Potentials of Ulva spp.-derived sulfated polysaccharides as gelling agents with promising therapeutic effects.

Ulvan, a sulfated polysaccharide extracted from Ulva spp., has garnered significant attention in the food and pharmaceutical industries due to its potential health benefits. These include immunomodulation, antiviral, anti-inflammatory, anti-hyperlipidemic, and anti-cancer effects. Nonetheless, practical applications in these fields remain limited due to an incomplete understanding of its gelation mechanisms. Additionally, the underlying mechanisms of its gelation have not been completely understood and thoroughly reviewed. The primary objective is to provide current insights into ulvan's gelling mechanisms and potential health impacts. This review also delves into the existing applications of ulvan polysaccharides. By unraveling these aspects, the information provided in this work is expected to deepen our understanding of ulvan's gelation mechanisms and its prospective role in enhancing health, holding promise for advancements in the fields of food science and disease prevention. This work's theoretical insights contribute significantly to a deeper understanding of these aspects, which holds paramount importance in unleashing the full potential of ulvan and elevating its scientific significance.

PBPK Modeling Approach to Predict the Behavior of Drugs Cleared by Metabolism in Pregnant Subjects and Fetuses.

This study aimed to develop a physiologically based pharmacokinetic (PBPK) model that simulates metabolically cleared compounds' pharmacokinetics (PK) in pregnant subjects and fetuses. This model accounts for the differences in tissue sizes, blood flow rates, enzyme expression levels, plasma protein binding, and other physiological factors affecting the drugs' PK in both the pregnant woman and the fetus. The PBPKPlus™ module in GastroPlus® was used to model the PK of metoprolol, midazolam, and metronidazole for both non-pregnant and pregnant groups. For each of the three compounds, the model was first developed and validated against PK data in healthy non-pregnant volunteers and then applied to predict the PK in the pregnant groups. The model accurately described the PK in both the non-pregnant and pregnant groups and explained well the differences in the plasma concentration due to pregnancy. When available, the fetal plasma concentration, placenta, and fetal tissue concentrations were also predicted reasonably well at different stages of pregnancy. The work described the use of a PBPK approach for drug development and demonstrates the ability to predict differences in PK in pregnant subjects and fetal exposure for metabolically cleared compounds.

Comparison of Effect of Hirudo， Notoginseng Radix et Rhizoma， and Their Combinations on Renal Fibrosis in Rats with Chronic Renal Failure / 中国实验方剂学杂志

ObjectiveTo observe the effects of Hirudo， Notoginseng Radix et Rhizoma， and drug pair on renal pathological morphology and protein phosphatase 2A （PP2A）/adenylate activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signal pathway in rats with chronic renal failure （CRF）. MethodThe 55 male SD rats were randomly divided into a normal group （n=11） and a modeling group （n=44）. The normal group was fed conventionally， and the modeling group was given 0.25 g·kg-1·d-1 adenine by gavage for 28 days to replicate the CRF model. After successful modeling， rats were randomly divided into model group， Hirudo group （3 g·kg-1·d-1）， Notoginseng Radix et Rhizoma group （3 g·kg-1·d-1）， and Hirudo + Notoginseng Radix et Rhizoma group （3 g·kg-1·d-1）， with 9 rats in each group. The normal group and model group were given a constant volume of normal saline by intragastric administration for 30 days. At the end of the experiment， the levels of serum creatinine （SCr） and urea nitrogen （BUN） in all groups were measured. The renal pathological morphology changes were observed by hematoxylin-eosin （HE） staining， Masson staining， and electron microscopy. The mRNA expressions of PP2A， AMPK， and mTOR were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of PP2A， AMPK， phosphorylation（p）-AMPK， mTOR， and p-mTOR in renal tissue were detected by Western blot. ResultCompared with the normal group， the renal pathological structure changes were obvious， and the levels of SCr and BUN were significantly increased. The mRNA expression of PP2A， protein expression of PP2A， and p-mTOR/mTOR expression were significantly increased， and the p-AMPK/AMPK was significantly decreased in the model group （P<0.05）. Compared with the model group， the renal pathological morphology changes were significantly improved， and the levels of SCr and BUN were significantly decreased. The mRNA expression of PP2A， protein expression of PP2A， and p-mTOR/mTOR expression in the renal tissue were significantly decreased， and the p-AMPK/AMPK was significantly increased （P<0.05） in all groups after drug intervention. In addition， the effect in the Hirudo+Notoginseng Radix et Rhizoma group was better. The mRNA expression levels of AMPK and mTOR in the renal tissue were not significantly different among the normal group， model group， and other groups. ConclusionThe efficacy of Hirudo and Notoginseng Radix et Rhizoma pairs in improving renal fibrosis in rats with CRF is significantly better than that of the single drug， and its improvement on renal fibrosis in rats with CRF may be related to the regulation of PP2A/AMPK/mTOR signaling pathway.

