ObjectiveTo construct a rat model of psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type）， and evaluate the macroscopic manifestations and microscopic indicators of the model. MethodsTwenty-two SD rats were divided into normal group （n=3）， common psoriasis group （n=5）， spleen deficiency and dampness obstruction syndrome （external dampness type） group （n=7）， and psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group （n=7）. The spleen deficiency and dampness obstruction syndrome （external dampness type） rat model was established through 32-week exposure to an artificially simulated high-humidity environment， while the common psoriasis model was developed via 7-day topical application of imiquimod cream， and these two approaches were combined to construct a composite model of psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type）. Rats in the normal group were housed under normal humidity conditions. The general state， tongue manifestation of rats were observed to evaluate the macroscopic syndrome manifestations； the microscopic syndrome manifestations of rats were evaluated through adipose tissue and liver tissue changes； the severity of psoriasis in rats was evaluated through skin pathological changes， psoriasis area and severity index （PASI）， proliferating cell nuclear antigen （PCNA） expression and spleen tissue changes； changes in rat CD4⁺ interferon-γ⁺ cells （CD4⁺IFN-γ⁺ cells）， CD4⁺ tumour necrosis factor-α+ cells （CD4⁺ TNF-α⁺ cells）， and forkhead framing protein P3⁺ regulatory T cells （CD3⁺CD4⁺FoxP3⁺ Treg cells） were detected by flow cytometry. ResultsMacroscopically， both the spleen deficiency and dampness obstruction syndrome （external dampness type） group and psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group exhibited manifestations of spleen deficiency and dampness obstruction， including lethargy， huddling behavior， dull and disheveled fur， as well as soft or loose stools and perianal soiling in some individuals； both these two groups displayed enlarged tongue， swollen， and moist tongue texture， accompanied by slippery tongue surface. Microscopically， compared to the common psoriasis group， the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group showed increased epididymal fat index （P＜0.05）； compared to the normal group and spleen deficiency and dampness obstruction syndrome （external dampness type） group， the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group demonstrated significantly elevated spleen mass （P＜0.05）， while hepatic gross morphology and HE staining revealed no significant histopathological changes across all groups. Dorsal skin lesions were markedly exacerbated in the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group when compared to those in common psoriasis group. Both the common psoriasis group and psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group exhibited significantly higher erythema scores， scaling scores， infiltration scores， PASI total scores， and proportions of CD3⁺CD4⁺FoxP3⁺Treg cells compared to the normal group and spleen deficiency and dampness obstruction syndrome （external dampness type） group （P＜0.05）， with pronounced PCNA-positive expression observed in the epidermal basal layer and dermis； the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group displayed significantly increased proportions of CD4⁺TNF-α⁺cells compared to the spleen deficiency and dampness obstruction syndrome （external dampness type） group （P＜0.05）； whereas no significant differences were detected in CD4⁺IFN-γ⁺cell proportions among groups （P＞0.05）. ConclusionThe rat model of psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） can be successfully constructed by artificially simulating a high-humidity environment combined with imiquimod induction.

As a hot spot in clinical research today, immune checkpoint inhibitor has been recommended by guidelines in the first- and second-line treatments of advanced cervical cancer as immune monotherapy or combination therapy. It has also achieved good efficacy in clinical practice. In locally advanced cervical cancer, immune checkpoint inhibitors have been included in the guidelines for adjuvant therapy, and good tumor regression effects have been achieved in clinical practice. Based on the results of existing trials, immune checkpoint inhibitors have also shown good clinical potential as neoadjuvant therapy. Furthermore, the issue of immunotherapy rechallenge has increasingly captured clinicians’ attention, offering a potential new therapeutic strategy for cervical cancer patients with prior immunotherapy exposure. In this article, the clinical application and research progress of immune checkpoint inhibitors in the treatment of cervical cancer in recent years are summarized to provide valuable ideas and directions for clinical treatment.

