To summarize the distribution characteristics of human papillomavirus(HPV) infection types in patients with cervical squamous intraepithelial lesion(SIL) and cervical cancer(CC), and to explore the impact of HPV vaccination, HPV infection types, and general clinical data on different grades of cervical lesions.

Objective To explore risk factors of sodium-dependent glucose transporters 2 （SGLT2） inhibitor-associated euglycemic diabetic ketoacidosis （euDKA） and to construct a risk prediction model. Methods A retrospective analysis was performed on the clinical data of type 2 diabetes patients treated with SGLT2 inhibitors in Dongnan Hospital of Xiamen University from January 2020 to December 2023, including age, gender and course of diabetes. The risk factors of SGLT2 inhibitor-associated euDKA were analyzed by univariate analysis and multivariate Logistic regression, and a prediction model was established. According to the receiver's operating characteristic （ROC） curve, the area under the curve （AUC） and the optimal critical value of the prediction model were determined. The prediction model was subjected to both internal and external validation. Results A total of 119 patients with type 2 diabetes treated with SGLT2 inhibitors were included in this study. Among them, there were 98 cases without euDKA （non-euDKA group）and 21 cases with euDKA （euDKA group）. Multivariate Logistic regression analysis showed the DKA history (OR=114.153), appetite or diet decreased three days before admission (OR=21.774), elevated neutrophil count (OR=2.056) and pre-hospital adjustment of hypoglycemic agents (OR=45.745) were independent factors to increase risks of euDKA associated with SGLT2 inhibitors （P<0.05）. Surgical history before admission was an independent factor to reduce this risk （OR=0.007, P<0.05）. By establishing the calculation formula of the prediction model = neutrophil count+6.571 （DKA history）−6.874 （surgical history before admission）+4.273 （appetite or diet decreased three days before admission）+5.302 （pre-hospital adjustment of hypoglycemic drugs）, the ROC curve was drawn. The AUC of the ROC of the prediction model was 0.982 （95%CI: 0.961-1.000, P<0.001）, with accuracy of 94.96%, sensitivity of 0.905, specificity of 0.959 and a critical value of 7.405. The AUC of ROC curve after the model’s ten-fold cross validation was 0.930. And the accuracy of the external validation of the prediction model was 85.29%. Conclusion The DKA history, appetite or diet decreased three days before admission, elevated neutrophil count and pre-hospital adjustment of hypoglycemic agents increased the risk of SGLT2 inhibitor-associated euDKA, while the surgical history before admission reduced this risk. The risk prediction model constructed on this basis could better predict the risk of SGLT2 inhibitor-associated euDKA.

AIM: To analyze the clinical outcomes of cyclosporine combined with lacrimal plug in the treatment of dry eye in patients with primary Sjögren's syndrome.METHODS: The clinical data of 60 patients(120 eyes)who were admitted to the ophthalmology department and rheumatology and immunology department of Baoding No.1 Central Hospital and were diagonosed with siogren's syndrome dry eye after multidisciplinary consultation from June 2022 to September 2023 were retrospectively analyzed. All the patients received regular treatment of primary Sjögren's syndrome, and they were divided into three groups according to treatment methods: A, B and C, with 20 cases(40 eyes)in each group. The group A received 0.3% sodium hyaluronate eyedrops, the group B received 0.3% sodium hyaluronate eyedrops plus 0.05% cyclosporine eyedrops, and the group C received 0.3% sodium hyaluronate eyedrops plus 0.05% cyclosporine eyedrops combined with binocular lacrimal plugs. The ocular surface disease index(OSDI)score, conjunctival hyperemia score, tear film breakup time(BUT), tear meniscus height(TMH), corneal fluorescein staining(FL)score and tear secretion of the three groups of patients were compared before and at 4, 8 and 12 wk after treatment. The contents of inflammatory factors such as interleukin-6(IL-6), tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in tears were detected before and at 12 wk after treatment.RESULTS: At 4, 8 and 12 wk after treatment, the scores of OSDI, conjunctival hyperemia score and FL in the three groups of patients were lower than those before treatment, and the BUT, TMH and tear secretion were higher than those before treatment(all P<0.001). The OSDI score of the group C was lower than that of the group A and B, and the group B was lower than the group A(all P<0.001). The BUT, TMH and tear secretion of the group C were higher than those of the group A and B, with the group B higher than the group A(all P<0.001). At 12 wk after treatment, the levels of IL-6, TNF-α and IL-1β in the tears of the three groups of patients were lower than those before treatment, with the group C lower than the group A and B, and the group B lower than the group A(all P<0.001). There was no statistical significant difference in the incidence of adverse reactions among the three groups of patients(P>0.05).CONCLUSION: The combined use of cyclosporine and lacrimal plug is safe and effective in improving the clinical symptoms of patients with moderate and severe dry eye, promoting the function of tear film and cornea, increasing tears secretion, and reducing the level of tear inflammatory factors.

