Acute liver failure (ALF) is a life-threatening condition associated with macrophage-mediated inflammatory responses. Effective therapies and drugs are still lacking to date. Here, we reveal that a derivative of xanthohumol, CAM12203, alleviates lipopolysaccharide (LPS) + d-galactosamine (D-GalN)-induced ALF through limiting macrophage-mediated inflammation, with the most significant impact on interleukin-1β (IL-1β) transcription. Through biotin labeling-mediated pull-down and LC-MS/MS analysis, diacylglycerol kinase ζ (DGKζ), a lipid-metabolizing kinase, is identified as the direct target of CAM12203. Mechanistically, DGKζ is induced in macrophages upon inflammatory stimuli and is upregulated observed on clinical liver failure samples. Its product phosphatidic acid (PA) boosts phospholipase C (PLC)-inositol 1,4,5-trisphosphate (IP₃)-Ca²⁺ signaling and subsequent janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) cascade, ultimately promoting IL-1β production and liver failure. DGKζ knockdown/ablation or inhibition significantly impairs the DGKζ-STAT3-IL-1β pathway along with ALF progression. Finally, CAM12203 is confirmed to be a new DGKζ inhibitor and acts against inflammation in a DGKζ-reliant manner. Taken together, CAM12203 inhibits IL-1β transcription in macrophages by binding to DGKζ and blocking the DGKζ-STAT3 axis, thereby exerting an ameliorative effect on ALF. These results not only highlight CAM12203 as a promising lead compound for ALF treatment, but also define DGKζ as a novel therapeutic target.

OBJECTIVES: We aimed to compare the apical sealing properties of three endodontic sealers, namely, C-Root SP (C-R), iRoot SP, and GuttaFlow Bioseal (GFB) in vitro. METHODS: Eighty-two single-rooted premolars and anterior teeth were prepared by using M3 machine with nickel-titanium file and randomly divided into six experimental groups (n=12) and two control groups (n=5). Group A1: single-cone technique (SC)+C-R; group B1: SC+iRoot SP; group C1: SC+GFB; group A2: single-cone with ultrasonic activation (SU)+C-R; group B2: SU+iRoot SP; group C2: SU +GFB; group D: positive control group, and group E: negative control group. Dye penetration length and lateral root canal filling in each group were measured by dye penetration test. A scanning electron microscope (SEM) was used to observe the interface between gutta pertscha, root canal sealer, and dentin wall. Dye penetration length was measured and analyzed by Kruskal-Wallis test, and data on lateral root canal filling were evaluated using Chi-square. RESULTS: The dye penetration length in group A1 was lower than that in groups C1 and A2 (P<0.05) but was not significantly different from the other groups (P>0.05). Lateral root canal filling was not significantly different among all groups (P>0.05). SEM showed that GFB was slightly better than C-R and iRoot SP in binding to gutta pertcha and dentin wall. CONCLUSIONS GFB, C-R, and iRoot SP demonstrate excellent apical sealing ability. Under the conditions tested in this study, SU did not yield significantly improve the apical sealing ability of the three root canal sealers.
Root Canal Filling Materials/chemistry* ; Humans ; Gutta-Percha ; Microscopy, Electron, Scanning ; Root Canal Obturation/methods* ; Ceramics ; Dimethylpolysiloxanes ; Drug Combinations

