Atopic dermatitis (AD) is a common chronic inflammatory skin disorder affecting all age groups, especially children, with a prevalence of up to 20% globally. AD remains burdensome and incurable with current therapeutic strategies-ranging from trigger avoidance and skincare to medication-primarily address symptoms rather than disease modification, underscoring the imperative for innovative therapeutic paradigms. RNA-targeted therapies, particularly antisense molecules, have emerged as a transformative approach in precision medicine, with proven clinical success in diseases such as spinal muscular atrophy and familial chylomicronemia syndrome. These therapeutics achieve post-transcriptional regulation unattainable by conventional therapies, enabling direct targeting of messenger RNA (mRNA) and regulatory non-coding RNAs (ncRNAs) implicated in disease pathogenesis. Furthermore, skin is better suited to the antisense modulation due to the relatively easy access to target cells. Numerous studies have explored antisense-based targeting of key drivers in AD progression, yielding promising proof-of-concept results and prompting several early-stage clinical trials. This modality represents a paradigm shift in AD management-one that aligns with the broader revolution in RNA therapeutics reshaping modern medicine. This review critically examines the evolving role of antisense technology in AD, addressing both its mechanistic rationale and the translational challenges that must be overcome to realize its full clinical potential.

[Objective] To explore the application of pelvic floor ultrasonography in the treatment of mixed urinary incontinence (MUI) by transvaginal retropubic midurethral synthetic sling (RMUS), in order to understand the relationship between the morphological changes of pelvic floor structures and the efficacy of RMUS. [Methods] Clinical data of 44 female MUI patients undergoing RMUS during Jan.2018 and Dec.2020 were retrospectively analyzed.Urodynamics detected detrusor overactivity (DO) in 9 cases (20.5%). During RMUS procedure, the tension of the sling was adjusted based on the anatomical landmarks. The changes of ultrasonic parameters before and after operation, the relationship between the ultrasonic results, surgical efficacy and urodynamic results were analyzed. [Results] The patients averaged (58.59±9.08) years, with the body mass index being 24.71±2.77.The subjective cure rate was 91.3% (21/23) 3 months after surgery, and 85.0% (34/40) 2 years after surgery.Pelvic floor ultrasonography showed significant differences in posterior urethravesical angel at rest and during Valsalva, bladder neck descent distance and the rate of urethral funneling during Valsalva (P<0.05). According to the group analysis of the preoperative ultrasonic results, there was no statistical significance in the subjective cure rate between the funneling group and the non-funneling group during Valsalva, and the bladder neck non downward group/mild downward group/moderate downward group/severe downward group during Valsalva 3 months and 2 years after surgery (P>0.05). At 3-month follow-up, all pre-RMUS urethral funneling during Valsalva disappeared in patients without preoperative DO.Comparatively, 50.0% (3/6) urethral funneling still presented in DO patients, who had a lower cure rate (55.6%, 5/9) at the 2-year follow-up. [Conclusion] RMUS can reduce the posterior urethravesical angel at rest and during Valsalva, reduce bladder neck descent distance and the rate of urethral funneling during Valsalva in MUI patients, which can enhance urinary continence.There seems to be a correlation between DO and urethral funneling during Valsalva, while RMUS may potentially reverse the two markers.

