Clinical practice guidelines represent the best recommendations for patient care. They are developed through systematically reviewing currently available clinical evidence and weighing the relative benefits and risks of various interventions. However, clinical practice guidelines have to go through a long translation cycle from development and revision to clinical promotion and application, facing problems such as scattered distribution, high duplication rate, and low actual utilization. At present, the clinical practice guideline information platform can directly or indirectly solve the problems related to the lengthy revision cycles, decentralized dissemination and limited application of clinical practice guidelines. Therefore, this paper systematically examines different types of clinical practice guideline information platforms and investigates their corresponding challenges and emerging trends in platform design, data integration, and practical implementation, with the aim of clarifying the current status of this field and providing valuable reference for future research on clinical practice guideline information platforms.

BACKGROUND: Neoadjuvant chemoradiotherapy followed by radical surgery has been a common practice for patients with locally advanced rectal cancer, but the response rate varies among patients. This study aimed to develop a ResNet-Vision Transformer based magnetic resonance imaging (MRI)-endoscopy fusion model to precisely predict treatment response and provide personalized treatment. METHODS: In this multicenter study, 366 eligible patients who had undergone neoadjuvant chemoradiotherapy followed by radical surgery at eight Chinese tertiary hospitals between January 2017 and June 2024 were recruited, with 2928 pretreatment colonic endoscopic images and 366 pelvic MRI images. An MRI-endoscopy fusion model was constructed based on the ResNet backbone and Transformer network using pretreatment MRI and endoscopic images. Treatment response was defined as good response or non-good response based on the tumor regression grade. The Delong test and the Hanley-McNeil test were utilized to compare prediction performance among different models and different subgroups, respectively. The predictive performance of the MRI-endoscopy fusion model was comprehensively validated in the test sets and was further compared to that of the single-modal MRI model and single-modal endoscopy model. RESULTS: The MRI-endoscopy fusion model demonstrated favorable prediction performance. In the internal validation set, the area under the curve (AUC) and accuracy were 0.852 (95% confidence interval [CI]: 0.744-0.940) and 0.737 (95% CI: 0.712-0.844), respectively. Moreover, the AUC and accuracy reached 0.769 (95% CI: 0.678-0.861) and 0.729 (95% CI: 0.628-0.821), respectively, in the external test set. In addition, the MRI-endoscopy fusion model outperformed the single-modal MRI model (AUC: 0.692 [95% CI: 0.609-0.783], accuracy: 0.659 [95% CI: 0.565-0.775]) and the single-modal endoscopy model (AUC: 0.720 [95% CI: 0.617-0.823], accuracy: 0.713 [95% CI: 0.612-0.809]) in the external test set. CONCLUSION The MRI-endoscopy fusion model based on ResNet-Vision Transformer achieved favorable performance in predicting treatment response to neoadjuvant chemoradiotherapy and holds tremendous potential for enabling personalized treatment regimens for locally advanced rectal cancer patients.
Humans ; Rectal Neoplasms/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Middle Aged ; Neoadjuvant Therapy/methods* ; Aged ; Adult ; Chemoradiotherapy/methods* ; Endoscopy/methods* ; Treatment Outcome

AIM To investigate the consistency of chemical constituents between formula granules and standard decoction of Coptidis Rhizoma.METHODS Eighteen batches of standard decoctions were prepared,after which the extraction rate and contents,transfer rates of magnolflorine,jatrorrhizine,columbamine,epiberberine,coptisine,palmatine,berberin were determined,HPLC characteristic chromatograms were established.RESULTS There were 11 common peaks in the characteristic chromatograms of 18 batches of standard decoctions and 24 batches of formula granules with the similarities of 0.861-1.000,which were clusterd into two categories.The formula granules and standard decoction demonstrated approximated extraction rate and contents,transfer rates of index constituents.CONCLUSION The chemical constituents between formula granules and standard decoction of Coptidis Rhizoma display good consistency,which can provide references for the quality control,process research and clinical application of the former.

