Objective To analyze the epidemiological characteristics and disease burden of liver cancer in Guangdong Province in 2020, and to provide a scientific foundation for the development of regionalized prevention and control strategies for liver cancer. Methods According to the cancer registry data of Guangdong Province, the incidence, mortality and age-standardized rate by Chinese standard population in 2020 were calculated to analyze the epidemiological characteristics of liver cancer. The disability adjusted life years (DALYs), year of life loss (YLL), year of lived with disability (YLD), and cause-eliminated life expectancy were used to assess the disease burden of liver cancer. Results In 2020, the crude incidence rate and the age-standardized incidence rate of liver cancer in Guangdong Province were 27.79/100 000 and 20.84/100 000，respectively, and the crude mortality rate and the age-standardized mortality rate of liver cancer were 25.49/100,000 and 17.64/100 000, respectively. The total DALY and DALY rate of liver cancer in Guangdong Province were 515 311 person-years and 513.83/100 000, respectively. After eliminating the causes of death from liver cancer, the life expectancy in Guangdong Province increased from 84.60 years to 84.99 years. All indicators consistently demonstrated that the burden of liver cancer was higher in males than that in females, and the burden of liver cancer was higher in rural areas than that in urban areas. Conclusion Liver cancer in Guangdong Province exhibits a high incidence, mortality and disease burden level in 2020. There are obvious differences of gender, age and region in cancer burden. It is necessary to strengthen liver cancer screening and diagnosis and treatment in men, the elderly and those in rural areas to reduce the burden of liver cancer gradually in Guangdong Province.

OBJECTIVE To investigate the neuroprotective effect and mechanism of eleutheroside B （ELB） on Parkinson’s disease （PD） model mice by regulating the IκB kinase β （IKKβ）/nuclear factor-κB （NF-κB） signaling pathway. METHODS Fifty mice were randomly divided into normal control group， model group， positive control group （selegiline hydrochloride， 10 mg/kg）， and ELB low-dose and high-dose groups （80， 160 mg/kg）， with 10 mice in each group. Each group was given relevant medicine or normal saline intragastrically for 14 consecutive days. Starting from the 10th day of administration， the model group and all administration groups were intraperitoneally injected with 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP） 30 mg/kg， for five consecutive days to establish the chronic PD model. After the last administration for 24 h， six mice were randomly selected from each group to test their behavioral abilities； detect the levels of interleukin-1β （IL-1β）， IL-10， tumor necrosis factor-α （TNF-α） in brain tissue and their mRNA expressions were measured， and positive expression of tyrosine hydroxylase （TH）， protein expressions of TH， α -synuclein （ α -syn）， ionized calcium-binding adaptor molecule 1 （Iba-1）， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in the brain tissue were detected. The ultrastructure of neurons in substantia nigra was observed. RESULTS Compared with the model group， rotarod endurance time and climbing score of each administration group （except for the ELB low-dose group） were increased significantly （ P ＜0.05）， while the levels and mRNA expressions of IL-1β， TNF-α， α -syn， and Iba-1， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in brain tissue were decreased significantly （except for TNF-α in the ELB low-dose group）. Conversely， the level and mRNA expression of IL-10 （except for the ELB low-dose group）， TH positive expression and protein expressions were significantly increased （ P ＜0.05）. Typical neurodegenerative pathological changes， such as neuronal karyopyknosis， mitochondrial swelling and vacuolization， and endoplasmic reticulum dilation， all showed varying degrees of improvement. CONCLUSIONS ELB may exert neuroprotective effects by inhibiting the activation of the IKKβ/NF-κB signaling pathway， alleviating inflammatory responses， reducing abnormal α -syn aggregation and neuronal loss， and further improving motor dysfunction in PD mice.

