Present and future of new systemic therapies for early and intermediate stages of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Notwithstanding the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical challenge.Emergent systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of HCC.This review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent.We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent.Finally,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.

Single-cell profiling of the pig cecum at various developmental stages

The gastrointestinal tract is essential for food digestion,nutrient absorption,waste elimination,and microbial defense.Single-cell transcriptome profiling of the intestinal tract has greatly enriched our understanding of cellular diversity,functional heterogeneity,and their importance in intestinal tract development and disease.Although such profiling has been extensively conducted in humans and mice,the single-cell gene expression landscape of the pig cecum remains unexplored.Here,single-cell RNA sequencing was performed on 45572 cells obtained from seven cecal samples in pigs at four different developmental stages(days(D)30,42,150,and 730).Analysis revealed 12 major cell types and 38 subtypes,as well as their distinctive genes,transcription factors,and regulons,many of which were conserved in humans.An increase in the relative proportions of CD8^(+)T and Granzyme A(low expression)natural killer T cells(GZMA^(low)NKT)cells and a decrease in the relative proportions of epithelial stem cells,Tregs,RHEX^(+)T cells,and plasmacytoid dendritic cells(pDCs)were noted across the developmental stages.Moreover,the post-weaning period exhibited an up-regulation in mitochondrial genes,COX2 and ND2,as well as genes involved in immune activation in multiple cell types.Cell-cell crosstalk analysis indicated that IBP6^(+)fibroblasts were the main signal senders at D30,whereas IBP6^(−)fibroblasts assumed this role at the other stages.NKT cells established interactions with epithelial cells and IBP6^(+)fibroblasts in the D730 cecum through mediation of GZMA-F2RL1/F2RL2 pairs.This study provides valuable insights into cellular heterogeneity and function in the pig cecum at different development stages.

Novel method for identifying the stages of discharge underwater based on impedance change characteristic

It is difficult to determine the discharge stages in a fixed time of repetitive discharge underwater due to the arc formation process being susceptible to external environmental influences. This paper proposes a novel underwater discharge stage identification method based on the Strong Tracking Filter(STF) and impedance change characteristics. The time-varying equivalent circuit model of the discharge underwater is established based on the plasma theory analysis of the impedance change characteristics and mechanism of the discharge process. The STF is used to reduce the randomness of the impedance of repeated discharges underwater, and then the universal identification resistance data is obtained. Based on the resistance variation characteristics of the discriminating resistance of the pre-breakdown, main, and oscillatory discharge stages, the threshold values for determining the discharge stage are obtained. These include the threshold values for the resistance variation rate(K) and the moment(t).Experimental and error analysis results demonstrate the efficacy of this innovative method in discharge stage determination, with a maximum mean square deviation of Scrless than 1.761.

Nutritional Composition and Distribution of Heracleum dissectum Ledeb.at Different Growth Stages

Heracleum dissectum Ledeb.(HD)with high edible and medicinal values is distributed in Northeast Asia.To provide a reference for selecting appropriate parts and periods to harvest HD,the nutrient contents in different parts of HD at three growth stages were determined.The nutrients being determined are essential nutrients closely related to human needs,and the crude protein content of HD was 3.58‒28.43 g•100 g^(-1)DW(dry weight),sugar content was 2.33‒30.92 g•100 g^(-1)DW,and soluble dietary fiber content was 9.71‒26.09 g•100 g^(-1)DW.Crude protein was mainly distributed in leaf blades and inflorescences,sugar was primarily found in roots,and dietary fiber was predominantly located in leaves.From the leaf development stage to the flowering stage and then to the late seed harvest stage,the content of moisture,crude protein and soluble sugar first decreased and then increased.In contrast,the content of dietary fiber and crude fat first increased and then decreased.