Carthami Flos, as a traditional blood-activating and stasis-resolving drug, possesses anti-tumor, anti-inflammatory, and immunomodulatory pharmacological activities. Flavonoid glycosides are the main bioactive components in Carthamus tinctorius. Glycosyltransferase deserves to be studied in depth as a downstream modification enzyme in the biosynthesis of active glycoside compounds. This study reported a flavonoid glycosyltransferase CtUGT49 from C. tinctorius based on the transcriptome data, followed by bioinformatic analysis and the investigation of enzymatic properties. The open reading frame(ORF) of the gene was 1 416 bp, encoding 471 amino acid residues with the molecular weight of about 52 kDa. Phylogenetic analysis showed that CtUGT49 belonged to the UGT73 family. According to in vitro enzymatic results, CtUGT49 could catalyze naringenin chalcone to the prunin and choerospondin, and catalyze phloretin to phlorizin and trilobatin, exhibiting good substrate versatility. After the recombinant protein CtUGT49 was obtained by hetero-logous expression and purification, the enzymatic properties of CtUGT49 catalyzing the formation of prunin from naringenin chalcone were investigated. The results showed that the optimal pH value for CtUGT49 catalysis was 7.0, the optimal temperature was 37 ℃, and the highest substrate conversion rate was achieved after 8 h of reaction. The results of enzymatic kinetic parameters showed that the K_m value was 209.90 μmol·L~(-1) and k_(cat) was 48.36 s~(-1) calculated with the method of Michaelis-Menten plot. The discovery of the novel glycosyltransferase CtUGT49 is important for enriching the library of glycosylation tool enzymes and provides a basis for analyzing the glycosylation process of flavonoid glycosides in C. tinctorius.
Carthamus tinctorius/chemistry* ; Phylogeny ; Flavonoids/analysis* ; Glycosides/analysis* ; Glycosyltransferases/genetics* ; Anti-Inflammatory Agents ; Chalcones

Deficiencies in the clearance of peripheral amyloid β (Aβ) play a crucial role in the progression of Alzheimer's disease (AD). Previous studies have shown that the ability of blood monocytes to phagocytose Aβ is decreased in AD. However, the exact mechanism of Aβ clearance dysfunction in AD monocytes remains unclear. In the present study, we found that blood monocytes in AD mice exhibited decreases in energy metabolism, which was accompanied by cellular senescence, a senescence-associated secretory phenotype, and dysfunctional phagocytosis of Aβ. Improving energy metabolism rejuvenated monocytes and enhanced their ability to phagocytose Aβ in vivo and in vitro. Moreover, enhancing blood monocyte Aβ phagocytosis by improving energy metabolism alleviated brain Aβ deposition and neuroinflammation and eventually improved cognitive function in AD mice. This study reveals a new mechanism of impaired Aβ phagocytosis in monocytes and provides evidence that restoring their energy metabolism may be a novel therapeutic strategy for AD.
Animals ; Mice ; Alzheimer Disease ; Amyloid beta-Peptides ; Monocytes ; Cognition ; Energy Metabolism ; Phagocytosis

The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic. Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022. Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020, BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood. In particular, severe/critical cases of COVID-19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment. Importantly, the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototype-inactivated vaccines, supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records. Furthermore, even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection, vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged ≽ 60 years old. Together, our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines.
Humans ; Aged ; Middle Aged ; COVID-19/prevention & control* ; SARS-CoV-2 ; Pandemics/prevention & control* ; China/epidemiology* ; Disease Outbreaks/prevention & control* ; Vaccination

In addition to the essential pharmacologi-cal effects of opioids,situational cues associated with drug addiction memory are key triggers for drug seeking.CircRNAs,an emerging hotspot regulator in crown genet-ics-play an important role in central nervous system-relat-ed diseases.However,the internal mediating mechanism of circRNA in the field of drug reward and addiction mem-ory remains unknown.Here,we trained mice on a condi-tional place preference(CPP)model and collected nucle-us accumbens(NAc)tissues from day 1(T0)and day 8(T1)for high-throughput RNA sequencing.qRT-PCR revealed that circTmeff-1 was highly expressed in the NAc core but not in the NAc shell,suggesting that it plays a role in addiction memory formation.Meanwhile,the reverse regulation of circTmeff-1 by adeno-associated viruses could both inhibit the formation of addiction mem-ory in the NAc core or shell.Subsequently,the GO and KEGG analyses indicated 21 that circTmeff-1 might regu-late the addiction memory via the MAPK and AMPK path-ways.These findings suggest that circTmeff-1 in NAc plays a crucial role in morphine-dependent memory for-mation.