Grape seed proanthocyanidins regulate mitophagy of endothelial cells and promote wound healing in mice through p-JNK/FOXO3a/ROS signal pathway.

Skin wound healing is a dynamic and complex process that involves multiple physiological and cellular events. Grape seed proanthocyanidins (GSP) have strong anti-oxidation and elimination of oxygen free radicals, and have been shown to significantly promote wound healing, but the underlying mechanism remains unclear. Studies have indicated that reactive oxygen species (ROS) acts as an upstream signal to induce mitophagy, suggesting that GSP can regulate mitophagy through the signal pathway. This study aimed to investigate whether GSP regulates mitophagy by down-regulating oxidative stress to promote wound healing. In vivo, GSP treatment accelerated wound healing, granulation tissue formation, collagen deposition, and angiogenesis in mice. Moreover, GSP down-regulated ROS levels and promoted the expression of antioxidant proteins by up-regulating the expression of p-JNK/FOXO3a protein, thereby regulating the expression of mitophagy-related proteins. In vitro, 4 µg/mL GSP showed no apparent toxic effects on cells and effectively reduce the oxidative stress damage of cells induced by H2O2. Western blot and superoxide anion fluorescence probe further confirmed that GSP effectively reduced Dihydroethidium content and up-regulated the expression of antioxidant proteins by activation of p-JNK/FOXO3a protein expression, thereby regulating mitophagy. Taken together, the findings from in vitro and in vivo experiments provide new insights into the promotion of wound healing by GSP.

Bronchial epithelial gene expression and interstitial lung abnormalities.

INTRODUCTION: Interstitial lung abnormalities (ILA) often represent early fibrotic changes that can portend a progressive fibrotic phenotype. In particular, the fibrotic subtype of ILA is associated with increased mortality and rapid decline in lung function. Understanding the differential gene expression that occurs in the lungs of participants with fibrotic ILA may provide insight into development of a useful biomarker for early detection and therapeutic targets for progressive pulmonary fibrosis. METHODS: Measures of ILA and gene expression data were available in 213 participants in the Detection of Early Lung Cancer Among Military Personnel (DECAMP1 and DECAMP2) cohorts. ILA was defined using Fleischner Society guidelines and determined by sequential reading of computed tomography (CT) scans. Primary analysis focused on comparing gene expression in ILA with usual interstitial pneumonia (UIP) pattern with those with no ILA. RESULTS: ILA was present in 51 (24%) participants, of which 16 (7%) were subtyped as ILA with a UIP pattern. One gene, pro platelet basic protein (PPBP) and seventeen pathways (e.g. TNF-α signalling) were significantly differentially expressed between those with a probable or definite UIP pattern of ILA compared to those without ILA. 16 of these 17 pathways, but no individual gene, met significance when comparing those with ILA to those without ILA. CONCLUSION: Our study demonstrates that abnormal inflammatory processes are apparent in the bronchial airway gene expression profiles of smokers with and without lung cancer with ILA. Future studies with larger and more diverse populations will be needed to confirm these findings.

The tumor immune microenvironment of nasopharyngeal carcinoma after gemcitabine plus cisplatin treatment.

