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*

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 investigate the role of an inflammatory microenvironment induced by Porphyromonasgingivalis ( P. gingivalis) in the occurrence of esophageal squamous cell carcinoma (ESCC) in mice. Methods:A total of 180 C57BL/6 mice were randomly divided into 6 groups, i.e. control group, P. gingivalis group, 4NQO group, 4NQO + P. gingivalis group, 4NQO + P. gingivalis + celecoxib group, and 4NQO + P. gingivalis + antibiotic cocktail (ABC, including metronidazole, neomycin, ampicillin, and vancomycin) group, with 30 mice in each group, using the random number table. All mice were normalized by treatment with ABC in drinking water for 2 weeks. In the following 2 weeks, the mice in the control group and the P. gingivalis group were given drinking water, while the other 4 groups were treated with 30 μg/ml 4NQO in the drinking water. In weeks 11-12, the mice in the P. gingivalis group, the 4NQO + P. gingivalis group, the 4NQO + P. gingivalis + celecoxib group, and the 4NQO + P. gingivalis + ABC group were subjected to ligation of the second molar in oral cavity followed by oral P. gingivalis infection thrice weekly for 24 weeks in weeks 11-34. In weeks 13-34, the mice in 4NQO + P. gingivalis+celecoxib group and 4NQO + P. gingivalis + ABC group were administered with celecoxib and ABC for 22 weeks, respectively. At the end of 34 weeks, gross and microscopic alterations were examined followed by RT-qPCR and immunohistochemistry to examine the expression profiles of inflammatory- and tumor-molecules in esophagi of mice. Results:At 34 weeks, 4NQO treatment alone did not affect the foci of papillary hyperproliferation, diseased area, and the thickness of the esophageal wall, but significantly enhanced the foci of hyperproliferation (median 1.00, P＜0.05) and mild/moderate dysplasia (median 2.00, P＜0.01). In addition, the expression levels of IL-6 [8.35(3.45,8.99)], IL-1β [6.90(2.01,9.72)], TNF-α [12.04(3.31,14.08)], c-myc [2.21(1.80,3.04)], pSTAT3, Ki-67, and pH2AX were higher than those in the control group. The pathological changes of the esophageal mucosa were significantly more overt in the 4NQO + P. gingivalis group in terms of the foci of papillary hyperproliferation (median 2.00), diseased area (median 2.51 mm 2), the thickness of the esophageal wall (median 172.52 μm), the foci of hyperproliferation (median 1.00, P＜0.05), and mild/moderate dysplasia (median 1.00, P＜0.01). In mice of the 4NQO + P. gingivalis group, the expression levels of IL-6 [12.27(5.35,22.08)], IL-1β [13.89(10.04,15.96)], TNF-α [19.56(6.07,20.36)], IFN-γ [11.37(8.23,20.07)], c-myc [2.62(1.51,4.25)], cyclin D1 [4.52(2.68,7.83)], nuclear pSTAT3, COX-2, Ki-67, and pH2AX were significantly increased compared with the mice in the control group. In mice of the 4NQO + P. gingivalis group, the diseased area, invasive malignant foci as well as pSTAT3 and pH2AX expression were significantly blunted by celecoxib. Treatment with ABC markedly reduced the papillary hyperproliferative foci, invasive malignant foci, and pSTAT3 expression but not pH2AX. Conclusions:P. gingivalis promotes the occurrence of esophageal squamous cell carcinoma in mice by inducing an inflammatory microenvironment primed with 4NQO induced DNA damage. Clearance of P. gingivalis with ABC or anti-inflammatory intervention holds promise for prevention of esophageal squamous cell malignant pathogenesis via blockage of IL-6/STAT3 signaling and amelioration of inflammation.

