Objective To compare the efficacy and safety of gemcitabine combined with conventional-dose cisplatin(70 mg/m2,day 2)versus split-dose cisplatin(35 mg/m2,days 1 and 8)in neo-adjuvant therapy for muscle-invasive bladder cancer(MIBC).Methods The clinical data of 33 MIBC patients receiving(gemcitabine+cisplatin,GC)-based neoadjuvant chemotherapy in the Department of Urology of Xinhua Hospital,during Jan.2021 and Aug.2024 were retrospectively analyzed,including 18(54.5％)patients treated with a conventional-dose regimen(GC group),and 15(45.5％)patients treated with a split-dose regimen(GCs group).The efficacy endpoints and incidence/severity of adverse reactions were compared between the two groups.Results Baseline characteristics were well-balanced between the two groups(P＞0.05).No significant differences were observed in the complete response rate(CR:33.3％vs.22.2％),objective response rate(ORR:66.7％vs.61.1％),or disease control rate(DCR:80.0％vs.88.9％)between the GCs and GC groups(P＞0.05).The GCs group exhibited a significantly lower incidence of chemotherapy-related renal injury(6.7％vs.38.9％,P＜0.05),while the occurrence of other adverse events was comparable between the two groups.Notably,the GCs group demonstrated significantly attenuated nephrotoxicity,as evidenced by markedly smaller changes in estimated glomerular filtration rate[eGFR:(4.5±4.7)％vs.(18.0±11.8)％]and serum creatinine[SCr:(5.7±5.6)％vs.(20.2±19.5)％]compared to the GC group(P＜0.05).Conclusion Compared with the conventional-dose regimen,the split-dose regimen maintains equivalent clinical efficacy of GC-based neoadjuvant chemotherapy while significantly reducing chemotherapy-related nephrotoxicity,thereby providing MIBC patients with a safer therapeutic option.

Objective To deeply understand the anatomical basis of temporomandibular joint disorders,and explore and master the pathological characteristics of anterior displacement of temporomandibular joint disc through cadaveric dissection and 3D printing technology.Methods By dissecting the temporomandibular joints of 40 head and neck specimens,the bilateral structures of the temporomandibular joints were measured to obtain condyle and articular disc data.3D modeling was carried out using 3ds Max software and printed out a model of temporomandibular joint.The pathological model of the anterior disc displacement with reduction(ADDwR)was simulated by adjusting the opening degree,the position of the articular disk,and the position of the condyle of the model.Results The precise data of the right and left temporomandibular joint discs and condyle were successfully obtained by dissection and measurement.The thickness of the anterior band of left temporomandibular joint discs was(2.02±0.57)mm,the thickness of the middle band was(1.46±0.33)mm,the thickness of the posterior band was(3.00±0.46)mm,the anterior-posterior diameter was(9.60±0.72)mm,and the internal-external diameter was(17.73±0.84)mm.While the thickness of the anterior band of right temporomandibular joint discs was(1.84±0.35)mm,and the thickness of the middle band was(1.43±0.28)mm,the thickness of posterior band was(3.08±0.49)mm,the anterior-posterior diameter was(9.30±0.88)mm,and the internal-external diameter was(17.38±1.10)mm.The internal-external diameter of the left temporomandibular joint condyle was(18.97±0.41)mm,and the anterior-posterior diameter was(8.56±0.43)mm;the internal-external diameter of the right temporomandibular joint condyle was(18.86±0.75)mm,and the anterior-posterior diameter was(8.40±0.30)mm.The standard temporomandibular joint model was printed out by the measured data.The model was utilized to simulate the physiological state of temporomandibular joint under normal conditions,as well as the three pathological states of closed mouth,closed mouth to open mouth,and open mouth in the case of ADDwR.Conclusion The temporomandibular joint model can more intuitively present the changes of anatomical structure in reversible temporoman-dibular joint disorders,which is helpful for understanding and mastering the different classification of this disease.

AKT,also known as Protein Kinase B(PKB),plays a critical role in cell proliferation and metabolism.There are three isoforms of AKT:AKT1,AKT2,and AKT3.The effects of these isoforms on the pluripotency and differentiation of mouse embryonic stem cells(mESCs)remain unclear.This study aims to explore the impact of three AKT isoform-specific knockouts on the self-renewal and differen-tiation of mouse embryonic stem cells.Using CRISPR/Cas9 gene-editing technology,AKT isoform-spe-cific knockout cell lines were established.The phenotypic and molecular changes were analyzed through Western blotting,flow cytometry,qRT-PCR,CCK-8 assays,Alkaline Phosphatase(AP)staining,and RNA-seq.The construction of AKT isoform-specific knockout cell lines was successful.The loss of AKT1 and AKT2 inhibited the proliferation of mESCs.The knockout of any single AKT isoform did not affect the expression of pluripotency genes at both mRNA or protein levels.However,during embryoid body forma-tion,the deletion of any of the three AKT isoforms affected the mRNA expression levels of genes in all three germ layers.Transcriptome analysis showed that compared to wild-type mESCs,995,547,and 429 differentially expressed genes(|log2FC|≧1,P＜0.05)were identified inAKT1,AKT2,and AKT3 isoform-specific knockout cells,respectively.There was some overlap in the differentially expressed genes regulated by these three isoforms.In conclusion,the independent knockout of AKT isoforms does not af-fect the maintenance of pluripotency in mouse embryonic stem cells,but they are crucial for differentia-tion.The three AKT isoforms can collectively regulate gene expression while retaining their own regulato-ry specificity.This study provides a foundation for understanding the unique and overlapping roles of AKT isoforms in stem cell biology,highlighting their importance in maintaining stem cell function and differen-tiation.

