ObjectiveTo investigate the effects of 7-dehydrocholesterol reductase （DHCR7） in promoting proliferation， migration， and invasion of lung adenocarcinoma cells and the underlying signaling mechanisms. MethodsThe expression level of DHCR7 in lung adenocarcinoma and its prognosis were analyzed by using public databases. DHCR7 protein expression levels in the lung adenocarcinoma cell lines H1299 and A549 were assessed by Western blot， using the normal lung epithelial cell line BEAS-2B as a control. Small interfering RNA （siRNA） was used to knock down DHCR7 expression in H1299 and A549 cells. Assays including colony formation， CCK-8， wound healing， and Transwell experiments were conducted to assess the proliferation， migration， and invasion of the knockdown cells. Next， Western blot was employed to assess the phosphorylation levels of key signaling molecules in the phosphoinositide 3-kinase/protein kinase B （PI3K/AKT）， janus kinase/signal transducer and activator of transcription 3 （JAK/STAT3），mitogen-activated protein kinase/extracellular signal-regulated kinase pathway （MAPK/ERK） （p-AKT， p-STAT3， p-ERK）. ResultsBioinformatics results indicated that both DHCR7 mRNA and protein were highly expressed in lung adenocarcinoma compared with normal tissues adjacent to cancer. Furthermore， higher DHCR7 mRNA level was associated with poor prognosis （P<0.001）. The expression levels of DHCR7 were significantly higher in both H1299 and A549 cells than that in BEAS-2B cells （P<0.05， P<0.01）. Compared with si-control， the proliferation， migration， and invasion abilities of si-DHCR7 H1299 and A549 cells significantly decreased. Among the phosphorylated signaling molecules detected， p-ERK was significantly downregulated （P<0.000 1， P<0.01） whereas p-AKT and p-STAT3 levels were not significantly changed. ConclusionDHCR7 has prominent effects in promoting the proliferation， migration， and invasion of lung adenocarcinoma cells， and the underlying mechanisms are related to the MAPK/ERK signaling pathway.

Effective symptom management can alleviate the physical and psychological distress experienced by patients with cancer, improve quality of life, and contribute to treatment adherence and improve clinical outcomes. However, most existing guidelines are developed for healthcare professionals, and patients and the public have limited access to standardized and comprehensible guidance on symptom management. To address this gap and to facilitate effective communication and shared decision-making, this study proposes the development of a patient version of the cancer symptom management guideline. The development process will adhere to the methodological framework recommended by the Guidelines International Network and the World Health Organization. The GRADE approach will be employed to assess the certainty of evidence and to formulate recommendations. In addition, the process will be informed by the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ) instrument and the Reporting Items for Practice Guidelines in Healthcare-Public or Patient Versions of Guidelines (RIGHT-PVG). This protocol outlines the establishment of the guideline working group, the identification and prioritization of key questions, evidence retrieval and appraisal, and the formulation of recommendations, with the aim of ensuring methodological rigor and transparency in the development of the patient guideline and providing methodological reference for similar guideline initiatives.

Objective: The efficacy of antidepressants is influenced by a combination of genetic, individual, and environmental factors. This study aimed to investigate the association between the miR-182 rs76481776 polymorphism and the response to antidepressant treatment in major depressive disorder (MDD) patients, and its underlying molecular mechanisms. Methods: This study enrolled 180 MDD patients and 180 healthy controls. The rs76481776 genotype was determined using TaqMan-based qPCR. The severity of depression and treatment response were assessed using the Hamilton Depression Rating Scale (HAMD). The expression of miR-182 and BDNF was measured using RT-qPCR. The regulatory relationship between miR-182 and BDNF was confirmed through a luciferase reporter gene assay. The correlation between miR-182 and BDNF expression was evaluated using the Pearson correlation coefficient. Results: The T allele of rs76481776 was a significant risk factor for MDD (OR = 2.182, 95% CI: 1.424−3.345, p ＜ 0.001) and was significantly associated with higher baseline scores on the HAMD. Moreover, individuals carrying the T allele (CT/TT genotype) exhibited a significantly poorer response to antidepressant treatment and a lower remission rate within 12 months compared to those with the CC genotype (p ＜ 0.05). Mechanistically, miR-182 was highly expressed in patients with MDD (p ＜ 0.05), and its expression was even higher in T allele carriers (p ＜ 0.05). miR-182 could directly target and suppress BDNF, leading to decreased BDNF expression in MDD patients, and its expression was significantly and inversely correlated with BDNF expression. Conclusion The T allele of rs76481776 diminished the therapeutic efficacy of antidepressants by up-regulating miR-182 expression and subsequently suppressing BDNF expression.

Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

Traditional Chinese medicine （TCM）， through its multi-target and systematic regulatory effects， has demonstrated unique advantages in the treatment of gastric precancerous lesions （GPL）. At present， TCM theoretical research on GPL is mainly reflected in three aspects， the integration of macroscopic syndrome differentiation， the inflammation-carcinoma transformation mechanism， as well as the systematization and scientization of theoretical inheritance from famous TCM practitioners. High-quality evidence-based research findings serve as the foundation for clinical practice guidelines on GPL， and TCM has gained international academic recognition in the field of GPL prevention and treatment. Research on TCM mechanisms has yielded a series of important outcomes in the aspects of signaling pathways， gene expression regulation， cellular epigenetics， histone modification， and intestinal microecology. It is proposed that future research on GPL should focus on four key directions， establishing multi-omics data， exploring targeted intervention strategies on key regulatory nodes， advancing the standardization process of integrated traditional Chinese and western medicine prevention and treatment technologies， and constructing stratified screening and intervention platforms. The in-depth integration of TCM microcosmic mechanism of action with its macroscopic syndrome differentiation and treatment system， coupled with interdisciplinary research， will provide valuable references for the clinical treatment and scientific research of GPL.

Clinical trials represent a pivotal stage in the development of pharmaceutical drugs. Nevertheless， given the unique characteristics of traditional Chinese medicine （TCM） and the diagnostic and treatment principle of syndrome differentiation and treatment in TCM， the clinical evaluation techniques and methods that can comprehensively reflect the characteristics of TCM and are tailored to its specificities are still in need of refinement and innovation. This paper systematically summarizes the key techniques and methods for designing and evaluating the clinical research on the treatment of the spleen and stomach diseases with TCM from three aspects including clinical research design， evaluation， and platform construction， compares domestic and international research landscapes， and proposes for future directions. It is suggested that a multidimensional evaluation system integrating modern medicine and TCM theory should be established， and further innovation is needed in TCM research design and methodologies， leveraging intelligent devices and technologies powered by next-generation information technology to transform clinical data into high-quality TCM evidence. Moreover， standardized and shared platforms for TCM clinical data should be accelerated， so as to provide references for the design， implementation， and evaluation of future clinical research on the treatment of the spleen and stomach diseases with TCM.

Symptom and syndrome efficacy evaluation scales are indispensable tools for clinical efficacy assessment in traditional Chinese medicine （TCM）， and hold significant value at all stages of new drug research development for spleen and stomach diseases. These scales can provide scientific basis for clinical positioning， efficacy evaluation， and expansion of indications of new drugs. By analyzing the current hotspots and difficulties in research， this study aims to explore the important significance of these scales in the development of new drugs for spleen and stomach diseases， summarize the domestic research progress， and conduct comparative analyses with international studies. Future development trends are also discussed in order to promote the application of symptom and syndrome efficacy evaluation scales in the development of new drugs for spleen and stomach diseases and to advance the moder-nization process of TCM.

Triple-negative breast cancer (TNBC) represents a distinctive subtype, characterized by the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). Due to its high inter-tumor and intra-tumor heterogeneity, TNBC poses significant chanllenges for personalized diagnosis and treatment. The advant of clustered regular interspaced short palindromic repeats (CRISPR) technology has profoundly enhanced our understanding of the structure and function of the TNBC genome, providing a powerful tool for investigating the occurrence and development of diseases. This review focuses on the application of CRISPR/Cas technology in the personalized diagnosis and treatment of TNBC. We begin by discussing the unique attributes of TNBC and the limitations of current diagnostic and treatment approaches: conventional diagnostic methods provide limited insights into TNBC, while traditional chemotherapy drugs are often associated with low efficacy and severe side effects. The CRISPR/Cas system, which activates Cas enzymes through complementary guide RNAs (gRNAs) to selectively degrade specific nucleic acids, has emerged as a robust tool for TNBC research. This technology enables precise gene editing, allowing for a deeper understanding of TNBC heterogeneity by marking and tracking diverse cell clones. Additionally, CRISPR facilitates high-throughput screening to promptly identify genes involved in TNBC growth, metastasis, and drug resistance, thus revealing new therapeutic targets and strategies. In TNBC diagnostics, CRISPR/Cas was applied to develop molecular diagnostic systems based on Cas9, Cas12, and Cas13, each employing distinct detection principles. These systems can sensitively and specifically detect a variety of TNBC biomarkers, including cell-specific DNA/RNA and circulating tumor DNA (ctDNA). In the realm of precision therapy, CRISPR/Cas has been utilized to identify key genes implicated in TNBC progression and treatment resistance. CRISPR-based screening has uncovered potential therapeutic targets, while its gene-editing capabilities have facilitated the development of combination therapies with traditional chemotherapy drugs, enhancing their efficacy. Despite its promise, the clinical translation of CRISPR/Cas technology remains in its early stages. Several clinical trials are underway to assess its safety and efficacy in the treatment of various genetic diseases and cancers. Challenges such as off-target effects, editing efficiency, and delivery methods remain to be addressed. The integration of CRISPR/Cas with other technologies, such as 3D cell culture systems, human induced pluripotent stem cells (hiPSCs), and artificial intelligence (AI), is expected to further advance precision medicine for TNBC. These technological convergences can offer deeper insights into disease mechanisms and facilitate the development of personalized treatment strategies. In conclusion, the CRISPR/Cas system holds immense potential in the precise diagnosis and treatment of TNBC. As the technology progresses and becomes more costs-effective, its clinical relevance will grow, and the translation of CRISPR/Cas system data into clinical applications will pave the way for optimal diagnosis and treatment strategies for TNBC patients. However, technical hurdles and ethical considerations require ongoing research and regulation to ensure safety and efficacy.

