Drug resistance is one of the key factors affecting the effectiveness of cancer treatment methods, including chemotherapy, radiotherapy, and immunotherapy. Its occurrence is related to factors such as mRNA expression and methylation within cancer cells. If drug resistance in patients can be accurately identified early, doctors can devise more effective treatment plans, which is of great significance for improving patients' survival rates and quality of life. Cancer drug resistance prediction based on artificial intelligence (AI) technology has emerged as a current research hotspot, demonstrating promising application prospects in guiding clinical individualized and precise medication for cancer patients. This review aims to comprehensively summarize the research progress in utilizing AI algorithms to analyze multi-omics data including genomics, transcriptomics, epigenomics, proteomics, metabolomics, radiomics, and histopathology, for predicting cancer drug resistance. It provides a detailed exposition of the processes involved in data processing and model construction, examines the current challenges faced in this field and future development directions, with the aim of better advancing the progress of precision medicine.

Human carboxylesterase 2A (hCES2A) plays pivotal roles in prodrug activation and hydrolytic metabolism of ester-bearing chemicals. Targeted inhibition of intestinal hCES2A represents a feasible strategy to mitigate irinotecan-triggered gut toxicity (ITGT), but the orally active, selective, and efficacious hCES2A inhibitors are rarely reported. Here, a novel drug-like hCES2A inhibitor was developed via three rounds of structure-based drug design (SBDD) and structural optimization. Initially, donepezil was identified as a moderate hCES2A inhibitor from 2000 US Food and Drug Administration (FDA)-approved drugs. Following two rounds of SBDD and structural optimization, a donepezil derivative (B7) was identified as a strong reversible hCES2A inhibitor. Subsequently, nine B7 carbamates were rationally designed, synthesized and biologically assayed. Among all synthesized carbamates, C3 showed the most potent time-dependent inhibition on hCES2A (IC₅₀ = 0.56 nmol/L), excellent specificity and favorable drug-like properties. C3 could covalently modify the catalytic serine of hCES2A with high selectivity, while this agent also showed favorable safety profiles, high intestinal exposure, and impressive effects for ameliorating ITGT in both human intestinal organoids and tumor-bearing mice. Collectively, this study showcases a rational strategy for developing drug-like and serine-targeting covalent inhibitors against target serine hydrolase(s), while C3 emerges as a promising orally active drug candidate for ameliorating ITGT.

Objective To investigated the effect of tripterygium glycosides(TG)on dextran sodium sulfate(DSS)-induced colonic mucosal damage in ulcerative colitis(UC)mice and its regulatory mechanism.Methods Forty C57BL/6J mice were randomly divided into a normal group,a model group,and a tretinoin low,medium,and high dose group(administered at concentrations of 9.00mg/kg,27.03mg/kg,and 81.09mg/kg,respectively).The mice in the normal group were free to drink distilled water,and the rest of the mice drank 5％DSS to induce UC modeling.After modeling,mice in the model group were given 0.4ml of saline by gavage daily,and the rest of the mice in the treatment group were given the corresponding dose of TG for gavage intervention.The mass and disease activity index of the mice in each group were compared,and the pathological and histological damage of the colon was observed.Tumor necrosis factor-α(TNF-α),malondialdehyde(MDA),and superoxide dismutase(SOD)levels were measured using the corresponding kits.Western blot Detection of Nur77,tumor necrosis factor receptor-associated factor 2(Traf2),nucleoporin 62(P62),autophagy protein-microtubule associated protein1 light chain 3(LC3)molecular expression.Results Compared with the blank group,the body weight,colon length,SOD,Nur77,Traf2,and LC3Ⅱ/LC3Ⅰ levels of mice in the model group were significantly decreased(P<0.05),and the DAI level,colon pathology score,TNF-α,MDA level,and P62 of the mice were significantly increased(P<0.05).Compared with mice in the UC model group,mice in the low,medium and high dose groups of tretinoin polyphenols showed significant increases in body weight,colon length,SOD,Nur77,Traf2,LC3Ⅱ/LC3Ⅰlevels(P<0.05),and mice with DAI scores,TNF-α,MDA levels in the colon,and P62 levels were significantly decreased(P<0.05).Mice in the medium and high dose groups of tretinoin polyphenols pathological scores were significantly reduced(P<0.05).Conclusion TG is able to treat ulcerative colitis through Nur77-Traf2-P62 signaling pathway.