Gemcitabine plus cisplatin (GP) chemotherapy is the standard of care for nasopharyngeal carcinoma (NPC). However, the mechanisms underpinning its clinical activity are unclear. Here, using single-cell RNA sequencing and T cell and B cell receptor sequencing of matched, treatment-naive and post-GP chemotherapy NPC samples (n = 15 pairs), we show that GP chemotherapy activated an innate-like B cell (ILB)-dominant antitumor immune response. DNA fragments induced by chemotherapy activated the STING type-I-interferon-dependent pathway to increase major histocompatibility complex class I expression in cancer cells, and simultaneously induced ILB via Toll-like receptor 9 signaling. ILB further expanded follicular helper and helper type 1 T cells via the ICOSL-ICOS axis and subsequently enhanced cytotoxic T cells in tertiary lymphoid organ-like structures after chemotherapy that were deficient for germinal centers. ILB frequency was positively associated with overall and disease-free survival in a phase 3 trial of patients with NPC receiving GP chemotherapy ( NCT01872962 , n = 139). It also served as a predictor for favorable outcomes in patients with NPC treated with GP and immunotherapy combined treatment (n = 380). Collectively, our study provides a high-resolution map of the tumor immune microenvironment after GP chemotherapy and uncovers a role for B cell-centered antitumor immunity. We also identify and validate ILB as a potential biomarker for GP-based treatment in NPC, which could improve patient management.

Underwater 3D reconstruction using a photometric stereo with illuminance estimation.

Underwater image sensing is directly affected by the change in illuminance towards a camera caused by the refraction of light in different media. In this study, the convergence of a near-field point light source in water is analyzed using a light propagation model. The photometric stereo (PS) formula is determined based on an accurate estimation of the illuminance entering the camera. An underwater PS system is designed to verify the proposed method's feasibility. The experimental results demonstrate improved accuracy in normal calculation. This helps achieve accurate underwater 3D reconstruction of objects that is suitable for underwater surface microdefect detection.

Construction of a Nomogram Prediction Model for Prognosis in Patients with Large Artery Occlusion-Acute Ischemic Stroke.

BACKGROUND: Patients with large artery occlusion-acute ischemic stroke (LAO-AIS) can experience adverse outcomes, such as brain herniation due to complications. This study aimed to construct a nomogram prediction model for prognosis in patients with LAO-AIS in order to maximize the benefits for clinical patients. METHODS: Retrospective analysis of 243 patients with LAO-AIS from January 2019 to January 2022 with medical history data and blood examination at admission. Univariate and multivariate analyses were conducted through binary logistic regression equation analysis, and a nomogram prediction model was constructed. RESULTS: Results of this study showed that hyperlipidemia (odds ratio [OR] = 2.849, 95% confidence interval [CI] = 1.100-7.375, P = 0.031), right cerebral infarction (OR = 2.144, 95% CI = 1.106-4.156, P = 0.024), D-Dimer>500 ng/mL (OR = 2.891, 95% CI = 1.398-5.980, P = 0.004), and neutrophil-lymphocyte ratio >7.8 (OR = 2.149, 95% CI = 1.093-4.225, P = 0.027) were independent risk factors for poor early prognosis in patients with LAO-AIS. In addition, hypertension (OR = 1.947, 95% CI = 1.114-3.405, P = 0.019), hyperlipidemia (OR = 2.594, 95% CI = 1.281-5.252, P = 0.008), smoking (OR = 2.414, 95% CI = 1.368-4.261, P = 0.002), D-dimer>500 ng/mL (OR = 3.170, 95% CI = 1.533-6.553, P = 0.002), and neutrophil-lymphocyte ratio >7.8 (OR = 2.144, 95% CI = 1.231-3.735, P = 0.007) were independent risk factors for poor long-term prognosis. The early prognosis nomogram receiver operating characteristic curve area under the curve value was 0.688 for the training set and 0.805 for the validation set, which was highly differentiated. The mean error was 0.025 for the training set calibration curve and 0.016 for the validation set calibration curve. Both the training and validation set decision curve analyses indicated that the clinical benefit of the nomogram was significant. The long-term prognosis nomogram receiver operating characteristic curve area under the curve values was 0.697 for the training set and 0.735 for the validation set, showing high differentiation. The mean error was 0.041 for the training set calibration curve and 0.021 for the validation set calibration curve. Both of the training and validation set decision curve analyses demonstrated a substantial clinical benefit of the nomogram. CONCLUSIONS: The nomogram prediction model based on admission history data and blood examination are easy-to-use tools that provide an accurate individualized prediction for patients with LAO-AIS and can assist in early clinical decisions and in obtaining an early prognosis.