Objective To explore the efficacy of retropubic midurethral synthetic sling(RMUS)in relieving urgency and urge urinary incontinence(UUI)symptoms in patients with mixed urinary incontinence(MUI).Methods Clinical data of 44 female MUI patients treated with RMUS during Jan.2018 and Dec.2020 in Shanghai Renji Hospital were retrospectively analyzed.All patients had positive results in stress test and Marshall-Marchetti test before operation,and 27 of them completed ICIQ-FLUTS-LF questionnaire.Urodynamic(UDS)tests suggested that 9 patients(20.5％)presented detrusor overactivity(DO).During RMUS procedure,the tension of the sling was adjusted based on the anatomical landmarks.The postoperative efficacy and improvement of urinary incontinence were analyzed.Results The patients aged(58.59±9.08)years,with a body mass index of 24.71±2.77.Among the 40 patients who completed telephone interview 2 years after surgery,the subjective cure rate was 85.0％(34/40).Among the 27 patients with records of questionnaires before and after surgery,there were significant differences in the incidence of urine leakage[100％(27/27)vs.18.5％(5/27)],stress urinary incontinence(SUI)[100％(27/27)vs.18.5％(5/27)]and UUI[70.4％(19/27)vs.29.6％(8/27)](P＜0.05).However,no statistical differences were found regarding nocturia voiding episode(≥1 times),urgency,dysuria,hesitancy,strain to void,intermittent stream and enuresis(P＞0.05).Based on preoperative UDS test,there were significant differences regarding the subjective cure rate in patients with or without preoperative DO[55.6％(5/9)vs.93.5％(29/31)],incidence of SUI[66.7％(4/6)vs.4.8％(1/21)],and UUI[66.7％(4/6)vs.19.0％(4/21)](P＜0.05),while there was no statistical difference regarding urgency[66.7％(4/6)vs.33.3％(7/21)](P＞0.05).Conclusion RMUS is effective in treating MUI patients with positive stress test and Marshall-Marchetti test results,which can relieve SUI and UUI symptoms,but has no effects on urgency symptoms.DO on preoperative urodynamics results in poorer subjective outcomes.

Objective:To assess the effectiveness and safety of beat chemotherapy in treating non-small cell lung cancer, and to investigate its anti-tumor molecular mechanism.Methods:In this study, we developed a subcutaneous tumor model of lung cancer in mice.The mice were subsequently divided into two groups: the beat chemotherapy group and the placebo group(negative control group).Throughout the treatment period, we monitored the changes in body weight and tumor size of the mice.At the conclusion of the treatment, we collected blood samples from the mice to conduct blood routine and biochemical examinations.Furthermore, we obtained tumor tissues from the mice to perform immunohistochemical staining and sequencing of the transcriptome.Results:The study found that beat chemotherapy could effectively delay the growth of lung cancer.The tumor tissues in the beat chemotherapy group were significantly smaller compared to the placebo group.The results of routine blood and blood biochemistry tests showed that the levels of red blood cells(RBCs), white blood cells(WBCs), alanine aminotransferase(ALT), aspartate aminotransferase(AST)and blood creatinine(Scr)were similar between the placebo group and the beat chemotherapy group.The values for RBCs, WBCs, ALT, AST and Scr in the placebo group were(6.97 ± 0.41)× 10 12/L, (13.26 ± 0.29)× 10 9/L, (33.33 ± 2.51)U/L, (235.33 ± 57.62)U/L and(20.67 ± 2.08)μmol/L, respectively.The corresponding values in the beat chemotherapy group were(6.87 ± 0.66)× 10 12/L, (12.59 ± 2.27)× 10 9/L, (38.67 ± 3.79)U/L, (225.33 ± 6.81)U/L and(20.33 ± 3.79)μmol/L.Statistical analysis showed no significant differences between the two groups( t=0.509, 0.209, 2.032, 0.299, 0.134, P=0.638, 0.845, 0.112, 0.780, 0.900).Furthermore, there were no signs of inflammatory infiltration or pathological changes in the liver, kidney, spleen, and lung tissues of the mice.Transcriptome analysis identified 68 differentially expressed genes, which were mainly associated with signal transduction and immunity.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis revealed the involvement of several signaling pathways, including the transforming growth factor β(TGF-β)signaling pathway, the interleukin-17(IL-17)signaling pathway, and the tumor necrosis factor(TNF)signaling pathway. Conclusions:The use of chemotherapy has been proven to be safe and effective in treating non-small cell lung cancer.It primarily functions by regulating tumor growth through various signaling pathways, including the TGF-β signaling pathway, IL-17 signaling pathway, and TNF.