Objective:To evaluate the nutritional status of patients with decompensated liver cirrhosis and explore the correlation with malnutrition and the risk factors of depressed mood.Methods:190 cirrhotic patients admitted to the Department of Gastroenterology of the First Hospital of Shanxi Medical University from June to September 2023 were selected according to the inclusion and exclusion criteria. Eligible patients were divided into subgroups based on the presence or absence of malnutrition as determined by subjective global assessment (SGA). The Center for Epidemiological Studies Depression (CES-D) scale was used to assess patients' propensity for depressed mood. Relevant clinical data were also collected and analyzed.Results:A total of 185 patients were included, of which 126 were in the non-malnutrition group and 59 malnutrition group. There were significant between-group differences in terms of CES-D results, age, body mass index, platelets, D-dimer, serum sodium, third lumbar skeletal muscle index, grip strength, triceps skinfold thickness, and upper arm muscle circumference (all P<0.05). Correlation analysis showed that grip strength, triceps skinfold thickness, upper arm muscle circumference, serum sodium, and depressed mood tendency status were correlated with the development of cirrhotic malnutrition ( P<0.05). The diagnostic model for malnutrition in cirrhosis using these five indicators showed the area under the curve of 81.9%. Conclusions:Depression is closely related to the development of malnutrition in patients with liver cirrhosis. Independent risk factors for malnutrition in cirrhosis include serum sodium≤135 mmol/L, grip strength, triceps skinfold thickness, lower-than-normal upper arm circumference , and the tendency of depression , which demonstrate the combined contribution to the diagnosis of malnutrition in cirrhosis.

Video-based intelligent action recognition remains challenging in the field of computer vision.The review analyzes the state-of-the-art methods of video-based intelligent action recognition,including machine learning methods with handcrafted features,deep learning methods with automatically extracted features,and multi-information fusion methods.In addition,the important medical applications and limitations of these technologies in the past decade are introduced,and the interdisciplinary views on the future application to improve human health are also shared.

Objective:To explore whether tryptophan metabolism is related to bone growth by comparing the differences in tryptophan metabolism after rotator cuff tear (RCT) repair between rats with normal bone remodeling capability and those with defective bone remodeling capability.Methods:Of the 50 adult female Sprague Dawley (SD) rats used for this study, 18 were randomly selected to undergo bilateral ovariectomy (OVX) (OVX group), and the remaining 32 underwent bilateral OVX sham surgery (sham surgery group). All rats were maintained in standard conditions. Three months after surgery, 4 rats were randomly selected from OVX group and the sham surgery group, respectively, for Micro CT identification of bone loss at the rat humeral head. The remaining rats in OVX group underwent RCT modeling and surgical repair of acute supraspinatus muscle transection (OVX+RCT group) ( n=14); the remaining rats in the sham surgery group were subjected to either surgical repair of acute supraspinatus muscle transection (RCT group, n=14) or RCT sham surgery (SO group, n=14). The grip power of the rats was tested 2 weeks after surgery. The supraspinatus tendon-bone complex was harvested for evaluation of new bone formation and growth through real-time fluorescence quantitative polymerase chain reaction (qPCR), hematoxylin eosin (HE) staining, and immunohistochemistry (IHC) staining. The tryptophan metabolism was analyzed using ultra high performance liquid chromatography (UPLC). Results:The grip power test showed that SO group had the greatest grip power, followed by RCT group and OVX+RCT group, with statistically significant differences between the 3 groups ( P<0.05). The qPCR showed that the relative expression of osteosclerosis in the tendon-bone complex in SO group was significantly higher than that in OVX+RCT group and RCT group; IHC staining showed that the relative expression of osteocalcin in RCT group was significantly higher than that in SO group and OVX+RCT group ( P<0.05). The UPLC showed that the content of tryptophan in the rotator cuff tendon-bone complex was similar among SO, RCT, and OVX+RCT groups, showing no significant difference ( P>0.05). The qPCR showed that the expression of indoleamine 2, 3-dioxygenase 2 in the Kynurenic acid metabolism pathway showed an increasing trend from SO group to RCT group to OVX+RCT group, with OVX+RCT group significantly higher than SO group ( P<0.05). The expression of 3-hydroxybenzoate 3, 4-dioxygenase in OVX+RCT group was significantly higher than that in RCT group and in SO group ( P<0.001). The subtypes A and B of monoamine oxidase in the 5-hydroxytryptamine metabolism pathway increased from SO group to RCT group to OVX+RCT group. The subtypes A and B of monoamine oxidase in the 5-hydroxytryptamine metabolism pathway increased among SO, RCT, and OVX+RCT groups( P<0.001). The expression of dopamine decarboxylase in the indole metabolism pathway in OVX+RCT group was significantly higher than that in SO group ( P<0.01). The expression of cytochrome P450 oxidoreductase increased from SO group to RCT group to OVX+RCT group ( P<0.001). Conclusions:The tryptophan metabolism in the supraspinatus tendon-bone complex after RCT in rats is mainly dominated by kynurenic acid metabolism, followed by 5-hydroxytryptamine metabolism. In RCT bone remodeling, the 5-hydroxytryptamine metabolic pathway changes the most, followed by the indole pathway. The contents of niacin and xanthurenic acid in the kynurenic acid metabolism pathway are related to bone growth; the 5-hydroxytryptamine, hydroxyindoleacetic acid, and melatonin in the 5-hydroxytryptophan metabolic pathway are related to bone growth; the tryptophan and indole lactate in the indole metabolism pathway are related to bone growth. Therefore, tryptophan metabolism is related to bone growth, providing potential therapeutic targets for RCT repair.

