Immunotherapy has achieved good efficacy in clinical anti-tumor therapy， especially chimeric antigen receptor T cell （CAR-T cell） therapy， as an emerging tumor immunotherapy， has achieved breakthrough efficacy in the clinical treatment of hematologic malignancies. However， CAR-T cell face the problem of gradual exhaustion during the treatment process， especially in the treatment of solid tumors， which will lead to poor anti-tumor efficacy and possible risks such as recurrence. This paper analyzed the possible mechanism of CAR-T cell exhaustion and describes the relevant research progress in inhibiting CAR-T cell exhaustion， with a view to designing reasonable therapeutic strategies to reduce CAR-T cell exhaustion and improve the efficacy of CAR-T cell.
Objective To explore the effects of Thymosin β4 （Tβ4） on the lipopolysaccharide （LPS）-induced polarization tendency of murine monocyte-macrophage RAW264.7 cells and its influence on inflammatory responses. Methods An inflammation model was established by LPS induction in RAW264.7 cells. Cell viability was assessed using the CCK-8 assay. The concentrations of cytokines [tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6）] were detected by enzyme-linked immunosorbent assay （ELISA）. Nitric oxide （NO） secretion in the cell culture supernatant was detected using the Griess method. Real-time quantitative polymerase chain reaction （RT-qPCR） was employed to detect mRNA expression levels of nuclear factor-κB （NF-κB）， cyclooxygenase-2 （COX-2）， TNF-α， and IL-6. Western blotting was used to analyze protein levels of inducible nitric oxide synthase （iNOS）， NF-κB， phosphorylated NF-κB （p-NF-κB）， NF-κB inhibitor α （IκB-α）， and phosphorylated IκBα （p-IκB-α）. The polarization status of macrophages was observed using double fluorescence staining. Immunofluorescence staining was performed to examine NF-κB localization and expression. Results After treatment with 1 000 μg/L Tβ4 for 24 hours， the cell viability of RAW 264.7 cells was 90.2%， showing a statistically significant difference compared to the blank control group （P < 0.05）. Tβ4 at various concentrations effectively inhibited NO production （all P < 0.000 1）. Tβ4 decreased the concentrations of pro-inflammatory cytokines（TNF-α and IL-6） and NO in the LPS-induced RAW264.7 inflammatory model. It also downregulated mRNA expression of NF-κB， COX-2， TNF-α， and IL-6， as well as protein expression of iNOS， p-NF-κB， and p-IκBα. Additionally， Tβ4 inhibited NF-κB nuclear translocation and decreased CD80 expression （all P < 0.05）. Conclusion Tβ4 exhibits anti-inflammatory effects， the mechanisms of which may be associated with the inhibition of the NF-κB signaling pathway and suppression of macrophage M1 polarization.
Objective To analyze the diagnostic value and safety of transbronchial lung cryobiopsy （TBLC） in interstitial lung disease （ILD） and malignant lung lesions. Methods This study is a non-randomized controlled trial. Using the method of non-random sampling， 55 patients with ILD and pulmonary space-occupying lesions who were hospitalized in the Department of Respiratory and Critical Care Medicine of Beijing Tsinghua Changgung Hospital affiliated with Tsinghua University from January 2015 to February 2022 were selected. All patients were divided into the ILD group （n = 31） and pulmonary space-occupying lesion group （n = 24）. Basic information and clinical data were collected in both groups. Transbronchial forceps biopsy （TBFB） and TBLC techniques were sequentially employed to obtain lung biopsy samples based on intraoperative conditions， with no pre-inserted balloon in the TBLC group. Biopsy samples in both groups were sent for pathological examination. Kappa test was used to compare the consistency of pathological diagnosis between TBFB and TBLC. The receiver operating characteristic （ROC） curve and Logistic regression analysis were used to analyze the diagnostic efficiency of TBLC and TBFB alone or these two combined for malignant pulmonary lesions. Results Among the 55 patients， 61.8% （34/55） were male and 40.0% （22/55） were smokers. 40 cases （72.7%） had mild bleeding， 14 cases （25.5%） had moderate bleeding， and 1 case （1.8%） had no bleeding. No severe bleeding events or pneumothorax events occurred. In the ILD group， 19 patients were male and 12 female， aged （58.65±14.47） years on average， ranged from 16 to 76 years. The diagnoses of 17 patients were confirmed and 14 unconfirmed cases in this group. Among the confirmed cases， idiopathic pulmonary interstitial fibrosis （n = 4） and organizing pneumonia （n = 4） accounted for the highest percentage. In the pulmonary space-occupying lesion group， 15 patients were male and 9 female， aged （63.17±10.77） years old on average， ranged from 40 to 79 years. The diagnoses of 21 patients were finally confirmed and 3 unconfirmed cases in this group. Among the confirmed cases， there were 16 cases of malignant lung lesions， primarily lung adenocarcinoma （n = 7）. In the ILD group， the diagnostic rate of TBFB was 19.4% and 51.6% for TBLC， and the diagnostic rate in the TBLC group was higher than that in the TBFB group （P = 0.008）. In the pulmonary space-occupying lesion group， the diagnostic rate of TBLC was also superior to that of TBFB （79.2% vs. 37.5%， P = 0.002）. The area under the ROC curve of TBFB and TBLC in the diagnosis of malignant lung lesions was 0.77 （95%CI： 0.57-0.98） and 0.83 （95%CI： 0.66-1.00）， respectively. Conclusion TBLC has significant advantages in the diagnosis of ILD and lung malignancies， with a low risk of bleeding and high safety in clinical practice.
