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.

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

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.

OBJECTIVES: To investigate the inhibitory effect of multimerin-2 (MMRN2) overexpression on growth and metastasis of cutaneous melanoma cells. METHODS: Clinical data of patients with cutaneous melanoma were obtained from the GEO database to compare MMRN2 expressions between normal and tumor tissues. A protein-protein interaction network was constructed using the STRING database, and the intersecting genes from GEPIA2.0 were subjected to GO and KEGG enrichment analysis. The prognostic relevance of MMRN2 expression level was assessed using Cox regression and "timeROC". The correlations of MMRN2 expression level with immune infiltration and angiogenesis-related genes were analyzed using GSCA database and the ssGSEA algorithm. Colony-forming assay, Transwell assay, and wound healing assay were used to examine the changes in proliferation and migration of cultured cutaneous melanoma cells following MMRN2 knockdown. In a mouse model bearing cutaneous melanoma xenograft, the effect of MMRN2 knockdown on vital organ pathologies, survival of the mice and GM-CSF, CXCL9, and TGF‑β1 protein expressions were analyzed. RESULTS: MMRN2 was significantly upregulated in metastatic cutaneous melanoma (P<0.001). Protein interaction network analysis identified 15 intersecting genes, which were enriched in endothelium development and cell-cell junctions. In patients with cutaneous melanoma, a high MMRN2 expression was correlated with a poor prognosis, an advanced T stage, a greater Breslow depth, and ulceration (P<0.05). MMRN2 expression level was strongly correlated with 24 immune cell types (P<0.001), fibroblasts, endothelial cells, and expressions of the pro-angiogenic genes (KCNJ8, SLCO2A1, NRP1, and COL3A1; P<0.001). In cultured B16F10 cells, MMRN2 knockdown significantly suppressed cell proliferation, migration and invasion and caused remo-deling of the immunosuppressive microenvironment. CONCLUSIONS MMRN2 overexpression drives progression of cutaneous melanoma by enhancing tumor metastasis, angiogenesis and immune evasion, highlighting its potential as a therapeutic target for melanomas.
Humans ; Melanoma/metabolism* ; Animals ; Cell Movement ; Prognosis ; Skin Neoplasms/metabolism* ; Mice ; Cell Proliferation ; Neoplasm Invasiveness ; Cell Line, Tumor ; Protein Interaction Maps

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.

ObjectiveTo assess the current status of medical waste management in Jinshan District of Shanghai, China, to identify existing issues, and to provide a scientific basis for formulating targeted strategies. MethodsData were collected from the routine supervision and inspection records of the Jinshan District Health Commission Supervision Institute from 2017 to 2021, covering all aspects of medical waste management, including collection, classification, transportation, storage, and administrative penalties. ResultsThe compliance rates for the establishment of institutional frameworks, staffing, internal handover, and registration in medical and healthcare institutions all exceeded 95.00%. However, only 2.31% of the medical and healthcare institutions met the 48-hour storage limit requirement for medical waste. Private institutions had significantly lower compliance rates (P<0.05) in aspects such as proper classification and collection, maintaining records for three years, adhering to the 48-hour storage limit, refraining from commercial transactions, timely disinfection and cleaning, and implementing emergency measures for waste loss. Compliance rates also varied among different types of institutions regarding the establishment of temporary storage facilities and the implementation of the transfer manifest system, with community healthcare institutions exhibiting relatively lower compliance rates (P<0.05). Over the past five years, private medical and healthcare institutions accounted for 63.33% of administrative penalty cases. ConclusionWhile medical waste management in Jinshan District, Shanghai, has gradually become more standardized, challenges remain. To address the issue of medical waste being stored for over 48 hours, medical waste transfer stations should be established to improve transfer efficiency and ensure complete waste collection. Additionally, for private and community healthcare institutions, weak links in management should be addressed by establishing medical waste quality control teams, enhancing supervision through digital tools, and optimizing management processes to comprehensively elevate medical waste management.

