NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome mediates inflammation, induces pyroptosis, and regulates periodontal tissue remodeling through the maturation and secretion of its downstream cysteine protease 1 (Caspase-1)-dependent pro-inflammatory cytokines, interleukin (IL)-1β and IL-18. Orthodontic force mediates the aseptic inflammation of periodontal tissues and triggers adaptive alteration of periodontal tissues, thereby promoting the movement and stability of orthodontic teeth. NLRP3 inflammasome plays an important role in orthodontic tooth movement and causes periodontal tissue inflammation and orthodontic inflammatory root resorption in orthodontic patients. Literature review suggests that NLRP3 inflammasome is involved in the activation and differentiation of periodontal ligament fibroblasts, periodontal ligament stem cells, macrophages, osteoblasts, and osteoclasts in orthodontic tooth mobile tissue remodeling. Additionally, it targets the upstream nuclear factor kappa-B signaling pathway; downstream effectors, such as Caspase-1, IL-1β, and IL-18; and the NLRP3 inflammasome components for regulating tooth movement as well as treating and preventing orthodontics-associated periodontitis and orthodontic-induced inflammatory root resorption. Future studies can be focused on the specific mechanism of NLRP3 inflammasome tissue modification during orthodontic tooth movement. This article reviews the effects and regulatory mechanisms of the NLRP3 inflammasome signaling pathway on the corresponding tissue remodeling during orthodontic tooth movement.

Objective To evaluate the clinical efficacy and safety of Jiangzhi Hugan Soft Extract(composed of stir-fried Dioscoreae Rhizoma,Poria,Ginseng Radix et Rhizoma,Bupleuri Radix,Citri Sarcodactylis Fructus,Persicae Semen,Polygoni Cuspidati Rhizoma,etc.)in treating non-alcoholic fatty liver disease(NAFLD)with internal dampness-turbidity accumulation syndrome.Methods Sixty patients with NAFLD of dampness-turbidity accumulation syndrome treated at the Gastroenterology Department of Maoming Hospital of Guangzhou University of Chinese Medicine(Maoming Hospital of Traditional Chinese Medicine)from November 2023 to December 2024 were enrolled.The patients were divided into trial group and control group using stratified randomization,with 30 patients in each group.Both groups received lifestyle interventions(diet control and exercise),with the trial group additionally receiving Jiangzhi Hugan Soft Extract for 4 weeks.Outcomes included body mass index(BMI),liver function indicators[alanine aminotransferase(ALT),aspartate aminotransferase(AST),gamma-glutamyl transferase(GGT)],lipid profiles[total cholesterol(TC),triglycerides(TG)],traditional Chinese medicine(TCM)syndrome scores,efficacy evaluation,and safety assessment.Results(1)After 4 weeks of treatment,the overall response rate in the trial group was 93.33％(28/30),while that in the control group was 60.00％(18/30).The intergroup comparison(by rank sum test)showed that the efficacy of TCM syndrome in the trial group was significantly superior to that in the control group,with a statistically significant difference(P＜0.01).(2)After treatment,the BMI of patients in both groups was improved significantly compared to before treatment(P＜0.01).The improvement in BMI was significantly greater in the trial group than in the control group.The difference in the change of BMI between the two groups was statistically significant before and after treatment(P＜0.05).(3)After treatment,the levels of ALT,AST,and GGT in both groups decreased compared to before treatment(P＜0.01).The trial group showed a significantly greater reduction in ALT,AST,and GGT levels than the control group.The difference between the two groups was statistically significant before and after treatment(P＜0.05).(4)After treatment,both groups showed a significant decrease in TC and TG levels compared to pre-treatment levels(P＜0.05).The trial group demonstrated a more pronounced reduction in TC levels than the control group.The difference between the two groups was statistically significant before and after treatment(P＜0.05).(5)There were no significant adverse reactions occurring in either group during treatment,indicating a high level of safety.Conclusion Jiangzhi Hugan Soft Extract effectively improves BMI,liver function,and lipid profile in NAFLD patients with dampness-turbidity accumulation syndrome,demonstrating good clinical efficacy and high safety,warranting further clinical application.

