Decoction. In the early stage of DKD, treatment primarily focuses on clearing and penetrating latent heat to treat DKD, aiming to prevent toxic heat from transitioning from qi to blood. The approach emphasizes clearing heat and re-penetrating, detoxification, and re-clearing, often using a self-made modified Qingre Xiaozheng Decoction. In the middle and late stages of DKD, the focus shifts to clearing heat, eliminating zheng, strengthening vital qi, and dispelling turbidity, with commonly used treatments including the self-made modified Xiezhuo Xiaozheng Formula, Jingui Shenqi Pill, and Zhenwu Decoction.

OBJECTIVE: To observe the clinical efficacy of wrist-ankle acupuncture in the treatment of functional frequent premature ventricular contractions (PVCs). METHODS: A total of 64 patients with functional frequent PVCs were randomly divided into an observation group and a control group, 32 cases in each group. The observation group was treated with wrist-ankle acupuncture at bilateral upper 1 and upper 2 on the wrist. The control group received sham acupuncture at the same points as the observation group. Both groups were treated once every day from Monday to Friday, with the needles retained for 60 min each time, for a total of 4 weeks. The TCM syndrome score, the 24-hour PVC count, and MOS 36-item short form health survey (SF-36) score were compared between the two groups before and after treatment, and the clinical efficacy was evaluated after treatment. RESULTS: After treatment, the TCM syndrome scores and the 24-hour PVC counts in both groups were reduced compared with those before treatment (P<0.01), and the above indexes in the observation group were lower than those in the control group (P<0.01). After treatment，scores of all SF-36 items in the observation group were increased compared with those before treatment (P<0.01); in the control group, the scores of general health (GH), social function (SF) and role-emotional (RE) were increased compared with those before treatment (P<0.05). After treatment, scores of all SF-36 items in the observation group were higher than those in the control group (P<0.01). The total effective rate in the observation group was 90.6% (29/32), which was higher than 46.9% (15/32) in the control group (P<0.01). CONCLUSION Wrist-ankle acupuncture has a significant clinical efficacy in the treatment of functional frequent PVCs. It can effectively improve symptoms such as chest tightness and palpitations, reduce 24-hour PVC count, and improve patients' quality of life.
Humans ; Acupuncture Therapy ; Male ; Female ; Middle Aged ; Adult ; Ventricular Premature Complexes/physiopathology* ; Ankle/physiopathology* ; Wrist/physiopathology* ; Acupuncture Points ; Treatment Outcome ; Aged ; Young Adult

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

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 To investigate the in vitro effect of lncRNA UCA1 on gemcitabine(GEM)resistance of blad-der cancer cell line T24 and its related molecular mechanism.Methods The mRNA expression of UCA1 in T24 cells and in T24/GEM cells was detected by RT-qPCR.The T24/GEM cells were incubated with varying concentra-tions(0.1,1,and 10 μmol/L)of GEM for 48 hrs.LC3 staining microscopy was employed to visualize autophagic puncta,while the expression of autophagy-related proteins was assessed by Western blot.UCA1-shRNA and UCA1-shRNA+pcDNA-Bcl-2 were transferred into T24/GEM cells,the sensitivity of cells to GEM was evaluated by MTT method and flow cytometry;the expressions of p53 and Bcl-2 were detected by Western blot.Results The expres-sion level of UCA1 in T24/GEM cells was significantly higher than that of parental T24 cells(P＜0.05).The con-centration of GEM in the range of 0-10 p.mol/L significantly induced dose-dependent autophagy in T24/GEM cells(P＜0.05).Knockdown of UCA1 enhanced the sensitivity of T24/GEM cells to GEM(P＜0.05),while reducing autophagy(P＜0.05)and down-regulating the expression of p53 and Bcl-2(P＜0.05).Over-expression of Bcl-2 partially reversed the GEM sensitization and autophagy inhibition of UCA1-shRNA in T24/GEM cells(P＜0.05).Conclusions Knockdown of lncRNA UCA1 reduces GEM resistance of T24/GEM cells by inhibiting Bcl-2 mediated autophagy.

Objective To investigate the role of lncSIL in transforming growth factor-β1(TGF-β1)-induced alveo-lar epithelial interstitial transformation(EMT)and its related signaling pathways.Methods Western blot was used to detect the effect of lncSIL silencing on the expression of E-cadherin(E-cad),alpha-smooth muscle actin(α-SMA)and Collagen I(Col I)in the process of EMT induced by TGF-β1.LncSIL interacting proteins were ana-lyzed by RNA pulldown.Western blot was used to detect the effect of overexpression or silencing of lncSIL on the expression of its target gene enhancer of zeste homolog 2(EZH2)and its downstream factors P21 and cyclin-de-pendent kinase 6(CDK6).Flow cytometry was used to analyze the effect of lncSIL on cell cycle progression.Re-sults After lncSIL silencing,the expression of α-SMA and Col I increased,the expression of E-cad decreased.RNA pulldown assay showed that EZH2 was the target protein that interacted with lncSIL,and the expression of EZH2 increased after silencing lncSIL,the expression of EZH2 downstream gene P21 decreased,CDK6 increased.Flow cytometry showed that the number of cells in S phase significantly increased.When lncSIL was overexpressed,the expression of EZH2 and CDK6 was down-regulated,the expression of P21 was up-regulated,and the number of S phase cells significantly decreased.Conclusion LncSIL inhibits TGF-β1-induced alveolar epithelial cell mesen-chymal transition by negatively regulating EZH2/P21/CDK6 signaling pathway to inhibit cell cycle progression.

BACKGROUND:Autophagy has become a rapidly developing research hotspot in the biomedical fields.Many researchers are actively exploring the molecular regulatory mechanism of autophagy in a variety of diseases.However,the role of autophagy in hair growth is still unknown. OBJECTIVE:To review the current research progress and application value of autophagy in hair growth and regeneration,to understand the role of autophagy in hair growth,to explore the pathogenesis of autophagy in pathological hair loss,and to provide new ideas for the study of drugs for hair loss. METHODS:Using"hair follicle growth,hair growth,hair regeneration,autophagy associated proteins,autophagy activity,autophagy associated genes,autophagy"as Chinese search terms and"hair growth,hair follicle,hair regeneration,autophagy"as English search terms,PubMed and CNKI databases were searched.The research progress on autophagy,hair growth and the role of autophagy in hair growth in and outside China in recent years was reviewed and summarized.Articles incompatible with the subject content of the paper were excluded.Finally,78 articles were included for the result analysis. RESULTS AND CONCLUSION:(1)Autophagy is a normal metabolic process in eukaryotes with complex molecular mechanisms and functional properties,which is beneficial to cell survival and cell death.(2)Alopecia-related diseases are associated with changes in autophagy activity,which can regulate hair growth cycle.Knockout or overexpression of autophagy-related genes can change the state of hair growth.Multiple autophagy related signaling pathways have been found to be related to hair follicle growth.Activators or inhibitors of autophagy can be used to treat or prevent hair loss.