Objective: To analyze the effects of blue light on the formation of kidney stones. Methods: A total of 40 rats were randomly divided into 4 groups：A，B，C，and D，with 10 rats in each group.Rats in groups C and D were administered with a mixture of 10 g/L ethylene glycol，20 g/L ammonium chloride，and 100 g/L calcium gluconate via gavage (2 mL per mouse)，while rats in groups A and B received an equal volume of physiological saline via gavage.From the second day after gavage，rats in groups A and C were subjected to twice-daily blue light irradiation (one hour per session) as an intervention，while rats in groups B and D were subjected to fluorescent lamp irradiation using the same method.After 4 weeks of intervention，the 24-hour urine samples were collected，and the rats were then euthanized for the collection of blood and kidney tissue samples.Serum levels of antidiuretic hormone (ADH)，urinary Ca ，and urinary oxalate (Oxa) were measured.Levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in kidney tissues were detected using ELISA.Von Kossa staining was performed to observe pathological changes in kidney tissues and the presence of calcium salt crystals in the kidneys. Results: Compared with groups A and B，groups C and D showed higher accumulation of calcium salt crystals in renal tissues，as well as elevated levels of ADH，urinary Ca ，urinary Oxa，and MDA in renal tissues, additionally，the SOD level in renal tissues was lower (P<0.05).Compared with group D，group C exhibited higher accumulation of calcium salt crystals in renal tissues，along with increased levels of ADH，urinary Ca ，urinary Oxa，and MDA in renal tissues；conversely，the SOD level in renal tissues was lower (P<0.05). Conclusion: Blue light may increase the formation of kidney stones in rats by promoting the secretion of ADH in serum and oxidative stress in kidney tissues through the brain-kidney axis.

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

The heterogeneity of exhausted T cells (Tex) is a critical determinant of immune checkpoint blockade therapy efficacy. However, few studies have explored exhausted T cell subpopulations in human cancers. In the present study, we examined samples from two cohorts of 175 patients with head and neck squamous cell cancer (HNSCC) by multiplex immunohistochemistry (mIHC) to investigate two subsets of Tex, CD8⁺PD1⁺TCF1⁺ progenitor exhausted T cells (TCF1⁺Tex^prog) and CD8⁺PD1⁺TCF1^- terminally exhausted T cells (TCF1^-Tex^term). Moreover, fresh tumor samples from 34 patients with HNSCC were examined by flow cytometry and immunohistochemistry to further investigate their properties and cytotoxic capabilities and their correlation with regulatory T cells (Tregs) in the tumor immune microenvironment (TIME). mIHC and flow cytometry analysis showed that TCF1^-Tex^term represented a greater proportion of CD8⁺PD1⁺Tex than TCF1⁺Tex^prog in most patients. TCF1⁺Tex^prog produced abundant TNFα, while TCF1^-Tex^term expressed higher levels of CD103, TIM-3, CTLA-4, and TIGIT. TCF1^-Tex^term exhibited a polyfunctional TNFα⁺GZMB⁺IFNγ⁺ phenotype; and were associated with better overall survival and recurrence-free survival. The results also indicated that larger proportions of TCF1^-Tex^term were accompanied by an increase in the proportion of Tregs. Therefore, it was concluded that TCF1^-Tex^term was the major CD8⁺PD1⁺Tex subset in the HNSCC TIME and that these cells favor patient survival. A high proportion of TCF1^-Tex^term was associated with greater Treg abundance.
CD8-Positive T-Lymphocytes ; Head and Neck Neoplasms/therapy* ; Humans ; Immunotherapy/methods* ; Prognosis ; Programmed Cell Death 1 Receptor ; Squamous Cell Carcinoma of Head and Neck/therapy* ; Tumor Microenvironment ; Tumor Necrosis Factor-alpha