Coronary artery calcification is associated with increased difficulty and complications during interventional procedures,and adequate pretreatment prior to stent placement might be effective in reducing the incidence of adverse outcomes.Intravascular lithotripsy(IVL)is effective in disrupting calcified plaques,facilitating optimal stent delivery and expansion.Optical coherence tomography(OCT)can accurately identify calcified lesions,assess the effect of pretreatment with IVL,and guide the selection of treatment strategies.The aim of this article is to summarize the recent research progresses on the role of OCT in IVL for the treatment of calcified coronary lesions.

[Objective]To summarize the theoretical viewpoints and therapeutic applications of Professor FU Wenbin in the treatment of persistent somatoform pain disorder(PSPD).[Methods]By following the teacher's clinical evidence,organizing medical cases and combining with literature search,this article analyzed and summarized Professor FU's identification ideas and clinical experience in treating PSPD by using the integrated acupuncture model with a medical case attached.[Results]Professor FU believes that the disease is the result of the joint influence of emotional factors and body meridians Qi and blood lesions,which belongs to"pain caused by Qi injury".The diagnosis and treatment concepts of"soothing the liver"and"regulating the mind"are also emphasized,as well as the combination of"acupuncture at the top priority,followed by moxibustion and consolidation at the end"integration of acupuncture and moxibustion mode of treatment.This article cites the case of a female patient with long-term lower abdominal distension and pain to detail the application of therapies.The pain was the main symptom associated with emotional effects,mostly due to the meridian Qi and blood stagnation,so it took acupuncture for"soothing the liver and regulating the mind"as the key rule of treatment.In the operation of acupuncture,Professor FU suggested the need to pay attention to patient's mind,to enter and exit the needle slowly,and to cross-reference the pulse with the symptoms.The selection of acupuncture points emphasized the elevation and harmonization of Qi and blood.Acupuncture,moxibustion,bloodletting and intradermal needle embedding and other traditional Chinese medicine special therapy treatments were used to treat PSPD.[Conclusion]Professor FU's treatment of PSPD focuses on"soothing the liver and regulating the mind",treating the mind and body together,and using acupuncture and moxibustion to achieve good clinical efficacy.The experience can also provide ideas for the treatment of psychosomatic diseases with acupuncture and moxibustion,which is worthwhile to learn from in the clinic.

Objective To systematically evaluate the efficacy and safety of ciprofol for sedation and anesthesia outside the operating room.Methods Databases such as PubMed,Embase,Cochrane Library,Web of Science,CNKI,Wanfang Data,CBM,and VIP were searched for randomized controlled trials(RCTs)related to the efficacy and safety of ciprofol for sedation and anesthesia outside the operating room.The search covered all publications up to June 2023.Statistical analysis was performed using RevMan 5.4 software and Stata 15.0.Results Twelve RCTs were included,involving 2 192 patients,of which 1 154 were in the ciprofol group and 1 038 in the propofol group.Compared with the propofol group,the anesthesia induction time(MD=0.28 min,95％CI 0.08-0.47 min,P=0.006)and recovery time(MD=1.16 min,95％CI 0.44-1.87 min,P=0.001)were significantly longer in the ciprofol group,and the inci-dences of injection pain(OR=0.04,95％CI 0.02-0.06,P＜0.001),hypotension(OR=0.64,95％CI 0.49-0.83,P=0.0008),hypoxemia(OR=0.44,95％CI 0.21-0.91,P=0.03),and respirato-ry depression(OR=0.19,95％CI 0.11-0.32,P＜0.001)were significantly lower.There were no sta-tistically significant differences between the two groups in terms of sedation success rate,physician satisfac-tion,the difference in heart rate before and after anesthesia induction,incidence of body movement,brady-cardia,nausea and vomiting,and dizziness.Conclusion The anesthetic effect of cyclopofol and propofol is similar when used for anesthesia outside the operating room.Compared to propofol,ciprofol offers comparable anesthetic effects for sedation and anesthesia outside the operating room,with a lesser impact on respiratory function and more stable hemodynamics.Ciprofol also significantly lowers the incidence of adverse reactions such as injection pain,hypotension,hypoxemia,and respiratory depression.

