Objectives: . Head and neck squamous cell carcinoma (HNSCC) exhibits high recurrence rates, particularly in cases of radioresistant HNSCC (RR-HNSCC). Non-thermal plasma (NTP) therapy effectively suppresses the progression of HNSCC. However, the therapeutic mechanisms of NTP therapy in treating RR-HNSCC are not well understood. In this study, we explored the regulatory role of NTP in the RR-HNSCC signaling pathway and identified its signature genes. Methods: . After constructing two RR-HNSCC cell lines, we prepared cell lysates from cells treated or not treated with NTP-activated media (NTPAM) and performed RNA sequencing to determine their mRNA expression profiles. Based on the RNA sequencing results, we identified differentially expressed genes (DEGs), followed by a bioinformatics analysis to identify candidate molecules potentially associated with NTPAM therapy for RR-HNSCC. Results: . NTPAM reduced RR-HNSCC cell viability in vitro. RNA sequencing results indicated that NTPAM treatment activated the reactive oxygen species (ROS) pathway and induced ferroptosis in RR-HNSCC cell lines. Among the 1,924 genes correlated with radiation treatment, eight showed statistical significance in both the cell lines and The Cancer Genome Atlas (TCGA) cohort. Only five genes—ABCC3, DUSP16, PDGFB, RAF1, and THBS1—showed consistent results between the NTPAM data sequencing and TCGA data. LASSO regression analysis revealed that five genes were associated with cancer prognosis, with a hazard ratio of 2.26. In RR-HNSCC cells, NTPAM affected DUSP16, PDGFB, and THBS1 as activated markers within 6 hours, and this effect persisted for 12 hours. Furthermore, enrichment analysis indicated that these three DEGs were associated with the extracellular matrix, transforming growth factor-beta, phosphoinositide 3-kinase/protein kinase B, and mesenchymal-epithelial transition factor pathways. Conclusion . NTPAM therapy exerts cytotoxic effects in RR-HNSCC cell lines by inducing specific ROS-mediated ferroptosis. DUSP16, PDGFB, and THBS1 were identified as crucial targets for reversing the radiation resistance induced by NTPAM therapy, providing insights into the mechanisms and clinical applications of NTPAM treatment in RR-HNSCC.

Objectives: . Head and neck squamous cell carcinoma (HNSCC) exhibits high recurrence rates, particularly in cases of radioresistant HNSCC (RR-HNSCC). Non-thermal plasma (NTP) therapy effectively suppresses the progression of HNSCC. However, the therapeutic mechanisms of NTP therapy in treating RR-HNSCC are not well understood. In this study, we explored the regulatory role of NTP in the RR-HNSCC signaling pathway and identified its signature genes. Methods: . After constructing two RR-HNSCC cell lines, we prepared cell lysates from cells treated or not treated with NTP-activated media (NTPAM) and performed RNA sequencing to determine their mRNA expression profiles. Based on the RNA sequencing results, we identified differentially expressed genes (DEGs), followed by a bioinformatics analysis to identify candidate molecules potentially associated with NTPAM therapy for RR-HNSCC. Results: . NTPAM reduced RR-HNSCC cell viability in vitro. RNA sequencing results indicated that NTPAM treatment activated the reactive oxygen species (ROS) pathway and induced ferroptosis in RR-HNSCC cell lines. Among the 1,924 genes correlated with radiation treatment, eight showed statistical significance in both the cell lines and The Cancer Genome Atlas (TCGA) cohort. Only five genes—ABCC3, DUSP16, PDGFB, RAF1, and THBS1—showed consistent results between the NTPAM data sequencing and TCGA data. LASSO regression analysis revealed that five genes were associated with cancer prognosis, with a hazard ratio of 2.26. In RR-HNSCC cells, NTPAM affected DUSP16, PDGFB, and THBS1 as activated markers within 6 hours, and this effect persisted for 12 hours. Furthermore, enrichment analysis indicated that these three DEGs were associated with the extracellular matrix, transforming growth factor-beta, phosphoinositide 3-kinase/protein kinase B, and mesenchymal-epithelial transition factor pathways. Conclusion . NTPAM therapy exerts cytotoxic effects in RR-HNSCC cell lines by inducing specific ROS-mediated ferroptosis. DUSP16, PDGFB, and THBS1 were identified as crucial targets for reversing the radiation resistance induced by NTPAM therapy, providing insights into the mechanisms and clinical applications of NTPAM treatment in RR-HNSCC.