Design of flexible wearable sensing systems / 生物医学工程学杂志

The aging population and the increasing prevalence of chronic diseases in the elderly have brought a significant economic burden to families and society. The non-invasive wearable sensing system can continuously and real-time monitor important physiological signs of the human body and evaluate health status. In addition, it can provide efficient and convenient information feedback, thereby reducing the health risks caused by chronic diseases in the elderly. A wearable system for detecting physiological and behavioral signals was developed in this study. We explored the design of flexible wearable sensing technology and its application in sensing systems. The wearable system included smart hats, smart clothes, smart gloves, and smart insoles, achieving long-term continuous monitoring of physiological and motion signals. The performance of the system was verified, and the new sensing system was compared with commercial equipment. The evaluation results demonstrated that the proposed system presented a comparable performance with the existing system. In summary, the proposed flexible sensor system provides an accurate, detachable, expandable, user-friendly and comfortable solution for physiological and motion signal monitoring. It is expected to be used in remote healthcare monitoring and provide personalized information monitoring, disease prediction, and diagnosis for doctors/patients.

Glutamate-releasing BEST1 channel is a new target for neuroprotection against ischemic stroke with wide time window

Many efforts have been made to understand excitotoxicity and develop neuroprotectants for the therapy of ischemic stroke. The narrow treatment time window is still to be solved. Given that the ischemic core expanded over days, treatment with an extended time window is anticipated. Bestrophin 1 (BEST1) belongs to a bestrophin family of calcium-activated chloride channels. We revealed an increase in neuronal BEST1 expression and function within the peri-infarct from 8 to 48 h after ischemic stroke in mice. Interfering the protein expression or inhibiting the channel function of BEST1 by genetic manipulation displayed neuroprotective effects and improved motor functional deficits. Using electrophysiological recordings, we demonstrated that extrasynaptic glutamate release through BEST1 channel resulted in delayed excitotoxicity. Finally, we confirmed the therapeutic efficacy of pharmacological inhibition of BEST1 during 6-72 h post-ischemia in rodents. This delayed treatment prevented the expansion of infarct volume and the exacerbation of neurological functions. Our study identifies the glutamate-releasing BEST1 channel as a potential therapeutic target against ischemic stroke with a wide time window.

Anti-motion Artifact Performance Test System for Ambulatory ECG Monitoring Equipment / 中国医疗器械杂志

Anti-motion artifact is one of the most important properties of ambulatory ECG monitoring equipment. At present, there is a lack of standardized means to test the performance of anti-motion artifact. ECG simulator and special conductive leather are used to build the simulator, it is used to simulate human skin, to generate ECG signal input for the ECG monitoring equipment attached to it. The mechanical arm and fixed support are used to build a motion simulation system to fix the conductive leather. The mechanical arm is programmed to simulate various motion states of the human body, so that the ECG monitoring equipment can produce corresponding motion artifacts. The collected ECG signals are read wirelessly, observed, analyzed and compared, and the anti-motion artifact performance of ECG monitoring equipment is evaluated. The test results show that by artificially creating the small difference between the two groups of ambulatory ECG monitoring equipment, the system can accurately test the interference signals introduced under the conditions of controlled movement such as tension and torsion, and compare the advantages and disadvantages. The research shows that the test system can provide convenient and accurate verification means for the research of optimizing anti-motion interference.

Analysis of HIV-1 subtypes and pretreatment drug resistance in newly reported HIV/AIDS cases in Hangzhou, 2020-2022 / 中华微生物学和免疫学杂志

