Development and validation of machine learning-based prediction model for severe pneumonia: A multicenter cohort study.

Severe pneumonia (SP) is a prevalent respiratory ailment characterized by high mortality and poor prognosis. Current scoring systems for pneumonia are not only time-consuming but also exhibit limitations in early SP prediction. To address this gap, this study aimed to develop a machine-learning model using inflammatory markers from peripheral blood for early prediction of SP. A total of 204 pneumonia patients from seven medical centers were studied, with 143 (68 SP cases) in the training cohort and 61 (32 SP cases) in the test cohort. Clinical characteristics and laboratory test results were collected at diagnosis. Various models including Logistic Regression, Random Forest, Naïve Bayes, XGBoost, Support Vector Machine, and Decision Tree were built and evaluated. Seven predictors-age, sex, WBC count, T-lymphocyte count, NLR, CRP, TNF-α, IL-4/IFN-γ ratio, IL-6/IL-10 ratio-were selected through LASSO regression and clinical insight. The XGBoost model, exhibiting best performance, achieved an AUC of 0.901 (95 % CI: 0.827 to 0.985) in the test cohort, with an accuracy of 0.803, sensitivity of 0.844, specificity of 0.759, and F1_score of 0.818. Indeed, SHAP analysis emphasized the significance of elevated WBC counts, older age, and elevated CRP as the top predictors. The use of inflammatory biomarkers in this concise predictive model shows significant potential for the rapid assessment of SP risk, thereby facilitating timely preventive interventions.

Estimation of suspected estrogenic transformation products generated during preservative butylparaben chlorination using a simplified effect-based analysis approach.

Estrogenic transformation products (TPs) generated after water chlorination can be considered as an environmental and health concern, since they can retain and even increase the estrogenicity of the parent compound, thus posing possible risks to drinking water safety. Identification of the estrogenic TPs generated from estrogenic precursor during water chlorination is important. Herein, butylparaben (BuP), which was widely used as preservative in food, pharmaceuticals and personal care products (PPCPs), was selected for research. A simplified effect-based analysis (EDA) approach was applied for the identification of estrogenic TPs generated during BuP chlorination. Despite the removal of BuP corresponds to the decrease of estrogenicity in chlorinated samples, an significant increase of estrogenicity was observed (at T = 30 min, presented an estrogenicity equivalent to 17ß-estradiol). Chemical analysis of the estrogenic chlorinated samples that have been previously subjected to biological analysis (in vitro assays), in combination with the principal component analysis (PCA) evaluation, followed by validating the estrogenic potency of most relevant estrogenic TPs through an in silico approach (molecular dynamics simulations), identified that the halogenated TP3 (3,5-Dichloro-butylparaben) increased by 62.5 % and 61.8 % of the estrogenic activity of the parent compound in samples chlorinated with 30 min and 1 h, respectively being classified as a potentially estrogenic activity driver after BuP chlorination. This study provides a scientific basis for the more comprehensive assessment of the environmental and health risk associated with BuP chlorination, highlighting the necessity of identifying the unknown estrogenic TPs generateded from estrogenic precursors chlorination.

Therapeutic effects of focused ultrasound on vulvar squamous intraepithelial lesions in rat.

OBJECTIVE: In this study, we established a Sprague-Dawley rat model of vulvar squamous intraepithelial lesions and investigated the impact of focused ultrasound on the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and mutant type p53 (mtp53) in the vulvar skin of rats with low-grade squamous intraepithelial lesions (LSIL). MATERIALS AND METHODS: The vulvar skin of 60 rats was treated with dimethylbenzanthracene (DMBA) and mechanical irritation three times a week for 14 weeks. Rats with LSIL were randomly allocated into the experimental group or the control group. The experimental group was treated with focused ultrasound, while the control group received sham treatment. RESULTS: After 14 weeks treatment of DMBA combined with mechanical irritation, LSIL were observed in 44 (73.33%) rats, and high-grade squamous intraepithelial lesions (HSIL) were observed in 14 (23.33%) rats. 90.91% (20/22) of rats showed normal pathology and 9.09% (2/22) of rats exhibited LSIL in the experimental group at four weeks after focused ultrasound treatment. 22.73% (5/22) of rats exhibited LSIL, 77.27% (17/22) of rats progressed to HSIL in the control group. Compared with the control-group rats, the levels of HIF-1α, VEGF and mtp53 were significantly decreased in experimental-group rats (p < 0.05). CONCLUSIONS: These results indicate that DMBA combined with mechanical irritation can induce vulvar squamous intraepithelial lesion in SD rats. Focused ultrasound can treat LSIL safely and effectively, prevent the progression of vulvar lesions, and improve the microenvironment of vulvar tissues by decreasing the localized expression of HIF-1α, VEGF, and mtp53 in rats.