Objectives: . Head and neck squamous cell carcinoma (HNSCC) exhibits high recurrence rates, particularly in cases of radioresistant HNSCC (RR-HNSCC). Non-thermal plasma (NTP) therapy effectively suppresses the progression of HNSCC. However, the therapeutic mechanisms of NTP therapy in treating RR-HNSCC are not well understood. In this study, we explored the regulatory role of NTP in the RR-HNSCC signaling pathway and identified its signature genes. Methods: . After constructing two RR-HNSCC cell lines, we prepared cell lysates from cells treated or not treated with NTP-activated media (NTPAM) and performed RNA sequencing to determine their mRNA expression profiles. Based on the RNA sequencing results, we identified differentially expressed genes (DEGs), followed by a bioinformatics analysis to identify candidate molecules potentially associated with NTPAM therapy for RR-HNSCC. Results: . NTPAM reduced RR-HNSCC cell viability in vitro. RNA sequencing results indicated that NTPAM treatment activated the reactive oxygen species (ROS) pathway and induced ferroptosis in RR-HNSCC cell lines. Among the 1,924 genes correlated with radiation treatment, eight showed statistical significance in both the cell lines and The Cancer Genome Atlas (TCGA) cohort. Only five genes—ABCC3, DUSP16, PDGFB, RAF1, and THBS1—showed consistent results between the NTPAM data sequencing and TCGA data. LASSO regression analysis revealed that five genes were associated with cancer prognosis, with a hazard ratio of 2.26. In RR-HNSCC cells, NTPAM affected DUSP16, PDGFB, and THBS1 as activated markers within 6 hours, and this effect persisted for 12 hours. Furthermore, enrichment analysis indicated that these three DEGs were associated with the extracellular matrix, transforming growth factor-beta, phosphoinositide 3-kinase/protein kinase B, and mesenchymal-epithelial transition factor pathways. Conclusion . NTPAM therapy exerts cytotoxic effects in RR-HNSCC cell lines by inducing specific ROS-mediated ferroptosis. DUSP16, PDGFB, and THBS1 were identified as crucial targets for reversing the radiation resistance induced by NTPAM therapy, providing insights into the mechanisms and clinical applications of NTPAM treatment in RR-HNSCC.

ObjectiveTo compare the clinical features of patients with hepatitis B virus （HBV）-related early-onset liver cancer and those with late-onset liver cancer， to assess the severity of the disease， and to provide a theoretical basis for the early diagnosis and treatment of liver cancer. MethodsA retrospective analysis was performed for 695 patients who were diagnosed with HBV-related liver cancer for the first time in Guangzhou Eighth People’s Hospital， Guangzhou Medical University， from January 2019 to August 2023， among whom 93 had early-onset liver cancer （defined as an age of50 years for female patients and40 years for male patients） and 602 had late-onset liver cancer （defined as an age of ≥50 years for female patients and ≥40 years for male patients）. Related clinical data were collected， including demographic data， clinical symptoms at initial diagnosis， comorbidities， smoking history， drinking history， family history， routine blood test results， biochemical parameters of liver function， serum alpha-fetoprotein（AFP）， virological indicators， coagulation function， and imaging findings. The pan-inflammatory indices neutrophil-to-lymphocyte ratio （NLR）， platelet-to-lymphocyte ratio （PLR）， and lymphocyte-to-monocyte ratio （LMR） were calculated， as well as FIB-4 index， aspartate aminotransferase-to-platelet ratio index （APRI）， S index， Model for End-Stage Liver Disease （MELD） score， Child-Turcotte-Pugh （CTP） score， albumin-bilirubin （AIBL） grade， and Barcelona Clinic Liver Cancer （BCLC） stage. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or Fisher’s exact test were used for comparison of categorical data between two groups. ResultsThere were significant differences between the two groups in the proportion of male patients and the incidence rates of diabetes， hypertension， and fatty liver disease （χ²=6.357， 15.230， 11.467， and 14.204， all P0.05）， and compared with the late-onset liver cancer group， the early-onset liver cancer group had a significantly higher proportion of patients progressing to liver cancer without underlying cirrhosis （χ²=24.657， P0.001） and a significantly higher proportion of patients with advanced BCLC stage （χ²=6.172， P=0.046）. For the overall population， the most common clinical symptoms included abdominal