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.

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.

Objective To explore the diagnosis and clinical characteristics of atypical severe pneumonia caused by Chlamydia abortus(C.abortus).Methods Clinical data of 4 patients diagnosed with atypical severe pneumonia caused by C.abortus in a hospital from January 2021 to November 2022 were collected.Clinical characteristics,dia-gnosis and treatment,and precautions of the disease were comprehensively analyzed.Results All 4 patients were male,aged 63-73 years old,with acute onset,high fever,cough and expectoration.Three patients had a history of contact with poultry,one patient had a history of contact with abortion goat.The interval between the emerging of clinical symptoms and the onset of acute respiratory failure in 4 patients was 1-6 days,and the oxygenation index(PaO2/FiO2)at admission was less than 200 mmHg,which gradually decreased with the progression of the disease,active support with a ventilator was necessary.Two patients had an increase in white blood cell count,4 had an in-crease in neutrophil percentage,3 had a mild decrease in platelet count.Among 4 patients,2,2,3 and 4 patients showed elevated levels of aspartate aminotransferase,alanine aminotransferase,creatine kinase,and serum creati-nine respectively,2 patients had mild hyponatremia,4 patients showed significant increase in C-reactive protein,procalcitonin,and interleukin-6 levels.Four patients'chest CT findings showed main involvement of single or mul-tiple lung lobes,with exudation and consolidation,and later involvement of multiple lobes of lung.The metageno-mic next-generation sequencing of bronchoalveolar lavage fluid detected the DNA sequence of C.abortus.Based on the clinical manifestations,contact history,chest CT,and metagenomic next-generation sequencing results of 4 pa-tients,the diagnosis was C.abortus.atypical severe pneumonia.After timely adjustment of the treatment of anti-in-fection regimen based on doxycycline,the patients'condition improved and were discharged.Conclusion C.abor-tus may also cause human pneumonia,which can lead to serious clinical outcome after infection.Patient had a histo-ry of animal contact should be alert to such diseases.Metagenomic next-generation sequencing can detect C.abortus.

Objective:To investigate the efficacy and side effects of concurrent chemoradiotherapy with or without nimotuzumab in the treatment of locally advanced nasopharyngeal carcinoma after neoadjuvant chemotherapy.Methods:In the prospective study, 100 patients with stage Ⅲ-Ⅳa locally advanced nasopharyngeal carcinoma (except T 3N 0M 0 stage) who met the inclusion criteria were randomly divided into the experimental and control groups using the random number table method. Patients in both groups were treated with neoadjuvant chemotherapy using TPF (paclitaxel liposome, cisplatin, and 5-fluorouracil) regimen for 2 cycles. At 2 weeks after chemotherapy, concurrent chemoradiotherapy plus nimotuzumab targeted therapy was given in the experimental group, and concurrent chemoradiotherapy was delivered in the control group. The main observation index was the distant metastasis-free survival (DMFS) rate. Log-rank test and multivariate Cox regression analysis were used. Results:The objective remission rate and complete remission rate in the experimental and control groups were 100% vs. 98% ( P=1.000) and 92.0% vs. 80% ( P=0.084). The 3-year DMFS in the experimental and control groups were 91.4 % vs. 76.1 % ( P=0.043). The 3-year progression-free survival (PFS), locoregional recurrence-free survival (LRFS) and overall survival (OS) in two groups were 87.3 % vs. 74.1 % ( P=0.097), 94.5 % vs. 85.6 % ( P=0.227) and 90.5% vs. 85.2% ( P=0.444). Subgroup analysis showed that patients with age<60 years ( HR=0.34, 95% CI=0.12-0.94, P=0.037), neutrophil-to-lymphocyte ratio (NLR)≤4 ( HR=0.34, 95% CI=0.13-0.89, P=0.028) received concurrent chemoradiotherapy plus nimotuzumab obtained better PFS. Multivariate analysis showed that NLR was an independent risk factor for disease progression ( HR=5.94, 95% CI=1.18-29.81, P=0.030) and distant metastasis ( HR=13.76, 95% CI=1.52-124.36, P=0.020). Conclusions:Compared with concurrent chemoradiotherapy alone, concurrent chemoradiotherapy combined with nimotuzumab after neoadjuvant chemotherapy can significantly increase DMFS rate for patients with locally advanced nasopharyngeal carcinoma. The incidence of side effects is similar in two groups. Concurrent chemoradiotherapy plus nimotuzumab after neoadjuvant chemotherapy may be a preferred treatment strategy for locally advanced nasopharyngeal carcinoma.

ObjectiveTo analyze the epidemiological distribution and temporal trends of liver cancer incidence among Luzhou residents from 2016‒2022， and to provide a theoretical basis for improving liver cancer prevention and treatment strategies in Luzhou. MethodsData on liver cancer incidence among Luzhou residents from 2016 to 2022 were collected， and the incidence rate， age-specific incidence rate， and annual percentage change （APC） were calculated. A Joinpoint regression model was used to fit a time series segment to the monthly number of new cases in each district and county of Luzhou to explore the trend of liver cancer incidence rate. ResultsThe incidence rate of liver cancer in Luzhou increased from 22.96/10⁵ in 2016 to 32.31/10⁵ in 2022. The incidence rate of liver cancer in men was higher than that in women in both 2016 and 2022， and the incidence rate of liver cancer in men increased from 34.83/10⁵ in 2016 to 47.95/10⁵ in 2022， with an APC of 3.3%； the incidence rate of liver cancer in women increased from 10.50/10⁵ in 2016 to 15.95/10⁵ in 2022， with an APC of 3.0%， and the differences in the change trends were not statistically significant （P>0.05）.The incidence of liver cancer was low in the age group of 0‒<40 years from 2016 to 2022 and increased with age； the incidence of liver cancer in the age group of 55 years and above was increasing at an average annual rate of 16.4%. ConclusionThe overall incidence of liver cancer in Luzhou is on the rise， and the incidence of liver cancer in men is higher than that in women. Middle-aged and elderly men are the key population for liver cancer prevention and treatment， and liver cancer prevention and treatment should be carried out in a targeted manner， taking into account regional development differences.

