A clinical-radiomic-pathomic model for prognosis prediction in patients with hepatocellular carcinoma after radical resection.

PURPOSE: Radical surgery, the first-line treatment for patients with hepatocellular cancer (HCC), faces the dilemma of high early recurrence rates and the inability to predict effectively. We aim to develop and validate a multimodal model combining clinical, radiomics, and pathomics features to predict the risk of early recurrence. MATERIALS AND METHODS: We recruited HCC patients who underwent radical surgery and collected their preoperative clinical information, enhanced computed tomography (CT) images, and whole slide images (WSI) of hematoxylin and eosin (H & E) stained biopsy sections. After feature screening analysis, independent clinical, radiomics, and pathomics features closely associated with early recurrence were identified. Next, we built 16 models using four combination data composed of three type features, four machine learning algorithms, and 5-fold cross-validation to assess the performance and predictive power of the comparative models. RESULTS: Between January 2016 and December 2020, we recruited 107 HCC patients, of whom 45.8% (49/107) experienced early recurrence. After analysis, we identified two clinical features, two radiomics features, and three pathomics features associated with early recurrence. Multimodal machine learning models showed better predictive performance than bimodal models. Moreover, the SVM algorithm showed the best prediction results among the multimodal models. The average area under the curve (AUC), accuracy (ACC), sensitivity, and specificity were 0.863, 0.784, 0.731, and 0.826, respectively. Finally, we constructed a comprehensive nomogram using clinical features, a radiomics score and a pathomics score to provide a reference for predicting the risk of early recurrence. CONCLUSIONS: The multimodal models can be used as a primary tool for oncologists to predict the risk of early recurrence after radical HCC surgery, which will help optimize and personalize treatment strategies.

F-box proteins and gastric cancer: an update from functional and regulatory mechanism to therapeutic clinical prospects.

Gastric cancer (GC) is a prevalent malignancy characterized by significant morbidity and mortality, yet its underlying pathogenesis remains elusive. The etiology of GC is multifaceted, involving the activation of oncogenes and the inactivation of antioncogenes. The ubiquitin-proteasome system (UPS), responsible for protein degradation and the regulation of physiological and pathological processes, emerges as a pivotal player in GC development. Specifically, the F-box protein (FBP), an integral component of the SKP1-Cullin1-F-box protein (SCF) E3 ligase complex within the UPS, has garnered attention for its prominent role in carcinogenesis, tumor progression, and drug resistance. Dysregulation of several FBPs has recently been observed in GC, underscoring their significance in disease progression. This comprehensive review aims to elucidate the distinctive characteristics of FBPs involved in GC, encompassing their impact on cell proliferation, apoptosis, invasive metastasis, and chemoresistance. Furthermore, we delve into the emerging role of FBPs as downstream target proteins of non-coding RNAs(ncRNAs) in the regulation of gastric carcinogenesis, outlining the potential utility of FBPs as direct therapeutic targets or advanced therapies for GC.

Unleashing the potential: transarterial chemoembolization combined with intra-arterial infusion of bevacizumab for unresectable hepatocellular carcinoma.

BACKGROUND: The purpose of this study is to compare the efficacy and safety of transarterial chemoembolization (TACE) alone with transarterial chemoembolization combined with the arterial infusion of bevacizumab (TACE + Bev) in patients with unresectable hepatocellular carcinoma (uHCC). METHODS: A retrospective analysis was conducted on 446 uHCC patients treated with TACE or TACE + Bev between January 2021 and March 2023. The study evaluated objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events in both treatment groups. RESULTS: Finally, the TACE group comprised 295 patients, and the TACE + Bev group comprised 151 patients. Patients in the TACE + Bev group exhibited significantly prolonged median PFS (7.9 months vs. 10.3 months, P = 0.013) and median OS (16.1 months vs. 21.4 months, P = 0.041), improved ORR (26.8% vs. 37.7%, P = 0.017) and DCR (71.5% vs. 80.8%, P = 0.033) compared to the TACE group. Multifactorial Cox analysis identified alpha-fetoprotein (AFP) > 400 ng/ml as an independent prognostic factor for PFS and OS. Meanwhile, portal vein cancer thrombosis and distant metastasis are poor prognostic factors for OS. The overall incidence of adverse events was similar between the two groups. CONCLUSION: In comparison with the TACE group, the TACE + Bev group demonstrated efficacy in improving outcomes for patients with uHCC with a manageable safety profile.