Objective:To analyze the HIV-1 subtypes and drug resistance among newly reported HIV/AIDS cases before antiretroviral therapy (ART) in Hangzhou.Methods:Blood samples were collected from newly diagnosed HIV-1/AIDS cases not receiving ART in Hangzhou from 2020 to 2022. HIV-1 pol gene was amplified and then sequenced. A phylogenetic tree was construct using MEGA7.0 software to analyse the HIV-1 subtypes, The sequences were submitted to the Stanford University drug resistance database to identify drug resistance mutation sites and drug sensitivity. Results:A total of 2 700 sequences were obtained. Twelve subtypes were identified, and the predominant subtypes were CRF07_BC (46.8%, 1 263/2 700) and CRF01_AE (34.6%, 933/2 700). The overall drug resistance rate before ART was 8.1% (220/2 700) and the resistance rates to protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) were 2.8% (75/2 700), 1.3% (36/2 700) and 4.4% (119/2 700), respectively. Among the 220 drug-resistant cases, mutations conferring resistance to PIs (Q58E), NRTIs (M184V/I) and NNRTIs (K103N/S and E138A/G/K/Q) were detected in 47 (21.4%), 13 (5.9%), 42 (19.1%) and 41 (18.6%) patients, respectively.Conclusions:HIV-1 genotypes were highly complex in newly reported HIV/AIDS cases in Hangzhou from 2020 to 2022. There were cases showing moderate or high resistance to backbone drugs before ART, indicating that HIV-1 monitoring should be strengthened to avoid treatment failure and reduce the spread of drug-resistant strains.

Clinical efficacy and influencing factors of 125I seeds implantation in the treatment of patients with advanced lung cancer after radiotherapy and chemotherapy / 中华核医学与分子影像杂志

Objective:To investigate the clinical efficacy and prognostic factors of 125I seeds implantation in the treatment of patients with advanced lung cancer after radiotherapy and chemotherapy. Methods:From January 2017 to December 2019, 44 patients (39 males, 5 females, age 41-84 years) with advanced lung cancer after radiotherapy and chemotherapy who received 125I seeds implantation in Hebei General Hospital were retrospectively analyzed. All patients were followed up for ≥12 months, and the clinical efficacies were observed. χ2 test was used to analyze the difference of effective rates between groups. The cut-off value of postoperative dose delivered to 90% gross tumor volume ( D90) was obtained by ROC curve analysis. Kaplan-Meier method was used to calculate the survival rate and log-rank test was used for univariate analysis. Cox proportional hazards model was used for multivariate analysis to find the influencing factors for clinical efficacy. Results:The total effective rate was 72.73%(32/44) after 6 months treatment. The cut-off value of D90 was 120 Gy with the AUC of 0.771. The short-term effective rate of D90≥120 Gy group was better than that of D90<120 Gy group (18/19 vs 56.00%(14/25); χ2=8.17, P=0.004). The 1-year survival rate was 77.27%(34/44). Univariate analysis showed that age ( χ2=3.99, P=0.046), preoperative Hb ( χ2=10.60, P=0.001), tumor maximum diameter ( χ2=11.50, P=0.001) and postoperative D90( χ2=5.81, P=0.016) could affect the survival of patients. Multivariate analysis showed that preoperative Hb (hazard ratio ( HR)=0.023, 95% CI: 0.001-0.882, P=0.043) and tumor maximum diameter ( HR=40.889, 95% CI: 1.458-1 146.586, P=0.029) were prognostic factors. Conclusions:125I seeds implantation shows a good effect in the treatment of lung cancer patients after the progress of radiotherapy and chemotherapy. The short-term effect of patients with D90≥120 Gy is better than that of patients with D90<120 Gy. Preoperative Hb and tumor maximum diameter are prognostic factors of survival after implantation.

To compare the different hepatic portal exposure techniques in Kasai surgery during their different perioperative periods / 中华肝胆外科杂志