The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Neurodegenerative diseases encompass a diverse array of disorders that have a profoundly detrimental impact on human health, characterized by their intricate and multifaceted pathogenesis. In the recent past, a growing body of scientific research has begun to shed light on the critical involvement of the neuro-immune axis in the onset and advancement of these debilitating conditions. This comprehensive review article delves into the intricate composition of the neuro-immune axis, elucidating the complex mechanisms through which it exerts its influence in the context of neurodegenerative diseases. Furthermore, it explores the potential therapeutic applications of targeting the neuro-immune axis for the management and treatment of these diseases. This extensive examination aims to offer new perspectives and innovative strategies that could pave the way for more effective treatments for neurodegenerative diseases, thereby providing hope for those afflicted by these challenging conditions.
Humans ; Neurodegenerative Diseases/metabolism* ; Animals ; Neuroimmunomodulation/physiology*

Objective:To investigate the efficacy and prognosis of biliary drainage via endoscopic retrograde cholangiopancreatography (ERCP) before steroid therapy in treating autoimmune pancreatitis (AIP) complicated with obstructive jaundice.Methods:A retrospective analysis was performed on clinical data of patients with AIP complicated with obstructive jaundice who received steroid therapy at the First Affiliated Hospital of Naval Medical University from 2010 to 2023. Patients were divided into a drainage group (receiving ERCP biliary drainage before steroid therapy) and a steroid group (receiving only steroid therapy). Short-term efficacy, long-term efficacy, hospitalization costs and postoperative complications of ERCP biliary drainage were compared between the two groups.Results:A total of 69 patients were included, with 32 in the drainage group, aged 62.78±11.21 years, which demonstrated significantly higher costs (34 816.57±11 688.85 yuan VS 16 518.50±6 544.37 yuan, t=7.0, P<0.001), with 25.00% (8/32) experiencing ERCP-related complications, compared with 37 patients in the steroid group, aged 55.41±2.15 years. There was no significant difference in hospitalization duration between the drainage group (10.38±4.56 days) and the steroid group (8.95±4.99 days, t=1.2, P=0.219). After 1 month of treatment, total bilirubin [118.5 (76.2, 309.3) μmol/L VS 48.7 (30.5, 148.4) μmol/L, U=1 728.5, P<0.001] and direct bilirubin [84.5 (47.7, 236.3) μmol/L VS 37.7 (18.3, 105.7) μmol/L, U=1 588.5, P=0.001] levels in the drainage group remained higher than those in the steroid group, while alanine aminotransferase levels were lower [74.0 (46.5,110.5) U/L VS 143.0 (51.0,253.5) U/L, U=769.0, P=0.006]. No significant differences were observed in these biochemical indices between the two groups at 4-month and 12-month follow-ups ( P>0.05). The recurrence rates were 28.1% (9/32) in the drainage group and 21.6% (8/37) in the steroid group, with no significant difference in recurrence rate between groups ( χ2=0.4, P=0.266). Conclusion:ERCP biliary drainage does not significantly improve long-term efficacy or reduce recurrence rates in AIP patients with obstructive jaundice. Instead, it increases the risk of postoperative complications and medical costs. Direct steroid therapy is safe and feasible for confirmed AIP with obstructive jaundice.