Objective:To explore the clinical application and long-term safety of hydroxychloroquine sulfate (HCQ) in the treatment of rheumatic diseases.Methods:A multi-center cross-sectional study was conducted between August 2017 and August 2018 in a random sample of eleven medical institutions of rheumatology and immunology in China. Patients who took HCQ for more than 3 months were enrolled into this study. The cumulative dose and long-term side effects of HCQ were recorded. The changes of laboratory indexes before and after treatment with HCQ were analyzed. Categorical variables were presented with counts and proportions, and evaluated by Chi-square test. Continuous parametric data were presented as Mean±standard deviation, and evaluated by Student's t test or Mann-Whitney U test. P-values less than 0.05 were considered statistically significant. Results:A total of 886 patients with rheumatic diseases were enrolled into this study, including 505 cases with systemic lupus erythematosus (57.0%), 210 cases with rheumatoid arthritis (23.7%), 80 cases with Sj?gren's syndrome (9.0%), 57 cases with undifferentiated connective tissue disease (6.4%), 12 cases of systemic vasculitis (1.4%), 10 cases of mixed connective tissue disease (1.1%), 7 cases of myositis (0.8%) and 5 cases with systemic sclerosis (0.6%). The most common long-term side effects of HCQ was skin or mucous lesions (12.4%) and vision problems (8.0%). Other adverse reactions included problems of digestive system (3.0%), nervous system (2.1%), musculoskeletal system (1.1%) and cardiovascular system (0.9%). 140 cases (15.8%) had stopped taking HCQ during the treatment. More than half of them decided to stop taking medicine by themselves. Fifty-four patients (6.1%) stopped using HCQ due to side effects while 24 of them took it again, and another 12 patients (1.4%) stopped the drug due to remission of illness. Patients were divided into three groups according to the cumulative dose of HCQ: less than 500 g, 500-1 000 g and more than 1 000 g respectively. There was significant difference in the incidence of long-term side effects among the three groups ( χ2=6.382, P=0.041). The last group (more than 1 000 g) suffered the highest incidence of long-term adverse reactions (37.1%). No severe adverse drug reactions were observed in this study. Conclusion:Hydroxychloroquine is widely used in the treatment of rheumatic diseases. The incidence of long-term side effects is 20.4%, is 6.1% lead to drug withdrawal, which are especially related to the cumulative doses. It should be adjusted properly according to the clinical application.

Objective:To analyze the disease spectrum among children who were using hydroxychloroquine (HCQ), and evaluate the drug′s safety and compliance.Methods:From January 2008 to December 2019, children from Children′s Hospital of Fudan University who used HCQ were selected as subjects, the disease spectrum of HCQ was analyzed, and the drug safety and compliance were evaluated for the patients who were followed up for more than 6 months. Demographic information, diagnosis, initial dose, time of continuous use, cumulative dosage and related adverse reactions report, project and the results of eye test were collected.Results:A total of 528 cases used HCQ during the 12 years, with 156 male cases and 372 female cases, and age at initial medication was (10.5±3.2) years. Among them, 514 cases (97.3%) had rheumatic disease, 5 had pulmonary interstitial lesions and 9 had other system diseases. The top three of the rheumatic diseases were systemic lupus erythematosus (SLE) in 316 cases (316/514,61.5%), juvenile idiopathic arthritis in 69 cases (69/514,13.4%), and juvenile dermatomyositis in 56 cases (56/514,10.9%). During the same period, 397 cases were diagnosed with SLE, and the utilization rate was 79.6% (316/397), which was the highest compared with other diseases and increased year by year. Pulmonary interstitial lesions included 4 cases with SFTPC gene defect related interstitial lung disease. Of the 528 ceses who were treated with HCQ, 397 cases were included for evaluating HCQ′s safety and compliance, the initial dose was (4.2±1.0) mg/kg, duration was 29.6 (14.9, 48.8) months, the longest usage time was 127 months, the largest cumulative dosage was 566.8 g. The continuous usage duration ( Z=-3.191, P=0.001) of SLE was significantly higher than those of other diseases, as well as cumulative dosage ( Z=-5.355, P=0.001). All cases received comprehensive eye exams before medication, 354 cases (354/397, 89.2%) were followed up in the ophthalmological department, and 65.5% (232/354) of them could be reviewed regularly at least 1 time per year. One case suffered from severe skin adverse reactions when the drug was used for 32.7 months, and no other serious adverse reactions were reported. HCQ related retinopathy was not seen during the follow-up period. There were 5 cases stopped HCQ on their own. Conclusions:HCQ was widely used in rheumatic disease in children, especially in those with SLE. It was safe for long-time usage in children, and the medication compliance and the ophthalmic follow-up was good.