Objective To elucidate the role of C-type lectin domain family 7 member A （CLEC7A） in high-grade serous ovarian carcinoma （HGSOC） and its underlying mechanisms. Methods Using the Cancer Genome Atlas-Ovarian Cancer （CGA-OV） dataset， combined with transcriptional regulatory network analysis and master regulator analysis （MRA）， the impact of CLEC7A on immune-related genes in HGSOC was determined. Pathway enrichment analysis and validation identified the regulatory mechanism of CLEC7A on the Janus Kinase （JAK）/signal transducer and activator of transcription 3 （STAT3） pathway. The GSE184880 single-cell sequencing dataset was analyzed to reveal differences in immune cell proportions and cellular communication between CLEC7A low-expression and high-expression HGSOC tumors. Paraffin-embedded tumor tissues and corresponding adjacent tissues， along with clinicopathological data， were collected from 70 HGSOC and 70 ovarian clear cell carcinoma （OCCC） patients diagnosed and surgically treated at the First Affiliated Hospital of the University of Science and Technology of China/Anhui Provincial Hospital between January 2017 and December 2022. Differences in prognostic factors between HGSOC and OCCC were compared. Immunohistochemical staining was used to detect the expression levels of CLEC7A and PD-L1 in HGSOC， OCCC， and corresponding adjacent tissues. A short hairpin RNA （shRNA） vector targeting CLEC7A was constructed to assess changes in the proliferation and apoptosis of HGSOC cells both after CLEC7A inhibition. In a mouse tumor model with high CLEC7A expression， the proportion of myeloid-derived suppressor cells （MDSCs） and CD8+ T cells， as well as the functional changes of MDSCs， were observed. Results Transcriptional regulatory network analysis revealed that forkhead box protein P3 （FOXP3） and CLEC7A both regulate immune-related genes. CLEC7A was not only correlated with overall patient survival but also highly expressed in HGSOC tumor tissues（all P <0.05）. Knockdown of CLEC7A promoted apoptosis and inhibited the proliferation of HGSOC cell lines both in vitro and in vivo （all P < 0.05）. CLEC7A regulated the expression of programmed death ligand-1 （PD-L1） through the JAK/STAT3 signaling pathway. In CLEC7A high-expressing tumor tissues， the proportion of CD8+ T cells decreased， while the proportion of MDSCs increased， and the functionality of MDSCs was enhanced （all P < 0.05）. Conclusion CLEC7A induces PD-L1 expression in HGSOC， promotes HGSOC proliferation， and activates immunosuppressive signaling pathways， potentially leading to the malignant growth of HGSOC.