Radiomics-guided prognostic assessment of early-stage hepatocellular carcinoma recurrence post-radical resection.

PURPOSE: The prognosis of early-stage hepatocellular carcinoma (HCC) patients after radical resection has received widespread attention, but reliable prediction methods are lacking. Radiomics derived from enhanced computed tomography (CT) imaging offers a potential avenue for practical prognostication in HCC patients. METHODS: We recruited early-stage HCC patients undergoing radical resection. Statistical analyses were performed to identify clinicopathological and radiomic features linked to recurrence. Clinical, radiomic, and combined models (incorporating clinicopathological and radiomic features) were built using four algorithms. The performance of these models was scrutinized via fivefold cross-validation, with evaluation metrics including the area under the curve (AUC), accuracy (ACC), sensitivity (SEN), and specificity (SPE) being calculated and compared. Ultimately, an integrated nomogram was devised by combining independent clinicopathological predictors with the Radscore. RESULTS: From January 2016 through December 2020, HCC recurrence was observed in 167 cases (64.5%), with a median time to recurrence of 26.7 months following initial resection. Combined models outperformed those solely relying on clinicopathological or radiomic features. Notably, among the combined models, those employing support vector machine (SVM) algorithms exhibited the most promising predictive outcomes (AUC: 0.840 (95% Confidence interval (CI): [0.696, 0.984]), ACC: 0.805, SEN: 0.849, SPE: 0.733). Hepatitis B infection, tumour size > 5 cm, and alpha-fetoprotein (AFP) > 400 ng/mL were identified as independent recurrence predictors and were subsequently amalgamated with the Radscore to create a visually intuitive nomogram, delivering robust and reliable predictive performance. CONCLUSION: Machine learning models amalgamating clinicopathological and radiomic features provide a valuable tool for clinicians to predict postoperative HCC recurrence, thereby informing early preventative strategies.

Effect of nursery on asthma and acute upper respiratory infection in healthy preschool children.

Aim: The aim of the study was to investigate the effect of admission to nursery on the incidence of acute upper respiratory infection (AURI) in healthy preschool children, analyse the aetiology of AURI, and provide reference for its clinical diagnosis and treatment. Material and methods: Pharyngeal swab samples were dynamically collected from 119 healthy preschool children who were first time admitted to a local public nursery for multiple etiological detection to explore the time of the first occurrence of AURI after admission to the nursery and the causes of infection. The effect of nursery on pathogen colonization in the pharynx in preschool children was also analysed. Results: A total of 91 children developed AURI in the nursery. There was a significant difference between genders (χ2 = 4.078, p = 0.043). The common pathogens of AURI showed a concentrated distribution. The proportions of bacterial, mycoplasma, and viral infections were 51.65%, 15.38%, and 12.09%, respectively, of which the proportions of mixed infection of two bacteria and mixed infection of bacteria and non-bacteria were 5.50% and 5.50%, respectively. A total of 28 children did not develop AURI in the nursery. There was no significant difference in the number of pathogens in the pharynx between the results before and after admission to the nursery (t = 0.700, p = 0.488). Conclusions: Collective living in the nursery causes a concentrated incidence of AURI in preschool children and has no effect on pathogen colonization in the pharynx in uninfected children. Bacteria are the main pathogen of AURI. The health education of children in nurseries needs to be strengthened to avoid the cross-infection in the population.

The differences of corneal astigmatism in different populations and its quantitative analysis.

OBJECTIVE: To analyze the differences of corneal astigmatism in different age groups. METHODS: The clinical data of the patients from the outpatient Department of Ophthalmology of the Tengzhou Central People's Hospital from April 2014 to June 2014 was screened and statistically analyzed. The corneal curvature was measured by three different instruments: Keratometer, IOL Master and Sirius corneal topography. The changes of the corneal astigmatism in different groups were evalutaed in the study. RESULTS: Corneal astigmatism of different groups showed no statistical difference and the average corneal astigmatism of 70˜79 age group were higher than younger groups. As the age grew, the with-the-rule astigmatism gradually reduced from 85.8% ( A Group) to 31.0% (F Group). The against-the-rule astigmatism increased from 6.7% ( A Group ) to 45.0% (F Group). CONCLUSION: The proportion of the with-the-rule astigmatism gradually reduced with the growth of age. The proportion of the against-the-rule astigmatism increased significantly. The oblique astigmatism had no obvious change before the age of 40. The proportion of oblique astigmatism increased obviously at the 40˜49 group and tended to be stable. After the age of 60, the proportion of different types of astigmatism tended to be stable.