Autophagy-dependent ferroptosis may play a critical role in early stages of diabetic retinopathy

Diabetic retinopathy(DR),as one of the most common and significant microvascular complications of diabetes mellitus(DM),continues to elude effective targeted treatment for vision loss despite ongoing enrichment of the understanding of its pathogenic mechanisms from perspectives such as inflammation and oxidative stress.Recent studies have indicated that characteristic neuroglial degeneration induced by DM occurs before the onset of apparent microvascular lesions.In order to comprehensively grasp the early-stage pathological changes of DR,the retinal neurovascular unit(NVU)will become a crucial focal point for future research into the occurrence and progression of DR.Based on existing evidence,ferroptosis,a form of cell death regulated by processes like ferritinophagy and chaperone-mediated autophagy,mediates apoptosis in retinal NVU components,including pericytes and ganglion cells.Autophagy-dependent ferroptosis-related factors,including BECN1 and FABP4,may serve as both biomarkers for DR occurrence and development and potentially crucial targets for future effective DR treatments.The aforementioned findings present novel perspectives for comprehending the mechanisms underlying the early-stage pathological alterations in DR and open up innovative avenues for investigating supplementary therapeutic strategies.

Lymph node dissection does not affect the survival of patients with tumor node metastasis stages Ⅰ and Ⅱ colorectal cancer

BACKGROUND The effect of the number of lymph node dissections(LNDs)during radical resection for colorectal cancer(CRC)on overall survival(OS)remains controver-sial.AIM To investigate the association between the number of LNDs and OS in patients with tumor node metastasis(TNM)stage Ⅰ–Ⅱ CRC undergoing radical resection.METHODS Patients who underwent radical resection for CRC at a single-center hospital between January 2011 and December 2021 were retrospectively analyzed.Cox regression analyses were performed to identify the independent predictors of OS at different T stages.RESULTS A total of 2850 patients who underwent laparoscopic radical resection for CRC were enrolled.At stage T1,age[P<0.01,hazard ratio(HR)=1.075,95%confidence interval(CI):1.019-1.134]and tumour size(P=0.021,HR=3.635,95%CI:1.210-10.917)were independent risk factors for OS.At stage T2,age(P<0.01,HR=1.064,95%CI:1.032-1.098)and overall complications(P=0.012,HR=2.297,95%CI:1.200-4.397)were independent risk factors for OS.At stage T3,only age(P<0.01,HR=1.047,95%CI:1.027-1.066)was an independent risk factor for OS.At stage T4,age(P<0.01,HR=1.057,95%CI:1.039-1.075)and body mass index(P=0.034,HR=0.941,95%CI:0.890-0.995)were independent risk factors for OS.However,there was no association between LNDs and OS in stages Ⅰ and Ⅱ.CONCLUSION The number of LDNs did not affect the survival of patients with TNM stages Ⅰ and Ⅱ CRC.Therefore,insufficient LNDs should not be a cause for alarm during the surgery.

Effects of Short-term High Temperature Stress on the Photosynthesis of Potato in Different Growth Stages

[Objective] The aim was to study the effects of short-term high temperature stress on the photosynthesis of potato in different growth stages. [Method] Choosing powder potato named Longshu No.3 widely cultivated in Ningxia as test material,the changes of stomata conductance （Gs）,transpiration rate （Tr） and CO2 concentration difference between internal and external leaf chamber,net photosynthetic rate （Pn） and photosynthetic water use efficiency （WUE） in different growth stages under short-term high temperature were analyzed. [Result] During seedling stage,the hysteretic nature of net photosynthetic rate and CO2 concentration difference between internal and external leaf chamber of potato could be found under high temperature stress,while the change trends of stomata conductance and transpiration rate under high temperature stress were consistent to that at normal temperature,but stomata conductance and transpiration rate were higher than those at normal temperature,and CO2 concentration difference between internal and external leaf chamber affected net photosynthetic rate most obviously. During branching stage,the change trends of net photosynthetic rate,CO2 concentration difference between internal and external leaf chamber,stomata conductance and transpiration rate under high temperature stress and normal temperature were similar,but they changed abruptly and reached peak value at noon under high temperature stress,while there existed consistent variation of water use efficiency under high temperature stress and at normal temperature,and CO2 concentration difference between internal and external leaf chamber also affected net photosynthetic rate most greatly,next came transpiration rate. [Conclusion] High temperature stress affected the photosynthesis of potato in different growth stages,and it was more obvious during branching stage than seedling stage,while CO2 concentration difference between internal and external leaf chamber had the most important influence on net photosynthetic rate.