OBJECTIVES: This study aims to compare the effects of two orthodontic treatment modalities for skeletal class Ⅲ malocclusion on specific changes in airway volume, morphology, palatal angle, mandibular rotation, and bone displacement. Results provide scientific evidence for the selection of orthodontic treatment plans and reduce the risk of developing obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: Thirty-six patients diagnosed with skeletal class Ⅲ malocclusion at the Department of Orthodontics, the Affiliated Stomatological Hospital of Nanjing Medical University from September 2018 to December 2023 were divided into two groups: orthodontic-orthognathic treatment group (18 patients) and camouflage orthodontic treatment group (18 patients). Changes in airway volume, cross-sectional area, palatal angle, mandibular, and tongue positions were observed through pre- and post-operative cone beam computed tomography and 3D cephalometric measurements. RESULTS: In the camouflage orthodontic treatment group, nasopharyngeal volume and oropharyngeal volume statistically increased after treatment (P<0.05). In the orthodontic-orthognathic treatment group, changes in nasopharyngeal volume, nasopharyngeal airway, distance from posterior tongue to pharyngeal wall, palatal angle, mandibular rotation, and hyoid bone displacement were statistically significant after surgery (P<0.05). In the comparison between the two groups after treatment, changes in the distance from posterior tongue to pharyngeal wall, palatal angle, and distance from hyoid bone to sella turcica point were statistically significant (P<0.05). CONCLUSIONS Patients in the orthodontic-orthognathic treatment group showed significantly greater changes in oropharyngeal cross-sectional area, palate angle, and tongue position compared with patients in the camouflage orthodontic treatment group. As individuals susceptible to OSAHS often exhibit mandibular retrusion and decreased minimum airway cross-sectional area, special attention should be paid to airway morphology changes when adopting orthodontic-orthognathic treatment to avoid adverse consequences.
Humans ; Hyoid Bone/diagnostic imaging* ; Malocclusion, Angle Class III/therapy* ; Male ; Female ; Cone-Beam Computed Tomography ; Cephalometry ; Orthodontics, Corrective/methods* ; Adult ; Mandible ; Pharynx/diagnostic imaging* ; Sleep Apnea, Obstructive/etiology* ; Orthognathic Surgical Procedures

OBJECTIVES: The objective of this study is to measuring the morphology and position of bilateral temporomandibular joints in patients with unilateral and bilateral molar scissor bite and simulating the deformation of the mandible during occlusion, in order to provide thesis for the diagnosis of temporomandibular joint disease in patients with unilateral and bilateral molar scissor bite. METHODS: This study was a retrospective study. A total of 10 patients with unilateral molar scissor bite (the unilateral molar scissor bite group) and 10 patients with bilateral molar scissor bite (the bilateral molar scissor bite group) were selected as the experimental group, and 20 adult patients with classⅠ of angle classification of similar ages were selected as the control group. All patients underwent cone beam computed tomography scans, by measuring the width of the fossa, height of the fossa, articular eminence inclination, long axis of the condyle, minor axis of the condyle, horizontal angle of the condyle and the space of the temporomandibular joint, compare temporomandibular joint morphology and position. The three-dimensional finite element analysis of the mandible morphology was carried out to evaluate the force and deformation of the mandible by using software to simulate the occlusion of the patients. It was further explored the relationship between the force of the mandible morphology and the possible temporomandibular joint disorder symptoms of the patients. RESULTS: Intergroup comparisons for the unilateral molar scissor bite group and left sides of the other groups revealed that the superior articular space in the group with unilateral molar scissor bite was shorter than that in the control group (P<0.05); the long axis of the condyle in the unilateral and bilateral molar scissor bite group were both shorter than that of the control group (P<0.05); among which the unilateral group was larger than the bilateral group, and the minor axis of the condyle in bilateral molar scissor bite group was smaller than in the control group (P<0.05), and the unilateral and bilateral condylar groups were larger than the control group (P<0.05); and the condylar horizontal angle in the unilateral and bilateral groups were larger than that in the control group (P<0.05). The normal sides of the unilateral molar scissor bite group and right sides of the other groups had smaller superior articular space than the control group (P<0.05); and the condylar long-axis in bilateral group was smaller than the control group (P<0.05); and the normal side of the condylar short-axis unilateral group was larger than that of the bilateral condylar group. Three-dimensional finite element analysis: the condyle of patients with molar scissor bite was a concentrated area of deformation during the bite of the mandible, when the first molar occlusion of the scissors bite side was simulated, the maximum deformation was located in the condyle in the X-axis and Z-axis directions. The amount of deformation was greater than that of the scissor bite side in the X-axis direction, while in the Z-axis direction, the normal side was greater than the scissor bite side. The maximum sites of local deformation in the X-axis direction were located in anterior and posterior the transverse crest of scissor bite side, and the minimum sites of local deformation was at 1/3 of the anterior slope of the inner pole of the normal side, the maximum local deformation sites in the Z-axis direction were located in the outer pole and below the outer pole of the normal side. The X-axis deformation value was the largest in the molars occlusion on the normal side, the Y-axis deformation value was in the premolars occlusion on the normal side, and the Z-axis deformation value was the largest in the centric occlusion, the deformation value of the condyle was not most significant in molar scissor bite. CONCLUSIONS Unilateral and bilateral molar scissor bite resulting in a short condyle morphology, and the bilateral group had a shorter condylar morphology than the unilateral group. The condyle of the patient with molar scissor bite is a concentrated area of poor occlusal deformation, and the largest sites of deformation are distributed near the transverse ridge of the inner and outer poles of the condyle. Different occlusion conditions have an effect on condylar deformation values, but do not indicate whether there is a clear association between them.
Humans ; Finite Element Analysis ; Retrospective Studies ; Temporomandibular Joint/pathology* ; Cone-Beam Computed Tomography ; Mandible/pathology* ; Imaging, Three-Dimensional ; Adult ; Temporomandibular Joint Disorders/diagnostic imaging* ; Mandibular Condyle/diagnostic imaging* ; Female ; Male ; Molar