Objective:This study aims to investigate the differences in emotional status and cognitive function among patients with vestibular migraine (VM), Meniere′s disease (MD), and their comorbidity (VMMD), and to analyze key factors influencing cognitive function.Methods:This cross-sectional study included 96 outpatients (32 males, 64 females, aged 21-73 years) from the Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, between December 2022 and December 2023. The study population consisted of 31 VM patients (VM group), 36 MD patients (MD group), and 29 VMMD patients (VMMD group), along with 32 healthy controls (16 males, 16 females, aged 19-74 years). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), while emotional status and somatization symptoms were evaluated through the Generalized Anxiety Disorder scale, Patient Health Questionnaire Depression scale, Symptom Checklist-90, and the Self-rating Somatization Symptom scale. Multiple linear regression analysis was conducted to explore the influence of different variables on cognitive function.Results:The total MoCA score in the VMMD group (26.0 [24.5, 28.0]) was significantly lower than that in the control group (28.0 [27.0, 29.0]) and the MD group (28.0 [26.0, 30.0]) ( P=0.006). VMMD patients exhibited significant impairments in specific cognitive domains, including visuospatial/executive function, delayed recall, and orientation ( P<0.05). Patients with VM, MD, and VMMD showed higher rates of anxiety, depression, and somatization symptoms compared to the control group ( P<0.05), with the VMMD group experiencing the most severe emotional distress. Multiple linear regression analysis identified education level and vestibular disease type as key factors affecting cognitive function, with a university-level education predicting higher MoCA scores ( P<0.001), while VMMD was associated with cognitive decline ( P<0.01). Conclusions:Patients with VM and MD, particularly those with comorbid VMMD, exhibit significant emotional distress. Cognitive impairments are present in VM and VMMD patients, affecting different cognitive domains. These factors should be comprehensively considered in clinical assessments to develop more effective treatment strategies.

Objective:To investigate the genetic causal relationship of leukocyte telomere length(LTL)with prostatitis,orchi-tis and epididymitis by two-sample Mendelian randomization(MR).Methods:Using LTL as the exposure factor and prostatitis,or-chitis and epididymitis as outcome factors,we mined the Database of Genome-Wide Association Studies(GWAS).Then,we analyzed the causal relationship of LTL with prostatitis,orchitis and epididymitis by Mendelian randomization using inverse variance weighting(IVW)as the main method and weighted median and MR-Egger regression as auxiliary methods,determined the horizontal multiplicity by MR-Egger intercept test,and conducted sensitivity analysis using the leaving-one-out method.Results:A total of 121 related sin-gle nucleotide polymorphisms(SNPs)were identified in this study.IVW showed LTL to be a risk factor for prostatitis(OR=1.383,95％CI:1.044-1.832,P=0.024),and for orchitis and epididymitis as well(OR=1.770,95％CI:1.275-2.456,P=0.000 6).Conclusion:Genetic evidence from Mendelian randomized analysis indicates that shortening of LTL reduces the risk of prostatitis,orchitis and epididymitis.