OBJECTIVE: To investigate the clinical characteristics and genetic etiology in a fetus with 12q14 microdeletion syndrome. METHODS: A fetus diagnosed with 12q14 microdeletion syndrome at Wenzhou People's Hospital in July 2019 was selected as the study subject. The fetus was from a twin pregnancy by in vitro fertilization-embryo transfer, with ultrasound findings including growth restriction, cleft lip/palate, ventricular septal defect, tricuspid regurgitation, and pericardial effusion. Clinical data and family history were collected. Amniotic fluid sample was collected from both twins, and peripheral blood samples were obtained from their parents. Amniocytic karyotyping analysis and chromosomal microarray analysis (CMA) were performed, and familial validation was conducted. This study was approved by the Medical Ethics Committee of Wenzhou People's Hospital (Ethics No.: KY-202408-034). RESULTS: Prenatal ultrasound showed no significant abnormality in one of the twins, whilst the other twin exhibited severe growth restriction accompanied by cleft lip/palate, ventricular septal defect, tricuspid regurgitation, and pericardial effusion. Karyotyping and CMA analyses of first twin showed no abnormalities, whilst the second twin had a chromosomal karyotype of 46,XN,t(3;12)(q26.3;q14), and CMA revealed a 4.9 Mb deletion in the 12q14.3-q15 region (arr[hg19]12q14.3q15(65,574,059_70,488,106)x1). Karyotyping and CMA analyses of both parents revealed no abnormalities, confirming that the fetus deletion was de novo in origin. Literature review suggested that prenatal diagnosis of 12q14 microdeletion syndrome has been extremely rare. CONCLUSION The fetus was diagnosed with 12q14 microdeletion syndrome. This de novo deletion may have dervied from chromosomal translocation. As a first-tier prenatal diagnostic technique, CMA can effectively detect microdeletion/microduplications missed by conventional karyotyping analysis.
Humans ; Female ; Pregnancy ; Chromosome Deletion ; Chromosomes, Human, Pair 12/genetics* ; Karyotyping ; Adult ; Prenatal Diagnosis ; Chromosome Disorders/diagnosis* ; Ultrasonography, Prenatal ; Fetus ; Male

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.

Objective:To analyze the changes and structural variations in hospitalization costs for patients with lung malignancies after the implementation of diagnosis-intervention packet (DIP) payment system, and to evaluate its effectiveness.Methods:Data from the first page of medical records and hospitalization cost data from the hospital information system of a tertiary general hospital in Henan Province were extracted for patients diagnosed with lung malignancies from 2020 to 2023. The data were divided into pre-implementation group (2020—2021) and post-implementation group (2022—2023) based on the implementation time of DIP. Chi-square test, t test, and Wilcoxon rank-sum test were used to analyze the differences in basic characteristics and hospitalization costs of patients with lung malignancies before and after the implementation of DIP. Grey relational analysis was employed to examine the internal associations between total hospitalization costs and various cost components. Structural variation analysis was used to assess the changes in the structure of hospitalization costs after the implementation of DIP. Results:A total of 14 587 hospitalized patients with lung malignancies were included, with 6 807 cases in the pre-implementation group and 7 780 cases in the post-implementation group. The average length of hospital stay decreased from (13.17±6.74) days before implementation to (12.02±6.49) days after implementation ( P<0.05). The proportion of level-four surgeries increased from 46.4% to 57.0% ( P<0.05). The average hospitalization cost per patient with lung malignancies decreased from 56 952 yuan before DIP implementation to 55 560 yuan after implementation ( P<0.05). For patients with lung malignancies diagnosed as C34.1, C34.2, C34.3, and C34.8, the top four cost components most strongly associated with total hospitalization costs were treatment costs, material costs, comprehensive medical service costs, and diagnostic costs, with correlation coefficients all>0.80. For patients with C34.9, the top four cost components most strongly associated with total hospitalization costs were treatment costs, comprehensive medical service costs, diagnostic costs, and Western medicine costs, with correlation coefficients>0.95. For patients diagnosed as C34.1, C34.2, C34.3, and C34.9, diagnostic costs, Western medicine costs, and material costs contributed significantly to the structural variation of hospitalization costs, with contribution rate of structure variation all exceeding 75%, among which Western medicine costs and material costs showed negative variation. For patients diagnosed as C34.8, treatment costs, Western medicine costs, and material costs contributed significantly to the structural variation of hospitalization costs, with contribution rate of structure variation all exceeding 80%, among which Western medicine costs showed negative variation. Conclusions:The implementation of DIP reduced the hospitalization costs for patients with lung malignancies, optimized the structure of hospitalization costs, improved the efficiency of medical services, and promoted the rational allocation of medical resources.

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.