OBJECTIVES: This study aimed to evaluate the filling effects of three biomaterial root canal sealers [iRoot SP, C-Root SP, and GuttaFlow Bioseal (GFB)] by using Micro-CT. METHODS: Sixty single-canal detached premolars were selected. After crown amputation, their uniform working length was set at 12 mm and prepared to a 06 taper 30# with M3 nickel-titanium file. The samples were randomly divided into six groups with different sealers and obturation techniques: iRoot SP+single-cone technique (SC), C-Root SP+SC, GFB+SC, iRoot SP+single cone-mediated ultrasonic technique (SU), C-Root SP+SU, and GFB+SU. Samples were scanned by Micro-CT, and the total and segmented filling rates were calculated with Mimics 22.0 software after 3D reconstruction. RESULTS: The overall filling rate of the three biomaterial root canal sealers was higher than 90%. The overall and coronal third and middle third segment filling rate of groups iRoot SP+SC, C-Root SP+SC was higher than that of group GFB+SC (P<0.01), with no significant difference between groups iRoot SP+SC and C-Root SP+SC (P>0.05). On the apical third, no significant difference was found among each group (P>0.05). The overall and segment filling rate of groups iRoot SP+SU and C-Root SP+SU was higher than that of GFB+SU (P<0.01), with no significant difference between groups iRoot SP+SU and C-Root SP+SU (P>0.05). The filling rate of the apical 1/3 of group C-Root+SC was lower than that of group C-Root+SU (P<0.01), and the filling rate of the coronal 1/3 of group GFB+SC was higher than that in the GFB+SU (P<0.01). Nevertheless, no significant difference was found in other filling rate of two obturation techniques (P>0.05). CONCLUSIONS The overall filling rate of the three biomaterial root canal sealers using SC and SU are satisfactory. iRoot SP and C-Root SP have similar filling rates, which are significantly higher than that of GFB. C-Root SP combined with SU technique can improve the filling quality of the root apical.
Root Canal Filling Materials ; X-Ray Microtomography ; Humans ; Root Canal Obturation/methods* ; Gutta-Percha ; Dimethylpolysiloxanes ; Drug Combinations ; Dental Pulp Cavity/diagnostic imaging* ; Bicuspid

Objective To observe the therapeutic effect and mechanism of astragalus polysaccharide on lipopolysaccharide(LPS)-induced periodontitis in vivo and in vitro.Methods Ligation/LPS induction was used to construct a mouse model of periodontitis,and LPS treatment was used to establish a periodontitis cellular model.After administration of astragalus polysaccharide intervention,hematoxylin-eosin(HE)staining was used to detect pathological damage in mouse periodontal tissues,and kits were used to detect reactive oxygen species(ROS)and malondialdehyde(MDA)content as well as oxidative stress-related indexes such as superoxide dismutase(SOD)and catalase(CAT)activities,and tartrate-resistant acid phosphatase(TRAP)staining was used to detect the formation of osteoclasts in periodontal tissues and the RAW264.7 cell differentiation to osteoblasts,actin cytoskeleton/focal adhesion protein(Vinculin)staining method was used to analyze the formation of F-actin ring in RAW264.7 cells,alkaline phosphatase(ALP)staining and alizarin red S(ARS)staining and ALP activity assays were performed to evaluate the osteoclast formation ability of mouse bone marrow mesenchymal stem cells(mBMSCs),and Western Blot was used to detect the expression levels of osteoclast-and osteoblast-related proteins.Results Astragali polysaccharide significantly reduced LPS-induced alveolar bone loss and histopathological damage,as well as improved the parameters related to periodontal bone regeneration in mice.Astragalgali polysaccharide reduced ROS production in LPS-induced periodontal ligament cells(mPDLCs),inhibited MDA content and increased SOD and CAT activities in LPS-treated mPDLCs and in periodontal tissues and serum in periodontitis mice.Astragalus polysaccharide decreased TRAP expressions in LPS-treated mouse periodontal tissues and RAW264.7 cells,and F-actin ring formation in RAW264.7 cells.Astragalgali polysaccharide decreased ALP expression and activity in LPS-treated mBMSCs cells,and reduced calcium deposition.In addition,astragalus polysaccharide down-regulated the expressions of osteoclast-related proteins[cathepsin k(CTSK),nuclear factor of activated T-cells 1(NFATcl)and c-Fos]in LPS-inducedRAW264.7 cells,and up-regulated the expressions of osteoblast-related proteins[ALP,runt-related transcription factor 2(Runx2),collagen type Ⅰ(COL-1)and DMP1)]in mBMSCs.Conclusion Astragalus polysaccharide can alleviates LPS-induced periodontitis by inhibiting oxidative stress and promoting ERK/AMPK pathway-mediated bone formation capacity.

To analyze the disease burden and trends of motor neuron disease(MND) in China and globally from 1990 to 2021, providing evidence for the formulation of relevant health strategies inChina.