distension， abdominal pain， poor appetite， weakness， a reduction in body weight， edema of both lower limbs， jaundice， yellow urine， and nausea， and 55 patients （7.9%） had no obvious symptoms at the time of diagnosis and were found to have liver cancer by routine reexamination， physical examination suggesting an increase in AFP， or radiological examination indicating hepatic space-occupying lesion； compared with the late-onset liver cancer group， the patients in the early-onset liver cancer group were more likely to have the symptoms of abdominal distension， abdominal pain， and jaundice （all P0.05）. Compared with the late-onset liver cancer group， the early-onset liver cancer group had a significantly larger tumor diameter （Z=2.845， P=0.034）， with higher prevalence rates of multiple tumors and intrahepatic， perihepatic， or distant metastasis （χ²=5.889 and 4.079， both P0.05）， and there were significant differences between the two groups in tumor location and size （χ²=3.948 and 11.317， both P0.05）. Compared with the late-onset liver cancer group， the early-onset liver cancer group had significantly lower FIB-4 index， proportion of patients with HBsAg ≤1 500 IU/mL， and levels of LMR and Cr （all P0.05）， as well as significantly higher positive rate of HBeAg and levels of log₁₀ HBV DNA， AFP， WBC， Hb， PLT， NLR， PLR， TBil， ALT， Alb， and TC （all P0.05）. ConclusionCompared with late-onset liver cancer， patients with early-onset liver cancer tend to develop liver cancer without liver cirrhosis and have multiple tumors， obvious clinical symptoms， and advanced BCLC stage， which indicates a poor prognosis.

BACKGROUND:There are differentially expressed genes in acute intracerebral hemorrhage,which are related to the occurrence and development of intracerebral hemorrhage. OBJECTIVE:To screen differentially expressed genes and key genes in brain tissue of a rat model with acute intracerebral hemorrhage,to validate them through qPCR,and to analyze the relationships between key genes and the neurological function and brain tissue water content after intracerebral hemorrhage. METHODS:Seventy-eight Sprague-Dawley rats were randomly divided into two groups:in intracerebral hemorrhage group,a rat model of acute intracerebral hemorrhage was made using collagenase injection at the right caudate nucleus;and in sham-operated group,rats were injected with equal amount of saline at the same site.RNA was extracted from rat brain tissues of both groups using the TRIzol method and transcriptome sequencing technology was used to identify differentially expressed genes in brain tissues of acute intracerebral hemorrhage,which were then verified by qPCR and analyzed for the relationships between the genes and neurological function and brain tissue water content after intracerebral hemorrhage.And the key genes were analyzed by GO and KEGG functional enrichment analysis in combination with bioinformatics. RESULTS AND CONCLUSION:Ten key genes were identified,including CXCL8,SERPINE1,TFPI2,CXCR4,GDA,KCNQ5,ERICH3,SCN3B,CACNA1E,and CCL20.The contents of GDA,KCNQ5,ERICH3,SCN3B,and CACNA1E in the intracerebral hemorrhage group were lower than those in the sham-operated group(P＜0.05).The contents of CXCL8,SERPINE1,TFPI2,CXCR4 and CCL20 in the intracerebral hemorrhage group were higher than those in the sham-operated group(P＜0.05).The contents of GDA,KCNQ5,ERICH3,SCN3B,and CACNA1E were positively correlated with brain tissue water content and neurologic deficit score(P＜0.05),while the contents of CXCL8,SERPINE1,TFPI2,CXCR4 and CCL20 were negatively correlated with brain tissue water content and neurologic deficit score(P＜0.05).GO analysis indicated that differentially expressed genes were mainly enriched in two biological processes(leukocyte chemotaxis and chemokine-mediated signaling pathways),two cell components(cation channel complexes and ion channel complexes),and two molecular functions(gated channel activity and ion channel activity).KEGG analysis indicated that differentially expressed genes were concentrated in tumor necrosis factor signaling pathway,glutamatergic synapses and GABAergic synapses.To conclude,the differentially expressed genes in intracerebral hemorrhage include CXCL8,SERPINE1,TFPI2,CXCR4,GDA,KCNQ5,ERICH3,SCN3B,CACNA1E,and CCL20,and these genes are related to brain tissue water content and neurological function after intracerebral hemorrhage.These genes are mainly enriched in cell components,binding functions,cellular protrusions,and other related biological functions.

