ObjectiveTo explore effect of Xianlian Jiedu prescription on the recurrence of colorectal cancer （CRC） and investigate the related mechanisms. MethodsA postoperative recurrence model was established in 25 Balb/c mice by injecting CT26 cells subcutaneously into the armpit， followed by surgical removal of 99% of the subcutaneous tumor. The mice were randomly divided into model group， low-dose Xianlian Jiedu prescription （XLJDP-L） group （6.45 g·kg^-1·d^-1）， medium-dose Xianlian Jiedu prescription （XLJDP-M） group （12.9 g·kg^-1·d^-1）， high-dose Xianlian Jiedu prescription （XLJDP-H） group （25.8 g·kg^-1·d^-1）， and 5-fluorouracil （5-FU） group （1×10^-3 g·kg^-1·d^-1）. The mice were euthanized after 14 days of continuous intervention， and recurrent tumor tissue was harvested. Hematoxylin and eosin （HE） staining was used to observe pathological and morphological changes in the recurrent tumor tissue. Immunohistochemistry （IHC） was employed to assess the expression of proliferating cell nuclear antigen （Ki67）， vascular endothelial growth factor （VEGF）， and platelet-endothelial cell adhesion molecule （CD31） in recurrent tumor tissue. The Western blot was used to detect the protein expression levels of angiopoietin-2 （ANG-2）， VEGF， phosphorylated-protein kinase B （p-Akt）， protein kinase B （Akt）， phosphorylated-phosphatidylinositol 3-kinase （p-PI3K）， and phosphatidylinositol 3-kinase （PI3K） in recurrent tumor tissue. ResultsBefore treatment， there were no statistical differences in tumor volume， tumor weight， and body mass among the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group compared to the model group， indicating model stability. After treatment， compared with those in the model group， the tumor volume and tumor weight in the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group were significantly reduced （P<0.01）， showing dose dependency. Meanwhile， there were no significant differences in body weight among the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group compared to the model group. HE staining showed that compared with that in the model group， tumor tissue in the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group had loosely arranged cells， increased intercellular spaces， small and shriveled nuclei， light staining， fewer mitotic figures and atypical nuclei， and increased necrotic areas. IHC showed that compared with those of the model group， the positive rates of Ki67， VEGF， and CD31 in the recurrent tumor tissue of the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group were significantly reduced （P<0.01） in a dose-dependent manner. Western blot results showed that compared with those of the model group， the protein expression levels of ANG-2 and VEGF in the recurrent tumor tissue of the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group were significantly downregulated （P<0.05， P<0.01）， and the p-Akt/Akt and p-PI3K/PI3K ratios were significantly decreased in a dose-dependent manner （P<0.05， P<0.01）. ConclusionXianlian Jiedu prescription significantly inhibits the recurrence of CRC in mice after subcutaneous tumor surgery. The mechanism may involve regulating the PI3K/Akt pathway and downregulating key angiogenic proteins such as ANG-2， VEGF， and CD31.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Sustained inflammatory responses are closely related to various severe diseases, and inhibiting the excessive activation of inflammasomes and pyroptosis has significant implications for clinical treatment. Natural products have garnered considerable concern for the treatment of inflammation. Huanglian-Wumei decoction (HLWMD) is a classic prescription used for treating inflammatory diseases, but the necessity of their combination and the exact underlying anti-inflammatory mechanism have not yet been elucidated. Inspired by the supramolecular self-assembly strategy and natural drug compatibility theory, we successfully obtained berberine (BBR)-chlorogenic acid (CGA) supramolecular (BCS), which is an herbal pair from HLWMD. Using a series of characterization methods, we confirmed the self-assembly mechanism of BCS. BBR and CGA were self-assembled and stacked into amphiphilic spherical supramolecules in a 2:1 molar ratio, driven by electrostatic interactions, hydrophobic interactions, and π-π stacking; the hydrophilic fragments of CGA were outside, and the hydrophobic fragments of BBR were inside. This stacking pattern significantly improved the anti-inflammatory performance of BCS compared with that of single free molecules. Compared with free molecules, BCS significantly attenuated the release of multiple inflammatory mediators and lipopolysaccharide (LPS)-induced pyroptosis. Its anti-inflammatory mechanism is closely related to the inhibition of intracellular nuclear factor-kappaB (NF-κB) p65 phosphorylation and the noncanonical pyroptosis signalling pathway mediated by caspase-11.