Purpose: In non-metastatic prostate cancer (nmPCa) setting, it is important to early identify the patients at risk of biochemical recurrence (BCR) for immediate postoperative intervention. Our study aimed to evaluate the potential clinical utility of circulating tumor DNA (ctDNA) for predicting disease recurrence. Materials and Methods: This real-world observational study evaluated 161 cases of nmPCa undergoing next-generation sequencing at our institution. A total of 139 ctDNA samples and 31 biopsied tumor tissue underwent genomic profiling. The study endpoint was BCR after radical prostatectomy. Relationships between the ctDNA status and the biochemical progression-free survival (bPFS) were analyzed by log-rank test and multivariate Cox regression. Results: Of 161 enrolled patients, 19 (11.8%) harbored deleterious alterations in NCOR2, followed by BRCA2 (3.7%), ATR (2.5%), and CDK12 (2.5%). Of available pre-operative blood samples (n=139), ctDNA was detectable in 91 (65.5%). Until last follow-up, 56 of 68 patients (85.3%) with detectable ctDNA had achieved BCR, whereas only eight of 39 patients (20.5%) with undetectable ctDNA had achieved BCR. Patients who had undetectable ctDNA experienced significantly longer bPFS compared with those who had detectable ctDNA (not available vs. 8.2 months; hazard ratio, 0.14; p < 0.01). Pre-operative ctDNA status was a significant prognostic factor of disease recurrence. Conclusion Pre-operative ctDNA detection could identify patients at high risk of recurrence and has the potential to inform immediate postoperative interventions, but these approaches remain to be validated in prospective studies. ctDNA studies can provide insights into accurate monitoring and precise treatment rather than simply following routine clinical care.

Cancer cell membrane (CCM) derived nanotechnology functionalizes nanoparticles (NPs) to recognize homologous cells, exhibiting translational potential in accurate tumor therapy. However, these nanoplatforms are majorly generated from fixed cell lines and are typically evaluated in cell line-derived subcutaneous-xenografts (CDX), ignoring the tumor heterogeneity and differentiation from inter- and intra- individuals and microenvironments between heterotopic- and orthotopic-tumors, limiting the therapeutic efficiency of such nanoplatforms. Herein, various biomimetic nanoplatforms (CCM-modified gold@Carbon, i.e., Au@C-CCM) were fabricated by coating CCMs of head and neck squamous cell carcinoma (HNSCC) cell lines and patient-derived cells on the surface of Au@C NP. The generated Au@C-CCMs were evaluated on corresponding CDX, tongue orthotopic xenograft (TOX), immune-competent primary and distant tumor models, and patient-derived xenograft (PDX) models. The Au@C-CCM generates a photothermal conversion efficiency up to 44.2% for primary HNSCC therapy and induced immunotherapy to inhibit metastasis via photothermal therapy-induced immunogenic cell death. The homologous CCM endowed the nanoplatforms with optimal targeting properties for the highest therapeutic efficiency, far above those with mismatched CCMs, resulting in distinct tumor ablation and tumor growth inhibition in all four models. This work reinforces the feasibility of biomimetic NPs combining modular designed CMs and functional cores for customized treatment of HNSCC, can be further extended to other malignant tumors therapy.
Animals ; Humans ; Squamous Cell Carcinoma of Head and Neck/therapy* ; Heterografts ; Photothermal Therapy ; Biomimetics ; Disease Models, Animal ; Head and Neck Neoplasms/therapy* ; Cell Line, Tumor ; Tumor Microenvironment