Objective:To compare the therapeutic effects of modified plantar skin grafting and thigh skin grafting on the deep burn wounds of the back and buttocks.Methods:A retrospective cohort study was conducted to analyze the clinical data of 30 patients with deep burn wounds on their back and buttocks who were admitted to the 910th Hospital of Joint Logistic Support Force of PLA from January 2021 to April 2023, including 26 males and 4 females, aged 21-72 years [(49.9±14.0)years]. The total burn size was 50%-97% of the total body surface area (TBSA), with the third-degree burn on the back and buttocks 6%-16% TBSA. The burn wounds on the back and buttocks were repaired using plantar skin grafts alone, thigh skin grafts alone or plantar skin grafts combined with the grafts from other body parts. The patients were grouped according to the skin graft donor sites and the times of harvesting skin grafts: there were 20 patients undergone plantar skin grafting including 10 patient with plantar skin graft harvested once (group of plantar skin graft harvested once) and 10 patients with plantar skin graft harvested twice or three times (group of plantar skin graft harvested more than once), and 10 patients undergone thigh skin grafting harvested once (group of thigh skin graft harvested once). The areas of plantar skin grafts harvested at the last time and the wound areas on the back and butts that could be repaired each time were calculated. After the last harvest, the thickness of the stratum corneum, 7-day survival rate of the skin grafts, proportion of 3-month residual wound area in the skin graft area, healing time of the donor sites, and 6-month Vancouver Scar Scale (VSS) scores of the donor sites in the group of plantar skin graft harvested once were compared with those in the group of thigh skin graft harvested once and the group of plantar skin graft harvested more than once. The appearance and texture of the skin graft, patients′ walking patterns and complications were observed at 6 months after the last skin harvest.Results:All the patients were followed up for 6-18 months [(7.8±1.6)months]. In the 20 patients with plantar skin grafts harvested, the areas of skin grafts harvested at the last time were 2.5%-4.5% TBSA [(3.4±0.6)% TBSA] and the wound areas that could be repaired each time were 3%-8% TBSA [(5.5±1.5)% TBSA]. After the last harvest, the thickness of the stratum corneum in the group of plantar skin graft harvested once was (190.4±8.9)μm, which was significantly thicker than that in the group of thigh skin graft harvested once [(50.0±6.6)μm] and that in the group of plantar skin graft harvested more than once [(166.8±21.9)μm] ( P<0.01); the 7-day survival rate of the skin grafts, proportion of 3-month residual wound area in the skin graft area, healing time of the donor sites, and 6-month VSS scores of the donor sites were (93.6±2.3)%, 2.0 (0.1, 3.5)%, (9.9±1.8)days and (1.7±0.7)points in the group of plantar skin graft harvested once, (78.0±6.6)%, 5.3 (4.0, 5.8)%, (14.0±1.4)days and (4.9±2.3)points in the group of thigh skin graft harvested once, and (93.4±2.6) %, 2.0 (0.1, 3.8)%, (10.0±1.2)days and (1.8±0.8)points in the group of plantar skin graft harvested more than once. The group of plantar skin graft harvested once showed a significant increase in the 7-day survival rate and a significant decrease in the proportion of 3-month residual wound area in the skin graft area, healing time of the donor sites, and 6-month VSS scores of the donor sites in comparison with the group of thigh skin graft harvested once ( P<0.05 or 0.01), while there were no significant differences in above mentioned indices between the group of plantar skin graft harvested once and the group of plantar skin graft harvested more than once ( P>0.05). At 6 months after the last skin harvest, the skin graft areas on the back and buttocks were flat, hard and firm and all the patients in the three groups could walk normally, with no complications such as severe itching, pain or folliculitis in the skin graft area. Conclusions:In the treatment of burn wounds on the back and buttocks, compared with thigh skin grafting, modified plantar skin grafting has advantages of thicker stratum corneum, better wear resistance and pressure resistance in the skin graft areas, a higher survival rate of skin grafts, rapid healing, mild scar, and undisturbed walking pattern after surgery and no common complications. Moreover, skin grafts can be harvested repeatedly from the donor sites, with no impact on the therapeutic effects.

