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.

OBJECTIVE: To explore the mechanism by which ω-3 polyunsaturated fatty acids (hereinafter referred to as "ω-3") exert antioxidant stress protection and promote osteogenic differentiation in MC3T3-E1 cells, and to reveal the relationship between ω-3 and the key antioxidant stress pathway involving nuclear factor E2-related factor 2 (Nrf2) and NAD (P) H quinone oxidoreductase 1 (NQO1) in MC3T3-E1 cells. METHODS: The optimal concentration of H ₂O ₂ (used to establish the oxidative stress model of MC3T3-E1 cells in vitro) and the optimal intervention concentrations of ω-3 were screened by cell counting kit 8. MC3T3-E1 cells were divided into blank control group, oxidative stress group (H ₂O ₂), low-dose ω-3 group (H ₂O ₂+low-dose ω-3), and high-dose ω-3 group (H ₂O ₂+high-dose ω-3). After osteoblastic differentiation for 7 or 14 days, the intracellular reactive oxygen species (ROS) level was measured by fluorescence staining and flow cytometry, and the mitochondrial morphological changes were observed by biological transmission electron microscope; the expression levels of Nrf2, NQO1, heme oxygenase 1 (HO-1), Mitofusin 1 (Mfn1), and Mfn2 were detected by Western blot to evaluate the cells' antioxidant stress capacity; the expression levels of Runt-related transcription factor 2 (RUNX2) and osteocalcin (OCN) were detected by immunofluorescence staining and Western blot; osteogenic potential of MC3T3-E1 cells was evaluated by alkaline phosphatase (ALP) staining and alizarin red staining. RESULTS: Compared with the oxidative stress group, the content of ROS in the low and high dose ω-3 groups significantly decreased, and the protein expressions of Nrf2, NQO1, and HO-1 significantly increased ( P<0.05). At the same time, the mitochondrial morphology of MC3T3-E1 cells improved, and the expressions of mitochondrial morphology-related proteins Mfn1 and Mfn2 significantly increased ( P<0.05). ALP staining and alizarin red staining showed that the low-dose and high-dose ω-3 groups showed stronger osteogenic ability, and the expressions of osteogenesis-related proteins RUNX2 and OCN significantly increased ( P<0.05). And the above results showed a dose-dependence in the two ω-3 treatment groups ( P<0.05). CONCLUSION ω-3 can enhance the antioxidant capacity of MC3T3-E1 cells under oxidative stress conditions and upregulate their osteogenic activity, possibly through the Nrf2/NQO1 signaling pathway.
Oxidative Stress/drug effects* ; NF-E2-Related Factor 2/metabolism* ; NAD(P)H Dehydrogenase (Quinone)/metabolism* ; Animals ; Mice ; Osteogenesis/drug effects* ; Cell Differentiation/drug effects* ; Fatty Acids, Omega-3/pharmacology* ; Signal Transduction/drug effects* ; Osteoblasts/drug effects* ; Reactive Oxygen Species/metabolism* ; Cell Line ; Hydrogen Peroxide/pharmacology* ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Antioxidants/pharmacology* ; Heme Oxygenase-1/metabolism*

Sepsis is a lethal condition resulting from the host's dysregulated response, involving complex pathophysiological mechanisms, including the host's biphasic immune response and metabolic disturbances. Diagnosing and treating sepsis remain formidable challenges, with the absence of definitive biomarkers and effective therapeutic interventions to date. Animal models of sepsis are pivotal in unraveling the disease's pathogenesis and identifying potential treatments, playing a crucial role in enhancing our comprehension of its intrinsic nature. However, there is no animal model that can comprehensively and accurately simulate the complex pathophysiological process of human sepsis. This review discusses the widely used sepsis animal models, exploring their advantages and limitations in terms of pathogenesis, inflammatory response, pathophysiological changes, and organ dysfunction. It summarizes the application scenarios and latest research advancements of these models and provides an outlook on potential future improvements.
Sepsis/physiopathology* ; Animals ; Disease Models, Animal ; Humans

