Qianjiang Central Hospital

Electronic integrated circuits are struggling to meet growing computational demands. Optical neural networks are considered a promising path to overcome computational bottlenecks. In this paper, a computational structure is proposed. By integrating a microring resonator (MRR) with the Mach-Zehnder modulator (MZM) and applying wavelength division multiplexing (WDM) technology, the computational density is improved. Firstly, a theoretical model of microring-assisted MZM was established based on the coupling matrix. Using this model, the relationship between the weights and the modulation phase was achieved. The corresponding simulation model was built and validated to assess the effectiveness of the theoretical model. Finally, experimental verification was performed on the fabricated photonic integrated chip (PIC). The results showed that the computational structure proposed in this paper can perform the convolutional computation. The computational density reached 3.3 TOPS/TOPSmm2mm2, and the power consumption required to modulate the smallest computing unit was 25.92 mW. This provides a practical technical solution for building high-efficiency optoelectronic hybrid computing systems.

N6-methyladenosine (m6A) RNA modification plays a critical role in cancer biology, yet its causal impact on lung squamous cell carcinoma (LSCC) remains poorly understood. To address this, we intersected 19 known m6A-related genes with cis-expression quantitative trait loci datasets and identified 12 genes with reliable expression quantitative trait loci data. These genes were then used as exposures in Mendelian randomization (MR) analyses, with LSCC as the outcome. Our MR analysis revealed that methyltransferase like 14 (METTL14) exerts a significant protective effect against LSCC development (odds ratio [OR] = 0.734, 95% confidence interval [CI] = 0.567-0.950, P = .019). Further MR analysis at the immune cell level identified CD19+ IgD- CD38dim as a potential mediator. Specifically, METTL14 was positively associated with increased CD19+ IgD- CD38dim (OR = 1.636, 95% CI = 1.306-2.050, P < .001), and higher CD19 expression was associated with a reduced risk of LSCC (OR = 0.858, 95% CI = 0.767-0.961, P = .008). Mediation analysis indicated CD19+ IgD- CD38dim accounted for ~24.3% of the total effect of METTL14 on LSCC risk. Altogether, these findings suggest that the m6A demethylase METTL14 plays a protective role in the pathogenesis of LSCC, potentially by upregulating CD19+ IgD- CD38dim. This study is the first to establish a causal link between an m6A demethylase and LSCC risk, highlighting a novel METTL14-CD19-LSCC regulatory axis. The results not only provide new mechanistic insights into LSCC pathogenesis but also suggest potential clinical implications, including the development of METTL14-related biomarkers and immune-based therapeutic strategies.

Acute lung injury (ALI) is a major contributor to the high morbidity and mortality associated with intestinal ischemia-reperfusion (II/R). Despite its severity, current clinical management of ALI remains limited to supportive care without addressing the cause of the disease, underscoring the urgent need to investigate the underlying mechanism and develop targeted therapies. In this study, we employed both in vitro and in vivo models to explore ALI in the setting of II/R. Our findings demonstrated that II/R-induced systemic inflammation activates nucleotide-binding oligomerization (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in lung endothelium, leading to the release of pro-inflammatory cytokine interleukin-1β (IL-1β) and pyroptotic cell death. This cascade ultimately damages lung vasculature and exacerbates ALI. Importantly, we revealed that sevoflurane, a commonly used anesthetic, can inhibit NLRP3 inflammation under II/R condition and provide protection against ALI. Mechanistically, sevoflurane downregulates NLRP3 expression via deactivating inhibitor of nuclear factor kappa-B kinase (IKK)/nuclear factor kappa-B kinase (NF-κB) signaling pathway, and simultaneously inhibits NLRP3 activation through protein kinase A (PKA)-mediated mechanism. These findings offered novel insights into the pathogenesis of II/R-induced ALI and highlighted the therapeutic potential of sevoflurane. Given sevoflurane's established clinical use, our results could have immediate implications for patient care in II/R situations.

The dysfunction of vascular endothelial cells (VECs) is an important cause of diabetes-related cardiovascular diseases. Coptisine is a bioactive component of Rhizoma coptidis with anti-diabetes property. The aim of this present study was to clarify the role and possible mechanism of coptisine underlying VEC dysfunction during gestational diabetes mellitus (GDM). Human umbilical vein endothelial cells (HUVECs) were treated with coptisine and/or high glucose (HG) medium. A GDM rat model was established by high-fat diet feeding and streptozotocin injection. Cell viability, migration, and angiogenesis were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, wound healing assay, Transwell assay, and tube formation assay. The levels of angiogenesis-related proteins and the key markers in the Adenosine monophosphateactivated protein kinase (AMPK)/nuclear factor-erythroid 2-related factor 2 (NRF2) signaling pathway were tested by western blot analysis. The pathological changes of placental tissues were observed by HE staining. We found that the cell viability of HUVECs was repressed in HG conditions in a dose-dependent manner, and 25mM HG reduced the HUVEC viability in a time-dependent manner. Coptisine (5 to 5o μM) did not cause cytotoxicity to HUVECs. In addition, HG-induced the decrease in cell viability and migration of HUVECs were rescued by coptisine in a dose-dependent manner. Coptisine restored the angiogenetic ability of HG-induced HUVECs by upregulating the protein expression of fibroblast growth factor 2, vascular endothelial-derived growth factor, and Angiotensin 1. Moreover, coptisine treatment re-activated the AMPK/NRF2 pathway in HG-stimulated HUVECs. Importantly, inhibition of AMPK/NRF2 signaling reverses the effect of coptisine on cell viability, migration, and angiogenesis of HUVECs. The in vivo study demonstrated that coptisine suppresses hyperglycemia and placenta injury in GDM rats. Coptisine protected HUVECs from hyperglycemic insult, suggesting the potential of coptisine which might be used as a therapeutic agent for VEC dysfunction in GDM.

