Acute pancreatitis (AP) is a life-threatening gastrointestinal disorder for which no effective pharmacological treatments are currently available. One of the pharmacological targets that merits further research is the neurokinin 1 receptor (NK1R), which is found on pancreatic acinar cells and responds to the neuropeptide substance P (SP) that participates in AP. Although a few studies have stated the involvement of SP/NK1R in neurogenic inflammation in AP development, the regulatory mechanism remains unclear. In this study, we found that following activation of NK1R by SP, β-arrestin1, a scaffold protein of NK1R, down-regulated transcription of Adss, Adsl, and Ampd in the purine nucleotide cycle, thereby inhibiting mitochondrial function through fumarate depletion. Interestingly, we identified magnolol as a new and natural NK1R inhibitor with a non-nitrogenous biphenyl core structure. It exhibited a beneficial effect on AP by restoring purine nucleotide cycle metabolic enzymes and fumarate levels. Our study not only provides new therapeutic strategies, leading compounds, and drug translation possibilities for AP, but also provides important clues for the study of downstream mechanisms driven by SP in other diseases.

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

Objective : To pathological changes and inducible nitric oxide synthase(iNOS), phosphorylated insulin receptor substrate 1 serine 307(p-IRS1ser 307), phosphorylated protein kinase B serine 473(p-AKTser 473), glycogen synthase kinase-3β(GSK-3β), and gluconeogenic synthase(GS) proteins were observed in the liver of rats under the condition of chronic intermittent hypoxia-replicated oxygen in control. And to explore the role of iNOS/IRS1/AKT/GSK-3β signaling pathway in chronic intermittent hypoxia-induced insulin resistance. Methods : Forty SD rats were randomly divided into a control group(NC group) and an experimental group(CIH group), with 20 rats in each group. The NC group was placed in a normoxic environment for 12 weeks, while the CIH group was first subjected to intermittent hypoxia for 8 weeks, and then resumed normoxic rearing until the 12th week. Fasting blood glucose(FBG) and fasting insulin(FINS) were measured at baseline, week 8 and week 12, and liver tissues were taken for pathology and measurement of iNOS, p-IRS1ser 307, p-AKTser 473, GSK3β and GS levels, to compare the differences between groups. Results: t baseline, there was no significant difference in liver pathology between the two groups, and the observed indexes were not statistically significant(P>0.05); at 8 weeks, compared with the NC group, liver pathology in the CIH group showed significant disorganization of hepatic blood sinusoids and hepatocyte cords, obvious hepatocyte edema, smaller nuclei, increased lymphocyte infiltration, and a small number of fat vacuoles, significantly higher levels of FBG, FINS, insulin resistance index(HOMA-IR), iNOS mRNA, p-IRS1ser 307 protein, GSK-3β protein levels, and decreased p-AKTser 473 protein and GS protein levels, all of which were statistically significant(allP<0.05). IRS1ser 307 protein, GSK-3β protein levels were increased, p-AKTser 473 protein and GS protein levels were decreased, and the differences were statistically significant(allP<0.05); at 12 weeks, no lymphocyte infiltration was seen in the CIH group compared with that of the NC group and fat vacuoles significantly increased, and there was no improvement in the other pathological damage that had already occurred, and the levels of p-AKTser 473 protein significantly increased. AKTser 473 protein level significantly increased, p-IRS1ser 307 protein and GS protein levels were significantly reduced, all of which were statistically significant(allP<0.05), and the rest of the observational indexes were not statistically significant. Pearson′s correlation analysis showed that HOMA-IR of CIH group was significantly positively correlated with the levels of iNOS mRNA, p-IRS1ser 307 protein, and GSK-3β protein at 8 weeks(r=0.874, 0.817,0.872;allP<0.05), and significantly negatively correlated with the levels of p-AKTser 473 protein and GS protein(r=-0.886,-0.879;allP<0.05). Conclusion Chronic intermittent hypoxia can lead to hepatic pathological damage that cannot be reversed even by reoxygenation interventions and may mediate the development of insulin resistance by upregulating the IRS1/AKT/GSK-3β signaling pathway through the upregulation of iNOS mRNA expression.

