AIM: To evaluate the surgical outcomes and changes in the ocular surface microenvironment following radiofrequency minimally invasive treatment for conjunctivochalasis-induced epiphora.METHODS: Patients with epiphora primarily caused by conjunctivochalasis were enrolled. All patients had conjunctivochalasis of ≥grade II, and their symptoms showed no significant improvement after previous pharmacological treatment. All patients underwent radiofrequency minimally invasive correction of conjunctivochalasis, supplemented with artificial tears, anti-inflammatory therapy, and ocular surface repair treatment postoperatively. At 8 wk post-surgery, the ocular surface disease index(OSDI), eye redness, tear secretion, non-invasive tear break-up time, lipid layer thickness, tear ferning test, and conjunctival impression cytology were assessed to compare treatment efficacy and observe changes in the ocular surface microenvironment.RESULTS: A total of 43 cases(43 eyes)of conjunctivochalasis and with a main complaint of epiphora were included, including 23 males and 20 males, with a mean age of 64.69±3.36 years. The total effective rate of surgery was 91% at 8 wk postoperatively. Compared with preoperative values, the OSDI scores significantly decreased and the non-invasive tear break-up time was prolonged at 8 wk post-surgery(all P<0.05). No statistically significant differences were observed in lipid layer thickness or tear secretion at 8 wk postoperatively(all P>0.05). The normal rate of chloramphenicol taste test increased from 21% preoperatively to 63% postoperatively; the normal rate of eye redness increased from 40% to 70%; normal rate of tear ferning grading improved from 30% to 63%; and normal conjunctival impression cytology grading increased from 21% to 74%.CONCLUSION: Radiofrequency minimally invasive treatment is effective for conjunctivochalasis and is straightforward to perform. Patients with conjunctivochalasis often present with other ocular surface issues beyond conjunctivochalasis itself, such as insufficient tear secretion, reduced lipid layer thickness, and other dry eye-related problems. Therefore, a comprehensive approach emphasizing tear dynamics should be adopted during treatment.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

From the theoretical perspective of "body fluids and blood stasis mixing"， environmental microplastics （MPs） are conceptualized as a "novel turbid-toxin". This study aims to elucidate the complete pathogenic pathway through which MPs act as a key driving force （the "crucible" of pathogenesis） in the initiation and progression of atherosclerosis （AS）. By tracing the classical theories in the Chapter The Occurrence of All Diseases of Miraculous Pivot （Ling Shu）， this paper clarifies the core connotations of "body fluids"-it not only refers to endogenous pathological fluids and lipid turbidity but also provides a theoretical basis for incorporating "exogenous turbid fluids"， thereby laying a logical foundation for conceptualizing MPs as a "novel turbid-toxin". Meanwhile， the implications of "blood" （encompassing both blood quality abnormalities and blood stasis） and the dynamic process of "mixing" are elucidated. Drawing upon modern toxicological evidence， this paper demonstrates the high homology between MPs and "exogenous turbid-fluids" from three aspects： Morphology， toxicity， and invasion routes. The micro/nano-scale particle morphology of MPs enables mobility within the bloodstream. The multiple exposure pathways of MPs correspond to the traditional Chinese medicine understanding of pathogens invading through the mouth， nose， and skin. The characteristics of accumulating in vivo while inducing oxidative stress and inflammatory responses of MPs fully embody the pathogenic features-adhesion， binding， and vessel damage-of "turbid-toxin". On this basis， the dynamic pathogenesis of MP-induced AS is systematically interpreted. Initially， MPs with the "turbid-toxin" nature impair nutrient-defense harmony and cause endothelial dysfunction. Subsequently， as the core of "mixing"， they interact with blood lipids and immune cells， generating heat and phlegm to form a major pathological hub of chronic inflammation. Ultimately， this process drives the coalescence of phlegm， stasis， and turbid-toxin into tangible plaques， evolving from stable lesions to vulnerable masses and accumulations. By integrating classical pathogenic model with contemporary environmental medicine， this study establishes an analytical framework that bridges macro-theory and micro-mechanisms for understanding the cardiovascular risks of MPs through an integrative Chinese-Western medicine lens.

Purpose: This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery. Materials and Methods: Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety. Results: From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events. Conclusion Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.