3563 Background: This CAPCET randomized phase II trial was designed to assess the efficacy and safety of modified capecitabine and oxaliplatin (mCapOX) plus cetuximab (CET) and modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus cetuximab (CET) for the first-line treatment of left-side unresectable RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC). Methods: CAPCET was an open-label, multicenter, randomized, non-comparative phase II trial. Patients with unresectable RAS/BRAF wt mCRC were randomly assigned (1:1) to receive up to 12 cycles biweekly mCapOX (capecitabine 1000mg/m 2 orally twice daily on Day 1-7 and oxaliplatin 85 mg/m 2 iv on Day 1) plus CET (500mg/m 2 iv on day 1) (arm A) or biweekly mFOLFOX6 (oxaliplatin 85 mg/m 2 iv on day 1, leucovorin 400 mg/m 2 iv on day 1, fluorouracil 400mg/m 2 iv bolus on day 1, then fluorouracil 2400 mg/m 2 continuous infusion over 46-48h) plus CET (500mg/m 2 iv on day 1)(arm B) followed by maintenance(either capecitabine plus CET or capecitabine alone at the discretion of the investigators) or treatment-free intervals until progression on treatment, toxicity, or death. The primary endpoint was progression-free survival (PFS) rate at 9 months from randomization. Results: Between September 2021 and April 2024, 168 patients (84 in arm A and 84 in arm B) were enrolled in 20 China centres. Baseline characteristics were well balanced between arms. After a median follow-up of 21.0 months (IQR,19.5-22.5), the 9 months-PFS rates were 70.9% (95% CI 61.1%-82.3%) in arm A and 66.8% (95% CI 56.7%-78.6%; HR = 1.11, P = 0.558) in arm B, and the primary endpoint was met. The median PFS (arm A/B) was 12.7 months (95% CI 10.8–15.2)/12.0 months (95% CI 9.7–14.1). The overall response rate (ORR) and disease control rate (DCR) in arm A were higher than those in arm B with 69.2% versus 60.3% and 96.2% versus 89.7%, respectively. The 2-year overall survival (OS) rate (arm A/B) was 66.8% (95% CI 54.2%–82.3%)/65.6% (95% CI 52.5%–82.0%), and the median OS not reached. Grade≥3 adverse events (AEs) occurred in 28.8% of safety population set (n = 156), with 7.7% in arm A and 21.2% in arm B. The most commonly Grade≥3 AEs was neutropenia, rash, leukopenia and there were no grade 5 AEs reported. Conclusions: The CAPCET study met its first endpoint of 9-month PFS rate in patients with RAS/BRAF wt mCRC. Biweekly mCapOX plus CET had higher ORR and DCR than mFOLFOX6 plus CET, with signally reduced toxicity. Longer follows-up and a multicenter, open-label, randomized, controlled Phase CAPCET- III study (NCT06616259) will be further validate this innovative regimen. Clinical trial information: NCT05022030 .

ABSTRACT The purpose of the study is mainly to investigate anti proliferation of non-small cell lung cancer A549 cells and its mechanism by inhibition of CHK1 expression combined with gemcitabine. The mRNA and protein levels of genes were analyzed by RT-qPCR and Western blot, respectively. Cell viability was detected by CCK-8 assay and clone formation assay. The detection of the cell cycle was used by Annexin V/7-amino-actinomycin D apoptosis detection kit. Analysis of DNA damage was done by immunofluorescence and alkaline comet assay. The results showed that inhibition of CHK1 and gemcitabine combination significantly reduced the proliferation ability of the two cell lines. We also revealed the degradation of full-length PARP and reduced Bcl-2/Bax ratio on increased apoptosis. Inhibition of CHK1 expression leads to DNA damage, induces phosphorylation of γ-H2AX, and affects the repair of homologous recombination ability through Rad51. Mechanistically, gemcitabine increased phosphorylation-ATR and phosphorylation-CHK1, indicating activation of the DNA repair system and ATR-CHK1-CDC25A pathway. Inhibition of CHK1 resulted in increased synthesis of CDK2/Cyclin A2 and CDK2/Cyclin E1 complexes, and more cells entered the subsequent cell cycle, leading to S phase arrest and mitotic catastrophe. We identified inhibition of CHK1 as a potential treatment for NSCLC and confirmed that inhibition of this kinase could overcome acquired gemcitabine resistance.