BACKGROUND:Previous studies have shown that puerarin can inhibit the differentiation of osteoclasts,and the expression of Notch signaling pathway-related proteins such as Notch1,HES1,and Jagged1 is decreased.However,the specific mechanism of the Notch1 signaling pathway for the inhibition of osteoclast differentiation by puerarin is not clear. OBJECTIVE:To explore the effect of Notch signaling pathway on puerarin inhibiting the differentiation of mouse macrophage Raw264.7 into osteoclasts. METHODS:Raw264.7 cells were divided into seven groups for intervention culture.Blank control group was cultured in high-sugar DMEM medium;the osteoclast induction group was cultured in osteoclast induction medium;the puerarin intervention group was cultured with 50 μmol/L puerarin at the same time of osteoclast induction;Notch1 siRNA control group,Notch1 siRNA group,Notch1 overexpression control group and Notch1 overexpression group were transfected with Notch1 siRNA control sequence,Notch1 siRNA,Notch1 overexpression control plasmid and Notch1 overexpression plasmid,respectively,and then cultured with osteoclast induction medium and puerarin.The number and size of osteoclasts were observed by tartrate-resistant acid phosphatase staining,the skeleton formation of osteoclasts was observed by F-actin staining,and the gene expression level of osteoclast formation markers was detected by RT-PCR. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining results showed that puerarin intervention could inhibit the generation of osteoclasts,Notch1 silencing could further reduce the number of osteoclasts,while the number of osteoclasts in the osteoclast-induced group increased significantly after Notch1 overexpression.The results of F-actin showed that Raw264.7 cells could form a well-defined F-actin ring after osteoclast induction.Puerarin intervention would inhibit the formation of cytoskeleton,and Notch1 silencing could aggravate the inhibitory effect of cytoskeleton formation,while Notch1 overexpression could alleviate this inhibitory effect of puerarin.RT-PCR results showed that puerarin could inhibit the mRNA expression levels of tartrate-resistant acid phosphatase,Cathepsin K and c-Fos,the expression of the above-mentioned three factors decreased significantly after Notch1 gene silencing,and Notch1 overexpression could upregulate the expression of these factors.These finding indicate that puerarin inhibits the differentiation of Raw264.7 cells into osteoclasts through the Notch signaling pathway.