ObjectiveHepatocyte nuclear factor 4-alpha (HNF4A) is a critical transcription factor in the liver and pancreas. Dysfunctions of HNF4A lead to maturity onset diabetes of the young 1 (MODY1). Notably, MODY1 patients with HNF4A pathogenic mutations exhibit decreased responses to arginine and reduced plasma triglyceride levels, but the mechanisms remain unclear. This study aims to investigate the potential target genes transcriptionally regulated by HNF4A and explore its role in these metabolic pathways. MethodsA stable 293T cell line expressing the HNF1A reporter was overexpressed with HNF4A. RNA sequencing (RNA-seq) was performed to analyze transcriptional differences. Transcription factor binding site prediction was then conducted to identify HNF4A binding motifs in the promoter regions of relevant target genes. ResultsRNA-seq results revealed a significant upregulation of transmembrane 4 L six family member 5 (TM4SF5) mRNA in HNF4A-overexpressing cells. Transcription factor binding predictions suggested the presence of five potential HNF4A binding motifs in the TM4SF5 promoter. Finally, we confirmed that the DR1 site in the -57 to -48 region of the TM4SF5 promoter is the key binding motif for HNF4A. ConclusionThis study identified TM4SF5 as a target gene of HNF4A and determined the key binding motif involved in its regulation. Given the role of TM4SF5 as an arginine sensor in mTOR signaling activation and triglyceride secretion, which closely aligns with phenotypes observed in MODY1 patients, our findings provide novel insights into the possible mechanisms by which HNF4A regulates triglyceride secretion in the liver and arginine-stimulated insulin secretion in the pancreas.

Ferritin, a ubiquitous protein in living organisms, plays a crucial role in storing and converting iron, as well as maintaining cellular iron metabolism balance. Due to the ability of self-assembling into unique nanocage-like structures in vitro and the special physicochemical properties, ferritin has garnered extensive attention in the biomedical field. This paper provides a brief overview of the structure and cargo loading strategies of ferritin, with a specific focus on its applications in various biological fields such as nanomedicine, bioimaging, and nanoparticle vaccine carriers. The aim is to offer a valuable reference for the future research involving ferritin nanoparticles.
Ferritins/chemistry* ; Nanoparticles/chemistry* ; Humans ; Nanomedicine/methods* ; Animals

The plant AT-rich sequence and zinc-binding protein (PLATZ) family is composed of plant-specific zinc finger-like transcription factors, which play important roles in plant growth, development, and stress tolerance. In this study, to gain a better understanding of the PLATZ gene in C. sinensis and elucidate its response under drought and high temperature conditions, the PLATZ gene family of the C. sinensis cultivar 'Tieguanyin' was systematically identified, and a total of 12 CsPLATZ family members were identified. Expasy online and other bioinformatics tools were used to analyze the members of the PLATZ gene family in terms of protein physicochemical properties, phylogenetic relationships, cis-acting elements, gene structures, and intra- and inter-species collinearity. The results of phylogenetic analysis classified the CsPLATZ family members into 2 subfamilies. The conserved domains and gene structures of PLATZ family members within the same subfamily had a high degree of consistency, whereas a certain degree of diversity was observed among the subfamilies. Twelve PLATZ genes were unevenly distributed across 7 chromosomes of C. sinensis and the promoter regions of these genes had multiple cis-acting elements related to hormone and stress responses. The collinearity analysis showed that there were 4 pairs of duplication events in the CsPLATZ gene family, all of which were segmental duplications. Based on this gene family, C. sinensis had a closer evolutionary relationship with A. thaliana than with O. sativa. The transcriptome analysis showed that the expression levels of CsPLATZ family members varied in different tissue samples of C. sinensis. 6 genes (CsPLATZ-1, CsPLATZ-2, CsPLATZ-3, CsPLATZ-4, CsPLATZ-6, and CsPLATZ-8) with high expression in shoots, young leaves, and roots were selected for high temperature and drought stress treatments, and their expression was quantified by qRT-PCR. The results indicated that the six genes might play important roles in the response to drought stress. In addition, CsPLATZ-2 and CsPLATZ-8 might have important functions in the response to high temperature stress. The results of this study will contribute to a better understanding of the biological functions of PLATZ genes and their possible roles in the growth, development, and stress responses of C. sinensis.
Droughts ; Camellia sinensis/physiology* ; Phylogeny ; Gene Expression Regulation, Plant ; Plant Proteins/genetics* ; Stress, Physiological/genetics* ; Multigene Family ; Transcription Factors/genetics* ; Hot Temperature ; Genes, Plant