This study aims to investigate the potential of oncolytic nanoparticles encapsulating Coxsackievirus A21 (CVA21) full-genome mRNA (CVA21@ONP) to resurrect CVA21 and induce apoptosis in host cells, as well as the antitumor immune effects of CVA21@ONP in immunocompetent tumor-bearing BALB/c mice. We used lipid nanoparticles (LNPs) to encapsulate CVA21 full-genome mRNA, thus preparing CVA21@ONP. The killing efficacy of CVA21@ONP was determined by the plaque assay and cell counting kit-8 (CCK-8), and the apoptosis in HT29 and CT26-iRFP cells was evaluated by flow cytometry. Mice were administrated with CVA21@ONP at high and low doses intratumorally, and the growth of tumors expressing infra-red fluorescent protein (iRFP) was monitored. Additionally, the types and changes of immune cells in the spleen were analyzed by flow cytometry. The results demonstrated that CVA21@ONP successfully resurrected CVA21 in both HT29 and U87MG cells. The plaque assay revealed robust killing effects of CVA21@ONP against both human and murine cell lines, and flow cytometry results showed increased early and late apoptotic cells. Notably, intratumoral detection revealed significantly down-regulated expression of iRFP in both high- and low-dose CVA21@ONP groups. Flow cytometry results further indicated that CVA21@ONP treatment effectively reduced the levels of immunosuppressive cells, including myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), in the spleen, while enhancing T cell-dependent antitumor immune responses. These findings suggest that CVA21@ONP can replicate and survive extensively both in vitro and in vivo, activating the immune system of mice administrated with CVA21@ONP to target cells at the tumor site, thereby remodeling the tumor immune microenvironment and accelerating the suppression or even complete regression of tumors. The oncolytic performance of CVA21@ONP has been verified through intratumoral injection administration in this study, aimed at further exploring its therapeutic potential and promoting the development of the field of tumor treatment.
Animals ; Nanoparticles/chemistry* ; Mice ; Mice, Inbred BALB C ; Humans ; Apoptosis ; Oncolytic Viruses/genetics* ; Oncolytic Virotherapy/methods* ; Cell Line, Tumor ; RNA, Messenger/genetics* ; HT29 Cells

Objective To investigate the ameliorative effect and potential mechanism of Cyclocaryae Paliuri Folium in sodium palmitate-induced lipid deposition in HepG2 cells.Methods The effect of sodium palmitate and lyophilized powder of Cyclocaryae Paliuri Folium on the viability of HepG2 cells was determined by the CCK-8 method to determine the subsequent dosage administered.The HepG2 cells were divided into blank group,model group,pioglitazone group and Cyclocaryae Paliuri Folium low-,medium-and high-dosage group,the lipid deposition model of HepG2 cells was established using 350 μmol/L sodium palmitate,the medication group were given pioglitazone and low-,medium-and high-dosage of Cyclocaryae Paliuri Folium(100,250,500 μg/mL)for 12 h respectively.The intracellular lipid deposition was observed by Nile red staining and BODIPY493/503 fluorescent probe staining,the content of TNF-α and IL-6 in supernatant of cell culture medium were detected by ELISA,Western blot was used to detect PI3K,Akt,sterol-regulatory element binding protein-1(SREBP-1),fatty acid synthase(FAS),Bcl-2,Bax protein expression,qPCR was used to detect the mRNA expression of adipose triglyceride lipase(ATGL)and CD36.Results Compared with the blank group,the lipid deposition of HepG2 cells in the model group increased,TNF-α and IL-6 contents in the supernatant of cell culture medium significantly increased(P<0.01),the protein expressions of p-PI3K,p-Akt,SREBP-1,FAS and Bax in cells significantly increased,while the protein expression of Bcl-2 significantly decreased(P<0.01),the mRNA expression of ATGL significantly decreased,and the mRNA expression of CD36 significantly increased(P<0.01).Compared with the model group,the intracellular lipid deposition of the pioglitazone group and Cyclocaryae Paliuri Folium groups improved to varying degrees,the contents of TNF-α and IL-6 in the cell supernatant decreased,the expressions of p-PI3K,p-Akt,SREBP-1,FAS and Bax proteins decreased,the expression of Bcl-2 protein increased,the expression of ATGL mRNA increased,and the expression of CD36 mRNA decreased,with statistical significance in pioglitazone group and Cyclocaryae Paliuri Folium high-dosage group(P<0.05,P<0.01).Conclusion Cyclocaryae Paliuri Folium may ameliorate sodium palmitate-induced lipid deposition in HepG2 model cells by modulating the PI3K/Akt/SREBP-1/FAS signaling pathway and affecting triacylglycerol metabolism.