Objective To explore the correlations of serum heat shock protein 70(Hsp70),high-mobility group box 1(HMGB1),glial fibrillary acidic protein(GFAP),and cognitive impair-ment(CI)in patients with cerebral small vessel disease(CSVD).Methods A total of 117 patients with CSVD who were treated at Kailuan General Hospital from July 2023 to July 2024 were selected as study subjects(CSVD group).According to varied scores of the Mini-Mental State Examination(MMSE),they were divided into CI group(54 cases)and non-CI group(63 cases).Additionally,120 healthy individuals who underwent health check-ups during the same period were selected as con-trol group.Clinical data of all subjects were collected.Enzyme-linked immunosorbent assay(ELISA)was used to detect the expression levels of Hsp70,HMGB1,and GFAP in serum.The Spearman method was employed to analyze the correlations of serum Hsp70,HMGB1,and GFAP levels with the occurrence of CI in CSVD patients.Logistic multivariate regression analysis was conducted to screen for influencing factors of CI in CSVD patients.The receiver operating characteristic(ROC)curve was used to analyze the predictive value of serum Hsp70,HMGB1,and GFAP levels for CI in CSVD patients.Results The serum levels of Hsp70,HMGB1,and GFAP in the CSVD group were higher than those in the control group(P＜0.05).There were no significant differences in gender,age,body mass index,smoking history,drinking history,nature of CSVD,education level,triglyc-erides(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),Trail Making Test-A(TMT-A),Trail Making Test-B(TMT-B),and low-density lipoprotein cholesterol(LDL-C)between the CI group and the non-CI group(P＞0.05).The levels of uric acid(UA),serum Hsp70,HMGB1,and GFAP in the CI group were higher than those in the non-CI group,while the Montreal Cognitive Assessment(MOCA)score was lower than that in the non-CI group(P＜0.05).The serum levels of Hsp70,HMGB1,and GFAP in CSVD patients were negatively correla-ted with MMSE scores(r=-0.458,-0.525,-0.431,P＜0.05)and MOCA scores(r=-0.462,-0.583,-0.484,P＜0.05).Logistic regression analysis showed that Hsp70,HMGB1,and GFAP were influencing factors for CI in CSVD patients(P＜0.05).The areas under the curve(AUC)for serum Hsp70,HMGB1,and GFAP levels and their combined prediction of cognitive function in CSVD patients were 0.734,0.769,0.766,and 0.902,respectively.The predictive ef-ficacy of the combined prediction was better than that of individual indicators(P＜0.05).Conclu-sion The serum levels of Hsp70,HMGB1,and GFAP are elevated in CSVD patients,which are closely related to the occurrence of CI.The combined detection of these three proteins has a high predictive value for CI in CSVD patients.

BACKGROUND: Lung cancer is currently the most prevalent malignancy and the leading cause of cancer deaths worldwide. Although the early stage non-small cell lung cancer (NSCLC) presents a relatively good prognosis, a considerable number of lung cancer cases are still detected and diagnosed at locally advanced or late stages. Surgical treatment combined with perioperative multimodality treatment is the mainstay of treatment for locally advanced NSCLC and has been shown to improve patient survival. Following the standard methods of neoadjuvant therapy, perioperative management, postoperative adjuvant therapy, and other therapeutic strategies are important for improving patients' prognosis and quality of life. However, controversies remain over the perioperative management of NSCLC and presently consensus and standardized guidelines are lacking for addressing critical clinical issues in multimodality treatment. METHODS: The working group consisted of 125 multidisciplinary experts from thoracic surgery, medical oncology, radiotherapy, epidemiology, and psychology. This guideline was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The clinical questions were collected and selected based on preliminary open-ended questionnaires and subsequent discussions during the Guideline Working Group meetings. PubMed, Web of Science, Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNKI) were searched for available evidence. The GRADE system was used to evaluate the quality of evidence and grade the strengths of recommendations. Finally, the recommendations were developed through a structured consensus-building process. RESULTS: The Guideline Development Group initially collected a total of 62 important clinical questions. After a series of consensus-building conferences, 24 clinical questions were identified and corresponding recommendations were ultimately developed, focusing on neoadjuvant therapy, perioperative management, adjuvant therapy, postoperative psychological rehabilitation, prognosis assement, and follow-up protocols for NSCLC. CONCLUSIONS This guideline puts forward reasonable recommendations focusing on neoadjuvant therapy, perioperative management, adjuvant therapy, postoperative psychological rehabilitation, prognosis assessment, and follow-up protocol of NSCLC. It standardizes perioperative multimodality treatment and provides guidance for clinical practice among thoracic surgeons, medical oncologists, and radiotherapists, aiming to reduce postoperative recurrence, improve patient survival, accelerate recovery, and minimize postoperative complications such as atelectasis.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; Lung Neoplasms/therapy* ; Combined Modality Therapy ; Perioperative Care

The renin-angiotensin-aldosterone system (RAAS) is crucial for regulating blood pressure and maintaining fluid balance, while clock genes are essential for sustaining biological rhythms and regulating metabolism. There exists a complex interplay between RAAS and clock genes that may significantly contribute to the development of various cardiovascular and metabolic diseases. Although current literature has identified correlations between these two systems, the specific mechanisms of their interaction remain unclear. Moreover, the interaction patterns under different physiological and pathological conditions need further investigation. This review summarizes the synergistic roles of the RAAS and clock genes in cardiovascular diseases, explores their molecular mechanisms and pathophysiological connections, discusses the application of chronotherapy, and highlights potential future research directions, aiming to provide novel insights for the prevention and treatment of related diseases.
Humans ; Renin-Angiotensin System/genetics* ; Cardiovascular Diseases/genetics* ; CLOCK Proteins/physiology* ; Animals