Objective To evaluate the effect of 0.5% ropivacaine for scalp nerve block on postoperative pain and recovery quality in craniotomy patients， and provide a reference for optimizing clinical anesthesia plans. Methods Sixty-six patients scheduled for craniotomy under general anesthesia were selected and randomly divided into ropivacaine group （R group） and control group （C group） in a 1∶1 ratio. The R group received bilateral scalp nerve blocks with 0.5% ropivacaine after anesthesia induction， while the C group was not treated. The primary outcome was the postoperative 6-hour Visual Analogue Scale （VAS） score. Secondary outcomes included VAS scores at 24， 48， and 72 hours postoperatively； remifentanil dosage during surgery； mean arterial pressure （MAP） and heart rate （HR） at key surgical time points， including before nailing， during nailing， before skin incision， during skin incision， before extubation， and after extubation； postoperative analgesic rescue rate； incidence of postoperative complications； incidence of postoperative nausea and vomiting， hypotension， fever， pneumonia， epilepsy， deep vein thrombosis， and pressure sores； time to first postoperative meal and ambulation； hospital stay length； and the scores of anxiety， depression， and sleep preoperatively and postoperative 24-hour. Results Sixty-one patients were finally included， with 30 in the R group and 31 in the C group. Compared to the C group， the R group had significantly lower VAS scores at 6 and 24 hours postoperatively （all P < 0.05）， but no significant difference at 48 and 72 hours （all P > 0.05）. The R group had lower remifentanil dosage （P < 0.05）， lower analgesic rescue rate （P <0.05）， lower MAP at three time points （before nailing， before skin incision， before extubation）， and lower HR during nailing （all P < 0.05）. The R group also had earlier time to first meal and ambulation， and shorter hospital stay （all P < 0.05）. No significant difference was found in postoperative nausea and vomiting， hypotension， fever， epilepsy， pneumonia， deep vein thrombosis， and pressure sores between the two groups （all P > 0.05）. The R group had lower anxiety and depression scores at 24 hours postoperatively compared to preoperatively （P < 0.05）， while the C group had higher Pittsburgh Sleep Quality Index （PSQI） scores （P < 0.05）. Conclusions Preoperative scalp nerve block with 0.5% ropivacaine can effectively relieve perioperative pain， reduce opioid use and cardiovascular stress response， and improve postoperative recovery quality in craniotomy patients， including anxiety， depression， time to first meal and ambulation， and hospital stay length， promoting the early rehabilitation of craniotomy patients.
Objective To analyze the clinical characteristics of children with Mycoplasma pneumoniae pneumonia （MPP） who progress into plastic bronchitis （PB） and identify the associated risk factors. Methods A total of 387 children diagnosed with MPP who underwent bronchoscopy were included in the study. They were divided into the MPP progressing into PB group and the MPP group based on the presence of plastic bronchial casts observed under microscopy. Clinical characteristics between two groups were compared， and the risk factors of the progression into PB were analyzed. Results The imaging findings， particularly from chest CT scans， revealed a higher incidence of atelectasis， lung necrosis， massive pleural effusion， bronchial stenosis or bronchial occlusion in the MPP progressing to PB group. Similarly， the occurrence of mixed infections， the levels of neutrophil percentage， lymphocyte percentage， neutrophil-to-lymphocyte ratio （NLR）， procalcitonin， C-reactive protein and lactate dehydrogenase （LDH） in the MPP progressing into PB group were significantly higher than those in the MPP group （all P < 0.05）. Multivariate logistic regression analysis demonstrated that NLR >3.15 ng/L [OR （95% CI） =2.084 （1.155， 3.759）]， LDH levels >408.5 U/L [OR （95% CI） =3.469 （1.797， 6.696）]， imaging changes [OR （95% CI） =2.707 （1.241， 5.907）]， and mixed infections [OR （95% CI） =4.517 （2.201， 9.271）] were the independent risk factors of MPP progressing into PB. Conclusions Characteristic imaging changes， mixed infections， and elevated levels of LDH and NLR are the independent risk factors for the progression of MPP into PB. Early identification of these factors by clinicians can enable prompt intervention.
Objective To systematically evaluate the efficacy and safety of intravenous magnesium sulfate in improving postoperative sleep quality. Methods Clinical randomized controlled trials assessing the role of intravenous magnesium sulfate in improving postoperative sleep quality were searched from PubMed， Web of Science， Embase， Cochrane Library， CNKI， Wanfang， VIP Database， and Grey Literature Database. The retrieval time was from the date of database inception to March 2024. The included literatures were subject to meta-analysis using RevMan 5.4 software after quality evaluation. Results A total of 256 surgical patients from five studies were included. The results of meta-analysis showed that the Visual Analogue Scale （VAS） score （mean difference was -1.49， 95%CI -1.87~-1.12， P < 0.000 01） of sleep quality in the first night in patients receiving perioperative intravenous magnesium sulfate was better than that in the control group， and there were no significant differences in postoperative VAS pain scores under activity status， and the outcomes of nausea and vomiting， shivering and hypotension between two groups （all P > 0.05）. Conclusion Intravenous magnesium sulfate during perioperative period can improve postoperative sleep quality and bring clinical benefits to patients without severe adverse reactions.