Objective:To investigate the application value of the teaching evaluation method guided by cultivating "excellent doctors" in the clinical teaching of dermatology and venereology.Methods:A non-simultaneous control study was conducted, and the medical students who received theoretical learning and clinical internship in Department of Dermatology and Venereology, Affiliated Hospital of North Sichuan Medical College, from March 2020 to February 2022, were enrolled as subjects. According to the order of enrollment, 32 students who were enrolled from March 2020 to February 2021 were set up as control group, and 31 students who were enrolled from March 2021 to February 2022 were set up as experimental group. The students in the control group received lecture-based learning, and those in the experimental group received clinical teaching using a teaching and evaluation method guided by cultivating "excellent doctors". After the course ended, the two groups were compared in terms of the scores of theoretical knowledge and operation skills, clinical thinking ability [Self-Assessment of Clinical Reasoning and Reflection (SACRR)], core competence [Mini-Clinical Evaluation Exercise (Mini CEX)], and degree of satisfaction with teaching. SPSS 25.0 software was used to perform the independent samples t-test, the Mann-Whitney U test, the chi-square test, and the rank sum test. Results:One student in the control group voluntarily withdrew from the study, and one student in the experimental group did not complete the contents of internship. Finally, 31 students in the control group and 30 in the experimental group were included in the study. After 4 weeks of internship, compared with the control group, the experimental group had significantly higher scores of theoretical knowledge (88.00±4.30 vs. 85.71±4.12, t=2.12, P=0.040) and operation skills (91.87±3.99 vs. 88.23±3.84, t=3.63, P<0.05). After 4 weeks of internship, compared with the control group, the experimental group had significantly higher information systematization score (47.23±3.11 vs. 45.16±3.00), analysis problem score (34.87±2.30 vs. 31.29±2.30), truth finding score (16.30±1.49 vs. 14.45±1.52), reflective ability score [3.50 (3.00, 4.00) vs. 3.00 (3.00, 3.00)], and total score of SACRR (101.87±4.47 vs. 93.90±4.47), with significant differences between the two groups ( t/ Z=2.65, 6.17, 4.79, 3.15, and 6.96, all P<0.05). After 4 weeks of internship, the experimental group had a significantly better core competence than the control group ( Z=2.12, P=0.030); compared with the control group, the experimental group had significantly higher classroom teaching score (20.17±1.98 vs. 18.45±2.23, t=3.17, P<0.05), clinical practice score (19.83±2.10 vs. 17.65±2.17, t=4.00, P<0.05), learning plan score (18.63±2.24 vs. 17.03±2.15, t=2.85, P<0.05), teaching resource score (20.07±1.82 vs. 18.58±2.00, t=3.04, P<0.05) and total score (78.70±3.67 vs. 71.71±4.13, t=6.98, P<0.05). Conclusions:The application of the teaching and evaluation method guided by cultivating "excellent doctors" in the clinical teaching of dermatology and venereology can improve clinical theoretical knowledge, practical operation skills, clinical thinking ability, and core ability among interns and thus help to improve teaching quality. Therefore, it holds promise for clinical application.

OBJECTIVE To analyze and evaluate serious adverse drug reaction(SADR) and drug-drug interactions(DDIs) in the real-world, so as to obtain the clinical evidence of DDIs-related SADR, and to provide a reference for rational clinical use. METHODS The SADR reports reported to the National Adverse Drug Reaction Monitoring Center from January 2011 to December 2020 were collected, and Lexi-Interaction® software in UpToDate was used to analyze ≥2 drugs in SADR to evaluate whether there were potential DDIs. And the possible adverse drug reactions caused by DDIs were statistically analyzed. RESULTS Among the 360 cases of SADR, males were slightly more than females(50.83% vs 49.17%), the mean age was (65.27±14.71) years old, and 56.39% were ≥65 years old. Cardiovascular agents were the most common implicated pharmacological group, and the gastrointestinal system was the most frequently affected system, and aspirin was the most frequently reported drug. Among 150 cases of SADR with at least two suspected drugs, 64 cases had potential DDIs, while 42 cases had clinically significant DDIs, of which only 16 and 2 cases of SADR were caused by actual DDIs in category D and X, respectively. The majority of reports(71.43%) were caused by additive pharmacodynamic interactions. Aspirin was the most common drug in both potential DDIs and actual DDIs, while aspirin and clopidogrel was the most commonly involved drug pair in actual DDIs, with gastrointestinal bleeding being the most common SADR. CONCLUSION Attention should be paid to the influence of drug interactions on SADR, and prescription should be optimized, especially in the elderly population. According to the results of potential DDIs, therapeutic drugs should be rationally selected. Meanwhile, monitoring of cardiovascular drugs and key populations should be strengthened to ensure drug safety.