OBJECTIVE To investigate the effect and mechanism of Panax notoginseng saponins （PNS） on wound healing after anal fistula surgery in rats by regulating the hypoxia-inducible factor-1α （HIF-1α）/vascular endothelial growth factor （VEGF）/ vascular endothelial growth factor receptor-2 （VEGFR2） signaling pathway. METHODS SD rats were selected to establish a postoperative rat model of anal fistula by infecting wound with Escherichia coli. The model rats were randomly grouped into model group， PNS low-dose and high-dose groups （15， 30 mg/cm2）， high-dose of PNS+2-methoxyestradiol （2ME2） group （PNS 30 mg/cm2+HIF-1α inhibitor 2ME2 4 mg/kg）， with 10 rats in each group. Another 10 normal rats were selected for back hair removal treatment as the control group. Each drug group was injected with the corresponding drug solution intramuscularly or （and） intraperitoneally， once a day， for 3 weeks. After the last administration， the wound healing rate （excluding the control group）， microvascular density （MVD）， the expression of collagen Ⅰ and fibronectin （FN） in the wound tissue were detected in each group； the levels of angiogenic factors [VEGF， E-mail：842710813@qq.com angiopoietin-Ⅰ （Ang-Ⅰ）， Ang-Ⅱ] in serum， the levels of inflammatory factors [interleukin-6 （IL-6） and IL-2] in serum binggui7183@163.com and wound tissue as well as the expressions of the related proteins of HIF-1α/VEGF/VEGFR2 signaling pathway in the wound tissue of rats were also detected in each group. RESULTS The MVD， the expression of collagen Ⅰ and FN in the wound tissue， and the levels of IL-6 and IL-2 in serum and wound tissue of rats increased significantly in the model group， compared to the control group （P＜0.05）， while the serum levels of VEGF， Ang- Ⅰ and Ang-Ⅱ decreased significantly （P＜0.05）. The wound healing rate， the MVD in wound tissue， the serum levels of VEGF， Ang-Ⅰ and Ang-Ⅱ， the expressions of collagen Ⅰ and FN in the wound tissue， and protein expressions of HIF-1α， VEGF and VEGFR2 in the PNS low-dose and high-dose groups increased significantly， compared to the model group （P＜0.05）， while the levels of IL-6 and IL-2 in serum and wound tissue decreased significantly （P＜0.05）； the high-dose PNS had a stronger effect （P＜ 0.05）. 2ME2 could weaken the effect of PNS on above indicators of rats after anal fistula surgery （P＜0.05）. CONCLUSIONS PNS can promote the production of angiogenic factors and inhibit the production of pro-inflammatory factors， thereby promoting wound healing in rats after anal fistula surgery. The above effects are related to the activation of HIF-1α/VEGF/VEGFR2 signaling pathway.

Objective:To observe the protective effects of Zhiganqing Prescription on the liver of C57BL/6J non-alcoholic fatty liver disease (NAFLD) mice induced by high fat diet and its effects on PI3K/Akt/FoxO1 signaling pathway, insulin resistance (IR) and gluconogenesis.Methods:A total of 48 8-week-old male C57BL/6J mice were divided into control group ( n=8) and modeling group ( n=40) according to random number table method. The control group was fed with ordinary diet, and the model group was fed with high-fat diet. The NAFLD model was established after 8 weeks of feeding. The modeling group was divided into model group, Pioglitazone group, Zhiganqing Prescription low-, medium-, and high-dosage group ( n=8 in each group) according to random number table method, and drug intervention lasted for 8 weeks. The body mass of mice was measured regularly during administration. Fasting blood glucose (FBG) levels were measured at 0 and 8 weeks of administration, and oral glucose tolerance tests (OGTT) were conducted. After the experiment, serum levels of GPT, GOT, TC, TG, LDL-C, HDL-C, FINS and C-P were detected and HOMA-IR was calculated. The pathological morphology of liver was observed by HE and PAS staining. The expression levels of PI3K and p-Akt were detected by IHC staining. The protein expression levels of PI3K, Akt, p-Akt, FoxO1, p-FoxO1, G6PC and PCK1 were detected by Western blot. Results:Compared with model group, the body weight of mice in each administration group decreased at 4, 6 and 8 weeks ( P<0.05 or P<0.01). At the 8th week of administration, the levels of FBG and OGTT AUC in each administration group decreased ( P<0.05 or P<0.01), the levels of GPT, TC, TG and LDL-C decreased ( P<0.01), and the GOT levels in Zhiganqing Prescription medium- and high-dosage groups decreased ( P<0.01). The HDL-C level in Zhiganqing Prescription medium-dosage group decreased ( P<0.05 or P<0.01), and the HOMA-IR level in Zhiganqing Prescription low- and medium-dosage groups decreased ( P<0.05 or P<0.01). The levels of FINS and C-P in each administration group increased ( P<0.05 or P<0.01), and the expressions of PI3K protein and p-Akt/Akt, p-FoxO1 /FoxO1 protein in liver tissues increased ( P<0.05 or P<0.01). The protein expressions of G6PC and PCK1 decreased ( P<0.05 or P<0.01). Conclusion:Zhiganqing Prescription can effectively control the body mass, blood glucose, liver function and blood lipids of NAFLD mice, improve IR and gluconeogenesis, the mechanism of which may be related to the activation of PI3K/Akt/FoxO1 signaling pathway.