Objective To explore the psychosocial factors affecting the recurrence of the patients with myasthenia gravis (MG).Methods The retrospective analysis was adopted.One hundred and sixty-one pa-tients with MG treated in the neurosurgery department of this hospital from January 2019 to January 2021 were selected as the research subjects.The psychosocial data of the patients were collected.The correlation be-tween the gender,age of onset,history of underlying diseases,body mass index (BMI),education level,occu-pational nature,per capita monthly family income,living environment,payment method of medical expenses and mental state with the disease recurrence was analyzed.Results Among 161 patients,111 cases developed the recurrence (included in the recurrence group) and 50 cases (included into the stable group).There were statistically significant differences in the age,gender and mental status between the two groups (P<0.05),but there were no statistically significant differences in the history of underlying diseases,BMI,education lev-el,occupational nature,per capita monthly household income,living environment and payment method of med-ical expenses between the two groups (P>0.05).The multivariate logistic regression analysis results showed that the age of onset (OR=0.304,95％CI:0.146-0.634) and anxiety combined with depression (OR=2.706,95％CI:1.090-6.719) were the influencing factors of the recurrence in the patients with MG (P<0.05).Conclusion It is necessary to pay special attention to MG patients with young onset age,anxiety and depression status,which are prone to relapse.

The ChatGPT, a lite and conversational variant of Generative Pretrained Transformer 4 (GPT-4) developed by OpenAI, is one of the milestone Large Language Models (LLMs) with billions of parameters. LLMs have stirred up much interest among researchers and practitioners in their impressive skills in natural language processing tasks, which profoundly impact various fields. This paper mainly discusses the future applications of LLMs in dentistry. We introduce two primary LLM deployment methods in dentistry, including automated dental diagnosis and cross-modal dental diagnosis, and examine their potential applications. Especially, equipped with a cross-modal encoder, a single LLM can manage multi-source data and conduct advanced natural language reasoning to perform complex clinical operations. We also present cases to demonstrate the potential of a fully automatic Multi-Modal LLM AI system for dentistry clinical application. While LLMs offer significant potential benefits, the challenges, such as data privacy, data quality, and model bias, need further study. Overall, LLMs have the potential to revolutionize dental diagnosis and treatment, which indicates a promising avenue for clinical application and research in dentistry.
Dentistry ; Artificial Intelligence

OBJECTIVES: The automatic delineation of organs at risk (OARs) can help doctors make radiotherapy plans efficiently and accurately, and effectively improve the accuracy of radiotherapy and the therapeutic effect. Therefore, this study aims to propose an automatic delineation method for OARs in cervical cancer scenarios of both after-loading and external irradiation. At the same time, the similarity of OARs structure between different scenes is used to improve the segmentation accuracy of OARs in difficult segmentations. METHODS: Our ensemble model adopted the strategy of ensemble learning. The model obtained from the pre-training based on the after-loading and external irradiation was introduced into the integrated model as a feature extraction module. The data in different scenes were trained alternately, and the personalized features of the OARs within the model and the common features of the OARs between scenes were introduced. Computer tomography (CT) images for 84 cases of after-loading and 46 cases of external irradiation were collected as the train data set. Five-fold cross-validation was adopted to split training sets and test sets. The five-fold average dice similarity coefficient (DSC) served as the figure-of-merit in evaluating the segmentation model. RESULTS: The DSCs of the OARs (the rectum and bladder in the after-loading images and the bladder in the external irradiation images) were higher than 0.7. Compared with using an independent residual U-net (convolutional networks for biomedical image segmentation) model [residual U-net (Res-Unet)] delineate OARs, the proposed model can effectively improve the segmentation performance of difficult OARs (the sigmoid in the after-loading CT images and the rectum in the external irradiation images), and the DSCs were increased by more than 3%. CONCLUSIONS Comparing to the dedicated models, our ensemble model achieves the comparable result in segmentation of OARs for different treatment options in cervical cancer radiotherapy, which may be shorten time for doctors to sketch OARs and improve doctor's work efficiency.
Female ; Humans ; Image Processing, Computer-Assisted/methods* ; Machine Learning ; Organs at Risk/radiation effects* ; Radiotherapy Planning, Computer-Assisted/methods* ; Uterine Cervical Neoplasms/radiotherapy*