Objective: To systematically evaluate the influencing factors for medication compliance in patients with comorbidities of chronic diseases, so as to provide the evidence for improving medication compliance. Methods: Literature on influencing factors for medication compliance in patients with comorbidities of chronic diseases were retrived from CNKI, Wanfang Data, VIP, SinoMed, PubMed, Web of Science, Cochrane Library and Embase from inception to January 20, 2024. After independent literature screening, data extraction, and quality assessment by two researchers, a meta-analysis was performed using RevMan 5.4 and Stata 16.0 softwares. Literature were excluded one by one for sensitivity analysis. Publication bias was assessed using Egger's test. Results: Initially, 7 365 relevant articles were retrieved, and 35 of them were finally included, with a total sample size of about 150 000 individuals. There were 30 cross-sectional studies and 5 cohort studies; and 11 high-quality studies and 24 medium-quality studies. The meta-analysis showed that the demographic factors of lower level of education (OR=2.148, 95%CI: 1.711-2.696), lower economic income (OR=1.897, 95%CI: 1.589-2.264), male (OR=0.877, 95%CI: 0.782-0.985), living alone (OR=2.833, 95%CI: 1.756-4.569) and unmarried (OR=2.784, 95%CI: 1.251-6.196); the medication treatment factors of polypharmacy (OR=1.794, 95%CI: 1.190-2.706), potentially inappropriate medication (OR=2.988, 95%CI: 1.527-5.847), low frequency of daily medication (OR=0.533, 95%CI: 0.376-0.754) and adverse drug reactions (OR=3.319, 95%CI: 1.967-5.602); the disease factors of long course of disease (OR=2.118, 95%CI: 1.643-2.730), more comorbidities (OR=1.667, 95%CI: 1.143-2.431) and cognitive impairment (OR=2.007, 95%CI: 1.401-2.874); and the psychosocial factors of poor belief in taking medication (OR=1.251, 95%CI: 1.011-1.547), poor self-rated health (OR=1.990, 95%CI: 1.571-2.522) and being guided by healthcare professionals (OR=0.151, 95%CI: 0.062-0.368) were the influencing factors for medication compliance in patients with chronic comorbidities. Conclusion The medication compliance in patients with comorbidities of chronic diseases is associated with demographic factors, pharmacological factors, disease factors and psychosocial factors, mainly including living alone, adverse drug reactions, course of disease, number of comorbidities and medication beliefs.

[ABSTRACT]OBJECTIVE To analyze the risk factors for relapse in patients with chronic rhinosinusitis with nasal polyps(CRSwNP)combined with asthm and provide favorable information for precise treatment and healthy prognosis of patients with CRSwNP combined with asthma.METHODS The clinical data of 161 patients with chronic rhinosinusitis with nasal polyps(CRSwNP)combined with asthm who underwent endoscopic surgery at the Department of Otolaryngology Head and Neck Surgery,Yantai Yuhuanding Hospital,affiliated to Qingdao University,from January 2016 to June 2021 were selected.Based on Lasso's Cox regression analysis and multifactorial Cox regression analysis,the associated risk factors were investigated,and the area under curve(AUC)was calculated to determine the performance of the model.Finally,the Kaplan-Meier(K-M)curves were plotted for the relevant influencing factors.RESULTS The Age[HR(95%CI):0.96(0.948-0.98),P<0.001],gender[HR(95%CI):1.94(1.21-3.14),P=0.006],tissue eosinophil percentage[HR(95%CI):1.01(1.01-1.02),P=0.004],and endoscopic nasal polyp score[HR(95%CI):0.86(0.78-0.96),P=0.005]were highly correlated with recurrence in patients with CRSwNP combined with asthma.Patients with CRSwNP combined with asthma had a higher likelihood of relapse after treatment when the tissue Eos%was>21.28%and the endoscopic nasal polyp score was>4.CONCLUSION The age,gender,tissue eosinophil percentage and endoscopic nasal polyp score are independent risk factors for disease recurrence in patients with CRSwNP combined with asthma.