Objective To observe the effect of tuina on glutamate content and synaptic ultrastructure in spinal dorsal horn of rats with chronic sciatic nerve compression injury;To explore the potential mechanism of tuina regulation of the SNAP25/VGLUT2 pathway in alleviating lumbar disc herniation.Methods A chronic sciatic nerve compression injury model was used to simulate neuropathic pain in lumbar disc herniation.24 SD rats were randomly divided into blank group,model group and tuina group,with 8 rats in each group.From the 4th day after modeling,the tuina group was intervened with the tuina method for 10 minutes once a day for 14 consecutive days.The paw withdrawal threshold(PWT)and paw withdrawal latency(PWL)of rats in each group on the day before modeling,and the 4th,10th,14th and 17th days after modeling were detected.The spinal cord tissue of the modeling side was taken,synaptic ultrastructure of spinal dorsal horn neurons was observed using transmission electron microscopy,immunofluorescence staining was used to detect the expression of NR2A in the spinal dorsal horn,Western blot was used to detect the expression of SNAP25 protein in the spinal dorsal horn,immunohistochemistry was used to detect the expression of VGLUT2 in the spinal dorsal horn,ELISA was used to detect the content of glutamate in the spinal dorsal horn.Results Compared with the blank group,PWT and PWL of the model group were significantly reduced on the 4th,10th,14th and 17th days after modeling(P<0.001),with accumulation of vesicles in the presynaptic membrane of the dorsal horn of the spinal cord,increase in the area of the postsynaptic dense zone,and enlargement of the synaptic cleft,while the protein expressions of NR2A,SNAP25 and VGLUT2 in the spinal dorsal horn increased(P<0.05,P<0.001),and the content of glutamate increased(P<0.001).Compared with the model group,PWT and PWL of the tuina group rats significantly increased on the 10th,14th and 17th days after modeling(P<0.001),synaptic vesicles were evenly distributed,the area of the postsynaptic dense zone decreased,and the synaptic cleft decreased,while the protein expressions of NR2A,SNAP25 and VGLUT2 in the spinal dorsal horn decreased(P<0.05,P<0.001),and the content of glutamate decreased(P<0.01).Conclusion Tuina may regulate the content of glutamate through the SNAP25/VGLUT2 pathway in the spinal dorsal horn,improve the synaptic ultrastructure of neurons,and have an analgesic effect on lumbar disc herniation.

Aim To explore the effect and mechanism of annexin A1 mimic peptide Ac2-26 on ferroptosis in hu-man umbilical vein endothelial cells(HUVEC).Methods Induction of HUVEC ferroptosis was achieved by the clas-sical ferroptosis agonist RSL3,with subsequent intervention by the annexin A1 mimtic peptide Ac2-26.The cell number and viability were detected by CCK-8 kit,the levels of malondialdehyde(MDA)and glutathione(GSH)were detected by ELISA,the expression of ferroptosis-related molecules and adhesion molecules was detected by Western blot,the lipid re-active oxygen species(ROS)levels were detected by C11-BODIPY fluorescent probe,and the mitochondrial reactive oxy-gen species(mtROS)levels were detected by MitoSOX probe.FeRhoNOX-1 fluorescent probe was used to detect intra-cellular Fe2+content,perspective microscopy was used to observe mitochondrial morphology,JC-1 fluorescent probe was used to detect mitochondrial membrane potential,kit was used to detect ATP levels,the Scratch assay was used to detect cell migration ability,and nitrate reductase assay was used to detect nitric oxide(NO)level.Results Ac2-26 inhibi-ted RSL3-induced decrease in HUVEC viability,up-regulated the expression of suppressor of ferroptosis proteolytic carrier family 7 member 11(SLC7A11),GPX4,and ferritin heavy chain 1(FTH1),increased the GSH content,decreased the MDA content,reduced the generation of intracellular lipid ROS,and decreased the intracellular Fe2+aggregation(P＜0.05 or P＜0.01);Ac2-26 inhibited RSL3-induced damage to HUVEC mitochondrial morphology and function,up-regulated ATP content(P＜0.05)and mitochondrial membrane potential(P＜0.001);Ac2-26 inhibited RSL3-induced decrease in HUVEC migratory ability,up-regulated NO levels,inhibited intercellular adhesion molecule-1(ICAM-1)and interleukin-1β(IL-1β)protein expression(P＜0.05 or P＜0.01).Conclusion Ac2-26 inhibits RSL3-induced ferroptosis in HUVEC and maintains mitochondrial morphology and function,as well as HUVEC function.