Objective:To explore the accuracy of a multi-task model based on vision Transformer for analyzing the three-dimensional (3D) upper airway and its subregions, and to evaluate its clinical applicability.Methods:According to the inclusion and exclusion criteria, cone-beam CT (CBCT) data of 10 patients [4 males and 6 females, (20.8±2.7) years] who had their first visit to the Department of Orthodontics in the Hospital of Stomatology, Wuhan University from January 2012 to January 2020 were retrospectively selected. The 3D slicer software was used to segment the upper airway and pharyngeal airway and measure their volumes as the gold standard. The Dolphin 3D software was used to segment the pharyngeal airway and its subregions and measure their volumes as the gold standard. A multi-task model based on vision Transformer developed by the research team for automatic segmentation and volume measurement of the upper airway and its subregions. All the measurements were conducted by the same attending physician. The Bland-Altman analysis and intraclass correlation coefficient ( ICC) were used to evaluate the consistency between the multi-task network and the gold standard in the upper airway segmentation and volume measurements, and the paired t test was used to compare the differences between the multi-tasking model and the gold standard. Results:The mean volume deviation of the upper airway segmented by multi-task model and 3D Slicer was -979.6 mm 3, and the ICC was 0.97. The mean volume deviation of the pharyngeal airway, nasopharynx, velopharynx, glossopharynx and hypopharynx segmented by multi-task network and Dolphin 3D were 2 069.5, -950.1, -823.6, -813.9 and 4 003.4 mm 3, respectively. In addition, ICC in pharyngeal airway, nasopharynx, velopharynx, glossopharynx and hypopharynx were 0.97, 0.94, 0.96, 0.96 and 0.69, respectively. Conclusions:The multi-task model based on vision Transformer produced different errors in the segmentation of 3D upper airway and its subregions. The segmentation of the nasopharynx, velopharynx and glossopharynx was in good agreement with the gold standard, while the segmentation of hypopharynx was poor, suggesting that the robustness and generalization of this model should be further enhanced.

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.

Objective Based on the process theory of stress effect,the structural equation model of the influencing factors of self-regulatory fatigue in maintenance hemodialysis patients is constructed,which provides theoretical bases and references for the formulation of intervention programs to relieve self-regulatory fatigue in patients.Method A total of 420 maintenance hemodialysis patients were surveyed using General Information Questionnaire,Self-Regulatory Fatigue Scale,Dialysis Symptom Index,Life Orientation Test-Revised,Perceived Social Support Scale,Brief Illness Perception Questionnaire and Medical Coping Styles Questionnaire.Results Total score of self-regulatory fatigue in maintenance hemodialysis patients was(49.52±10.93),and self-regulatory fatigue showed significant positive correlation with symptom distress,the illness perception,avoidance coping style,yieldly coping(r=0.476,0.428,0.303,0.611,all P＜0.01);self-regulatory fatigue showed significant negative correlation with perceived social support and dispositional optimism(r=-0.410,-0.652,all P＜0.01);it showed no significant correlation with facing coping(r=-0.032,P＞0.05).The Bootstrap analysis revealed that the mediation effect of yielding coping,dispositional optimism,perceived social support,and illness perception between symptom distress and self-regulatory fatigue was significant(95％CI:0.027～0.203).The overall effect of symptom distress on self-regulatory fatigue was(P＜0.001,95％CI:0.576～0.751);the direct effect was(P＜0.001,95％CI:0.170～0.357);the indirect effect was(P＜0.001,95％CI:0.332～0.485);the mediation effect accounted for 61.1％of the total effect value.Conclusion Maintenance hemodialysis patients have a high degree of self-regulatory fatigue,which needs to be further improved.Medical staff should timely identify and evaluate the symptom distress of patients,focus on guiding patients to adjust optimistic disease,provide patients with psychological guidance and stress coping strategies,reduce the negative coping behavior tendency,guide the patients correctly perceive support and care in social relations,help patients set up the correct disease cognition,thus reducing the patient's self-regulatory fatigue.

Objective:To explore the relationship between platform leadership, perceived overqualification, job crafting and career calling of clinical nurses, and provide references for formulating occupational calling strategies for clinical nurses.Methods:A total of 488 clinical nurses from Qingdao Hiser Hospital Affiliated of Qingdao University(Qingdao Traditional Chinese Medicine Hospital), Shandong University Qilu Hospital, and Qingdao Municipal Hospital were selected as the study subjects by the convenience sampling method from April to May 2023. A general data questionnaire, Platform Leadership Scale, Perceived Overqualification Scale, Job Crafting Scale, and Career Calling Scale were used to conduct a cross-sectional investigation on the research objects, and the relationship and mediating effect between platform leadership, perceived overqualification, job crafting, and career calling were analyzed.Results:Among the 488 clinical nurses, 79 were males and 409 were females, aged 23-51 (30.37 ± 6.40) years old. The scores of platform leadership, perceived overqualification, job crafting and career calling of clinical nurses were (86.12 ± 9.99), (21.79 ± 7.29), (70.61 ± 14.54) and (38.70 ± 7.54) points, respectively. The total effect of platform leadership on work engagement was 0.316. The mediating path of platform leadership to career calling included platform leadership→perceived overqualification→career calling; platform leadership→job crafting→career calling; platform leadership→perceived overqualification→job crafting→career calling. Three mediating effects accounted for 17.99%, 9.50% and 4.56% of the total effect, respectively.Conclusions:There is a chain-mediating effect of perceived overqualification and work remodeling on the relationship between platform leadership and the career calling of clinical nurses. Nursing managers should implement platform leadership to alleviate clinical nurses ′ perceived overqualification, improve job crafting, and then improve the level of clinical nurses ′ career calling.