First report of Aspergillus tubingensis causing leaf spot on Pogostemon cablin in China.

Patchouli (Pogostemon cablin (Blanco) Benth) is an important medicinal and aromatic plant widely cultivated in China, India, and other Southeast Asian countries. It is renowned for its diverse applications in traditional medicine and its detoxification, antibacterial, anti-inflammatory, and other pharmacological properties (Wu et al. 2016; Fang et al. 2022). In May 2023, a severe leaf spot disease was observed on Pogostemon cablin plants grown in most plantations in Yulin, Guangxi, China (22°26'N; 109°83'E), with over 50% incidence rate. Symptoms began as small, circular, brown spots on leaves, enlarging with yellow halos. Lesions expanded into irregular shapes with necrotic centers. Advanced stages showed extensive yellowing, browning, and leaf senescence. A total of 20 symptomatic plants were sampled from 5 different locations within the detected area, with 4 plants sampled per location. To isolate the pathogen, 20 affected leaves were collected from these plants and preliminarily washed with sterile distilled water (SDW). Five small tissue pieces (5×5 mm) were excised from the lesion edge of each leaf, surface-disinfected with 75% ethanol and 1% NaClO, rinsed thrice with SDW, and placed on potato dextrose agar (PDA) at 28 °C in darkness for 7 days. Out of these, 18 plants (90%) yield fungal isolate with recurrent and similar morphological characteristics. Four representative isolates (X5-1-1, X5-1-3, X5-1-5, and X5-1-7) were selected for further analysis. On PDA, colonies were initially white, gradually turning black on the surface, with light yellow on the reverse side of the plate. Conidia were brown to black, globose, rough-walled, and 2.6 to 5.2 µm in diameter. Conidial heads were brown-black, and conidiophores were smooth and hyaline. Morphological characteristics matched those of Aspergillus sp. (Guo et al. 2017). For molecular identification, the internal transcribed spacer (ITS) region and the ß-tubulin (TUB) gene of all four isolates were sequenced (Lim et al. 2019). All four isolates (X5-1-1, X5-1-3, X5-1-5, and X5-1-7) showed consistent morphological characteristics and 100% identical ITS and TUB sequences. Representative sequences from isolate X5-1-5 were submitted to GenBank (ITS: PP789632; TUB: PP798205). The obtained ITS and TUB sequences showed 99% similarity to Aspergillus tubingensis (ITS: OP737633; TUB: MG991377). Based on morphological and molecular analyses, the fungus was identified as A. tubingensis (Palmer et al. 2019). For pathogenicity tests, a spore suspension (1 × 10^6 conidia/mL) was prepared from 7-day-old cultures of A. tubingensis grown on PDA. The suspension was sprayed onto leaves of 10 healthy Pogostemon cablin plants until runoff. Control plants were sprayed with SDW. All plants were kept in a controlled greenhouse (12/12h light/dark, 25 ± 2 °C, 90% humidity). After 7 d, symptoms identical to those observed in the field developed on all pathogen inoculated plants, while control plants remained asymptomatic. The fungus was successfully re-isolated from infected leaves in three successive trials, fulfilling Koch's postulates. Notably, A. tubingensis has previously been reported causing field diseases on strawberry in California, Jatropha curcas and Helleborus species in China (Palmer et al. 2019; Guo et al. 2017, Liaquat et al. 2019), and vine canker on table grape in Italy (Vitale et al. 2012). To our knowledge, this is the first report of A. tubingensis causing leaf spot on Pogostemon cablin in China. This finding provides a foundation for further investigate into the biology, epidemiology, and management of this disease.