Background and objective The incidence rate of lung cancer in Xuanwei has been continuously in-creasing in recent years,and it also features high incidence across all age groups and high mortality rates among female lung cancer patients.Therefore,the search for more stable biomarkers for the diagnosis of Xuanwei lung cancer holds tremendous clinical application prospects.This study aims to explore the clinical application value of these four microRNAs(miRNAs)in-dividually and in combination with traditional lung cancer tumor markers in the detection and diagnosis of Xuanwei lung can-cer.Methods By detecting the expression levels of four miRNAs and five traditional lung cancer tumor markers in the serum of 45 Xuanwei lung cancer patients and healthy physical examination participants,the Logistic regression model was employed to comprehensively evaluate the sensitivity,specificity,diagnostic efficacy,and other relevant statistical indicators of the four miR-NAs in the diagnosis of Xuanwei lung cancer.Results Among the individual miRNAs,miR-4646-5p and miR-3654 showed significant differences in expression levels between the Xuanwei lung cancer group and the control group(P＜0.05).miR-3654 demonstrated the best diagnostic performance with a sensitivity of 86.7％ ,specificity of 82.2％ ,and an area under the curve of 0.847.Combining miR-3654 with miR-4646-5p and carcinoembryonic antigen(CEA)resulted in the highest diagnostic ef-ficacy for Xuanwei lung cancer,with a sensitivity of 73.3％ ,specificity of 93.3％ ,area under the curve of 0.901,and a positive predictive value of 91.7％ .Conclusion Among the four miRNAs,serum miR-3654 exhibits the best diagnostic efficacy for Xuanwei lung cancer.Combined with miR-4646-5p and CEA,its diagnostic value for Xuanwei lung cancer can be effectively enhanced,making it a promising screening indicator for Xuanwei lung cancer.

Objective:To retrieve, evaluate, and integrate the best evidence for prevention of hemodialysis catheter thrombosis, so as to provide evidence-based basis for catheter thrombosis prevention in hemodialysis patients.Methods:Guidelines, clinical decisions, evidence summaries, systematic reviews, and expert consensus on the prevention of hemodialysis catheter thrombosis were systematically searched on Guidelines International Network, Scottish Intercollegiate Guidelines Network, Agency for Healthcare Research and Quality, Registered Nurses' Association of Ontario, National Institute for Health and Clinical Excellence, UpToDate, British Medical Journal (BMJ) Best Practice, Joanna Briggs Institute Evidence-Based Health Care Center Database, European Renal Association, National Kidney Foundation, UK Kidney Association, Canadian Society of Nephrology, Japanese Society for Dialysis Therapy, Medlive, Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure, VIP, and Wanfang Data and Chinese Biomedical Database. The search period was from database establishment to March 31, 2023. Investigators conducted quality evaluations separately and extracted and summarized evidence based on the theme.Results:A total of 16 articles were included, including five clinical decisions, four guidelines, two evidence summaries, and five expert consensuses. Finally, 15 best pieces of evidence were formed, including four themes of indwelling dialysis catheters, anticoagulation strategies, flushing and sealing techniques, and daily management.Conclusions:Nursing staff should choose the best evidence for preventing thrombosis in hemodialysis catheters based on clinical situations, reduce the occurrence of catheter thrombosis, extend the usage time of catheters, and improve patient outcomes.

Objective:To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China.Methods:This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis.Results:Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z=1.30, P=0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs. 4(3, 7) points, Z=6.56, P<0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs. 82(76, 88) points, Z=5.90, P<0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) ( Z=6.59, 4.23, both P<0.001). There was no significant difference between pSOFA and PCIS ( Z=1.35, P=0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P<0.05). Conclusion:Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.

OBJECTIVE To study the chemical composition and analgesia molecular mechanism of Shuanghu Zhongtongning tincture by UPLC-Q-TOF-MS/MS and network pharmacology. METHODS By comparing the chromatogram and blank chromatogram of Shuanghu Zhongtongning tincture, combined with PubChem, HMDB, MassBank database spectrum and the lysis information of reference substance, the chemical composition of Shuanghu Zhongtongning tincture was analyzed and identified. Protein-protein interaction network was constructed by using STRING database, and potential targets of analgesic effect of Shuanghu Zhongtongning tincture were screened. And GO and KEGG enrichment analysis were performed to analyze the core pathways related to analgesia. The network of "chemical composition-disease-target" was constructed by Cytoscape software to analyze the key compounds related to analgesia. RESULTS Seventeen core components of neochlorogenic acid, chlorogenic acid, hesperidin, neohesperidin, ferulic acid, berberine, ursolic acid, deoxyaconitine, mesaconitine, hypaconitine, benzoylmesaconine, benzoylhypacoitine, caffeic acid, quercetin, oleanolic acid, 4-hydroxycinnamic acid and mefenamic acid were identified, 3 core targets of STAT3, MAPK3 and MAPK1 were found, and 4 key signaling pathways of IL-17, TNF, PI3K-Akt and arachidonic metabolism were revealed. CONCLUSION This study preliminarily clarifies the chemical composition of Shuanghu Zhongtongning tincture and potential mechanism of analgesic effect, and provides a scientific theoretical basis for the study on the material basis and mechanism of Shuanghu Zhongtongning tincture.