ObjectiveTo investigate the mechanism of modified Si Junzitang and Shashen Maidong Tang ［Yiqi Yangyin Jiedu prescription （YQYYJD）］ in enhancing the sensitivity of cisplatin in epidermal growth factor receptor tyrosine kinase inhibitor （EGFR-TKI）-resistant lung adenocarcinoma cells based on aerobic glycolysis. MethodsThe effects of different concentrations of YQYYJD （0， 2， 3， 4， 5， 6， 7， 8 g·L^-1） and cisplatin （0， 3， 6， 9， 12， 15， 18， 21， 24， 27 mg·L^-1） on the proliferation and activity of PC9/GR cells were detected by the cell counting kit-8 （CCK-8） assay after 24 hours of intervention. The half-maximal inhibitory concentration （IC₅₀） for PC9/GR cells was calculated to determine the concentrations used in subsequent experiments. PC9/GR cells were divided into blank group （complete medium）， YQYYJD group （5 g·L^-1）， cisplatin group （12 mg·L^-1）， and combined group （YQYYJD 5 g·L^-1 + cisplatin 12 mg·L^-1）. After 24 hours of intervention， cell viability was measured using CCK-8 assay. Cell proliferation was assessed by colony formation assay， and cell migration was evaluated by scratch and Transwell assays. Glucose consumption， lactate production， and adenosine triphosphate （ATP） levels were measured by colorimetric assays. The expression levels of glycolysis-related proteins， including hexokinase 2 （HK2）， phosphofructokinase P （PFKP）， pyruvate kinase M2 （PKM2）， lactate dehydrogenase A （LDHA）， glucose transporter 1 （GLUT1）， and monocarboxylate transporter 4 （MCT4）， were determined by Western blot. ResultsBoth YQYYJD and cisplatin inhibited the viability of PC9/GR cells in a concentration-dependent manner. The IC₅₀ of PC9/GR cells for YQYYJD and cisplatin were 5.15 g·L^-1 and 12.91 mg·L^-1， respectively. In terms of cell proliferation， compared with the blank group， the cell survival rate and the number of colonies formed in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group showed a further significant reduction in cell survival rate and colony formation （P<0.01）. In terms of cell migration， compared with the blank group， the cell migration rate and the number of cells passing through the Transwell membrane in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group exhibited a further significant reduction in cell migration rate and the number of cells passing through the Transwell membrane （P<0.01）. In terms of glycolysis， compared with the blank group， glucose consumption， lactate production， and ATP levels in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group showed a further significant reduction in glucose consumption， lactate production， and ATP levels （P<0.05）. Compared with the blank group， the protein expression levels of HK2， PFKP， PKM2， and LDHA in the YQYYJD， cisplatin， and combined groups were significantly decreased （P<0.01）. The combined group showed a further significant reduction in the expression levels of these proteins compared with the YQYYJD and cisplatin groups （P<0.01）. No significant differences were observed in the protein expression levels of GLUT1 and MCT4 among the groups. ConclusionYQYYJD can synergistically inhibit the proliferation and migration of PC9/GR cells and enhance their sensitivity to cisplatin. The mechanism may be related to the downregulation of the expression of glycolysis-related rate-limiting enzymes， including HK2， PFKP， PKM2， and LDHA， thereby inhibiting glycolysis.

Ultrasound-mediated sonodynamic therapy,chemodynamic therapy,immunotherapy and gene editing synergize the precise control of ultrasound with targeted properties of nanomaterials,hence promising for overcome the limitations of traditional cancer treatments.The advancements in ultrasound-mediated nanotherapy of tumors were reviewed in this article.

Ultrasound-mediated sonodynamic therapy,chemodynamic therapy,immunotherapy and gene editing synergize the precise control of ultrasound with targeted properties of nanomaterials,hence promising for overcome the limitations of traditional cancer treatments.The advancements in ultrasound-mediated nanotherapy of tumors were reviewed in this article.