Most Pleiotropic Effects of Gene Knockouts Are Evolutionarily Transient in Yeasts.

Pleiotropy, the phenomenon in which a single gene influences multiple traits, is a fundamental concept in genetics. However, the evolutionary mechanisms underlying pleiotropy require further investigation. In this study, we conducted parallel gene knockouts targeting 100 transcription factors in 2 strains of Saccharomyces cerevisiae. We systematically examined and quantified the pleiotropic effects of these knockouts on gene expression levels for each transcription factor. Our results showed that the knockout of a single gene generally affected the expression levels of multiple genes in both strains, indicating various degrees of pleiotropic effects. Strikingly, the pleiotropic effects of the knockouts change rapidly between strains in different genetic backgrounds, and ∼85% of them were nonconserved. Further analysis revealed that the conserved effects tended to be functionally associated with the deleted transcription factors, while the nonconserved effects appeared to be more ad hoc responses. In addition, we measured 184 yeast cell morphological traits in these knockouts and found consistent patterns. In order to investigate the evolutionary processes underlying pleiotropy, we examined the pleiotropic effects of standing genetic variations in a population consisting of ∼1,000 hybrid progenies of the 2 strains. We observed that newly evolved expression quantitative trait loci impacted the expression of a greater number of genes than did old expression quantitative trait loci, suggesting that natural selection is gradually eliminating maladaptive or slightly deleterious pleiotropic responses. Overall, our results show that, although being prevalent for new mutations, the majority of pleiotropic effects observed are evolutionarily transient, which explains how evolution proceeds despite complicated pleiotropic effects.

The Burden and Clinical Features of Neovascular Glaucoma in A Major Tertiary Care Center in China.

PRCIS: This research presents the burden and clinical characteristics of NVG in Zhongshan Ophthalmic Center, employing the most extensive sample size and the longest uninterrupted temporal duration so far, which may provide a theoretical reference for the effective prevention and diagnosis of NVG. PURPOSE: To summarize the burden and clinical characteristics of neovascular glaucoma (NVG) in a major tertiary care center in China. METHODS: The clinical data of NVG patients in Zhongshan Ophthalmic Center (ZOC) between 2012 and 2021 were collected retrospectively, including their age, sex, affected eye, best-corrected visual acuity (BCVA), intraocular pressure (IOP), clinical stage and aetiology. RESULTS: In this study, we included 1877 eyes of 1749 patients who developed NVG, with 2.01:1 ratio of male to female. Their mean age was 53.14±16.69 years and those aged 41-70 years (65.2%) were most affected. Monocular patients were more predominant in most of them (92.7%), while 7.3% were binocular and 1667 eyes (88.8%) were at the angle­closure stage. The BCVA and IOP were 2.42±0.70 logMAR and 38.6±12.2 mmHg, respectively. Over the decade, the number of NVG patients and the proportion of NVG patients among glaucoma patients showed an increasing trend, with annual percentage changes (APCs) of 9.1% (95% CI: 5.0-13.3%, P=0.001) and 4.8% (95% CI: 2.2-7.4%, P=0.003), respectively. The top three primary conditions were diabetic retinopathy (DR), retinal vein occlusion (RVO), and retinal detachment (RD). Moreover, the APCs for the constituent ratio of DR and RVO were 4.4% (95% CI: 0.5-8.4%, P=0.031) and ï¹£4.6% (95% CI: ï¹£8.4% to ï¹£0.7%, P=0.028), respectively. However, the first and second causes of NVG in minors (<18 years old) were Coat's disease and ocular tumours, followed by RD and RVO in third place. The top cause of NVG in patients aged 65 years and older was RVO. CONCLUSIONS: The burden of NVG is increasing, emphasizing the need to improve preventive strategies focusing on primary diseases such as DR, RVO, and RD, particularly the increasing proportion of DR cases and the previously underemphasized RD patients, while also highlighting the differences in primary diseases across different age groups.

Fluxapyroxad induced toxicity of earthworms: Insights from multi-level experiments and molecular simulation studies.