Objective:To investigate the role of survival motor neuron ( SMN) gene knockout in mice with cisplatin-induced acute kidney injury (AKI). Methods:A mouse model (C57BL/6) of cisplatin-induced AKI was constructed. Twenty male wild type (WT) and SMN+/- mice weighing 22-24 g were randomly divided into four groups: WT mice with saline injection group (WT vehicle, n=5), SMN+/- mice with saline injection group ( SMN+/- vehicle, n=5), WT mice with cisplatin injection group (WT cisplatin, n=5) and SMN+/- mice with cisplatin injection group ( SMN+/- cisplatin, n=5). Mice were injected intraperitoneally with 20 mg/kg cisplatin or 0.9% saline. 72 hours later, the mice were sacrificed, and serum and kidney tissues were collected. The real time PCR and Western blotting were used to measure the expression levels of SMN mRNA and protein. The sarcosine oxidation and urease method were used to measure serum creatinine (Scr) and blood urea nitrogen (BUN) levels. Renal pathologic changes were observed by PAS staining. TUNEL immunofluorescence assay was used to detect the level of apoptosis. Western blotting and immunohistochemistry were used to detect the protein expression levels of apoptosis index poly (ADP-ribose) polymerase (PARP) and endoplasmic reticulum stress index CHOP. Results:Compared with WT mice, SMN mRNA and protein expression levels were lower in SMN+/- mice, and the expression level of SMN mRNA and protein was further decreased after intraperitoneal cisplatin injection (all P<0.05). Compared with WT mice with saline injection group, WT mice with cisplatin injection group had higher levels of Scr, BUN, tubular damage scores, TUNEL positive cell numbers, PARP and CHOP, while the expression levels of above indexes in the SMN+/- mice with cisplatin injection group were higher than those in the WT mice with cisplatin injection group (all P<0.05). Conclusions:SMN gene knockout can aggravate renal pathological damage and apoptosis of renal tubular epithelial cell in cisplatin-induced AKI mice. SMN may be a potential therapeutic target of AKI.

Objective:To effectively express the receptor binding domain (RBD) of SARS-CoV-2 spike protein in Pichia pastoris and to evaluate its immunogenicity. Methods:The gene encoding the RBD protein was synthesized and cloned into the pPICZαA plasmid. After linearization, the plasmid was transferred and integrated into the genome of Pichia pastoris. The expressed RBD protein in culture supernatant was analyzed by Western blot and Biolayer interferometry. After screening, a single clone expressing the RBD protein was selected. The high-level expression of RBD protein was achieved by optimizing the fermentation process, including the salt concentration adjusting of the medium and induction condition optimization (pH, temperature and duration). The immunogenicity of the expressed RBD protein was evaluated in a mouse model. Results:A single clone with a high expression level of RBD protein was obtained and named RBD-X33. The expression level of RBD protein in the fermentation supernatant reached up to 240 mg/L after optimization of the induction condition (HBSM medium, pH=6.5±0.3, 22℃ and 120 h). In the mouse experiment, the recombinant RBD protein was formulated with Alum+ CpG dual adjuvant and injected into mice. The binding IgG antibody levels were up to 2.7×10 6 tested by ELISA and the neutralizing antibody levels were up to 726.8 tested by live virus neutralizing antibody assay (prototype). Conclusions:The RBD protein could be efficiently expressed in Pichia pastoris and induce stronger immune response in animals. This study suggested that the recombinant SARS-CoV-2 RBD protein expressed in Pichia pastoris could serve as a candidate antigen in the development of SARS-CoV-2 vaccine.