Objective:To compare the impact of different portal exposure techniques in the Kasai surgery on children with type Ⅲ. biliary atresia during their different perioperative periods.Methods:A retrospective study was performed on the data of children with type Ⅲ. biliary atresia who underwent Kasai surgery at Fujian Children's Hospital from January 2017 to October 2020. Of 45 children enrolled in this study, there were 24 males and 21 females, aged (71.3±21.0) days. Patients who had left and right branches of the portal vein and the left and right hepatic arteries in the portal area being completely freed and elastically stretched during the Kasai operation were included into the free group ( n=22) and the remaining patients were included in the control group ( n=23). Postoperative hospital stay, postoperative direct bilirubin levels, postoperative complications and transplant-free survival after the Kasai operation were compared between the 2 groups. Results:Postoperative hospital stay of (17.1±4.4) d in the free group was significantly lower than that in the control group (20.1±5.4) d, ( t=2.07, P=0.044). The direct bilirubin level at 3 months after surgery for the control group was 30.0 (109, 108.0)μmol/L, which was significantly higher than that of 14.5 (4.0, 37.5) μmol/L in the free group ( Z=-2.16, P=0.031). Twenty-one patients (91.3%) in the control group had frequent attacks of postoperative cholangitis, compared with 13 patients (59.1%) in the free group. The difference was statistically significant (χ 2=4.69, P=0.030). Eleven surviving patients (47.8%) in the control group did not undergo liver transplantation at one year after surgery, compared with 15 patients (68.2%) in the free group. At two years after surgery, 7 surviving patients (30.4%) in the control group did not undergo liver transplantation compared with 10 patients (45.5%) in the free group. Conclusion:For children with type Ⅲ. biliary atresia, completely freeing the left and right branches of portal vein, and left and right hepatic arteries in the liver portal area, and elastically stretching these vessels to expose the portal area of the liver during Kasai surgery increased surgical safety and reduced hospital stay.

Resting-state functional connectivity alterations of ventral tegmental area in adult male smokers: a functional magnetic resonance imaging study / 中华行为医学与脑科学杂志

Objective:To investigate the alterations of resting-state functional connectivity (RSFC) in ventral tegmental area (VTA) and substantia nigra (SN) among male smokers, and its correlation with clinical characteristics of smoking.Methods:The resting-state functional magnetic resonance data of 131 subjects recruited from January 2014 to December 2018 were analyzed retrospectively, including 76 smokers (smoking group) and 55 non-smokers (control group). VTA/SN was selected as regions of interest (ROI), and then calculated RSFC between VTA/SN and the whole brain.Based on SPM12 software, independent sample t-test was conducted to compare the differences in RSFC between smoking group and control group.Based on SPSS 22.0 software, Pearson correlation analysis was used to investigate the relationships between the RSFC of brain regions with significant differences and Fagerstr?m test for nicotine dependence (FTND) score, pack-year of smokers. Results:Compared with control group, the results showed decreased RSFC between VTA and the brain regions related default mode network (DMN)(including posterior cingulate cortex, right anterior cuneiform lobe, bilateral superior temporal gyrus, right middle temporal gyrus and right inferior parietal lobule), and regions of limbic system(including right marginal lobe and right angular gyrus), right calcarine (MNI: x, y, z=24, -55, -14) and left insula(MNI: x, y, z=-35, -11, 9) in smoking group(GRF corrected, voxel level P<0.005, cluster level P<0.05). Taking SN as the seed, there was no significant difference between smoking group and control group ( P>0.05). RSFC of VTA-left superior temporal gyrus was positively correlated with pack-year( r=0.243, P=0.034) and FTND ( r=0.282, P=0.014). VTA-left insula RSFC was positively correlated with FTND ( r=0.316, P=0.006). Conclusion:The RSFC in the mesolimbic system and the VTA-DMN circuit exist abnormal changes in smokers.To some extent, it may explain the reward deficits and dysfunction of emotion regulation in smokers, which may provide clues for further understanding the mechanism of tobacco addiction.

Research progress of acetabular bone fractures treatment in the elderly / 国际外科学杂志

With the advent of an aging society, the proportion of acetabular fractures in the elderly is increasing. Acetabular fracture belongs to intra-articular fracture. The treatment principle should be to restore the continuity of articular surface anatomy and the concentric relationship between the acetabular load bearing area and the femoral head as far as possible, rebuild the stability of the hip joint, promote the functional recovery of the hip joint, and help patients to carry out functional exercise at an early stage, so as to obtain a good prognosis. However, the treatment plan of the elderly is different from that of young patients due to problems such as insufficient bone mass, basic diseases and physiological weakness, which is a new challenge for orthopedic doctors. In this paper, the selection of different treatment schemes for elderly acetabular fracture is summarized, in order to provide help for clinicians in the treatment of elderly acetabular fracture.