Effects of transport stress on pathological injury and expression of main heat shock proteins in the caprine stomach.

BACKGROUND: Transportation is necessary to introduce new breeds of goats to the farm and move the adult meat goat from the farm to the slaughterhouse. However, these actions may give rise to transport stress. Heat shock proteins (HSPs) are playing some important regulate roles during transport stress. The aim of this study was to evaluate the effects of transport stress on the pathological injury and HSPs expression in the stomach of goats. A total of three batches of Ganxi goats from western Jiangxi province were enrolled in this study. For each batch, twelve healthy adult male goats were randomly divided into three groups (four goats per batch and per group): Control group, stress group transported during 2 h and stress group transported during 6 h. RESULTS: Our results showed that the different degrees of stomach walls damage, with the change of expression levels of heat shock protein 27 (HSP27), heat shock protein 70 (HSP70) and heat shock protein 90 (HSP90), occurred after goats transportation. In rumen, the mRNA and protein expressions of HSP27 and HSP70 were increased after transport stress, but not HSP90. In reticulum, all three HSPs mRNA and protein levels were upregulated after 2 h transport, but decreased after 6 h transport. In omasum, HSP27 and HSP70 mRNA and protein were increased after transport stress, however, HSP90 mRNA level only had a slightly enhancement after transport stress. In abomasum, HSP70 and HSP90 mRNA and protein levels were increased after transport stress, but HSP27 was decreased after transport stress. CONCLUSIONS: Taken together, these results revealed that the pathological changes in the gastric tissues and the stomach HSPs expression in goats are related to transport stress and duration. Moreover, this study also provides some new data to advocate reducing transport stress of goats and improving animal welfare.

Detection of heat shock protein 27, 70, 90 expressions in primary parenchymatous organs of goats after transport stress by real-time PCR and ELISA.

Transport stress causes a series of problems to goat production, such as tissue injury and immunity damage. As a pro-survival pathway, the heat shock response protects healthy cells of goat from stressors. To evaluate the effects of transport stress on heat shock protein (HSPs) expression on goat primary parenchymatous organs, a total of three batches of goats were treated in this study. For each batch, 12 healthy adult male goats were randomly and averagely divided into three groups: Control group (non-transported group), 2 hr transported group and 6 hr transported group. Real-time PCR results indicated that the mRNA expression level of heat shock protein 27 (HSP27) in all examined organs of 2 hr transport-treated goats were upregulated (p < .05) except lung, and heat shock protein 70 (HSP70; except spleen) and heat shock protein 90 (HSP90; except liver and lung) were also increased (p < .05). In 6 hr transported group, the transcription levels of HSP27 (except heart and kidney), HSP70 (except heart, liver and lymph nodes) and HSP90 (except heart and spleen) were all backed to the original levels or even reduced (p < .05). Enzyme-linked immunosorbent assay (ELISA) results showed that the protein levels of HSP27 (except lymph nodes), HSP70 (except spleen) and HSP90 (except liver and lung) were all increased after 2 hr transport (p < .05). After 6 hr transport, HSP27 only in kidney and HSP70 only in heart and liver were upregulated (p < .05), while HSP90 in all the examined organs except liver and lung were also maintained in relatively high levels (p < .05). Taken together, these results suggested that the expression of HSPs in goat primary parenchymatous organs may be regulated by transport stress time. Moreover, this study also provides some new data to advocate reducing transport stress of goats and improving animal welfare.

Comparison of methane emissions among invasive and native mangrove species in Dongzhaigang, Hainan Island.