Objective:To analyze the impact of lymph node dissection on textbook outcomes (TO) and the prognosis of intrahepatic cholangiocarcinoma (ICC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 376 ICC patients who underwent hepatectomy in 4 medical centers, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from December 2011 to December 2017 were collected. There were 242 males and 134 females, aged 57(range, 48-63)years. According to the criteria of TO, patients were classified as two cate-gories, including patients achieving TO and not achieving TO. Measurement data with normal distri-bution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were represented as absolute numbers, and comparison between groups was conducted using the chi-square test, Yates adjusted chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the non-parameter rank sum test. Univariate and multivariate analyses were conducted using the Logistic regression model. The Kaplan-Meier method was used to draw survival curve. Survival analysis was conducted using the Log-rank test. Results:(1) TO situations. Of the 376 ICC patients who underwent hepatectomy, 199 cases achieved TO, including 40 cases with lymph node dissection and 159 cases without lymph node dissection, 177 cases did not achieve TO, including 76 cases with lymph node dissection and 101 cases without lymph node dissection. (2) Influencing factors for TO after hepatectomy of ICC patients. Results of multivariate analysis showed that lymph node dissection, microvascular invasion, nerve invasion and the volume of intraoperative blood loss >800 mL were independent risk factors for achieving TO after hepatec-tomy of ICC patients ( odds ratio=2.22, 2.95, 3.58, 4.09,95% confidence interval as 1.34-3.69, 1.43-6.07, 1.40-9.17, 1.35-12.43, P<0.05). Of the 116 patients with lymph node dissection, 40 cases achieved TO, 103 cases achieved R 0 resection, 38 cases had postoperative complications, 67 cases had delayed hospital stay. The above indicators were 159, 255, 41, 65 of 260 patients without lymph node dissection. There were significant differences in the above indicators between patients with and without lymph node dissection ( χ2=22.90, 15.16, 13.95, 37.78, P<0.05). (3) Follow-up. All the 376 patients were followed up for 19(range, 1-74)months. Of 199 patients achieving TO, the 1-, 2-and 3-year survival rates of 40 patients with lymph node dissection were 54.0%, 36.6% and 26.1%, respectively, versus 67.7%, 42.7% and 34.4% of 159 patients without lymph node dissection, showing no significant difference between them ( χ2=1.89, P>0.05). Of 177 patients not achieving TO, the 1-, 2-and 3-year survival rates of 76 cases with lymph node dissection were 58.9%, 25.7% and 10.3%, respectively, versus 53.0%, 28.5% and 17.2% of 101 cases without lymph node dissection, showing no significant difference between them ( χ2=0.25, P>0.05). Conclusions:Lymph node dissec-tion, microvascular invasion, nerve invasion and the volume of intraoperative blood loss >800 mL are independent risk factors for achieving TO after hepatectomy of ICC patients. Lymph node dissec-tion may increase the postoperative complication rate, prolong the hospital stay and decrease the rate of achieving TO. However, it does not affect the prognosis of patients.

Background: Serum C-peptide results from various routine methods used in China are highly variable, warranting well-performing methods to serve as an accuracy base to improve the harmonization of C-peptide measurements in China. We developed an accurate isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC–MS/MS) method for serum C-peptide measurement and explored its use in harmonization. Methods: After protein precipitation with ZnSO4 solution, C-peptide was extracted from serum samples by anion-exchange solid-phase extraction and quantified by ID-LC–MS/MS in positive ion mode. The precision and analytical recovery of the ID-LC–MS/MS method were assessed. Seventy-six serum samples were analyzed using the ID-LC–MS/MS method and six routine immunoassays. Ordinary linear regression (OLR) and Bland-Altman (BA) analyses were conducted to evaluate the relationship between the ID-LC–MS/MS method and routine immunoassays. Five serum pool samples assigned using the ID-LC–MS/MS method were used to recalibrate the routine assays. OLR and BA analyses were re-conducted after recalibration. Results: The within-run, between-run, and total precision for the ID-LC–MS/MS method at four concentrations were 1.0%–2.1%, 0.6%–1.2%, and 1.3%–2.2%, respectively. The analytical recoveries for the ID-LC–MS/MS method at three concentrations were 100.3%–100.7%, 100.4%–101.0%, and 99.6%–100.7%. The developed method and the immunoassays were strongly correlated, with all R2 >0.98. The comparability among the immunoassays was substantially improved after recalibration. Conclusions The performance of the ID-LC–MS/MS method was carefully validated, and this method can be used to improve the harmonization of serum C-peptide measurements in China.