Objective To observe the characteristics of gut microbiota in patients with type 2 diabetes mellitus(T2DM)with different traditional Chinese medicine(TCM)syndrome types,and to further explore the key microbial communities and functional differences affecting syndrome differentiation.Methods A total of 45 patients who visited the Department of Geriatrics,Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine in 2023 were enrolled.These included 15 T2DM patients with qi-yin deficiency and blood stasis syndrome(Group A),15 T2DM patients with qi-yin deficiency syndrome(Group B),and 15 non-diabetic patients from the same period(Group C).Fecal samples were collected,and 16S rRNA sequencing and analysis were performed.Results 1)A total of 1 564 operational taxonomic units(OTUs)were obtained from the three groups of patients,with 224,127,and 351 unique OTUs identified in Groups A,B and C,respectively.2)Both α-and β-diversity analyses indicated differences among the gut microbiota of the three groups.For instance,in the α-diversity analysis,the Sobs index showed significant inter-group differences(P＜0.01).Group A(264.00±88.84)was significantly higher than Group B(145.90±87.0)(P＜0.01),while Group B was significantly lower than Group C(229.7±112.4)(P＜0.05).In the β-diversity analysis,the principal coordinate analysis(PCoA)indicated a clear separation among groups(R=0.1610,P＜0.01).The R values in the Anosim/Adonis analysis ranged from 0.144 to 0.196,and the R2 values ranged from 0.067 to 0.083,all indicating differences in inter-group comparisons(P＜0.01).3)At the phylum level,Firmicutes,Actinobacteriota,and Bacteroidota were predominant in all groups.Among them,Bacteroidota exhibited significant inter-group differences(P＜0.05),with its abundance in Group A being significantly higher than that in Group B(P＜0.01).4)Analysis of differences in microbiota composition,combined with linear discriminant analysis effect size(LEfSe)and Random Forest analysis,revealed that,at the genus level,the microbiota biomarkers between Group A and Group B were Parabacteroides,Bacteroides,g_unclassified_f_Lachnospiraceae,Roseburia,and Aspergillus,those between Group B and Group C were Erysipelotrichaceae_UCG-003 and Ruminococcus,and those between Group A and Group C were Parabacteroides,Anaerotruncus,and Oscillibacter.The results were validated by receiver operating characteristic(ROC)curve analysis,which suggested that the microbiota biomarkers between Group A and Group B(AUC=0.91;95％CI,0.80-1.00),Group B and Group C(AUC=0.84;95％CI,0.69-0.99),Group A and Group C(AUC=0.87;95％CI,0.75-0.99)had good diagnostic efficacy.5)The study identified 116 major pathways with inter-group differences through Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis.For example,the enrichment degree of ABC transporter pathway in Group A(2.58±0.36)was significantly lower than those in Group B(2.90±0.48)and Group C(3.11±0.66)(P＜0.05).These pathways were associated with metabolism and environmental information processing.g.Conclusion The differences in the gut microbiota characteristics and functions among patients with specific TCM syndromes of T2DM may provide references for TCM syndrome differentiation and therapeutic mechanisms.

The cultivation of top innovative nursing talents with Chinese characteristics in the new era lends critical support to the accomplishment of the strategic goal of the Healthy China Initiative.Herein,we reviewed the historical development of nursing science in China,clarified the conceptual framework of nursing science with Chinese characteristics in the new era,and identified the essential qualities and competencies required for top innovative nursing talents.Furthermore,we analyzed the mission and challenges in cultivating these nursing talents,and put forward new approaches,including formulating new ethics and political education theories specific to nursing science with Chinese characteristics,establishing a cross-disciplinary educational model of Nursing+X,and creating a new nursing talent cultivation ecosystem adapted to the era of human-machine symbiosis.This study provides theoretical insights into the cultivation of top innovative nursing talents who align their development well with national strategic needs,embody patriotism,and possess a strong sense of contemporary responsibility.

Objective:To explore the function of LIM and calponin homology domains 1(LIMCH1)in the development and progression of oral squamous cell carcinoma(OSCC),along with their potential clinical applications.Methods:By utilizing transcriptome sequencing data from two groups of oral squa-mous cell carcinoma patients,along with bioinformatics analytical techniques such as Gene Ontology(GO)and gene co-expression networks,we identified genes that might play a pivotal role in the patho-genesis of oral squamous cell carcinoma.We employed real-time quantitative PCR and Western blotting to validate the expression patterns of these genes across twelve patient tissue samples.Furthermore,we con-ducted CCK-8 assays,flow cytometry analyses,and scratch wound healing assays to assess the impact of key genes on the biological behaviors of both the Ca127 oral squamous cell carcinoma cell line and the po-tentially malignant DOK oral lesion cell line.Additionally,we examined correlations between these key genes and clinical disease parameters in 214 oral squamous cell carcinoma patients using The Cancer Ge-nome Atlas(TCGA)data;gene set enrichment analysis(GSEA)analysis results were also incorporated to enhance our findings from real-time quantitative PCR and Western blotting regarding potential mecha-nisms underlying the action of these key genes.Results:The integrated analysis of sequencing data and bioinformatics revealed that LIMCH1 exhibited significantly reduced mRNA(P＜0.001)and protein levels(P＜0.01)in the oral squamous cell carcinoma tissues compared with normal control tissues.In the Ca127 cells,the low LIMCH1 level group demonstrated a larger wound healing area within 24 hours than the control group(P＜0.01),enhanced proliferation capacity over 72 hours relative to the control group(P＜0.01),and an increased apoptosis rate within 24 hours compared with the high expression group(P＜0.05).However,no significant differences were observed between the low and high level groups in DOK cells.Furthermore,it was determined that low LIMCH1 level correlated with poor prognosis in the patients(P=0.013)and a higher lymph node metastasis rate(P＜0.05).Investigations into the poten-tial mechanisms of action indicated that LIMCH1 did not influence the onset or progression of oral squa-mous cell carcinoma via the epithelial-mesenchymal transition pathway.Conclusion:LIMCH1 level may function as a promising biomarker to aid in the prognostic assessment of oral squamous cell carcinoma;however,its precise mechanistic role requires further investigation.