The strength of methane (CH4) source of mangroves is not well understood, especially when including all CH4 pathways in consideration. This study measured CH4 fluxes by five pathways (sediments, pneumatophores, water surface, leaves, and stems) from four typical mangrove forests, including Kandelia candel without pneumatophores and three species with pneumatophores: Sonneratia apetala, Laguncularia racemosa and Bruguiera gymnorhiza-Bruguiera sexangula. The CH4 fluxes from sediments were 4.82±1.46mgCH4m-2h-1 for K. candel and 1.36±0.17mgCH4m-2h-1 for the other three with pneumatophores. Among the three communities with pneumatophores, S. apetala community had significantly greater emission rate than the other two (P<0.05). Pneumatophores in S. apetala were found to significantly decrease CH4 emission from sediments (P<0.01), while those in B. gymnorhiza-B. sexangula were significantly increase it (P<0.05). CH4 fluxes from waters were 3.48±1.11mgCH4m-2h-1, with the highest emission rate in the K. candel community for the duck farming. Leaves of mangroves except for those of K. candel were a weak CH4 daytime sink, but stems were a weak source. The total 72ha of mangroves in the Changning river basin emitted about 8.10Gg CH4 per year, with a weighted emission rate of about 1.29mgCH4m-2h-1. Our results suggested that mangroves are only a small methane source to atmosphere with great contribution from sediments and waters, only slight contribution from leaves and stems. Pneumatophores of different mangrove species played different roles in CH4 fluxes from sediments.

Short-term acceptability of female condom use among low-fee female sex workers in China: a follow-up study.

BACKGROUND: Low-fee female sex workers (FSW) lack power to effectively negotiate male condom use with clients. Female condoms (FCs) may provide an alternative strategy. This study was conducted to assess the acceptability of FC use among low-fee FSWs, and to identify appropriate candidates for future FC promotion. METHODS: A one-month follow-up study was conducted. At entry into the study, eligible participants completed a baseline questionnaire and were given 10 FCs. At the one-month follow up encounter, the number of used FC packages were counted and each participant completed a follow-up questionnaire. Logistic regression was used to identify variables associated with more frequent use of FCs (> 2 times). RESULTS: A total of 312 low-fee FSWs were enrolled at baseline and all participants completed the follow-up evaluation. Among them, 123 (39.4%) participants had used more than two FCs. Participants who were illiterate or had completed at most primary school education (OR: 2.4, 95% CI: 1.4-7.2), charged ≤30 RMB per client (≤30 vs. 51-80 RMB, OR: 3.8, 95% CI: 1.9-7.6), or had consistently used condoms with regular clients in the past month (OR: 2.4, 95%CI: 1.4-4.2) were more likely to use FCs. CONCLUSION: Low-fee FSWs charging ≤30 RMB per client, and those who are less educated may be appropriate initial candidates for FC promotion in China. Strategies to consider include teaching FSWs tactics for negotiation of FC use that can initially be applied with regular clients, and providing education to maximize ease-of use, and minimize discomfort with FC usage.

[Risk factors for recurrent wheezing in infants and young children suffering from dust mite allergy after their first wheezing].

OBJECTIVE: To investigate the risk factors for recurrent wheezing in infants and young children suffering from dust mite allergy after their first wheezing. METHODS: A total of 1 236 infants and young children who experienced a first wheezing episode and were hospitalized between August 2014 and February 2015 were enrolled, among whom 387 were allergic to dust mites. These infants and young children were followed up to 1 year after discharge. A total of 67 infants and young children who experienced 3 or more recurrent wheezing episodes within 1 year were enrolled as the recurrent wheezing group, while 84 infants and young children who did not experience recurrent wheezing during follow-up were enrolled as the control group. Univariate analysis and multivariate logistic stepwise regression analysis were performed to investigate the risk factors for recurrent wheezing in these patients. RESULTS: The univariate analysis showed that the age on admission, wheezing time before admission, Mycoplasma pneumoniae infection rate, and influenza virus infection rate were associated with recurrent wheezing. The multivariate logistic stepwise regression analysis showed that the older age on admission (OR=2.21, P=0.04) and Mycoplasma pneumoniae infection (OR=3.54, P=0.001) were independent risk factors for recurrent wheezing. CONCLUSIONS: Infants and young children who are allergic to dust mites, especially young children, have a significantly increased risk of recurrent wheezing if they are complicated by Mycoplasma pneumoniae infection during the first wheezing episode.