Objective To evaluate the predictive value of a combined model based on clinical and radiomics features for the invasiveness of lung adenocarcinoma manifesting as ground glass nodule(GGN).Methods Clinical data of patients with GGN-type lung adenocarcinoma who underwent chest CT and were confirmed by surgical pathology at some hospital from January to December 2019 were analyzed retrospectively,and the extraction of imaging histological features was performed using Python-based open resource Pyradiomics.A clinical model was constructed based on independent risk factors obtained from univariate and multivariate analyses,a radiomics model was built using the screened radiomics features,and a combined model was established with the predictive values of the clinical models and radiomics scores(Radscore).The predictive performance of the three models in the training and test sets was assessed using ROC curves,the statistical significance of the differences in the ROC curves of the three models for predicting GGN-type lung adenocarcinoma was assessed using the Delong test,and the net benefits of the models were analyzed using clinical decision curves.Results Logistic multifactor analysis showed that age(P=0.020 2)and vascular characteristics(P=0.002 2)were the independent predictors of the degree of the invasiveness of lung adenocarcinoma.The AUCs of the radiomics model,clinical model and combined model were 0.876,0.867 and 0.904 on the training set,and 0.828,0.828 and 0.864 on the test set,respectively.The difference between the ROC curves of the combined model and the clinical and radiomics models was not statistically significant(P>0.05)on the test set.Clinical decision curves showed a higher clinical benefit when using the combined model to predict the invasiveness under most conditions of threshold probability.Conclusion The combined model based on clinical and radiomics features enhances the predictive performance for the invasiveness of GGN-type lung adenocarcinoma.

Objective: To explore the effect and mechanism of activation of peripheral blood mononuclear cell (PBMC) Toll-like receptor (TLR3) signaling pathway in recombinant HBsAg (rHBsAg) immune response. Methods: White blood cells were collected from peripheral blood of 13 healthy donors in the preparation of blood products. PBMC was isolated and treated with Poly I:C (Poly I:C group) and PBS (control group) respectively. 48 h later, some cells were collected and the expressions of TLR3 signaling pathway proteins were detected by flow cytometry. After activating (Poly I:C group)/inactivating (control group) TLR3 signaling pathway, rHBsAg was given to both groups for 72 h, and the proportions of DC, T, B cells and their subsets in PBMC were detected by flow cytometry. Paired t-test, paired samples wilcoxon signed-rank test and canonical correlation analyses were used for statistical analysis. Results: The percentage of TLR3 protein-positive cells (19.21%) and protein expression (8 983.95), NF-κB protein expression (26 193.13), the percentage of pNF-κB protein-positive cells (13.73%) and its proportion in NF-κB (16.03%), and the percentage of pIRF3 protein-positive cells (12.64%) and its proportion in IRF3 (21.80%) in Poly I:C group were higher than those in control group (11.54%, 8 086.00, 22 340.66, 8.72%, 9.71%, 9.57%, 19.12%) (P<0.05), and the percentage of TRIF protein-positive cells (89.75%) and protein expression (304 219.54) were higher in Poly I:C group than in the control group (89.64%, 288 149.72) (P>0.05). After PBMC stimulation by rHBsAg, the proportions of mDC (2.90%), pDC (1.80%), B cell (5.31%) and plasma cell (67.71%) in Poly I:C group were significantly higher than those in the control group (1.83%, 0.81%, 4.23%, 58.82%) (P<0.05). Results of canonical correlation analysis showed that the expression of TLR3 protein was positively correlated with the proportions of plasma cells, the expression of pIRF3 protein was positively correlated with the proportions of plasma cells and mDC, and the percentage of pNF-κB protein-positive cells and the percentage of pIRF3 protein-positive cells were positively correlated with the proportion of CD4⁺T cells. Conclusions: Poly I:C can activate TLR3/TRIF/NF-κB and TLR3/TRIF/IRF3 signaling pathway, promote the function of downstream signaling molecules, and then promote the maturation of DC, induce the immune responses of CD4⁺T cell, and promote the maturation and activation of B cells and the immune response of rHBsAg.
Adaptor Proteins, Vesicular Transport/pharmacology* ; Hepatitis B Surface Antigens ; Humans ; Immunity ; Leukocytes, Mononuclear/metabolism* ; NF-kappa B ; Poly I-C/pharmacology* ; Signal Transduction ; Toll-Like Receptor 3/metabolism* ; Toll-Like Receptors

Interaction exists in lung cancer and microbiota. Lung microecological homeostasis can improve the immune tolerance, enhance immune suppression, and inhibit inflammatory responses, to reduce the lung cancer; while lung cancer can lead to pulmonary microecological imbalance, change the lung environment, and promote tumor cell proliferation. Therefore, modulating microbial flora and microecological immunotherapy may be a potential and preventive treatment for lung cancer, to restore tumor immunosuppression and improve patient survival. However, the individual differences in the lung microecology, because of different genetics, ethnic characteristics, and dietary habits, increasing the difficulty of precise diagnosis and treatment, which is also the current bottleneck in the application of microecological immunotherapy. Otherwise, the effectiveness of regulatory measures such as probiotics, prebiotics or antimicrobials is questionable. The research on microbial flora is still in its infancy, and further exploration is needed to form a standardized, effective, and precise treatment plan. So, standardized, effective, and precise microbial flora treatment strategies need to be further explored.
Humans ; Probiotics ; Prebiotics ; Microbiota ; Lung Neoplasms