Oral solid dosage forms require processes such as disintegration and dissolution to release the drug before it can be absorbed and utilized by the body. In this manuscript, imaging technology was used to continuously visualize and characterize the in vitro static drug release process of gliclazide modified release tablets from 15 manufacturers, combined with the traditional method of in vitro dissolution testing, to determine the release profile of gliclazide modified release tablets, to evaluate the similarity of the release profiles by using the similarity factor (f₂) method and based on the analysis of the release profiles fitted with a variety of mathematical models. The results indicate that the gliclazide modified release tablets produced by 14 companies are hydrophilic gel matrix tablets. Compared to the reference listed drug, the release profiles of formulations from 11 companies show high similarity (f₂ > 50) to the reference. Among these, formulations with visual characteristics similar to the reference exhibit similar release curves. This study provides an alternative method for the in vitro consistency evaluation of gliclazide modified release tablets, aiming to assess the in vitro release behaviour of generic formulations more accurately and comprehensively.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Objective: To investigate the association between habitual reading/writing postures and the co-occurrence of common health conditions (overweight/obesity, visual impairment, hypertension, and scoliosis) and comorbidities among children and adolescents, in order to provide data support for the joint prevention of common diseases and comorbidities among children and adolescents. Methods: From September 2021 to June 2022, a multi-stage cluster random sampling method was used to select a total of 4 577 children and adolescents from 16 primary and secondary schools in Ningxia: Jinfeng District of Yinchuan City, Shapotou District of Zhongwei City, Yanchi County of Wuzhong City, and Pingluo County of Shizuishan City. A weighted complex sampling design was used to investigate the association of habitual reading and writing postures with common comorbidities in children and adolescents. Results: The prevalence rates of common diseases among children and adolescents in Ningxia were as follows: overweight/obesity was 22.87%, visual impairment was 62.52%, scoliosis was 2.30%, and hypertension was 1.30%. The prevalence of multimorbidity (co-occurrence of ≥2 conditions) among Ningxia children and adolescents was 15.95%. Multivariate unconditional Logistic regression analysis showed that frequent/always collapsing waist and sitting forward with head lowered increased the risk of common comorbidities in children and adolescents ( OR =1.90, P <0.05). Compared with the corresponding reference group, male children and adolescents aged 9 to 12 years and boys had relatively lower risks of overweight/obesity ( OR =0.71, 0.70); the risk of poor vision among children and adolescents aged 9 to 12 years, male, and urban was relatively low ( OR =0.59, 0.60, 0.73)( P < 0.05 ). Children and adolescents who often/always sat leaning to the left or right were at higher risk of poor vision ( OR =1.78); urban children and adolescents had a higher risk of developing scoliosis ( OR =3.71); children and adolescents aged 9 to 12 had a relatively low risk of developing hypertension ( OR =0.09), and children and adolescents who often/always bent their backs and sat forward on their knees had a higher risk of hypertension ( OR =5.03)( P <0.05). Conclusions Ningxia has a high incidence of common diseases and multiple diseases among children and adolescents, frequent or always collapsing waist and sitting forward with head lowered is associated with common comorbidities in children and adolescents in Ningxia. Proper postural measures for reading and writing should be carried out as soon as possible to encourage children and adolescents to develop good reading and writing habits for effectively preventing and controlling the occurrence of common diseases.

ObjectiveBola-like short peptides exhibit novel self-assembly properties due to the formation of peptide dimers via hydrogen bonding interactions between their C-terminals. In this configuration, hydrophilic amino acids are distributed at both terminals, making these peptides behave similarly to Bola peptides. The electrostatic repulsive interactions arising from the hydrophilic amino acids at each terminal can be neutralized, thereby greatly promoting the lateral association of β-sheets. Consequently, assemblies with significantly larger widths are typically the dominant nanostructures for Bola-like peptides. To investigate the effect of hydrophilic amino acids on the self-assembly behavior of Bola-like peptides, the peptides Ac-RI₃-CONH₂ and Ac-HI₃-CONH₂ were designed and synthesized using the Bola-like peptide Ac-KI₃-CONH₂ as a template. Their self-assembly behavior was systematically examined. MethodsAtomic force microscopy (AFM) and transmission electron microscopy (TEM) were employed to characterize the morphology and size of the assemblies. The secondary structures of the assemblies were analyzed using circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopy. Small-angle neutron scattering (SANS) was used to obtain detailed structural information at a short-length scale. Based on these experimental results, the effects of hydrophilic amino acids on the self-assembly behavior of Bola-like short peptides were systematically analyzed, and the underlying formation mechanism was explored. ResultsThe aggregation process primarily involved three steps. First, peptide dimers were formed through hydrogen bonding interactions between their C-terminals. Within these dimers, the hydrophilic amino acids K, R, and H were positioned at both terminals, enabling the peptides to self-assemble in a manner similar to Bola peptides. Next, β-sheets were formed via hydrogen bonding interactions along the peptide backbone. Finally, self-assemblies were generated through the lateral association of β-sheets. The