Effects of Waterlogging in Different Growth Stages on Nitrogen Uptake, Distribution, and Utilization of Cotton

[Objective] This study aimed to investigate the effects of waterlogging in different growth stages on nitrogen （N） uptake, distribution, and utilization of cotton. [Method] A pool-culture experiment in field was conducted to investigate the effects of wateriogging through comparing WL1 （waterlogging at peak squaring stage） and WL2 （waterlogging at flowering and boll-forming stage） treatments with their controls respectively. [Result] The results showed that the effect of WL1 on N uptake of cotton root was stronger than WL2. At 20 days （d） after WL1 treatment, the root biomass （RB）, N uptake （NU）, and N uptake rate （NUR） significantly decreased by 38.1%, 48.6%, and 53.0% respectively. At 20 d after WL2 treatment, the RB, NU, and NUR significantly decreased by 27.3%, 46.0%, and 44.8% respectively. More N was distributed to root and leaf after WL1 treatment, and to square, flower, and boll after WL2 treatment. N physiological use efficiency increased by 11.4% and 44.4% after WL1 and WL2 treatments respectively. Further analysis showed that the effects of WL1 on yield and its components of cotton were stronger than WL2. The boll number, boll weight, and lint yield per plant significantly reduced by 40.5%, 12.4%, and 49.5% after WL1 treatment, and significantly decreased by 23.1%, 6.9%, and 29.9% after WL2 treatment, respectively. [Conclusion] The negative effects of water- logging at peak squaring stage on N nutrition and yield of cotton were stronger than waterlogging at flowering and boll-forming stage, indicating that more attention should be paid to waterlogging at peak squaring stage and sound N management can improve cotton regrowth and reduce yield loss after waterlogging.

Characteristics of Soil Organic Carbon and Total Nitrogen in Rubber Plantations Soil at Different Age Stages in the Western Region of Hainan Island

[Objective]The aim was to study on the characteristics of soil organic carbon and nitrogen in rubber （Hevea brasiliensis Muell-Arg） plantations at different age stages in the western region of Hainan Island,so as to evaluate the ecological benefits of rubber plantations and provide basic data for studying the effect of tropical land utilization/cover change on the global carbon and nitrogen cycle. [Method]The situs was in Danzhou city,western region of Hainan Island,and the samples were four kinds of rubber plantations soil at different ages and one kind of control check （pepper,Piper nigrum L.） soil. In this research,four quadrats were set up in each sample,and the size of each was 20 cm×20 cm. Four specimens were gathered from four layers of 0-15,15-30,30-45,45-60,and the average of them was the last analysis result of each sample. Soil density was measured by cutting ring method,soil containing and hygroscopic water was detected by oven drying method,soil organic carbon （SOC） was measured by low temperature heated outside potassium dichromate oxidation-colorimetry method,and soil total nitrogen （STN） was detected by semimicro Kjeldahl method. [Result]SOC contents of different layers in rubber plantations soil at different age stages （including the CK pepper soil,the same as below） varied little,and the content of SOC in surface layer （0-15 cm） was higher,while the underlayer （45-60 cm） was lower than the average value; there was significant difference in SOC content among different kinds of soil,and the content was of 6.03-7.78 g/kg,tapping young trees （7 years） CK pepper mature age trees （30 years） prophase of young trees （2 years） tapping trees （16 years）; there was no significant difference in SOC storage among different kinds of soil,and the storage was of 61.33-74.29 t/hm2,mature age trees （30 years） tapping young trees （7 years） prophase of young trees （2 years） CK pepper tapping trees （16 years）; there was significant difference in STN content among rubber plantations soil at different age stages,the content was of 410.86-664.14 mg/kg2,CK pepper tapping young trees （7 years） prophase of young trees （2 years） mature age trees （30 years） tapping trees （16 years）,and STN content of tapping trees （16 years） soil was extremely lowest; there was significant difference in C/N ratio among different kinds of soil,the ratio was of 10.94-14.47,and the ratio of tapping trees （16 years） mature age trees （30 years） tapping young trees （7 years） CK pepper prophase of young trees （2 years）. [Conclusion]There wasn＇t unhealthy effect of rubber trees planted in tropical area on the content and storage of SOC,the content of STN and the ratio of C/N. there was no significant difference between rubber plantations and CK pepper soil,and the effects of rubber plantation on soil carbon-nitrogen was similar to that of other tropical crops （such as pepper）.