The Mechanism Underlying the Promoting Effect of Cancer-associated Fibroblasts on Chemoresistance / 中国生物化学与分子生物学报

The carcinogenesis and progression of cancer not only depend on the feature of tumor cell themselves, but also rely on the tumor microenvironment (TME). Numerous studies have shown that TME plays a crucial role in tumor progression and drug resistance. Cancer-associated fibroblasts (CAFs) are important stromal cells in TME containing multiple functions, such as remodeling the extracellular matrix, regulating angiogenesis, interacting with adjacent tumor cells, and releasing a variety of molecules (such as cytokines, growth factors and exosomes) to regulate cell proliferation, invasion and metastasis. CAFs exhibit heterogeneity of origin and phenotype, and play dual roles in tumor progression. Recent studies have shown that CAFs are also involved in chemoresistance, suggesting that CAFs themselves and their downstream molecules and signal pathways could be the potential therapeutic target for cancer treatment. In this review, we summarized the role of CAFs in chemoresistance and underlying mechanism, and discussed the potential of targeting CAFs in overcoming drug resistance. However, the exploration of strategy for targeting CAFs is still at an early stage and requires further in-depth research.

Machine learning modeling identifies hypertrophic cardiomyopathy subtypes with genetic signature / 医学前沿

Previous studies have revealed that patients with hypertrophic cardiomyopathy (HCM) exhibit differences in symptom severity and prognosis, indicating potential HCM subtypes among these patients. Here, 793 patients with HCM were recruited at an average follow-up of 32.78 ± 27.58 months to identify potential HCM subtypes by performing consensus clustering on the basis of their echocardiography features. Furthermore, we proposed a systematic method for illustrating the relationship between the phenotype and genotype of each HCM subtype by using machine learning modeling and interactome network detection techniques based on whole-exome sequencing data. Another independent cohort that consisted of 414 patients with HCM was recruited to replicate the findings. Consequently, two subtypes characterized by different clinical outcomes were identified in HCM. Patients with subtype 2 presented asymmetric septal hypertrophy associated with a stable course, while those with subtype 1 displayed left ventricular systolic dysfunction and aggressive progression. Machine learning modeling based on personal whole-exome data identified 46 genes with mutation burden that could accurately predict subtype propensities. Furthermore, the patients in another cohort predicted as subtype 1 by the 46-gene model presented increased left ventricular end-diastolic diameter and reduced left ventricular ejection fraction. By employing echocardiography and genetic screening for the 46 genes, HCM can be classified into two subtypes with distinct clinical outcomes.

Emerging role of miRNAs, lncRNAs, and circRNAs in pregnancy-associated diseases / 中华医学杂志(英文版)

Accumulating studies have demonstrated that non-coding RNAs (ncRNAs), functioning as important regulators of transcription and translation, are involved in the establishment and maintenance of pregnancy, especially the maternal immune adaptation process. The endometrial stromal cells (ESCs), trophoblast cells, and decidua immune cells that reside at the maternal-fetal interface are thought to play significant roles in normal pregnancy and pregnancy-associated diseases. Here, we reviewed the up-to-date evidence on how microRNA, long non-coding RNA, and circular RNA regulate ESCs, trophoblast cells, and immune cells and discussed the potential applications of these ncRNAs as diagnostic and therapeutic markers in pregnancy complications.

Prediction of vault after implantable collamer lens implantation and its research progress / 国际眼科杂志(Guoji Yanke Zazhi)

Myopia is considered to be a disease occurred under the influence of genetic and environmental factors, and it can only be restored by corrective surgeries. The current surgical methods include laser surgeries and phakic intraocular lens(PIOL)implantation, and PIOL has the advantages of wide range of correction, repeatable procession and small damage to corneal tissue. Furthermore, good visual acuity can be achieved after implantation of intraocular lens. Implantable collamer lens(ICL)is the most common surgical method in this group. The vertical distance between the highest point of the posterior central surface of the implanted lens and the anterior surface of the crystalline lens is called vault. It will cause serious complications if the vault turns out to be abnormal. Up to now, there is no optimal prediction method. This research focuses on vault, discusses the ideal range of postoperative vault, the safety and effectiveness of this surgery, and analyzes the existing prediction methods to provide directions for future clinical research.