Objective:To investigate the interfering factors in the determination of creatinine(Cr) using the American Clinical Laboratory Standards Association (CLSI) EP7-A3 document.Methods:According to the CLSI EP7-A3 document, fresh serum (no hemolysis, lipemia, and jaundice) was used on the day of the experiment and confirmed the interfering substances through the pairing difference experiment and the point-to-point analysis method was used in the dose effect experiment to clarify the difference of interfering substances.Results:Triglyceride (16.94 mmol/L), dobutamine hydrochloride (4.01 μmol/L), ascorbic acid (298 μmol/L) did not interfere with the determination of Cr. Free bilirubin (684 μmol/L), conjugated bilirubin (684 μmol/L), calcium hydroxybenzene sulfonate (144 μmol/L) and hemoglobin (10 g/L) were used as the maximum concentrations of interferences for the dose effect test, the results showed that the above interferences had negative interference on the determination of Cr.Conclusion:According to EP7-A3, it is valuable to evaluate the interference factors of creatinine determination.

Objective: To assess the differences between ultrasound cardiac output monitor (USCOM) and thermodilution (TD) systematically in cardiac function monitoring of critically ill patients. Methods: The Chinese and English literatures about the clinical trials which using USCOM and TD to monitor cardiac function published in CNKI, Wanfang database, China biomedical literature database, VIP database, China Clinical Trial Registration Center, PubMed, Embase and Cochrane Library were searched by computer from the establishment to December 2018. Some indicators, like cardiac output (CO), cardiac index (CI), stroke volume (SV) and other parameters were used to evaluate cardiac function. Literature search, quality evaluation and data extraction were conducted independently by two authors. The tailored Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used for literature quality evaluation. EndNote X6 was used for literature screening and management. RevMan 5.3 was used for Meta-analysis. Funnel chart analysis was used for publication bias. Results: A total of 26 studies involving 772 patients were included. Among them, there were 5 literatures found that the agreements of cardiac function between the USCOM and TD methods were poor. Meta-analysis showed that there was no significant difference between the two methods in CO and CI monitoring [CO: mean difference (MD) = -0.06, 95% confidence interval (95%CI) was -0.17 to 0.05, P = 0.31; CI: MD = -0.04, 95%CI was -0.13 to 0.05, P = 0.38]. Subgroup analysis of different TD methods [pulmonary artery catheter (PAC), pulse indicator continuous cardiac output (PiCCO)] and different windows of USCOM ultrasonic probe [aorta (AA), pulmonary artery (PA)] in CO monitoring was not shown significant difference yet (PAC: MD = -0.07, 95%CI was -0.18 to 0.04, P = 0.23; PiCCO: MD = 0.09, 95%CI was -0.31 to 0.50, P = 0.65; AA windows: MD = -0.14, 95%CI was -0.31 to 0.02, P = 0.09; PA windows: MD = -0.00, 95%CI was -0.15 to 0.14, P = 0.95; AA/PA windows: MD = 0.23, 95%CI was -0.40 to 0.86, P = 0.47). However, the difference in SV was statistically significant between the USCOM and TD method (MD = 1.48, 95%CI was 0.04 to 2.92, P = 0.04). Funnel chart showed that the literature distribution of CO and CI monitoring were basically symmetrical, indicating that the bias of literature publication is small. Conclusion USCOM has good consistency with TD method in monitoring the cardiac function parameters of CO and CI, and different windows of ultrasonic probe of USCOM have no significant influence on the monitoring results, but there is significant difference in the consistency of the two methods in SV monitoring.