Histologic Classification of Thymoma and Its Relationship with Myasthenia Gravis and Clinical Stages of the Tumor

Objective： To investigate the relationship among the latest WHO classification of thymoma, myasthenia gravis （MG） and clinical stages. Methods： To review the pathological sections of 74 patients with thymoma from 1980-2004 using WHO classification （1999）, the statistical software was used to analyze the relationship among the WHO classification, MG and clinical stages. Results： （1） Two cases of type A, 23 cases of type AB, 4 cases of type B1, 27 cases of type B2, 16 cases of type B3 and 2 cases of type C were classified. Type B2 more likely accompanied MG （P〈0.05）, while none with MG occurred for type C. （2） One patient was in stage Ⅰ, 30 were in stage Ⅱ, 38 were in stage Ⅲ, and 5 were in stage Ⅳ. The latest histologic classification was significantly correlated with Masaoka stages （P〈0.01）. Conclusion： The latest WHO classification was correlated with occurrence of MG and finely reflected clinical stage. It can also evaluate the prognosis of patients.

Improvement of pump-probe optical measurement technique using double moving stages

In order to improve the measurement precision and increase the reliability of the femtosecond laser transient thermoreflectance system, the relative optical path difference between pump and probe beams is prolonged, which can improve the fitting accuracy of the experimental data to the theoretical model. A modified experimental setup is devised with the pump path intercalated a moving stage identical to the one in the probe path, which extends the optical path difference of the probe beam relative to the pump beam from 4 to 8 ns. The measured results indicate that the uncertainty from the misalignment and divergence of both beams can be ignored when the last 4 ns experimental data are connected with those of the first 4 ns smoothly. The as-obtained thermal conductance of AI/Si and Cr/Si interfaces agrees well with the reported experimental values, which verifies the reliability of this modified version of this measurement.

Study on Nutritional Characteristics of Dianjiang Peony at Different Growth Stages

[Objective] This study aimed to investigate the nutritional characteristics of Dianjiang peony at different growth stages.[Method] The yield,nutrient content and nutrient uptake of Dianjiang peony at different growth stages and available nutrient content in soil were investigated by field survey and indoor chemical analysis.[Resuit] The results showed that biomass,leaf weight,tender stem weight and cortex moutan weight （yield） of 1-4 years old peony exhibited a significant quadratic regression relationship with the cultivation duration.The average content and uptake of 12 nutrients in leaves exhibited an overall order of Ca＞N＞K＞Mg＞S＞P＞Fe＞Mn＞ Zn＞Cu,which was consistent to that in tender stems.However,the average content and uptake of various nutrient elements in cortex moutan exhibited an overall order of N＞Ca＞K＞Mg＞P＞S＞Fe＞Zn＞Cu＞Mn,which was different from that in leaves and tender stems.In addition,the average content and uptake of various nutrient elements in petioles exhibited an overall order of Ca＞K＞N＞Mg＞S＞P＞Fe＞Mn＞Zn＞Cu.The content of organic matter in soil of Dianjiang peony at different growth stages varied greatly; to be specific,contents of N,S,Mn and Zn were higher.[Conclusion] This study provided theoretical basis for the production of high-quality and high-yield peony.