The organization of sex work in low- and high-priced venues with a focus on the experiences of ethnic minority women working in these venues.

Prior research on female sex workers (FSW) in China, and their risk for HIV and STI, neglects the nuanced experiences of ethnic minority FSW. We conducted participant observations and in-depth interviews with 33 FSW and six venue bosses to describe the experiences of FSW and management structures in low and high-priced sex work venues in Liuzhou, China. In low-priced venues, FSW had more autonomy and stronger relationships with their ethnic minority peers. Mid- and high-priced venues had more formal management structures. Ethnic minority FSW working in higher priced venues experienced less support and kinship with their peers. HIV/STI prevention outreach activities occurred in all of the venues, but they were not tailored for different venue types or for ethnic minority FSW. Our findings provide guidance for tailoring public health programs that meet the needs of ethnic minority women working in different types of sex work venues.

[Assessment of the young rat model of visceral hypersensitivity by measuring electrical discharge of external oblique].

OBJECTIVE: To study the value of measuring electrical discharge of external oblique in assessment of young rat model of visceral hypersensitivity. METHODS: Eight-day-old neonatal Sprague-Dawley rats were randomly assigned to two groups: an experimental group and a control group (n=16 each). Rats in the experimental group were subjected to mechanical colorectal irritation daily for 7 consecutive days, while the rats in the control group did not received colorectal irritation treatment. On the 6th week of their lives, the spike amplitude of external oblique were measured to evaluate the bowel sensitivity. RESULTS: When the colorectal distention (CRD) pressure was 30 and 45 mmHg, the 95% confidence interval of the spike amplitude in the experimental group was significantly higher than that in the control group (P<0.01). When the CRD pressure were 60 and 75 mmHg, the 95% confidence interval of the spike amplitude in female rats was significantly higher than that in males (P<0.05). CONCLUSIONS: The electrical discharge of external oblique confirmed that chronic colorectal irritation in neonatal rats can result in a chronic visceral hypersensitivity in the juvenile stage, with gender differences. Electrophysiological assessment is a quantitative test, and can objectively reflect visceral sensibility of pain.

Macrolactonization catalyzed by the terminal thioesterase domain of the nonribosomal peptide synthetase responsible for lichenysin biosynthesis.

The excised terminal thioesterase of the lichenysin nonribosomal peptide synthetase was found to be a highly efficient and versatile enzyme. Its activity strictly requires the R configuration of the beta-hydroxy fatty acid and the side chains of aspartate-5 and isoleucine-7, but tolerates changes in five other residues of the substrate. Characterization of this enzyme facilitates future effort to engineer the lichenysin synthetase for biotechnological applications.

B-cell responses in patients who have recovered from severe acute respiratory syndrome target a dominant site in the S2 domain of the surface spike glycoprotein.

Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease caused by a novel strain of coronavirus. Examination of the immune responses of patients who have recovered from SARS should provide important information for design of a safe and effective vaccine. We determined the continuous viral epitopes targeted by antibodies in plasma samples from convalescent SARS patients through biopanning with a vast M13 phage display dodecapeptide library. These epitopes converged to very short peptide fragments, one on each of the structural proteins spike and nucleocapsid and the nonstructural proteins 3a, 9b, and nsp 3. Immunoassays found that most of the patients who had recovered from SARS developed complementary antibodies to the epitope-rich region on the spike S2 protein, indicating that this is an immunodominant site on the viral envelope comprising the spike, matrix, and small envelope glycoproteins. These S2-targeting antibodies were shown to effectively neutralize the coronavirus, indicating that they provided protective immunity to help the patients recover from the viral infection. These results suggest that the SARS coronavirus might have an antigenic profile distinct from those of other human or animal coronaviruses. Due to the tested safety and protective effects of the convalescent-phase serological antibodies, identification of their complementary antigens may enable the design of an epitope-based vaccine to prevent potential antibody-mediated immunopathology.

cDNA cloning, identification and characterization of a novel cystatin from the tentacle of Cyanea capillata.