Objective To investigate the internalized weight bias and weight control beliefs regarding the current status,influencing factors,and impacts on eating behaviors of women losing weight. Methods A convenient sampling method was used to select the females who underwent physical examination in the Peking Union Medical College Hospital from August to December 2023.The general information questionnaire,Weight Bias Internalization Scale,Weight Control Belief Questionnaire,and Chinese version of Three-Factor Eating Questionnaire were utilized for investigation.Latent class analysis was conducted to explore the potential categories based on the characteristics of internalized weight bias and weight control beliefs.Univariate analysis and multiple-factor linear regression analysis were performed to explore influencing factors of potential categories and their effects on eating behaviors. Results A total of 518 subjects were included in this study.The internalized weight bias and weight control beliefs could be classified into three potential categories: low weight bias tolerance type(53.7%),medium weight bias persistence type(29.5%),and high weight bias overcritical type(16.8%).Logistic regression analysis showed that body mass index,unmarriage,and divorce were the influencing factors of the high weight bias overcritical type.The scores of non-control eating and emotional eating in medium weight bias persistence type and high weight bias overcritical type were higher than those in low weight bias tolerance type(all P<0.001). Conclusions The attitudes of Chinese women towards body weight can be categorized into low weight bias tolerance type,medium weight bias persistence type,and high weight bias overcritical type.The high weight bias overcritical type is characterized by high weight bias and high personal responsibility attribution,and it is closely associated with negative eating behaviors.A high body mass index,unmarriage,and divorce are high-risk factors for developing the high weight bias overcritical type.
Humans ; Female ; Feeding Behavior/psychology* ; Surveys and Questionnaires ; Adult ; Body Mass Index ; Weight Loss ; Body Weight ; Body Image ; Middle Aged ; Weight Prejudice

Objective To compare the application effects of plankton multiplex polymerase chain reac-tion-capillary electrophoresis(PCR-CE),SYBR Green Ⅰ real-time quantitative PCR(qPCR)and microwave digestion-vacuum filtration-automated scanning electron microscopy(MD-VF-Auto SEM)in the diagnosis of drowning.Methods Lung,liver and kidney tissues from 212 drowned corpses and 30 non-drowned corpses were examined respectively by the three drowning-related plankton testing methods,and the detection rates of plankton in each tissue by three methods were compared.Results In drowned corpses,the total detection rates of PCR-CE,qPCR,and MD-VF-Auto SEM were 93.9%,96.2%,and 95.3%,respectively,with no statistically significant difference(P>0.05).The detection rate of lung tissue by MD-VF-Auto SEM(100%)was higher than those of PCR-CE and qPCR(P<0.05),and there was no significant difference in the detection rates of the three methods in liver or kidney tissues(P>0.05).In non-drowning corpses,a small number of diatoms(less than 10 cells/10 g)were detected by MD-VF-Auto SEM method,only in liver and kidney tissues,while the other two methods yielded negative results for all tissues.Conclusion All three methods have good efficacy in the examination of drowned corpses.The MD-VF-Auto SEM method directly observes diatom morpho-logical characteristics through scanning electron microscopy,and the qualitative and quantitative analy-ses are intuitive and accurate.It has great advantages in the examination of difficult degradation samples.The PCR-CE method and qPCR method have a low sample demand(0.5 g),are easy to operate and have short detection time(4-7 h).They are easy to be applied in the grassroots depart-ments and are suitable for the rapid determination of drowned corpses in routin cases.The combina-tion of the two DNA methods with the MD-VF-Auto SEM method can increase the detection rate of plankton,ensuring the reliability of examination results.This combined use is of significant importance in the application of drowning diagnosis.

Aim To elucidate the molecular mecha-nism underlying the inhibitory effect of liquidambaric acid(LDA)targeting TNF receptor associated factor 6(TRAF6)in colorectal cancer.Methods This study employed microscale thermophoresis(MST),drug af-finity responsive target stability assay(DARTS)and cellular thermal shift assay(CETSA)to confirm the direct binding of LDA to TRAF6.Additionally,we generated TRAF6 knockout colorectal cancer HCT116 cells using CRISPR/Cas9 technology,and assessed the impact of LDA on TRAF6-regulated Hippo/YAP and Wnt signaling pathways through immunofluorescence a-nalysis and TOPFlash/Renilla luciferase reporter sys-tem.Co-IP and proximity ligation assays(PLA)were conducted to investigate LDA-regulated TRAF6 pro-tein-protein interactions and elucidate molecular mech-anisms.Results The direct binding of LDA to TRAF6 was confirmed in cell lysates and living cells.LDA promoted TRAF6-dependent nuclear translocation of YAP in colorectal cancer cells,and inhibited Wnt signaling by overexpressing TRAF6.Co-IP and PLA revealed that TRAF6 formed a tripartite complex with YAP and β-catenin in colon cancer cells,where TRAF6 was a key scaffolding protein of the tripartite complex.LDA disrupted the interactions between the TRAF domain of TRAF6 and YAP,as well as YAP and β-catenin.Conclusion LDA regulates Hippo/YAP signaling pathway by targeting TRAF6 and inhib-its colorectal cancer.