Background Previous studies have demonstrated that the vagus nerve stimulation improves upper limb function in patients with stroke sequelae(six month-two years).This study aimed to investigate whether the auricular intradermal acupuncture(AIA)acted on the auricular branch of the vagus nerve can facilitate the recovery of upper limb motor function and expedite the effects and characteristics of rehabilitation processes in flaccid phase after stroke in Phase Brunnstrom Ⅰ.Methods This study utilized a randomized controlled single-blinded clinical design.Patients with ischemic stroke in Phase Brunnstrom Ⅰ were randomly assigned to the auricular intradermal acupuncture(AIA)group(AIA,standard rehabilitation,conventional acupuncture)or the sham auricular intradermal acupuncture(sham AIA)group(the sham AIA,standard rehabilitation,conventional acupuncture)for 6 days of 1 week(6 times).Primary outcome measures:Brunnstrom(Ueda Assessment),Fugl-Meyer assessment of the upper extremity(FMA-UE)and its subtype score(FMA-UEFS,FMA-UEES),Wolf motor function test scale(WMFT).Secondary outcome measures:Upper limb active range of joint motion(AROM),manual muscle test(MMT)of upper limb muscles,Barthel index(BI).Results Of the 332 patients who were screened,70 patients met the criteria and were recruited.There were 35 patients in the AIA group,1 patient was fall off,34 patients were actually completed;35 patients in the sham AIA group had no falling off case.Primary outcome measures:The upper Ueda assessment of the AIA group were better than those of the sham AIA group after treatment on days 3 and 6(P<0.05,P<0.001,respectively).The FMA-UEFS score on days 6 of the AIA group were significantly better than those of the sham AIA group(P<0.05).FMA-UEES of the AIA group was more associated with FMA-UE than FMA-UEFS with FMA-UE after treatment on day 6(FMA-UEFS:r=0.728,P<0.001;FMA-UEES:r=0.744,P<0.001).After 3 days and 6 days of treatment,the AIA group of the WMFT were significantly improved in the sham AIA group(P<0.05,P<0.001,respectively).Secondary outcome measures:AROM:After 6 days of treatment,the AIA group of shoulder abduction were more improved than in the sham AIA group(P<0.05).MMT:The muscle strength of elbow flexion,and elbow extension muscle improved more in the AIA group than in the sham AIA group(P<0.05).Barthel index(BI):After 6 days of treatment,there was a significant improvement in the group compared with before treatment(P<0.05),but no difference compared with the group(P>0.05).Conclusions AIA combined with conventional rehabilitation and acupuncture,can effectively improve the upper limb motor function of patients with post-ischemic stroke flaccid hemiplegia and accelerates the rehabilitation process of upper limb motor function.Clinical Trial Registration The study protocol is registered withhttp://www.chictr.org.cn(accession number:ChiCTR2200058141).

Objective To observe the value of shear wave elastography(SWE)for evaluating therapeutic effect of ultrasound-guided drug injection for muscle injury.Methods Eighty patients with unilateral muscle injury were retrospectively included,including 40 cases underwent ultrasound-guided drug injection(group A)and 40 cases underwent electromagnetic wave physiotherapy plus external application of Yunnan Baiyao Gao(group B).Pain intensity was assessed using visual analogue scale(VAS)before treatment and 3 weeks after the final treatment,while the Young modulus(E)value of the injured muscle was measured before treatment and 1,2 and 3 weeks after final treatment,and the improvements of VAS scores and E values were compared between groups.Results The total effective rate in group A(35/40,87.50%)was higher than that in group B(21/40,52.50%;P＜0.05).Before treatment,no significant difference of VAS score was found between group A(8.07±0.83)and group B(7.88±0.85)(P＞0.05).After treatment,VAS scores decreased in both groups(both P＜0.05),which in group A(2.30±1.07)was more obviously than that in group B(4.80±0.82)(P＜0.05).After treatment,E values of injury muscles increased significantly in both groups(P＜0.05),while group A had a greater increase in overall magnitude and overall rate than group B(P＜0.05).Conclusion Ultrasound-guided drug injection therapy had significant therapeutic effect for muscle injuries,which could be dynamically monitored with SWE.