Gynecologic malignant tumors are among the leading diseases threatening women's lives and health,with the highest morbidity and mortality rates among all female diseases.These tumors originate from female reproductive organs and are typically classified based on the affected site.Ovarian cancer(OC),endometrial cancer(EC)and cervical cancer(CCA)are the most common types.Currently,gynecologic malignant tumors are primarily treated with a combination of surgery,chemotherapy and radiotherapy,where drugs play a critical role in the treatment process.However,the actual clinical effectiveness is often influenced by various factors,such as adverse reactions due to drug toxicity and the drug resistance and insensitivity observed in some patients,which limit improvements in patient survival rates.Recent studies have shown that the same type of tumor exhibits significant biological characteristics and drug response heterogeneity among different individuals,which is a key factor contributing to the varied clinical outcomes when using the same drug treatment for the same type of gynecologic malignant tumor.To achieve individualized and precise treatment for gynecologic malignant tumors,there is an urgent need to develop in vitro models that closely resemble human tumors for clinical research.Drug screening is a technique used to identify and evaluate compounds with pharmacological activity and potential therapeutic effects,providing doctors with scientific guidance on drug use,thereby avoiding blind drug testing and reducing patients'therapeutic pain and economic burden by assessing the effects of different drugs under specific conditions.Organoid models have been extensively studied as an innovative drug screening tool and personalized medicine for treating gynecologic malignancies.Organoids are tissue-like structures with a specific spatial arrangement formed in vitro through three-dimensional cell culture,capable of highly simulating the structure and function of tissues in vivo and displaying histological and genotypic characteristics very similar to human organs.This approach has largely overcome the limitations of traditional tumor models,such as patient-derived cancer cell models and patient-derived tumor xenograft models,becoming an essential research tool in oncology.It provides a more physiologically relevant experimental platform for drug screening studies of gynecologic malignancies.This paper compared the advantages and disadvantages of several preclinical cancer models,reviewed the development process of organoids,and described the establishment of gynecologic oncology organoids and their application in drug screening for ovarian,endometrial,and cervical cancers.Additionally,we discussed the current limitations of organoid technology in its application and envisioned its future development,aiming to provide insights for future medical research,particularly in new drug discovery and personalized medicine.

Objective:To compare iodine nutritional status of different populations consuming iodized salt and non-iodized salt in iodine adequate areas, and to provide a basis for formulating iodine supplementation strategies.Methods:In October 2021, Luyi County in Henan Province was selected as an iodine adequate area consuming iodized salt, while Ningling County was selected as an iodine adequate area consuming non-iodized salt. Stratified by water iodine (50 - 59, 60 - 69, 70 - 79, 80 - 89, 90 - 100 μg/L), one village was selected from each layer. One hundred children aged 8 - 10, one hundred adults, and 20 pregnant women were selected from each village to collect their urine and salt samples for testing salt and urinary iodine, and their thyroid gland was measured by ultrasound.Results:A total of 600 salt samples in Luyi County were collected, with the coverage rate of iodized salt (99.8%, 599/600) and the consuming rate of qualified iodized salt (95.5%, 573/600). A total of 1 008 salt samples in Ningling County were collected, with the rate of non-iodized salt (93.8%, 946/1 008). The median urinary iodine of children in Luyi County ( n = 240) was higher than that in Ningling County ( n = 468, 305.0 vs 232.0 μg/L, Z = - 8.10, P < 0.001). There was no statistically significant difference in median urinary iodine between pregnant women in Luyi County ( n = 120) and Ningling County ( n = 53, 240.0 vs 236.0 μg/L, Z = - 1.02, P = 0.306). The median urinary iodine of adults in Luyi County ( n = 238) was higher than that in Ningling County ( n = 486, 289.0 vs 178.5 μg/L, Z = - 11.14, P < 0.001). Children's urinary iodine ( r s = 0.21, P = 0.001) in Luyi County and adults' urinary iodine ( r s = 0.17, P < 0001) in Ningling County were positively correlated with water iodine. There was no statistically significant difference in the incidence of thyroid enlargement in children between Luyi County (0.8%, 2/240) and Ningling County (0.4%, 2/468, χ 2 = 0.80, P = 0.586), but the incidence of thyroid nodules in children in Luyi County (11.2%, 27/240) was higher than that in Ningling County (1.7%, 8/468, χ 2 = 27.36, P < 0.001). The incidence of thyroid nodules in pregnant women in Luyi County (23.3%, 28/120) was lower than that in Ningling County (46.5%, 33/71, χ 2 = 10.99, P = 0.001). There was no statistically significant difference in the incidence of adult thyroid nodules between Luyi County and Ningling County (χ 2 = 0.86, P = 0.354), with a ratio of 29.6% (71/240) to 32.9% (160/486). Conclusions:Providing population with non-iodized salt in iodine adequate areas, the overall iodine nutrition is at an appropriate level. However, children consuming iodized salt in iodine adequate areas have high level of iodine nutrition, and it is necessary to consider supplying non-iodized salt or reducing the concentration of iodized salt. Pregnant women in iodine adequate area should maintain the current policy of supplying iodized salt unchanged.