results demonstrated that both Ac-KI₃-CONH₂ and Ac-RI₃-CONH₂ could self-assemble into double-layer nanotubes with diameters of approximately 200 nm. These nanotubes were formed by the edge fusion of helical ribbons, which initially emerged from twisted ribbons. Notably, the primary assemblies of these peptides exhibited opposite chirality: nanofibers formed by Ac-KI₃-CONH₂ displayed left-handed chirality, whereas those formed by Ac-RI₃-CONH₂ exhibited right-handed chirality. This reversal in torsional direction was primarily attributed to the different abilities of K and R to form hydrogen bonds with water. In contrast, Ac-HI₃-CONH₂ formed narrower twisted ribbons with a significantly reduced width of approximately 30 nm, which was attributed to the strong steric hindrance caused by the imidazole rings. The multilayer height of these ribbons was mainly due to the unique structure of the imidazole rings, which can function as both hydrogen bond donors and acceptors, thereby promoting aggregate growth in the vertical direction. ConclusionThe final morphology of the self-assemblies resulted from a delicate balance of various non-covalent interactions. By altering the types of hydrophilic amino acid residues in Bola-like short peptides, the relative strength of non-covalent interactions that drive assembly formation can be effectively regulated, allowing precise control over the morphology and chirality of the assemblies. This study provides a simple and effective approach for constructing diverse self-assemblies and lays a theoretical foundation for the development of functional biomaterials.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Based on the etiology and clinical diagnostic criteria of type 2 diabetes mellitus （T2DM）， identification and typing of treatment from the perspective of traditional Chinese and western medicine， the criteria for evaluating the clinical compatibility of traditional Chinese and western medicine in animal models of T2DM were set up. The literature was reviewed to sort out and analyze the existing commonly used modeling methods， summarize the mechanism， compare the advantages and disadvantages， and calculate the consistency between the animal model and the clinical symptoms， syndromes， and indicators from the perspective of traditional Chinese and western medicine. The authors found that spontaneous animal models and high-fat diets combined with multiple low-dose streptozotocin （STZ） induction models were more in line with modern medical pathogenesis of T2DM. However， it fails to form some special syndromes required for traditional Chinese medicine （TCM） research. In addition， there are many methods of combining the etiology and pathogenesis of TCM， which can be divided into three categories： intervention carried out by drug administration， behavioral stimulation， or environmental changes according to TCM， or use of hormones according to clinical evidence and combination of the two methods mentioned above. All of them can successfully establish different types of animal models. However， different methods of establishing syndrome models have their own advantages and disadvantages， and there is no unified standard for the stability and evaluation of syndrome models. As for the clinical consistency criteria of traditional Chinese and western medicine established in this paper， the animal model with 100% consistency has not been calculated due to the conditions of incomplete symptoms and syndromes described in the studies and different selection indicators. Consequently， the establishment of a simple， easy-to-use， and affordable T2DM animal model with both traditional Chinese and western medicine disease characteristics and the improvement of the Chinese and western medicine evaluation system for different evidence types are of great significance for the future development of TCM research on T2DM.

Based on the etiology and clinical diagnostic criteria of type 2 diabetes mellitus （T2DM）， identification and typing of treatment from the perspective of traditional Chinese and western medicine， the criteria for evaluating the clinical compatibility of traditional Chinese and western medicine in animal models of T2DM were set up. The literature was reviewed to sort out and analyze the existing commonly used modeling methods， summarize the mechanism， compare the advantages and disadvantages， and calculate the consistency between the animal model and the clinical symptoms， syndromes， and indicators from the perspective of traditional Chinese and western medicine. The authors found that spontaneous animal models and high-fat diets combined with multiple low-dose streptozotocin （STZ） induction models were more in line with modern medical pathogenesis of T2DM. However， it fails to form some special syndromes required for traditional Chinese medicine （TCM） research. In addition， there are many methods of combining the etiology and pathogenesis of TCM， which can be divided into three categories： intervention carried out by drug administration， behavioral stimulation， or environmental changes according to TCM， or use of hormones according to clinical evidence and combination of the two methods mentioned above. All of them can successfully establish different types of animal models. However， different methods of establishing syndrome models have their own advantages and disadvantages， and there is no unified standard for the stability and evaluation of syndrome models. As for the clinical consistency criteria of traditional Chinese and western medicine established in this paper， the animal model with 100% consistency has not been calculated due to the conditions of incomplete symptoms and syndromes described in the studies and different selection indicators. Consequently， the establishment of a simple， easy-to-use， and affordable T2DM animal model with both traditional Chinese and western medicine disease characteristics and the improvement of the Chinese and western medicine evaluation system for different evidence types are of great significance for the future development of TCM research on T2DM.