Descriptions of the Immature Stages of Three Species of the Tribe Ozophorini (Heteroptera:Lygaeidae:Rhyparochrominae) from China

Immature stages of 3 species of the tribe Ozophorini from China are described for the first time, they are Bryanellocoris orientalis Hidaka (3rd^5th instars), Primierus longispinus Zheng (4th^5th instars) and Vertomannus brevicollum Zheng (4th^5th instars). Abrief study on fine structure of pale spots on head, pronotum and abdomen of 5th instar nymph of Bryanellocoris orientalis Hidaka was also given.

Descriptions of Male and Immature Stages of Cryptococcus ulmi Tang et Hao (Homoptera: Coccoidea: Eriococcidae) with Brief Notes on Its Biology

In this paper, the crawler, second instar female and male, prepupa, pupa and adult male of Cryptococcus ulmi are described and illustrated for the first time; adult female is redescribed; a key to all stages is given and the biology is briefly repor ted.

The Christian Doctrines of Salvation at the Earlier Stages of The Pilgrim's Progress

John Bunyan's The Pilgrim's Progress has been written to preach the Christian doctrines of salvation.Therefore its allegorical protagonists have gradually gone through four stages of development on the path to salvation.This paper is focused on the earlier two stages,that is,the repentance of sins and the temptations after conversion.

QTL Mapping for Drought Tolerance at Stages of Germination and Seedling in Wheat (Triticum aestivum L.) Using a DH Population

Drought is a major constraint in many wheat( Triticum aestivum L.) production regions. Quantitative trait loci (QTLs) conditioning drought tolerance at stages of germination and seedling in wheat were identified in a double haploid (DH) population derived from the cross, Hanxuan10×Lumai14, using amplified fragment length polymorphism (AFLP) and simple sequence repeat (SSR) markers. Interval mapping analysis revealed that QTLs for drought tolerance at germination stage were located on chromosomes 1B, 2B, 5A, 6B, 7A and 7B, respectively, and the most effective QTL was mapped on chromosome 2B, explaining 27.2% of phenotypic variance. The QTLs for drought tolerance at seedling stage were located on 1B, 3B and 7B, respectively, and the most effective QTL was mapped on chromosome 3B, explaining 21.6% of phenotypic variance. Their positions were different from those of QTLs conferring drought tolerance at germination stage, indicating that drought tolerance at germination stage and seedling stage was controlled by different loci. Most of the identified QTLs explained 18% or more of phenotypic variance for drought tolerance at germination and seedling stage, and would be useful in future for marker assisted selection programs and cultivar improvement.

Effects of Lodging at Different Filling Stages on Rice Yield and Grain Quality

The effects of lodging of rice plants from 20 d after full heading to maturity on yield and grain quality were investigated with a hybrid rice combination Liangyoupeijiu and a japonica rice cultivar CY-6. The results showed that, except for brown rice rate, almost all parameters for yield and grain quality including ratio of grain length to grain width, gelatinization temperature and gel consistency, were significantly influenced by lodging and thus deteriorated. Regression analysis suggested that, lodging one day earlier at the grain-filling stage could cause 2.66% to 2.71% of yield loss, 1.8 to 2.6 percentage points decrease of seed-setting rate, 0.26 to 0.32 g reduction of lO00-grain weight, 0.097 to 0. 155 percentage point decline of milled rice rate, as well as 0.13 to 0.27 percentage point increase of chalky grain rate, and 0.021 to 0.024 percentage point rise of protein content, and subsequently lower the eating quality.