This paper aimed to study phenylpropanoids of Tripterygium hypoglaucum. Twenty-four compounds were isolated from the 70% EtOH extracts of T. hypoglaucum by silica gel column chromatography, reversed phase column chromatography, gel column chromatography, preparative thin layer chromatography, and semi-preparative high performance liquid chromatography. Compounds 1-3 were three new phenylpropionds. Their structures were identified by ultraviolet spectrum, infrared spectroscopy, high resolution electrospray ionization mass spectrometry, and nuclear magnetic resonance data as: threo-2-(4-hydroxy-3-methoxyphenoxy)-3-(4-hydroxy-3-methoxyphenyl)-1,3-propanedol (1), erythro-2-(4-hydroxy-3-methoxyphenoxy)-3-(4-hydroxy-3-methoxyphenyl)-1,3-propanediol (2), erythro-3-(4-hydroxy-3,5-dimethoxyphenyl)-3-ethoxypropane-1,2-propanediol (3). Compounds 4-6, 9, 14, 15, 18, 19, and 21-24 were obtained from Tripterygium genus for the first time. The cytotoxicity assay of cancer cells suggested that compound 20 displayed cytotoxicity on the breast cancer 4T1 cells whose 50% inhibitory concentration was 125.60 μmol·L^-1.

ObjectiveAsthma is a common chronic inflammatory airway disease, and severe asthma poses a significant challenge in its diagnosis and management. Immune cells are involved in and altered by asthma pathogenesis, and several lipid metabolites can serve as diagnostic markers for the disease. In this study, we investigated the characterization of severe asthma at the metabolic and cellular level. MethodsDifferential metabolites in blood samples from severe asthma (41 cases) and controls (18 cases) were screened using multifactorial statistical analysis and independent samples t-tests; key pathways were identified by KEGG enrichment analysis, and biomarkers were characterized based on ROC curves; immune cell types and proportions in the blood were identified based on the results of cell-type annotations (5 severe and 3 control cases); and single-sample Gene Enrichment Analysis (ssGSEA) to investigate the characterization of differential metabolic pathways in single cells. ResultsCompared with controls, the abundance of 28 metabolites was increased and the abundance of 13 metabolites was decreased in the blood of patients with severe asthma (P<0.05); the differential metabolites were enriched in 4 pathways: sphingolipid metabolism, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism, and histidine metabolism. Among them, 13 differential metabolites could be used as biomarkers for the diagnosis of severe asthma, including L-glutamic acid (AUC=0.809), nicotinamide (AUC=0.886), phytosphingosine (AUC=0.882), and sphinganine (AUC=0.893). In single-cell transcriptome analysis,5 key cell types were identified: CD4⁺ T cells, CD8⁺ T cells, NK cells, B cells, and monocytes. The number of NK cells was increased in patients with severe asthma, and severe asthma exhibited more frequent cellular communication, particularly dense communication between CD8⁺ T cells and other cell types. In healthy samples, monocytes were the primary cells engaging in dense communication. Single-sample gene enrichment analysis (ssGSEA) showed that 4 pathways enriched for differential metabolites had lower scores (P<0.01) in CD4⁺ T and CD8⁺ T cells in severe patients, and it was hypothesized that the expression of genes associated with these pathways was suppressed in these two types of cells. The suppressed genes included DGKA and NT5C3A, which are associated with immune processes. We observed that these genes play key roles in the regulation of T cell signaling, activation, differentiation, and immune responses. ConclusionL-glutamic acid, nicotinamide, phytosphingosine, and sphinganine can be used as biomarkers for the diagnosis of severe asthma; genes of the severe asthma-associated pathway were suppressed in CD4⁺ T cells and CD8⁺ T cells.

In recent years,the development of acupuncture and moxibustion(shortened as acup-moxibustion)has flourished.With the verification of clinical efficacy of acup-moxibustion,its basic research has gradually drawn the attention of the practitioners accordingly.But how to scientifically perform the basic research of acup-moxibustion and to serve the clinic effectively has become a major problem for the contemporary Chinese medicine practitioners.By analyzing the characteristics of acup-moxibustion-related research projects funded by the National Natural Science Foundation of China,this paper outlined the current status of domestic research of acup-moxibustion,and proposed four suggestions after analyzing the problems and weaknesses of acup-moxibustion basic research in China:①the clinical evidence-based system in the current acup-moxibustion should be further constructed and the basic research should be focused on the area of advantages;② the key problems of acup-moxibustion basic research should be clarified,and the proportion of original researches should be increased;③ the integration of production,teaching and research of acup-moxibustion should be enhanced to adapt to the era of big science;④ the funding system and its polity and structure needed to be reformed.This study will help to increase the discipline ranking of acup-moxibustion,enhance its high-quality development,and promote its internationalization.