Fluxapyroxad, an emerging succinate dehydrogenase inhibitor fungicide, is widely used due to its excellent properties. Given its persistence in soil with a 50 % disappearance time of 183-1000 days, it is crucial to evaluate the long-term effects of low-dose fluxapyroxad on non-target soil organisms such as earthworms (Eisenia fetida). The present study investigated the impacts of fluxapyroxad (0.01, 0.1, and 1 mg kg-1) on Eisenia fetida over 56 days, focusing on oxidative stress, digestive and nervous system functions, and histopathological changes. We also explored the mechanisms of fluxapyroxad-enzyme interactions through molecular docking and dynamics simulations. Results demonstrated a significant dose-response relationship in the integrated biomarker response of 12 biochemical indices. Fluxapyroxad altered expression levels of functional genes and induced histopathological damage in earthworm epidermis and intestines. Molecular simulations revealed that fluxapyroxad is directly bound to active sites of critical enzymes, potentially disrupting their structure and function. Even at low doses, long-term fluxapyroxad exposure significantly impacted earthworm physiology, with effects becoming more pronounced over time. Our findings provide crucial insights into the chronic toxicity of fluxapyroxad and emphasize the importance of long-term, low-dose studies in pesticide risk assessment in soil. This research offers valuable guidance for the responsible management and application of fungicides.

Recent advances and clinical applications of red blood cell lifespan measurement.

The red blood cell (RBC) lifespan is a crucial indicator used in clinical diagnostics, treatment, and disease monitoring. This biomarker quantifies the duration that red blood cells (RBCs) circulate within the bloodstream after being released from the bone marrow, serving as a sensitive and direct indicator of red blood cell turnover. Conventional techniques for RBC lifespan measurement, including differential agglutination, 51Cr labeling, and 15N glycine labeling, each present their own set of challenges, such as complexity, radioactive exposure, and potential allergic reaction. The carbon monoxide (CO) breath test has emerged as an advanced and non-invasive alternative, indirectly assessing RBC lifespan through hemoglobin (Hb) renewal rates. This method is convenient, rapid, and lacks the drawbacks of traditional approaches. The CO breath test for RBC lifespan is widely utilized in benign anemia, malignant hematological disorders, neonatal hyperbilirubinemia, and diabetes mellitus, offering valuable insights into disease mechanisms, progression, and treatment outcomes.

Asymptomatic multicentric Castleman disease: A potential early stage of idiopathic MCD.

According to the diagnostic criteria for HHV-8 (human herpesvirus-8) negative/idiopathic multicentric Castleman disease (iMCD) proposed by Castleman Disease Collaborative Network (CDCN) in 2017, there is a group of HHV-8 negative multicentric Castleman disease (MCD) patients who do not have symptoms and hyperinflammatory state and do not meet the iMCD criteria. This retrospective study enrolled 114 such patients, described as asymptomatic MCD (aMCD), from 26 Chinese centers from 2000-2021. With a median follow-up time of 46.5 months (range: 4-279 months), 6 patients (5.3%) transformed to iMCD. The median time between diagnosis of aMCD and iMCD in these 6 patients was 28.5 months (range: 3-60 months). During follow-up, 7 patients died; three of them died from progression of MCD. Despite that 37.7% patients received systemic treatment targeting MCD, this strategy was neither associated with a lower probability of iMCD transformation nor a lower death rate. The 5-year estimated survival of all aMCD patients was 94.1% (95% CI 88.8-99.6%). Transformation to iMCD was an important predictor of death (log-rank p=0.01) (5-year estimated survival 83.3%). This study suggests that aMCD patients may represent a potential early stage of iMCD, who may not require immediate treatment but should be closely monitored.

Evolution and modeling of texture changes and drying kinetics of bamboo shoots under high-humidity air-impingement blanching.