OBJECTIVE To establish comprehensive quality evaluation method based on multi-index components combined with multivariate statistical analysis， and to comprehensively evaluate the quality of Periploca forrestii. METHODS Taking 11 batches of P. forrestii medicinal materials from different areas in Guizhou as samples， the contents of neochlorogenic acid， cryptochlorogenic acid， chlorogenic acid， procyanidin A2， isochlorogenic acid A and isochlorogenic acid C were determined by HPLC. Clustering heat map analysis， grey correlation analysis（GRA） and technique for order preference by similarity to ideal solution（TOPSIS） were used to evaluate the quality of P. forrestii. RESULTS The results of methodological investigation of content determination were in accordance with the relevant regulations， and the linear relationship and accuracy of each component were good in their respective sampling range. The contents of chlorogenic acid， cryptochlorogenic acid， neochlorogenic acid， procyanidin A2， isochlorogenic acid A and isochlorogenic acid C in 11 batches of samples were 3.650-7.302， 0.888-2.575， 1.371- 2.386， 0.947-1.469， 0.084-0.169 and 0.725-1.067 mg/g， respectively. The content of each component was significantly different， with the highest content of chlorogenic acid and the lowest content of isochlorogenic acid A. The comprehensive results of cluster heat map， GRA and TOPSIS analysis showed that the comprehensive quality of S5 and S10 was relatively good. CONCLUSIONS The established method is accurate， stable and simple. Combined with multivariate statistical analysis method， it can be used for quality evaluation of P. forrestii. The quality of samples from Jiuzhou Town and Caiguan Town of Xixiu District in Anshun City of Guizhou Province are relatively good among 11 different origin samples.

Metabolic-associated fatty liver disease (MAFLD), which is previously known as non-alcoholic fatty liver disease (NAFLD), represents a major health concern worldwide with limited therapy. Here, we provide evidence that ferroptosis, a novel form of regulated cell death characterized by iron-driven lipid peroxidation, was comprehensively activated in liver tissues from MAFLD patients. The canonical-GPX4 (cGPX4), which is the most important negative controller of ferroptosis, is downregulated at protein but not mRNA level. Interestingly, a non-canonical GPX4 transcript-variant is induced (inducible-GPX4, iGPX4) in MAFLD condition. The high fat-fructose/sucrose diet (HFFD) and methionine/choline-deficient diet (MCD)-induced MAFLD pathologies, including hepatocellular ballooning, steatohepatitis and fibrosis, were attenuated and aggravated, respectively, in cGPX4-and iGPX4-knockin mice. cGPX4 and iGPX4 isoforms also displayed opposing effects on oxidative stress and ferroptosis in hepatocytes. Knockdown of iGPX4 by siRNA alleviated lipid stress, ferroptosis and cell injury. Mechanistically, the triggered iGPX4 interacts with cGPX4 to facilitate the transformation of cGPX4 from enzymatic-active monomer to enzymatic-inactive oligomers upon lipid stress, and thus promotes ferroptosis. Co-immunoprecipitation and nano LC-MS/MS analyses confirmed the interaction between iGPX4 and cGPX4. Our results reveal a detrimental role of non-canonical GPX4 isoform in ferroptosis, and indicate selectively targeting iGPX4 may be a promising therapeutic strategy for MAFLD.

Objective:To establish the allowable total error (TEa) of the national external quality assessment (EQA) program in line with the current quality level of serum folate measurement in China.Methods:The data of serum total folate test in the clinical laboratory of a hospital in Beijing in 2016 were collected, and the Stata SE 15 software was used for Monte Carlo simulation to obtain the false-negative rate under different bias and inaccuracy conditions. The Origin Pro 9.1 software was used to make the contour figure. The TEa of serum total folate test is derived based on the acceptable false-negative rate. National EQA data of serum total folate in 2020 were collected to calculate the pass rate of participating laboratories and the laboratory pass rate of quality control products at each level under the five TEa derived from the analysis performance on clinical outcomes, biological variation, and the evaluation criterion of national EQA.Results:Based on the influence of analytical performance on clinical outcomes, the TEa was 10%. Under this TEa, the pass rate of the first EQA program of serum total folate in 2020 was more than 80%, and the pass rate of the second time was 73.1%. Under the minimum (46.57%) and appropriate level of TEa (15.52%) derived from biological variation and national EQA evaluation criterion, the pass rate of serum total folate in the two EQA programs in 2020 exceeded 85%.Conclusion:The analytical performance of serum total folate in China cannot meet the requirements of TEa derived based on the effect of analytical performance on clinical outcomes. An appropriate level of TEa derived based on biological variation (15.52%) is suggested as the recommended criterion for the TEa of serum total folate test.