Tripartite motif (TRIM) family proteins are important effectors of innate immunity against viral infections. Here we identified TRIM35 as a regulator of TRAF3 activation. Deficiency in or inhibition of TRIM35 suppressed the production of type I interferon (IFN) in response to viral infection. Trim35-deficient mice were more susceptible to influenza A virus (IAV) infection than were wild-type mice. TRIM35 promoted the RIG-I-mediated signaling by catalyzing Lys63-linked polyubiquitination of TRAF3 and the subsequent formation of a signaling complex with VISA and TBK1. IAV PB2 polymerase countered the innate antiviral immune response by impeding the Lys63-linked polyubiquitination and activation of TRAF3. TRIM35 mediated Lys48-linked polyubiquitination and proteasomal degradation of IAV PB2, thereby antagonizing its suppression of TRAF3 activation. Our in vitro and in vivo findings thus reveal novel roles of TRIM35, through catalyzing Lys63- or Lys48-linked polyubiquitination, in RIG-I antiviral immunity and mechanism of defense against IAV infection.
A549 Cells ; Animals ; Apoptosis Regulatory Proteins/immunology* ; DEAD Box Protein 58/immunology* ; Dogs ; HEK293 Cells ; Humans ; Influenza A Virus, H1N1 Subtype/immunology* ; Madin Darby Canine Kidney Cells ; Mice ; Mice, Knockout ; Orthomyxoviridae Infections/pathology* ; Proteolysis ; RAW 264.7 Cells ; Signal Transduction/immunology* ; THP-1 Cells ; TNF Receptor-Associated Factor 3/immunology* ; Ubiquitination/immunology* ; Viral Proteins/immunology*

Objective ToinvestigatetheenhancedCTfindingsandpathologicalfeaturesoflocalized malignantperitonealmesothelioma (LMPM)andimprovetheaccuracyofdiagnosis.Methods Theimagingandclinicaldataof5casesofLMPMconfirmedbypathology werecollected,thefeaturesofCTenhancedimagingwereanalyzedretrospectivelyandcomparedwiththepathologicalresults.Results Allofthe5caseswereisolatedsolidandcysticmasswithirregularshape,andtherangeofmaximumdiameterofthelesionbeing 8.4-13.3cm,inwhich1casewaspolycystic,andtheother4casesweresolidandcysticmass.CTvalueofthecysticpartwasabout 13.0-27.8 HU,andnoenhancementshowedoncontrast-enhancedphase.Thethicknessofcysticwallandseparationwasuneven, whiletheCTvalueofsolidpartwasabout32.6-40.8HU,andmoderateenhancementwasseeninarterialphase(△CTvaluewasabout30.9-38.4HU ),followedbyslightlyincreaseofenhancementdegreeinvenousphase,andthedecreaseofenhancementdegreeinequilibriumphase. Separationandalotofvesselshadowwereseenin3caseswhileperitonealcavity,pelviceffusionandintraperitonealimplantmetastasiswereseen in1case.Forthepathologicaltypesofpatientsinthisgroup,1casewasepithelialtype,mainlycomposedofcysticcomponent,andthe other4caseswerefibroustypeorbiphasictype,mainlycomposedofcysticandsolid,withsmallcysticdegeneration,necrosis,fibrousseptum, bloodsupplyvessels,andetc.Somelesionsinvadedthesurroundingstructure.Conclusion Thepathologicaltypesoflocalizedmalignantperitoneal mesotheliomaaremostlyfibroustypeandbiphasictypewhichCTfindingsaremostlymanifestedascysticandsolidmasses.Lobulatedand wallnodules,uneventhicknessofcysticwallandseptumcanbeseen,andthedensityofcysticpartialisrelativelyhigher.Solidpartis moderateenhancement,andinvenousphaseismoreobviouswithenhancedvascularseenintheseptum.CTenhancementcombined withclinicalmanifestationsarehelpfultomakeinsuggestivediagnosis.