This study investigated the effect of hot water blanching (HWB), high-humidity air-impingement blanching (HHAIB), different HHAIB blanching times (2, 4, 6, 8, and 10 min), and different HHAIB blanching temperatures (80, 85, 90, and 95°C) on texture quality, lignin content, weight loss, color, microstructure, and drying kinetics of bamboo shoots. After HWB treatment, the lignin content of bamboo shoots was apparently lower than that of HHAIB and the samples obtained the highest weight loss value of 6.13%. Both the texture values (brittleness and chewiness) and lignin content of bamboo shoots exhibited an overall downward trend as the HHAIB blanching time and blanching temperature increased. Specifically, the lignin content of bamboo shoots decreased from 5.59% to 4.58% with an increase in HHAIB blanching time from 2 to 10 min and dropped from 5.48% to 4.63% as HHAIB blanching temperature increased from 80 to 85°C, respectively. The lignin content was proved to be positively correlated (p < 0.05) with texture attributes (brittleness and chewiness). A second polynomial model was obtained for fitting the variation kinetics of lignin content during thermal processing. Reducing the HHAIB blanching time and blanching temperature would obtain a lower weight loss and a better color performance (ΔE and L*). Additionally, microstructure observation revealed that the distribution density of microchannels initially increased and then decreased with the extension of blanching time, while it continuously became firmer as HHAIB blanching temperature increased. Overall, the optimal processing parameters were achieved under the HHAIB blanching temperature of 85°C for 6 min, ensuring a high-quality performance of bamboo shoot products.

Artificial intelligence in the anterior segment of eye diseases.

Ophthalmology is a subject that highly depends on imaging examination. Artificial intelligence (AI) technology has great potential in medical imaging analysis, including image diagnosis, classification, grading, guiding treatment and evaluating prognosis. The combination of the two can realize mass screening of grass-roots eye health, making it possible to seek medical treatment in the mode of "first treatment at the grass-roots level, two-way referral, emergency and slow treatment, and linkage between the upper and lower levels". On the basis of summarizing the AI technology carried out by scholars and their teams all over the world in the field of ophthalmology, quite a lot of studies have confirmed that machine learning can assist in diagnosis, grading, providing optimal treatment plans and evaluating prognosis in corneal and conjunctival diseases, ametropia, lens diseases, glaucoma, iris diseases, etc. This paper systematically shows the application and progress of AI technology in common anterior segment ocular diseases, the current limitations, and prospects for the future.

iP3T: an interpretable multimodal time-series model for enhanced gait phase prediction in wearable exoskeletons.

Introduction: Wearable exoskeletons assist individuals with mobility impairments, enhancing their gait and quality of life. This study presents the iP3T model, designed to optimize gait phase prediction through the fusion of multimodal time-series data. Methods: The iP3T model integrates data from stretch sensors, inertial measurement units (IMUs), and surface electromyography (sEMG) to capture comprehensive biomechanical and neuromuscular signals. The model's architecture leverages transformer-based attention mechanisms to prioritize crucial data points. A series of experiments were conducted on a treadmill with five participants to validate the model's performance. Results: The iP3T model consistently outperformed traditional single-modality approaches. In the post-stance phase, the model achieved an RMSE of 1.073 and an R2 of 0.985. The integration of multimodal data enhanced prediction accuracy and reduced metabolic cost during assisted treadmill walking. Discussion: The study highlights the critical role of each sensor type in providing a holistic understanding of the gait cycle. The attention mechanisms within the iP3T model contribute to its interpretability, allowing for effective optimization of sensor configurations and ultimately improving mobility and quality of life for individuals with gait impairments.

Loncastuximab tesirine in Chinese patients with relapsed or refractory diffuse large B-cell lymphoma: a multicenter, open-label, single-arm, phase II trial.

Patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have a poor prognosis. Loncastuximab tesirine (Lonca), an antibody conjugate targeting CD19, has demonstrated significant clinical benefit in R/R DLBCL in a global phase 2 LOTIS-2 study. In the China bridging pivotal phase 2 OL-ADCT-402-001 study, eligible patients aged ≥18 years with R/R DLBCL who had failed ≥ 2 lines of systemic therapies were enrolled and treated with Lonca every 3 week with 150 µg/kg for 2 cycles; then 75 µg/kg for subsequent cycles (up to 1 year). The primary endpoint was overall response rate (ORR) assessed by independent review committee. Primary analyses for efficacy and safety were performed on the patients who received at least one treatment and had at least 6 months of follow-up following an initial documented response. As of data-cutoff, 64 patients received Lonca (median: 4.0 cycles [range: 1 to 17]). The median number of prior lines of therapies was 3.0 (range: 2 to 12). The ORR was 51.6% (95% CI: 38.7% to 64.2%), and the complete response rate was 23.4%. Hematological events accounted for the majority of the most common (≥15%) Grade ≥3 treatment-emergent adverse events (TEAEs), in which increased gamma glutamyltransferase (25.0%), and hypokalaemia (18.8%) also were reported. Serious TEAEs were reported in 35 of 64 patients with 4 fatal TEAEs. In conclusion, Lonca monotherapy demonstrated clinically meaningful efficacy and was well-tolerated in heavily pretreated Chinese patients with R/R DLBCL, which was consistent with the results of the LOTIS-2 study in Caucasian patients.

A rare submucosal eminence of the colon.

A 38-year-old man came to our outpatient department with abdominal pain. The computed tomography (CT) scan shows no obvious abnormalities. The colonoscopy showed a submucosal eminence about 0.6cm in diameter in ascending colon, with a yellow surface color and moderate motion. Subsequently, we performed endoscopic mucosal dissection (ESD) surgery on the patient. The postoperative pathology revealed a submucosal granular cell tumor (GCT) of the ascending colon with a diameter of about 4mm. The immunohistochemistry suggestsed CD117 (-), Desmin (mucosal muscle +), S-100 (+++), CD68 (++), SOX-10 (++), Syn (+), CgA (-) , and Ki-67 (approximately 5%+).

Aggregated health risk assessment of perfluoroalkyl acids migrated from convenience food contact materials.

Ingestion of perfluoroalkyl acids (PFAAs) via contaminated food contact materials (FCMs) is an important human exposure source. This study adopts a toxicity equivalent approach to evaluate the collective health risk of multiple PFAAs in FCMs. A comprehensive extraction and analysis of 21 PFAAs in FCMs was performed. Among the analyzed substances, 15 PFAAs were detected. Migration experiment using three food simulants revealed the migration range of seven PFAAs from FCMs into the simulant to be 0.47-46.7 ng/cm2. The hazard quotient results suggest minimal health risk, except for 9% of packaged samples where perfluorooctanoic acid (PFOA) poses a higher risk. Utilizing PFOA toxic equivalent concentrations, comprehensive risk calculations showed ∼77% of samples potentially posing elevated health risks due to PFAA exposure. This emphasizes the substantial contribution of PFAAs beyond PFOA and underscores the importance of considering them in related assessments. The aggregated risk assessment reflects actual exposure circumstances more accurately.

Development of an early mobilization practice for critically ill patients in intensive care units: a Delphi method study.

OBJECTIVE: To develop a comprehensive and evidence-based early rehabilitation framework for critically ill patients, aiming to establish a systematic and scientifically grounded rehabilitation system. METHODS: A Delphi survey study was conducted, involving two rounds of consultations with 24 experts from critical care medicine, nursing, respiratory therapy, and rehabilitation medicine. Based on evidence from the literature, a draft rehabilitation system was created and evaluated using a Likert 5-point scale. Entries were refined based on expert feedback, with criteria for inclusion being a mean score ≥4, a coefficient of variation <0.25, and agreement (percentage of ratings as "very important" or "important" and "very operative" or "strong operability") ≥75%. Entries were modified or deleted according to expert suggestions. RESULTS: The survey achieved recall rates of 95.8% (23/24) and 86.9% (20/23) in the first and second rounds, respectively. The experts' judgment basis, familiarity, and authority coefficients were 0.96, 0.94, and 0.95, respectively. Following the initial round, 20 questionnaire entries were amended, 14 new entries were added, and 1 was deleted. The second round of Delphi consultations resulted in an early rehabilitation system consisting of 5 primary indicators, 21 secondary indicators, and 56 tertiary indicators, totaling 82 entries. CONCLUSIONS: This study established the first Chinese early rehabilitation system for critically ill patients based on the scientific Delphi method. It provides a structured framework that can serve as a reference for early rehabilitation practices in settings for critically ill patients.