BackgroundPatients demonstrating depressive disorder with psychotic symptoms often have increased risk of death and poor prognosis. A large amount of research has explored the factors influencing psychotic symptoms in adult patients with depressive disorder， but few has focused on adolescent patients. ObjectiveTo explore the influencing factors of psychotic symptoms in adolescent patients with depressive disorder， so as to provide references for early screening and intervention in clinic. MethodsA total of 96 adolescent patients who met the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） for depressive disorder and were seen in the psychiatry departments of Chaohu Hospital of Anhui Medical University and The Fourth People's Hospital of Hefei from September 2022 to January 2023 were included. Another 56 healthy individuals from the health examination center of Chaohu Hospital of Anhui Medical University were concurrently recruited as control group. Patients were assigned into psychotic group （n=32） and non-psychotic group （n=64） according to the presence or absence of psychotic symptoms. Hamilton Depression Scale-24 item （HAMD-24）， Positive and Negative Syndrome Scale （PANSS）， Positive and Negative Suicide Ideation （PANSI） and Childhood Trauma Questionnaire-Short Form （CTQ-SF） were used for evaluation. Plasma brain-derived neurotrophic factor （BDNF） concentration was obtained using Meso Scale Discovery electrochemiluminescence assay. Pearson and Spearman correlation analysis were adopted to determine the correlation of PANSS positive symptom subscale score with plasma BDNF concentration and clinical characteristics of adolescent depression patients with psychotic symptoms. Binary Logistic regression analysis was used to identify the factors influencing the presence of psychotic symptoms in adolescent patients with depressive disorder， and multiple linear regression analysis was utilized to screen the factors affecting the severity of psychotic symptoms. ResultsThe plasma BDNF concentration of adolescent patients with depressive disorder was lower than that of control group （t=-3.080， P<0.01）.The plasma BDNF concentration of psychotic group was lower than that of non-psychotic group （t=2.418， P<0.05）， while the body mass index （BMI） PANSI scores， CTQ-SF scores and HAMD-24 total scores were all higher than those of non-psychotic group （t=-2.024， -2.530， -2.187， -4.977， P<0.05 or 0.01）. Correlation analysis showed that PANSS positive symptom subscale scores were negatively correlated with anxiety/somatization factor score and weight factor score in HAMD-24 of psychotic group （r=-0.438， -0.498， P<0.05 or 0.01）. Binary Logistic regression showed that BMI， plasma BDNF concentration， HAMD-24 total scores and cognitive dysfunction factor score were the influencing factors of psychotic symptoms in adolescent patients with depressive disorder. Multiple linear regression analysis demonstrated that weight factor scores （β=-0.349， P<0.05） and anxiety/somatization factor score （β=-0.433， P<0.05） in HAMD-24 were the factors influencing the severity of psychotic symptoms. ConclusionHigh BMI， low plasma BDNF concentration， severe depressive symptoms and cognitive dysfunction may be the risk factors of psychotic symptoms in adolescent patients with depressive disorder， furthermore， BMI and anxiety symptoms are found to be associated with the severity of psychotic symptoms. ［Funded by Scientific Research Fund Project of Anhui Institute of Translational Medicine （number， 2022zhyx-B01）； Central Finance Supported Provincial Key Clinical Specialty Construction Project of Anhui Province in 2019］

Objective:To investigate the role of an inflammatory microenvironment induced by Porphyromonasgingivalis ( P. gingivalis) in the occurrence of esophageal squamous cell carcinoma (ESCC) in mice. Methods:A total of 180 C57BL/6 mice were randomly divided into 6 groups, i.e. control group, P. gingivalis group, 4NQO group, 4NQO + P. gingivalis group, 4NQO + P. gingivalis + celecoxib group, and 4NQO + P. gingivalis + antibiotic cocktail (ABC, including metronidazole, neomycin, ampicillin, and vancomycin) group, with 30 mice in each group, using the random number table. All mice were normalized by treatment with ABC in drinking water for 2 weeks. In the following 2 weeks, the mice in the control group and the P. gingivalis group were given drinking water, while the other 4 groups were treated with 30 μg/ml 4NQO in the drinking water. In weeks 11-12, the mice in the P. gingivalis group, the 4NQO + P. gingivalis group, the 4NQO + P. gingivalis + celecoxib group, and the 4NQO + P. gingivalis + ABC group were subjected to ligation of the second molar in oral cavity followed by oral P. gingivalis infection thrice weekly for 24 weeks in weeks 11-34. In weeks 13-34, the mice in 4NQO + P. gingivalis+celecoxib group and 4NQO + P. gingivalis + ABC group were administered with celecoxib and ABC for 22 weeks, respectively. At the end of 34 weeks, gross and microscopic alterations were examined followed by RT-qPCR and immunohistochemistry to examine the expression profiles of inflammatory- and tumor-molecules in esophagi of mice. Results:At 34 weeks, 4NQO treatment alone did not affect the foci of papillary hyperproliferation, diseased area, and the thickness of the esophageal wall, but significantly enhanced the foci of hyperproliferation (median 1.00, P＜0.05) and mild/moderate dysplasia (median 2.00, P＜0.01). In addition, the expression levels of IL-6 [8.35(3.45,8.99)], IL-1β [6.90(2.01,9.72)], TNF-α [12.04(3.31,14.08)], c-myc [2.21(1.80,3.04)], pSTAT3, Ki-67, and pH2AX were higher than those in the control group. The pathological changes of the esophageal mucosa were significantly more overt in the 4NQO + P. gingivalis group in terms of the foci of papillary hyperproliferation (median 2.00), diseased area (median 2.51 mm 2), the thickness of the esophageal wall (median 172.52 μm), the foci of hyperproliferation (median 1.00, P＜0.05), and mild/moderate dysplasia (median 1.00, P＜0.01). In mice of the 4NQO + P. gingivalis group, the expression levels of IL-6 [12.27(5.35,22.08)], IL-1β [13.89(10.04,15.96)], TNF-α [19.56(6.07,20.36)], IFN-γ [11.37(8.23,20.07)], c-myc [2.62(1.51,4.25)], cyclin D1 [4.52(2.68,7.83)], nuclear pSTAT3, COX-2, Ki-67, and pH2AX were significantly increased compared with the mice in the control group. In mice of the 4NQO + P. gingivalis group, the diseased area, invasive malignant foci as well as pSTAT3 and pH2AX expression were significantly blunted by celecoxib. Treatment with ABC markedly reduced the papillary hyperproliferative foci, invasive malignant foci, and pSTAT3 expression but not pH2AX. Conclusions:P. gingivalis promotes the occurrence of esophageal squamous cell carcinoma in mice by inducing an inflammatory microenvironment primed with 4NQO induced DNA damage. Clearance of P. gingivalis with ABC or anti-inflammatory intervention holds promise for prevention of esophageal squamous cell malignant pathogenesis via blockage of IL-6/STAT3 signaling and amelioration of inflammation.