Objective To investigate the value of diffusion kurtosis imaging (DKI) in diagnosing early diabetic nephropathy. Methods Twelve pigs were divided into the experimental group (7 pigs) and the control group (5 pigs), used the random number table method. The experimental group was fed with high?fat high?sugar diet,and then repeatedly injected small doses(50 mg/kg) of Streptozotocin (STZ) through the ear vein. Meanwhile,the control group was fed with normal diet and injected with the same dose of citric acid?sodium citrate buffer solution.After the type 2 diabetes was established successfully, T1WI, T2WI and DKI sequence imaging were performed every month for 2 pigs from the experimental group and the control group,respectively.Mean kurtosis(MK), axial kurtosis (K∥), radial kurtosis (K⊥), fractional anisotropy (FA) and mean diffusivity(MD) were measured on the pseudo?color map of the post?processing workstation. fasting blood glucose(GLU),insulin (INS),renal function, urine routines and random albumin creatinine ratio(RACR) were measured before MRI scan. Specimens from bilateral kidneys were taken for pathological examination after MRI scan. The paired t test was used to compare the parameter values of the cortex and medulla. Independent sample t test was used tocompare the parameter values of the experimental group and the control group. Results In the experimental group,the MK, FA values of medulla were 0.66±0.07 and 0.19± 0.04, the MK, FA values of cortex were 0.60±0.06 and 0.16±0.03.In the control group,the MK, FA values of medulla were 0.59±0.03 and 0.20±0.04, the MK, FA values of cortex were 0.53±0.03 and 0.17±0.04.The MK and FA values of medulla were increased compared with the cortex and the difference were statistically significant (P<0.01). The MK, K⊥ values of cortex and medulla were increased in the experimental group compared with the control group and the difference were statistically significant (P<0.05). There was no significant differences in the K∥, FA and MD values between two groups (both cortex and medulla, P>0.05). Conclusion DKI sequencehas certain value in the diagnosis of early diabetic nephropathy, and to some extent reveals the pathological change in early diabetic nephropathy.

Objective To understand the motivation of blood donation and the main influencing factors of blood donation behav-ior to formulate a targeted recruitment strategy.Methods A stratified cluster sampling method was adopted to perform the ques-tionnaire investigation on the influencing factors of blood donation without payment in 583 non-donors and 554 blood donors of Fos-han City.The analysis was performed by using the chi square test and Logistic regression analysis method.Results The character-istics of blood donation population were more males,aged 20-<30 years old,high school or secondary education,monthly income in 1 000-<3 000 Yuan;the main motivation for donating blood wasdevotion to love and social responsibility;the blood donation behavior was affected by the factors ofdevotion to love and social responsibility,give repeated donors certificate and medalfear of infectious disease and blood donation will affect healthfear of painandblood donation site traffic inconvenience and other factors.Conclusion The factors of incentive measures,barriers measures,psychological factors,blood donation services,and so on will affect the citizens to donate blood.Different recruitment strategies should be developed for different crowds.

Nitrogen-doped carbon nanoparticles (N-CNPs) with a fluorescence quantum yield of 15.1％ were prepared from sucrose and urea in oleic acid medium by a one-pot solvothermal method.A new approach for quick,sensitive,and selective determination of free chlorine in water was developed based on fluorescence quenching of N-CNPs.There existed a good linear correlation between the fluorescence quenching and the concentration of ClO-in the range of 0.05-25.00 μmol/L.The limit of detection (LOD,S/N =3) was estimated to be 23 nmol/L.This method can be applied to the determination of free chlorine in real water samples.