Objective : To explore the predictive value of depression severity plasma thyroid-stimulating hormone(TSH) and brain-derived neurotrophic factor(BDNF) levels for agitated symptoms in patients with adolescent depressive disorder(MDD). Methods : Ninety-one patients with adolescent depressive disorder were enrolled, and the degree of agitation was assessed according to the modified outward aggressive behavior scale(MOAS); 24-item hamilton depression scale(HAMD24) was used to determine the severity of depression; chemiluminescence immunoassay(CLIA) was used to determine the plasma thyroid-stimulating hormone(TSH) level; and electrochemiluminescence immunoassay(ECL) was used to determine the plasma BDNF. SPSS 26.0 was used for statistical analysis of the data, Spearman correlation analysis was used to analyze the relationship between HAMD24and plasma TSH and BDNF levels and the degree of agitation, multiple linear regression analysis was used to analyze the factors influencing the degree of agitation in adolescents with MDD, and binary Logistic regression analysis and subjects′ work characteristic curves(ROC) were used to establish predictive models. Results: The degree of agitation in adolescent MDD patients was positively correlated with HAMD24total score(P<0.001); both HAMD24total score and plasma BDNF level were identified as risk factors for agitation severity(bothP<0.05); both HAMD24total score and plasma BDNF levels were risk factors for the degree of agitation(allP<0.05); HAMD24total score, plasma TSH, BDNF levels were all risk factors for concomitant agitation symptoms in adolescent MDD patients; ROC curve analysis showed that the three combined prediction models(AUC=0.889,P<0.001) had a higher predictive value than the single prediction model(P<0.01). Conclusion Concomitant agitation symptoms in adolescents with MDD are strongly associated with HAMD24total score and plasma TSH and BDNF levels, and the three combined models have good predictive power.

Macrophages are important immune cells involved in innate immunity,with significant heterogeneity and polarization.Macrophages can polarize into different phenotypes(mainly M1 and M2)under stimulation by various factors in the microenvironment,leading to different roles and functions.Macrophages play an important role in the pathophysiological mechanism of renal ischemia-reperfusion injury(RIRI).An excessive immune response will inevitably lead to tissue damage.M1 macrophages are pro-inflammatory cells involved in the clearance of pathogens,while M2-type macrophages have anti-inflammatory effects and participate in the repair and remodeling of renal tissue after RIRI.The balance between these macrophage phenotypes is thus an important factor affecting the outcome and treatment of RIRI.This review considers the pathophysiologic mechanism of macrophages in RIRI and the latest treatments from the perspective of macrophage polarization,with the aim of supporting further studies of the function of macrophage polarization in RIRI and adjusting the macrophage polarization process to improve RIRI treatment strategies.