OBJECTIVES: To investigate the effect of age-friendly social and family care environment on the long-term care (LTC) services for the disabled elderly people. METHODS: A questionnaire-based survey was conducted among disabled elderly people in three cities of Zhejiang province from June to August 2022, involving 311 subjects from Ningbo city (LTC service insurance pilot site, insured group) and 542 subjects from Hangzhou and Quzhou cities (uninsured group). The service provisions, including ensuring daily activities, preventive healthcare, and satisfying spiritual comfort, were compared among the groups. The family friendly care environment was evaluated with the Family Function Scale and assistance of daily activities, financial support and emotional comfort. The social friendly care environment was measured with the revised WHO recommended age-friendly city environmental framework, including accessibility guarantee environment, information dissemination environment, social participant environment, and life security environment. After controlling for covariates such as sociodemographic, elderly care status, and health risk characteristics, the impact of environment on the effectiveness of service provision of LTC insurance was explored by multiple logistic regression analysis. The mediating and moderating effects were tested to explore the role of age-friendly care environment. A fixed effects model was used to test the service provision effects of LTC insurance policy. RESULTS: Disabled elderly with LTC insurance had a higher proportion of their preventive health care and spiritual comfort needs met. Additionally, a multifactorial analysis found a significant positive association between LTC insurance and meeting the spiritual comfort needs. Compared with insured group (Ningbo city), disabled elderly people in Hangzhou urban area (OR=0.45, 95%CI:0.27-0.74, P<0.01) and Quzhou rural area (OR=0.21, 95%CI:0.12-0.37, P<0.01) were more likely to feel unsatisfied with spiritual comfort. The results of mediation analysis showed that the scores of accessibility guarantee environment (OR=1.22, 95%CI:1.02-1.45, P<0.05), information dissemination environment (OR=1.19, 95%CI:1.02-1.39, P<0.05), and social participation environment (OR=1.40, 95%CI:1.17-1.67, P<0.01) in a socially friendly care environment were positively correlated with the satisfaction rate of mental comfort services. The results of the moderation effect analysis indicated that a socially friendly care environment (OR=1.46, 95%CI:1.16-1.84, P<0.01) could compensate for the difference in effectiveness between insured (Ningbo) and uninsured (Hangzhou and Quzhou) areas of LTC insurance. A fixed effect model confirmed the policy chain of LTC insurance policy-social friendly care environment-mental health service satisfaction. CONCLUSIONS The implementation of LTC insurance has improved service accessibility, making disabled elderly people feel "seen and valued", and generating psychological and spiritual satisfaction. Accelerating the establishment and improvement of the LTC insurance system requires systematic design, especially emphasizing the supportive role of a socially friendly care environment, and promoting it in urban and rural areas according to the local conditions.
Humans ; Aged ; Persons with Disabilities ; Surveys and Questionnaires ; Long-Term Care ; Female ; Male ; China ; Social Environment ; Middle Aged ; Aged, 80 and over

Objective To explore the risk factors for postoperative secondary hydrocephalus in patients with severe craniocerebral injury and construct a nomogram prediction model.Methods A total of 360 patients with severe craniocerebral injury were selected as the study subjects,and divided into hydrocephalus group(n=34)and non-hydrocephalus group(n=326)based on the occurrence of postoperative secondary hydrocephalus.Logistic regression analysis was used to screen for risk fac-tors of postoperative secondary hydrocephalus.A nomogram model for predicting postoperative second-ary hydrocephalus in patients with severe craniocerebral injury was constructed based on the identified risk factors,and its predictive performance was validated.Results Among the 360 patients,34 de-veloped secondary hydrocephalus after surgery,with an incidence rate of 9.44％(34/360).Logistic regression analysis revealed that intracranial infection,ventricular hemorrhage,midline shift ≥12 mm,preoperative Glasgow Coma Scale(GCS)score of 3 to 5,decompressive craniectomy and dura mater o-pening were independent risk factors for postoperative secondary hydrocephalus in patients with severe traumatic brain injury(P＜0.05).The concordance index of the nomogram model constructed based on these risk factors was 0.874,and the area under the curve was 0.831.Conclusion The nomogram model constructed in this study based on factors such as intracranial infection,ventricular hemorrhage,midline shift,preoperative GCS score,decompressive craniectomy and dura mater opening,effectively predicts risk of postoperative secondary hydrocephalus in patients with severe traumatic brain injury.This model has clinical significance for early prevention and treatment.

Epidemiological investigations and clinical studies have shown that inappropriate ambient temperatures (high and low temperatures) are the independent risk factors for ischemic stroke, but their underlying physiological mechanisms are not fully understood. This article systematically reviews the potential mechanisms by which inappropriate ambient temperatures promote the occurrence of ischemic stroke through multiple pathways, such as activating the sympathetic-renin-angiotensin system, inducing systemic inflammation and oxidative stress, damaging the integrity of the intestinal barrier and blood-brain barrier, and disrupting coagulation-fibrinolysis balance.