Objective:To compare the clinical efficacy of ultrasound-guided spinal nerve block (SNB) and paraverteral nerve block (PVB) in treating postherpetic neuralgia.Methods:A total of 52 patients with postherpetic neuralgia who visited the Pain Clinic of the Xiangya Hospital, Central South University from February 2020 to December 2022 were selected and randomly divided into an ultrasound-guided SNB group and a PVB group using a random number table method, with 26 patients in each group. Patients in the SNB group received ultrasound-guided spinal nerve block therapy; The PVB group received ultrasound-guided paraverteral nerve block treatment. Visual Analog Scale (VAS) scores, 36-Item Short Form Survey (SF-36) scores, and total effective rate were observed in two groups of patients before treatment, 2 weeks after treatment, 1 month after treatment, 3 months after treatment, and 6 months after treatment. Complications during treatment were also observed.Results:The total effective rates of SNB group patients at 1, 3, and 6 months after treatment were significantly higher than those of PVB group (all P<0.05). After treatment, the VAS scores of both groups of patients at each time point were significantly reduced compared to before treatment (all P<0.05); The VAS scores of patients in the SNB group were lower than those in the PVB group at 1, 3, and 6 months after treatment, but the difference was not statistically significant (all P>0.05). There was no statistically significant difference in Physical Component Summary (PCS) and Mental Component Summary (MCS) scores between SNB and PVB groups before nerve block treatment (all P>0.05). The MCS and PCS scores of the two groups of patients were significantly higher than before treatment at 2 weeks, 1 month, 3 months, and 6 months after treatment (all P<0.05). The MCS scores of the SNB group were significantly higher than those of the PVB group at 2 weeks, 1 month, 3 months, and 6 months after treatment (all P<0.05), but there was no statistically significant difference in PCS scores between the two groups (all P>0.05). Both groups of patients did not experience any serious complications related to the treatment in this study during the follow-up period. Conclusions:Both ultrasound-guided spinal nerve block and paraverteral nerve block can safely and effectively treat postherpetic neuralgia. The clinical effect of ultrasound-guided spinal nerve block in treating postherpetic neuralgia is better than that of paraverteral nerve block.

Objective To investigate the temporal properties of dynamic functional connectivity of brain networks and the variability of network topology in patients with end-stage renal disease(ESRD).Methods Data of 30 ESRD patients(ESRD group)and 33 healthy subjects(control group)were retrospectively analyzed.Based on cranial resting-state functional MRI(rs-fMRI),dynamic functional connectivity(dFC)and graph theory analysis were employed,and the abnormalities in network topology and dFC in ESRD patients were assessed through comparison of groups.Pearson correlation analysis was used to observe the correlation between abnormal dFC indicators and clinical variables.Results Compared with control group,temporal scores and the mean residence time in ESRD group were significantly higher under state Ⅱ but significantly lower under state Ⅲ(both P＜0.05).The abnormal functional connectivity in ESRD patients under states Ⅱ and Ⅲ distributed mainly within and between default mode network,sensorimotor network,subcortical nuclei,execution and attention network,visual network and cerebellum networks.Network density and bilateral superior temporal gyrus nodal degrees in ESRD group were all significantly lower than those in control group(all P＜0.05).No significant correlation was found between the abnormal parameters of functional connectivity and graph theory attributes in ESRD group and clinical indicators under states Ⅱ nor Ⅲ(all P＞0.05).Conclusion ESRD patients had abnormal temporal attributes and network topology of brain dynamic networks related to cognitive impairments.

Objective:To analyze the correlation between peripheral blood lymphocyte subsets, especially B cells, and the relapse of autoimmune encephalitis (AE).Methods:A retrospective analysis was conducted on patients with AE who were diagnosed and treated in Peking Union Medical College Hospital from January 2012 to January 2023. The clinical data including gender, age and changes in related indicators of CD19 +B cells, CD16/56 +NK cells, CD3 +T cells, CD4 +T cells, CD8 +T cells, IgG, IgA, and IgM before and after recurrence were analyzed.Binary Logistic regression analysis was applied to the study of correlation between AE recurrence and gender, age, CD19 +B cells, CD16/56 +NK cells, CD3 +T cells, CD4 +T cells, CD8 +T cells, IgG, IgA and IgM. The receiver operating characteristic (ROC) curves of the cells that affect AE recurrence (CD19 +B cells, CD16/56 +NK cells, CD3 +T cells, CD4 +T cells and CD8 +T cells) were plotted separately. Results:A total of 198 eligible AE patients were included, including 98 males and 100 females, aged (39.52±17.91) years. Among these patients, 78 cases had relapses, with a recurrence rate of 39.4%. The results of Logistic regression analysis showed that CD19 +B cells ( B=0.006, P<0.001), CD16/56 +NK cells ( B=0.004, P<0.05), CD3 +T cells ( B=-0.011, P<0.05), CD4 +T cells ( B=0.014, P<0.05) and CD8 +T cells ( B=0.010, P<0.05) were highly correlated with the relapse of AE. ROC curve analysis showed that CD19 +B cells (area under the curve: 0.833, P<0.001, critical value: 73.5/μl; sensitivity: 69.2%, specificity: 86.7%), CD3 +T cells (area under the curve: 0.784, P<0.001), CD4 +T cells (area under the curve: 0.808, P<0.001), and CD8 +T cells (area under the curve: 0.742, P<0.001) all had a certain predictive value for AE relapse. Among all the indicators, the area under the curve of CD19 +B cells was the largest, which had a higher value in predicting AE recurrence. Conclusion:The increase in peripheral blood CD19 +B cells has high predictive value for the relapse of AE.