Radiomics approach for preoperative identification of stages Ⅰ-Ⅱand Ⅲ-Ⅳ of esophageal cancer

Objective： To predict preoperative staging using a radiomics approach based on computed tomography （CT）images of patients with esophageal squamous cell carcinoma （ESCC）.Methods： This retrospective study included 154 patients （primary cohort： n： t 14; validation cohort： n：40） withpathologically confirmed ESCC. All patients underwent a preoperative CT scan from the neck to abdomen. Highthroughput and quantitative radiomics features were extracted from the CT images for each patient. A radiomicssignature was constructed using the least absolute shrinkage and selection operator （Lasso）. Associations betweenradiomics signature, tumor volume and ESCC staging were explored. Diagnostic performance of radiomicsapproach and tumor volume for discriminating between stages Ⅰ-Ⅱand Ⅲ-Ⅳ was evaluated and compared usingthe receiver operating characteristics （ROC） curves and net reclassification improvement （NRI）.Results= A total of 9,790 radiomics features were extracted. Ten features were selected to build a radiomicssignature after feature dimension reduction. The radiomics signature was significantly associated with ESCCstaging （P〈0.001）, and yielded a better performance for discrimination of early and advanced stage ESCC comparedto tumor volume in both the primary [area under the receiver operating characteristic curve （AUC）： 0.795 vs. 0.694,P=0.003; NRI=0.424）] and validation cohorts （AUC： 0.762 vs. 0.624, P=0.035; NRI=0.834）.Conclusions： The quantitative approach has the potential to identify stage Ⅰ-Ⅱand Ⅲ-Ⅳ ESCC beforetreatment.

Three Stages of Mesozoic Bimodal Igneous Rocks and Their Tectonic Implications on the Continental Margin of Southeastern China

There are large-scale Mesozoic bimodal igneous rock associations on the continental margin of southeastern China. They aroused extensive attention in the 1980s because of their specific tectonic implications, and have been found frequently during recent geological surveys. This paper reviews the studies of regional Mesozoic bimodal rocks, and concludes that they can be subdivided into three stages, i.e., the Early Jurassic (209-170 Ma, the first (Ⅰ) stage), the Late Jurassic-early Early Cretaceous (154-121 Ma, the second (Ⅱ) stage), and the late Early Cretaceous-Late Cretaceous (115-85 Ma, the third (Ⅲ) stage). These three stages of bimodal rocks were formed in different tectonic settings, and are important indicators for regional Mesozoic tectonic evolution.

Prognostic and predictive significance of MSI in stages Ⅱ/Ⅲ colon cancer

In colon cancer,classic disease staging remains the key prognosis and treatment determinant.Although adjuvant chemotherapy has an established role in stageⅢcolon cancer patients,in stageⅡit is still a subject of controversy due to its restriction to a small subgroup of patients with high-risk histopathologic features.Patients with stageⅡtumors form a highly heterogeneous group,with five-year relative overall survival rates ranging from 87.5%(ⅡA)to 58.4%(ⅡC).Identifying those for whom adjuvant chemotherapy would be appropriate and necessary has been challenging,and prognostic markers which could serve in the selection of patients more likely to recur or benefit from adjuvant chemotherapy are eagerly needed.The stronger candidate in this category seems to be microsatellite instability(MSI).The recently reported European Society for Medical Oncology guidelines suggest that MSI should be evaluated in stageⅡcolorectal cancer patients in order to contribute in treatment decisionmaking regarding chemotherapy administration.Thehypothetical predictive role of MSI regarding its response to 5-fluorouracil-based adjuvant chemotherapy has proven a much more difficult issue to address.Almost every possible relation between MSI and chemotherapy outcome has been described in the adjuvant colon cancer setting in the international literature,and the matter is far from being settled.In this current report we critically evaluate the prognostic and predictive impact of MSI status in patients with stageⅡand stageⅢcolon cancer patients.