Cystatin is of interest from biochemical and evolutionary prospective, and also has been applied in biotechnology. In this paper, a novel cystatin was found by EST sequence analysis of the cDNA library of Cyanea capillata tentacle. The sequence of a full-length cDNA clone contained an open reading frame encoding a putative 18-residue signal peptide and a mature protein of 113 amino acids, which showed only 26% identities to Family 2 cystatins and had its own characteristic enzyme-binding motifs, Ser(97)-Trp(98), which had not been found in any other known cystatins. Thus, the novel cystatin cloned from jellyfish was designated as cystatin J, which may belong to a new family of cystatin, called Family 4. The mature cystatin J was produced in Escherichia coli as a thioredoxin (Trx) fusion protein using the pET expression system and purified by affinity and cation exchange chromatography. The recombinant cystatin J of approximately M(r) = 12,800 displayed an obvious inhibition of papain (K(i) value below 0.5 nM), in competition with substrate. Thus, the recombinant cystatin J was a functional cystatin in spite of relatively lower sequence similarity with other cystatins. Activity of the novel cystatin was stable at pH 4-11 at 4 degrees C, but unstable at neutral pH at >50 degrees C.

Effect of hypertension on hearing function, LDH and ChE of the cochlea in older rats.

The relationship between the hypertension and the aging process of hearing organ was investigated. Twenty Wistar 3-month old rats and 20 Wistar 12-month old rats, 20 spontaneously hypertensive rat stroke-prone (SHRSP) 3-month old rats and 20 SHRSP 12-month old rats free of middle ear infections as observed under otomicroscopy, with normal tympanic membrane and auricle reflex, were selected to be divided into two experimental groups and two control groups respectively. The tail artery blood pressure was measured non-invasively. The threshold of auditory brain-stem response (ABR) was measured by Spirit evoked potential meter. The LDH and ChE staining in the inner ear was performed and the optical density was analyzed by the HPIAS analysis system. The results showed that there was no difference in the ABR thresholds, the activities of LDH and ChE between Wistar 3-month old group and SHRSP 3-month old group (P > 0.05). The mean value of ABR threshold and the activities of LDH and ChE in the Wistar 12-month old group at relevant sections were significantly greater than those in the two 3-month old groups (P < 0.05), whereas the mean value of ABR threshold and the activities of LDH and ChE in the SHRSP 12-month old group at relevant sections were significantly higher than those in the 3-month old control group (P < 0.01). It was concluded that presbycusis existed in the Wistar 12-month old group rats. The glycogenosis and the abnormal secretion of neural transmitter were discerned after hypertension. All the above factors may worsen the aging of the hearing system.

EST analysis of gene expression in the tentacle of Cyanea capillata.

Jellyfish, Cyanea capillata, has an important position in head patterning and ion channel evolution, in addition to containing a rich source of toxins. In the present study, 2153 expressed sequence tags (ESTs) from the tentacle cDNA library of C. capillata were analyzed. The initial ESTs consisted of 198 clusters and 818 singletons, which revealed approximately 1016 unique genes in the data set. Among these sequences, we identified several genes related to head and foot patterning, voltage-dependent anion channel gene and genes related to biological activities of venom. Five kinds of proteinase inhibitor genes were found in jellyfish for the first time, and some of them were highly expressed with unknown functions.

Identification and Funtional Characterization of Three Postsynaptic Short-chain Neurotoxins from Hydrophiinae, Lapemis hardwickii Gray.

Three cDNA clones, sn12, sn36 and sn160, encoding isoforms of postsynaptic short-chain neurotoxins, were cloned by screening a cDNA library of the venom from Hydrophiinae, Lapemis hardwickii Gray. The sequences of three cDNA clones encoded proteins consisting of 60 amino acid residues. There was only one amino acid substitution among the three isoforms SN12, SN36 and SN160 at the position 46 of mature proteins, and they were Pro(46), His(46) and Arg(46), respectively. The three molecules were expressed in Escherichia coli and the recombinant proteins were characterized. Different LD(50) were obtained, namely 0.0956 mg/kg, 0.3467 mg/kg and 0.2192 mg/kg, when the SN12, SN36 and SN160 were injected into Kunming mice(i.p.). In analgesic effect assayed by the acetic acid-induced writhing method, SN12 and SN160 showed similar analgesic effect, but SN36 had effects significantly different with the other two. Our studies suggested that the amino acid residues on position 46 could affect the combination between the postsynaptic short-chain neurotoxins and the nicotinic acetylchoine receptor, since different amino acid substitution resulted in different biological activities.