Objective To investigate the efficacy of the therapy of soothing liver and strengthening spleen(shortened as Shugan Jianpi therapy)in the treatment of active thyroid-associated ophthalmopathy(TAO)complicated with dry eye,and to provide a reference basis for clinical treatment.Methods A total of 108 patients with active TAO complicated with dry eye of liver depression and qi stagnation type were randomly divided into observation group and control group,54 patients in each group.Both groups were given conventional treatment for intervention of Graves'disease,and additionally the control group was given hormone shock therapy by intravenous injection of Methylprednisolone Sodium Succinate,and the observation group was treated with Chinese medicine prescription for soothing liver and strengthening spleen orally and intravenous injection of Methylprednisolone Sodium Succinate.The treatment period lasted for 12 weeks,and then the patients were followed up till to the 6th month.The changes of clinical activity score(CAS),proptosis,ocular surface disease index(OSDI),corneal fluorescein staining(FL),Schirmer I test(SIT)and tear film break-up time(BUT)in the two groups were observed before and after the treatment.After treatment,the clinical efficacy of the two groups was evaluated.Results(1)After 6 months of treatment,the total effective rate in the observation group was 94.44%(51/54)and that in the control group was 74.07%(40/54),and the intergroup comparison(tested by chi-square test)showed that the efficacy of the observation group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the CAS,OSDI score and proptosis of the patients in the two groups were all lower than those before treatment(P＜0.01),and the reduction in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the indicators of tear secretion function such as SIT,FL score and BUT of patients in the two groups were improved compared with those before treatment(P＜0.01),and the improvement in the observation group was significantly superior to that in the control group,the differences being all statistically significant(P＜0.01).Conclusion Shugan Jianpi therapy exerts certain clinical efficacy in treating patients with active TAO complicated with dry eye of liver depression and qi stagnation type,which can effectively relieve the proptosis,prolong the tear film break-up time,promote the secretion of tears and the repair of corneal epithelium,improve the visual function,and enhance the quality of life of the patients.

Objective:To investigate the effects of methyltransferases like 3(METTL3)mediated m6A modification of double homology cassette A pseudogene8(DUXAP8)on the proliferation,migration and invasion of salivary adenoid cystic carcinoma SACC-LM cells and its potential molecular mechanisms.Methods:Whole-transcriptome sequencing showed that DUXAP8 was highly ex-pressed in SACC than in para-cancerous tissues(P＜0.05).The m6A modification sites on DUXAP8 were predicted using the SRAMP website,and the mRNA and protein expression of m6A-modified genes and the genes associated with the epithelial-mesen-chymal transition(EMT)was measured by qRT-PCR and Western blot,respectively.METTL3 and DUXAP8 was knocked down or overexpressed in SACC-LM cells,and the proliferation,migration,and invasion of the cells were assessed by CCK-8,scratch and Transwell assays.The correlation between METTL3 and DUXAP8 was evaluated using MeRIP-qPCR.Results:The expression of DUXAP8 in SACC tumor was higher than that in para-cancerous tissues(P＜0.05).Knockdown of DUXAP8 reduced proliferation,migration and invasion of SACC-LM cells,as well as the expression of EMT-related genes(P＜0.05).Multiple m6A modification sites of high confidence were found on DUXAP8.METTL3 was highly expressed in tumor tissues,more than other related genes(P＜0.05)and enzyme-encoding genes in SACC-LM cells(P＜0.05).METTL3 was found to function as a methyltransferase to regulate the expression of DUX-AP8,and downregulation of METTL3 inhibited prolifera-tion,migration and invasion of SACC-LM cells and partially reversed the promotion of these activities induced by DUX-AP8 overexpression(P＜0.05).Conclusion:METTL3-me-diated m6A modification upregulated DUXAP8 expression,which promotes the proliferation,migration and invasion of SACC cells.