Objective To investigate the clinical outcome of modified McDonald's procedure for the treatment of pregnant women with cervical insufficiency. Methods Clinical data of 113 women with singleton pregnancies with cervical insufficiency who underwent negative low cervical cerclage in the Sixth Affiliated Hospital of South China University of Technology from January 2012 to December 2022 were retrospectively analyzed. They were categorized into prophylactic cervical cerclage group （n = 23） and therapeutic cervical cerclage group （n = 90） according to the purpose of the procedure. The general status， pregnancy outcome， postoperative complications and neonatal status in two groups were recorded. Multivariate Logistic regression analysis was carried out with whether therapeutic cervical cerclage yielded poor prognosis （abortion） as the dependent variable. Results In the prophylactic cervical cerclage group， the number of pregnancy was higher， the gestational week was shorter， the proportions of women with a history of ≥2 previous mid-pregnancy miscarriages or preterm deliveries and intrauterine infection were higher than those in the therapeutic cervical cerclage group （all P < 0.05）. The differences were not statistically significant in post-operative comorbidities， neonatal birth quality， and 1-min neonatal Apgar scores between two groups （all P > 0.05）. Univariate analysis showed that cervical dilatation and urinary tract infection exerted certain effects on the pregnancy outcome of pregnant women in the therapeutic cervical cerclage group （both P <0.05）. Multivariate Logistic regression analysis demonstrated that cervical dilatation and urinary tract infection were the influencing factors for poor prognosis of pregnant women undergoing therapeutic cervical cerclage （both P < 0.05）. Conclusions Dilatation of the cervix and urinary tract infection are the main risk factors affecting the outcome of therapeutic cervical cerclage. For these pregnant women， early monitoring of the cervical condition， prompt treatment of urinary tract infection， and timely cervical cerclage can improve the outcome of mothers and neonates.
Objective To summarize the research progress and hotspots of cognitive behavioral therapy for insomnia and predict future research directions in this field. Methods Literature related to cognitive behavioral therapy for insomnia was retrieved from the Web of Science Core Collection （WoSCC） database from 2003 to 2024. VOSviewer and CiteSpace software were used for bibliometric visual analysis. Results A total of 3，256 articles from 3，254 institutions in 77 countries were included， primarily from the USA and China. Since 2017， research in this field has entered a rapid development phase. The journal with the highest publication volume on cognitive behavioral therapy for insomnia is Sleep， which is also the most cited journal， with a total of 13，349 authors contributing to these papers； “sleep quality”“acupuncture treatment”“mental health”“novel coronavirus pneumonia”“pregnancy”“quality of life”are current research hotspots and trends in this field. Conclusion Over the past 21 years， cognitive behavioral therapy for insomnia has developed rapidly， and future trends and research hotspots in this field may focus on “acupuncture treatment” and “mental health”.
The incidence of type 1 diabetes mellitus （T1DM） is increasing globally， with environmental factors playing a significant role in its onset and progression. Studies have shown that gut microbiota dysbiosis may lead to T1DM through mechanisms such as altering intestinal permeability， modifying the abundance of microbial metabolites， and regulating immune responses. While insulin remains the primary therapeutic means， targeting the gut microbiota has emerged as a promising research focus for T1DM intervention. This article reviews the relationship between gut microbiota and T1DM， discusses the preventive and therapeutic effects of probiotics on T1DM and their underlying mechanisms， aiming to provide new insights for T1DM prevention and treatment research.
With the continuous development of science and technology， 3D printing technology has been widely used in the medical field. Especially in the field of dental prosthetics and implants， 3D printing technology provides patients with more accurate， minimally invasive， fast and personalized solutions. This review discussed the application of 3D printing technology in oral prosthesis implantation， including its principle， advantages， application scope and future development trend， aiming to provide a reference for the clinical use of 3D printing technology.
Lupus nephritis （LN） is a major cause of mortality and morbidity in patients with systemic lupus erythematosus （SLE）. Previous studies have shown that the pathological types of LN can transform， and these types serve as critical bases for formulating individualized treatment plans and predicting disease progression in SLE patients， thereby improving survival rates and quality of life. Renal pathology remains the “gold standard” for diagnosing LN and can be used to monitor disease progression and assess the therapeutic efficacy. However， renal pathology requires invasive renal biopsy， creating an urgent need for non-invasive biomarkers for LN diagnosis， disease activity monitoring， and treatment evaluation. Current research on biomarkers for disease monitoring primarily focuses on blood-derived biomarkers. In contrast， urinary biomarkers offer advantages such as ease of collection， non-invasiveness， and the ability for continuous short-term monitoring. Compared to renal biopsy and blood biomarkers， urinary biomarkers demonstrate significant advantages in diagnosing and monitoring LN. Emerging studies on urinary biomarkers for LN prognosis are on the rise. This review summarizes recent advances in the role of urinary biomarkers for LN prognosis assessment， thereby providing a reference for the clinical diagnosis and treatment of LN.