Accurate identification of low-abundance point mutations is a crucial technical challenge in clinical diagnosis, particularly within high wild-type genomic backgrounds. We established an engineered CRISPR/Cas12a point mutation detection strategy (E-CRISPR) for low-abundance point mutations detection. By integrating the precise regulatory mechanism of strand displacement reaction (SDR) with the local high-concentration probe microenvironment created by tetrahedral DNA frameworks (TDFs), it has achieved simultaneous improvement in single-nucleotide resolution and ultrasensitive detection performance. This strategy was validated using an mitochondrial m.11778 G>A mutation associated with Leber’s hereditary optic neuropathy (LHON) and achieved a detection limit of 0.1% mutant allele frequency under isothermal conditions within 20 minutes. This approach represents a clinically versatile mutation diagnosis strategy with high sensitivity and specificity, which provides an innovative solution to breakthrough the existing technical bottlenecks.

Castleman disease, also known as Castleman syndrome, is a rare, nonmalignant lymphoproliferative disorder. The localized subtype of this disease is primarily the hyaline vascular type of Castleman disease (HVCD). Although this disease is a benign lesion, the histologic features are similar to those of some malignant lymphomas, so an accurate diagnosis of the disease is required. Lymph node hyperplasia lesions are usually diagnosed mainly by relying on biopsy histopathology, but the surgical process is time-consuming and expensive, and a part of patients usually refuse to undergo this examination method. Fine-needle aspiration cytology (FNAC) is a convenient, rapid, minimally invasive test for surface masses, and patients often receive cytopathology results in as little as a few minutes. Currently, there are few reports on the pathological features of FNAC in HVCD, so our cytopathological experience of using FNAC for rapid diagnosis of HVCD and other diseases that need to be differentiated are described in detail to give some meaningful references to the pathologists in recognizing HVCD from a rare cytological point of view. A late 50s female patient presented to the hospital with a single subcutaneous enlarged nodule in the right side of the neck, which had been present for >6 months. The nodule exhibited a relatively clear border, and the patient presented with no signs of pain, no skin damage, and no other notable symptoms, but was concerned about the benignity or malignancy of the enlarged nodule. To determine the exact diagnosis of the neck nodule, the patient first underwent FNAC, followed by surgical excision of the neck nodule for histopathologic examination. Since HVCD is a benign lesion and the superficial neck nodes were removed by minimally invasive surgery, the patient did not receive any other interventions. We successfully and accurately diagnosed the rare HVCD using FNAC. Histologically similar lesion features of HVCD were successfully observed in cytology. The cytologic pattern of HVCD is distinctly different from that of other benign lymphoid tissue proliferative lesions or metastatic carcinomas. This case shows important cytologic features for the diagnosis of HVCD using FNAC. The FNAC results showed abundant follicular dendritic cells and transparent blood vessels, and these cytologic features recapitulate the histopathologic alterations that were seen in HVCD. So by observing these cytologic features can help us to make an accurate diagnosis of HVCD using FNAC.

To investigate the feasibility of conventional (basketing + dusting) and Moses (pop-dusting) holmium lasers during flexible ureteroscopy (FURS) in the treatment of 2-3cm renal calculi and to compare the efficiency and safety of the two methods, a total of 230 patients with 2-3cm kidney stones who underwent FURS were randomly divided into the conventional group and the Moses group. The mode of lithotripsy in the conventional group was fragmentation and dusting. The mode of lithotripsy in the Moses group was dusting and pop-dusting. Clinical and perioperative variables and complications were compared between the two cohorts. Multivariate analyses of factors contributing to the stone-free rate (SFR) and operation time were performed. No statistically significant differences were found in the demographics, renal stone-related data, SFR, or complications between the cohorts. The laser energy was higher in the Moses cohort than in the conventional cohort (119.3 ± 15.2 vs. 92.8 ± 15.1kJ; P < 0.001), and the operation time was shorter in the Moses cohort than in the conventional cohort (99.5 ± 18.9 vs. 105.3 ± 13.7min; P = 0.009). When there was isolated stone, the operation time was shorter in the Moses cohort than in the conventional cohort (99.6 ± 17.5 vs. 111.4 ± 10.7min; P < 0.001), while there was no significant difference between the two cohorts when there were multiple stones (99.5 ± 20 vs. 101.2 ± 14min; P = 0.415). Multivariate analyses found that an increase in stone volume can decrease the SFR and prolong the operation time, and use of a Moses laser can shorten the operation time. Both holmium laser modes during FURS can effectively treat 2-3cm renal calculi. The Moses mode is recommended as the first choice for the treatment of isolated 2-3cm renal stones. When treating multiple stones, the efficiency of these two laser modalities is the same. TRIAL REGISTRATION: ChiCTR2200056091.