Objective:To study the expression of stomatin-like protein 2(STOML2)in oral squamous cell carcinoma(OSCC)tissue and the effects of STOML2 on the tumorigenicity of OSCC cells(OSCCCs)in vitro and in vivo,and the related mechanism.Methods:The protein expression of STOML2 in OSCC and adjacent tissues of 56 patients was detected.OSCCCs SCC-15 were divided into 2 groups.Stom12-siRNA plasmid was transfected into the cells of experimental group and Mock-siRNA plasmid was transfected into the cells of control group.The mRNA and protein expression of STOML2,CDK4 and P16 in the cells was detected by qPCR and Western blot respectively.The cell cycle of the cells was detected by flow cytometry,and the proliferation of the cells was detected by CCK8 asay.The tumorigenicity of the cells was detected by subcutaneous tumor model in nude mice.Results:The positive rate of STOML2 in OSCC and adjacent tissues was 92.86％(52/56)and 8.93％(5/56)respectively(P＜0.001).After siRNA transfection,STOML2 mRNA expression in SCC-15 cells of experimental group and control group was(0.43±0.09)and(1.23±0.19),STOML2 protein ex-pression was(0.52±0.11)and(0.94±0.17)respectively.CDK4 expression was(0.33±0.13)and(1.18±0.17),P16 expression was(0.93±0.12)and(0.29±0.03),respectively.In CCK8 assay the absorbance of SCC-15 cells in experimental group and control group was(1.11±0.24)and(2.19±0.28),in flow cytometry the percentage of cells in G2/M phase was 35.72％±5.33％and 18.65％±3.71％(P＜0.05),respectively.In vivo test showed that the volume(μm3)of subcutaneous transplanted tumor was 1 192.07 ±250.9 and 2 280.5±600.1,the weight(g)of mice was 0.65±0.30 and 1.62±0.40,respectively.Conclusion:STOML2 expression increases in OSCC,STOML2 affects the tumorigenic ability of OSCCCs in vitro and in vivo by regulating P16 related pathways.

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.

Objective:To compare the early clinical outcomes, screw placement accuracy and supradjacent facet joint violation between O-arm navigated minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and TLIF for the treatment of lumbar spondylolisthesis.Methods:We retrospectively reviewed a cohort of low-grade single level lumbar spondylolisthesis patients who have received O-arm navigated MIS-TLIF or open-TLIF treatment from May 2018 to July 2023. There were 60 patients in MIS-TLIF group including 24 males and 36 females, and the average age was 41.0±13.9 years (18-73 years). There were 120 patients in open-TLIF group including 43 males and 77 females, and the average age was 41.6±12.6 years (18-69 years). The demographic and perioperative data of patients were recorded. Preoperative lumbar CT and MRI were evaluated to assess the grade of adjacent facet joint degeneration and fatty infiltration in the lumbar paraspinal muscles. The slip parameters were measured by lateral X-ray films before and after operation, and the screw placement accuracy and supradjacent facet joint violation were evaluated by postoperative CT. Patient reported outcomes, including Oswestry disability index (ODI) and visual analogue scale (VAS) were collected preoperatively and 3 months postoperatively.Results:There was no significant difference in demographic data, adjacent facet joint degeneration, fatty infiltration of lumbar paraspinal muscles and preoperative ODI and VAS scores between the two groups ( P>0.05). The operation time in MIS-TLIF group (223.3±23.0 min) was significantly longer than that in open-TLIF group (187.0±30.5 min, t=8.130, P<0.001), while the intraoperative blood loss (150.7±56.8 ml vs. 392.8±161.5 ml, t=-11.253, P<0.001), postoperative drainage (60.4±19.8 ml vs. 215.2±57.2 ml, t=-20.328, P<0.001) and postoperative hospital stay (4.5±1.7 d vs. 8.4±2.5 d, t=-10.769, P<0.001) in MIS-TLIF group were significantly less. The 3-month postoperative VAS back pain of the MIS-TLIF group (2.0±1.7) was lower than the open-TLIF group (3.2±2.0, t=-3.956, P<0.001). Both groups had similar slip reduction results ( P>0.05). The accuracy of the pedicle screw placement in MIS-TLIF group (98.8%) was better than open-TLIF group (92.3%, P<0.001). The incidence of supradjacent facet joint violation in the MIS-TLIF group was lower than open-TLIF group (27.5% vs. 51.7%, χ 2=19.111, P<0.001). There were no notable surgical complications in MIS-TLIF group except temporary submuscular hematoma in one patient. In open-TLIF group, dural tear occurred in three patients intraoperatively, one patient experienced transient L 5 nerve root palsy after surgery and one patient had wound superficial tissue infection. All the complications were successfully treated with conservative measures. Conclusion:O-arm navigated MIS-TLIF had better short-term clinical effect and higher accuracy of pedicle screw placement in treating lumbar spondylolisthesis.