Background::Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized immune-mediated disorder that can affect almost any organ in the human body. IgG4-RD can be categorized into proliferative and fibrotic subtypes based on patients’ clinicopathological characteristics. This study aimed to compare the clinical manifestations, laboratory findings, and treatment outcomes of IgG4-RD among different subtypes.Methods::We prospectively enrolled 622 patients with newly diagnosed IgG4-RD at Peking Union Medical College Hospital from March 2011 to August 2021. The patients were divided into three groups according to their clinicopathological characteristics: proliferative, fibrotic, and mixed subtypes. We compared demographic features, clinical manifestations, organ involvement, laboratory tests, and treatment agents across three subtypes. We then assessed the differences in treatment outcomes among 448 patients receiving glucocorticoids alone or in combination with immunosuppressants. Moreover, risk factors of relapse were revealed by applying the univariate and multivariate Cox regression analysis.Results::We classified the 622 patients into three groups consisting of 470 proliferative patients, 55 fibrotic patients, and 97 mixed patients, respectively. We found that gender distribution, age, disease duration, and frequency of allergy history were significantly different among subgroups. In terms of organ involvement, submandibular and lacrimal glands were frequently involved in the proliferative subtype, while retroperitoneum was the most commonly involved site in both fibrotic subtype and mixed subtype. The comparison of laboratory tests revealed that eosinophils ( P = 0.010), total IgE ( P = 0.006), high-sensitivity C-reactive protein ( P <0.001), erythrocyte sedimentation rate ( P <0.001), complement C4 ( P <0.001), IgG ( P = 0.001), IgG1 (P <0.001), IgG4 (P <0.001), and IgA ( P <0.001), at baseline were significantly different among three subtypes. Compared with proliferative and mixed subtypes, the fibrotic subtype showed the lowest rate of relapse (log-rank P = 0.014). Conclusions::Our study revealed the differences in demographic characteristics, clinical manifestations, organ involvement, laboratory tests, treatment agents, and outcomes across proliferative, fibrotic, and mixed subtypes in the retrospective cohort study. Given significant differences in relapse-free survival among the three subtypes, treatment regimens, and follow-up frequency should be considered separately according to different subtypes.Trial Registration::ClinicalTrials. gov, NCT01670695.

Objective:To examine the burden and trends of acute viral hepatitis in Guangdong Province from 1990 to 2019, and provide reference evidences for hepatitis prevention and control in the province.Methods:Data on acute viral hepatitis (hepatitis A, B, C, and E) in Guangdong from 1990 to 2019 were extracted from the Global Burden of Disease Study 2019 database. The incidence, prevalence, mortality, and disability-adjusted life years (DALY) data were analyzed by age and gender, and the estimated annual percentage change (EAPC) was calculated to describe the changing trends in disease burden.Results:From 1999 to 2019, the standardized incidence, prevalence, mortality, and DALY of acute viral hepatitis in Guangdong were higher than the national averages. In 2019, 51.43% (2 245 087/4 365 221) of acute viral hepatitis cases in Guangdong Province were mainly attributed to hepatitis B, and 77.18% (106/138) of deaths were due to acute hepatitis B. In different age groups, except for acute hepatitis B, which was more common in adults, the incidence rates of other types of viral hepatitis such as hepatitis A, B, and E showed an overall decreasing trend with age. The mortality rates of different types of acute viral hepatitis, except for the <5 age group, increased with age. The overall incidence and mortality rates of acute viral hepatitis were higher in men than in women.Conclusions:The overall burden of acute viral hepatitis in Guangdong declined in 2019, but remained higher than the national level. Further efforts are needed to strengthen hepatitis prevention and screening in different population in Guangdong Province, especially in children and the elderly.

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).