ObjectiveTo explore the prevalence difference between northwest dryness syndrome and blood stasis syndrome of coronary heart disease （CAD） and their correlations with major adverse cardiovascular events （MACE）. MethodsThe medical records including general information and risk factors for vascular diseases （gender， age， smoking history， diabetes history， hypertension history， chronic kidney disease history and body mass index）， laboratory indicators （fasting blood glucose， triglyceride， high density lipoprotein cholesterol， etc.） of 499 CAD patients in the Department of Cardiology of the Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University from November 1st， 2015 to September 30th，2020 were collected， and whether they suffered from northwest dryness syndrome or blood stasis syndrome was judged. The incidence of MACE was followed up for one year. The differences of cardiovascular risk factors between the northwest dryness syndrome and blood stasis syndrome of CAD were compared， and the correlation with MACE was analyzed. ResultsAmong the 499 CAD patients， there were 128 cases （25.65%） of simple blood stasis syndrome， 33 cases （6.61%） of simple northwest dryness syndrome， 209 cases （41.88%） of northwest dryness syndrome plus blood stasis syndrome， and 129 （25.85%） cases of not blood statis syndrom either northwest dryness syndrome. Univariate regression analysis showed that smoking history， diabetes history， fasting blood glucose abnormality， triglyceride abnormality， and high density lipoprotein cholesterol abnormality were positively correlated with northwest dryness syndrome in CAD patients （OR＞1， P＜0.05）， while smoking history， abnormal triglyceride and abnormal high density lipoprotein cholesterol were positively correlated with blood stasis syndrome in CAD patients （OR＞1， P＜0.05）. Multivariate regression analysis showed that the history of diabetes， abnormal triglyceride and abnormal high density lipoprotein cholesterol were positively correlated with northwest dryness syndrome of CAD （P＜0.05）. Smoking history， abnormal triglycerides and abnormal high density lipoprotein cholesterol were positively correlated with blood stasis syndrome （P＜0.05）. Association rule analysis showed that the confidence of CAD patients with northwest dryness syndrome complicated with blood stasis syndrome was 86.36%， and that of patients with blood stasis syndrome complicated with northwest dryness syndrome was 62.02%. Among the 499 patients， 96 had MACE in one year， accounting for 19.24% of the total. Logistics regression analysis showed that the correlation with incidence of MACE in CAD patients within one year from strong to weak was northwest dryness syndrome plus blood stasis syndrome ［OR = 5.113， 95%CI （3.118， 8.387）， P＜0.001）］， blood stasis syndrome［OR = 4.630， 95%CI （2.394， 8.955）， P＜0.001］， northwest dryness syndrome ［OR = 4.395， 95%CI （2.642， 7.309）， P＜0.001］. ConclusionBlood stasis syndrome is the main syndrome type of CAD in Xinjiang Uygur Autonomous Region. CAD patients with northwest dryness syndrome are more likely to have blood stasis syndrome， and most suffer from both northwest dryness syndrome and blood stasis syndrome simultaneously. There is the strongest correlation between northwest dryness syndrome plus blood stasis syndrome and 1-year occurrence of MACE in CAD.