Objective:To establish an accurate quantitative method for the determination of serum glycated albumin (GA) based on isotope dilution liquid chromatography tandem mass spectrometry (ID-LC/MS/MS).Methods:This study optimized the ID-LC/MS method recommended by the Japan Society of Clinical Chemistry (JSCC). Albumin (Alb) was purified by anion exchange chromatography. The standard solution of purified sample, lysine (Lys) and deoxyfructosyl lysine (DOF-Lys) and their mixed internal standard were weighed accurately by weight method. The Alb was hydrolyzed to amino acid, and Lys and DOF-Lys were detected to determine GA. The method was evaluated and compared with the routine method.Results:The purity of Alb was 100%. The R 2 ranges of Lys and DOF-Lys linear standard curves were 0.997 8-0.999 9 and 0.999 4-1.000 0. The results of three-day precision evaluation of low, medium and high concentrations of serum were 0.69%-1.97%, 1.13%-2.33% and 1.37%-2.54% in intra, inter and total Coefficient of variation ( CV). In the accuracy evaluation, the deviations between the results of three concentration standards and the certified value were -2.56%, -1.87% and-2.94%. The matrix effects of Lys and DOF-Lys were 89.92% and 109.98%, and the carryover rates were -1.13% and -3.27% respectively. The detection limit and quantitative limit of Lys were 0.075 nmol/g and 0.248 nmol/g, and the DOF-Lys were 0.007 nmol/g and 0.024 nmol/g. The relative expanded uncertainty was 1.60%-2.03%. The fitting regression curve R 2 with the routine method was 0.970 7. Conclusions:A method was established for the detection of serum GA. The method evaluation was accurate and reliable. It was expected to be a candidate reference method for the detection of serum GA.

Objective: To observe the improving effect of Hypericum Perforatum L Extracts (HPLES)on depression induced by chronic unpredictable mild stress in mice. Methods: The depression model was established by the method of chronic unpredictable mild stress. Fifty depression model mice were divided into model control group, fluoxetine hydrochloride group (2.6 mg / kg), Hypericum perforatum extract low, medium and high (0.2 g / kg, 0.4 g / kg, 0.8 g / kg) dose groups according to the random number table method. Another 10 normal mice matched with body weight were taken as the normal control group. The mice in normal control group and the model control group were given pure water by gavage every day, and the mice in other groups were given corresponding solution by gavage for 4 weeks. In addition to the normal control group, the mice in other groups continued to undergo chronic unpredictable mild stress during gavage.The sugar water preference test and forced swimming test were performed after the last administration. Blood samples were collected from the posterior orbital venous plexus, and the levels of dopamine (DA) and brain-derived neurotrophic factor (BDNF) were measured by Elisa. The hippocampal tissues of mice were examined by HE staining. Results: Compared with the normal control group, the body mass of mice in the model control group decreased significantly at the first, second, third and fourth weeks (t=2.739, 4.162, 4.082, 3.957; all P<0.05). At the first, second, third and fourth weeks, the body mass of mice in the low, middle and high dose group of Hypericum perforatum extract were not significantly different from those in the model control group (all P>0.05). Compared with the normal control group, the sugar water preference index of mice in the model control group was significantly reduced((61.3±4.5)%, (52.6±5.2)%; t=2.721, P<0.05), the swimming immobility time was prolonged((44.3±20.00) s, (101.8±50.8) s; t=2.939, P<0.05), the difference were statistically significant. Compared with the model control group, the sugar water preference index of mice in the low, middle and high dose group of Hypericum perforatum extract increased((61.8±4.7)%, (65.2±4.1)%, (62.6±5.6)%, t=-3.005, 5.073, -2.928, all P<0.05), the swimming immobility time decreased ((47.2±17.9) s, (54.8±50.3) s, (61.3±44.2) s; t=2.803, 1.921, 1.903, all P<0.05). The results of Elisa showed that compared with the normal control group, the levels of serum DA and BDNF of mice in the model control group were significantly lower (t=3.031, 8.507, all P<0.05); compared with the model control group, the levels of serum DA of mice in the low dose and high dose group of Hypericum perforatum were significantly higher (t=5.025, 3.414, P<0.05), and the serum BDNF of mice in the high dose group of Hypericum perforatum was also significantly higher (t=6.098, P<0.05), the difference was statistically significant. HE staining showed that compared with the normal control group, the neurons in CA3 area of hippocampus in the model control group mice were seriously damaged, suggesting the establishment of the mouse model. Compared with the model control group, the atrophy and degeneration of hippocampal CA3 cells in the three dose groups were significantly reduced. The atrophy and deformation of hippocampal CA3 neurons in the low, middle and high dose groups of Hypericum perforatum extract were relieved. Conclusion HPLES have obvious improving and antidepressant effects on the depression model mice induced by chronic unpredictable stress.The above effects may be related to the improvement of serum DA, DBNF level and reduce neuronal damage in CA3 area.