Advancements in nutritional diagnosis and support strategies during the perioperative period for patients with liver cancer.

Liver cancer represents a grave hepatic condition and constitutes a significant global health concern. Surgical resection remains the principal therapeutic modality for liver cancer. Nevertheless, perioperative malnutrition exerts a notable impact on patients with liver cancer, emerging as an independent risk factor for disease mortality and adverse outcomes. Hence, precise nutritional diagnosis and timely nutritional support hold the potential to enhance therapeutic efficacy and quality of life for liver cancer patients. This study represents a meticulous foray into the literature, extracting data from PubMed, Web of Science, and EMBASE databases, with a focus on the past 5 years. It scrutinizes the impact of malnutrition on patients undergoing liver cancer surgery, the etiological underpinnings of malnutrition within this patient cohort, the critical assessment of perioperative nutritional status, and the strategic approaches to nutritional support. Utilizing rigorous inclusion and exclusion criteria, the amassed scholarly works are meticulously synthesized, methodically organized, and categorically elaborated upon. Ultimately, the authors propose the incorporation of a multidisciplinary nutrition management team during the perioperative period, comprising nutritionists, pharmacists, physicians, nurses, psychologists, and rehabilitation therapists, among other specialized professionals. Together, they collaborate to devise and implement personalized nutritional support plans, monitor patients' nutritional status, and make necessary adjustments as required. Through comprehensive management and intervention, improvements in the nutritional status of liver cancer patients can be achieved, thereby enhancing surgical success rates and facilitating postoperative recovery. It is believed that this manuscript will offer valuable insights to advance the nutritional management during the perioperative phase of liver cancer, aiding in ameliorating patients' nutritional status and treatment outcomes.

Co-delivery of PROTAC and siRNA via novel liposomes for the treatment of malignant tumors.

Targeted elimination of damaged or overexpressed proteins within the tumor serves a pivotal role in regulating cellular function and restraining tumor cell growth. Researchers have been striving to identify safer and more effective methods for protein removal. Here, we propose the synergistic employment of a small molecule degrading agent (PROTAC) and siRNA to attain enhanced protein clearance efficiency and tumor therapeutic effects. Co-delivery liposomes were prepared to facilitate the efficient encapsulation of PROTAC and siRNA. Specifically, the cationic liposome significantly improved the solubility of the insoluble PROTAC (DT2216). The cationic polymer (F-PEI) achieved efficient encapsulation of the nucleic acid drug, thereby promoting endocytosis and enhancing the therapeutic impact of the drug. Both in vivo and in vitro experiments demonstrated remarkable degradation of target proteins and inhibition of tumor cells by the co-delivery system. In conclusion, the co-delivery liposomes furnished a nano-delivery system proficient in effectively encapsulating both hydrophilic and hydrophobic drugs, thereby presenting a novel strategy for targeted combination therapy in treating tumors.

Role of extracellular vesicle-associated proteins in the progression, diagnosis, and treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, characterized by difficulties in early diagnosis, prone to distant metastasis, and high recurrence rates following surgery. Extracellular vesicles (EVs) are a class of cell-derived particles, including exosomes, characterized by a phospholipid bilayer. They serve as effective carriers for intercellular communication cargo, including proteins and nucleic acids, and are widely involved in tumor progression. They are being explored as potential tumor biomarkers and novel therapeutic avenues. We provide a brief overview of the biogenesis and characteristics of EVs to better understand their classification standards. The focus of this review is on the research progress of EV-associated proteins in the field of HCC. EV-associated proteins are involved in tumor growth and regulation in HCC, participate in intercellular communication within the tumor microenvironment (TME), and are implicated in events including angiogenesis and epithelial-mesenchymal transition (EMT) during tumor metastasis. In addition, EV-associated proteins show promising diagnostic efficacy for HCC. For the treatment of HCC, they also demonstrate significant potential including enhancing the efficacy of tumor vaccines, and as targeting cargo anchors. Facing current challenges, we propose the future directions of research in this field. Above all, research on EV-associated proteins offers the potential to enhance our comprehension of HCC and offer novel insights for developing new treatment strategies.