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.

OBJECTIVE To explore the effect of volatile oil of Ligusticum chuanxiong on the transdermal properties and cytotoxicity of triptolide in vitro. METHODS The chemical constituents of the volatile oil of L. chuanxiong were analyzed by gas chromatography-mass spectrometry. The lower abdominal skin of KM mice was separated and divided into triptolide group， triptolide in compatibility with volatile oil of L. chuanxiong groups at 1∶10， 1∶50， 1∶100 （hereinafter referred to as “compatibility 1∶10”“compatibility 1∶50”“compatibility 1∶100” groups）. After the skin of mice in each group was fully exposed to 0.2 g of the corresponding cream for 24 h， the cumulative transdermal dose （Qn） of triptolide in the receiving solution of each group was determined by high-performance liquid chromatography， and the transdermal absorption rate （Jss） was calculated. Human immortalized keratinocytes （HaCat） were used as a model， the CCK-8 method was used to detect the cell survival rate of different concentrations of the volatile oil of L. chuanxiong and triptolide before and after compatibility. RESULTS A total of 62 chemical constituents of the volatile oil of L. chuanxiong were identified， including Z-ligustilide， senkyunolide， and β-selinene. The Qn （P＜ 0.01） and Jss of triptolide increased within 24 h in the compatibility 1∶10 and 1∶50 groups， while the Qn （P＜0.05） and Jss decreased in the compatibility 1∶100 group as compared with the triptolide group. Compared with the triptolide group， the cell survival rate of HaCat was significantly increased in the compatibility 1∶10 and 1∶50 groups when the triptolide concentrations were 36， 72 and 144 ng/mL （P＜0.05 or P＜0.01）； while the cell survival rate of HaCat was decreased in the compatibility 1∶100 group， but the difference was not statistically significant （P＞0.05）. CONCLUSIONS When the compatibility ratio of triptolide and volatile oil of L. chuanxiong was 1∶10 or 1∶50， it can promote the transdermal absorption of triptolide and reduce the cytotoxicity of triptolide to HaCat.

OBJECTIVE To study the extraction technology of Sophora flavescens-Phellodendron chinense drug pair and provide a reference for the development of new drugs for the treatment of anorectal diseases. METHODS Using the contents of total alkaloids of S. flavescens （matrine+oxymatrine）， berberine hydrochloride and total flavonoid， and extract yield as evaluation indicators， analytic hierarchy process-entropy weight method was used to calculate the weight coefficient of each indicator， and was combined with Box-Behnken design-response surface method to study the extraction technology of S. flavescens-P. chinense drug pair and verify it. RESULTS The optimal extraction technology of S. flavescens-P. chinense drug pair was immersed in 12-fold amount of 58% ethanol for 30 minutes and extracted twice， each time for 120 minutes. The relative error between the verification experimental results and the predicted value was 1.88%. CONCLUSIONS The obtained extraction technology is stable and feasible and can provide reference for the application of S. flavescens-P. chinense drug pair and development of new drugs.

ObjectiveTo observe the efficacy and safety of Uyghur medicine Yangxin Dawayimixike Honey Paste （养心达瓦依米西克蜜膏， YDMHP） in the treatment of stable angina pectoris （SAP） of qi stagnation and blood stasis syndrome. MethodsA randomized ， double-blind， positive-controlled，multi-center clinical trial was conducted， in which 370 patients with SAP of qi stagnation and blood stasis syndrome were randomly divided into treatment group（279 cases）and control group（91cases）at a ratio of 3∶1. The treatment group was orally administered with YDMHP， 3 g each time， and placebo of Xuefu Zhuyu Capsule （血府逐瘀胶囊）， 2.4 g each time， while the control group was treated with Xuefu Zhuyu Capsule， 2.4 g each time， and placebo of YDMHP， 3 g each time， both twice a day for a course of 12 weeks. The primary outcome was the effect of angina pectoris symptom. The secondary outcomes include single angina symptom scores such as number of attacks， duration of attacks， pain intensity and usae of nitroglycerin scores， the total angina symptom score before and after the treatment， the usage of nitroglycerin， the exercise duration in treadmill exercise test （TET） and the Duck treadmill score among patients，the scores of Seattle Angina Questionnaire （SAQ） on five dimensions including physical limitations， anginal stability， anginal frequency， treatment satisfaction， and disease perception， and efficacy of TCM syndrome and of each single TCM symptom after treatment. The safety were evaluated by examine blood routine， urine routine， liver and kidney function， fasting blood sugar， electrocardiogram， adverse events. ResultsThe total effective rate of angina symptom in the treatment group was 71.69% （200/279）， significantly higher than 51.64% （47/91） in the control group （P＜0.01）. The curative and markedly effective rate of TCM syndrome in the treatment group was 53.05% （148/279）， which was significantly higher than 25.27% （23/91） in the control group （P＜0.01）. After treatment， scores of the number as well as duration of angina attacks and pain severity， the total score of angina symptoms， and the usage of nitroglycerin significantly decreased in both groups， and more changes were seen in the treatment group than in the control group； the scores of physical limitations， anginal stability， anginal frequency， treatment satisfaction， and disease perception in both groups significantly increased， and more improvement were shown in the experimental group regarding the anginal stability， anginal frequency and treatment satisfaction （P＜0.05 or P＜0.01）. The effects of chest pain， chest tightness， palpitation， shortness of breath and fatigue in experimental group were significantly higher than those in control group （P＜0.05 or P＜0.01）. There was no significant difference in the exercise duration of treadmill test and Duke score among patients between the two groups either before or after treatment （P＞0.05）. Adverse events occurred in 66 cases （23.66%） of the experimental group and 16 cases （17.58%） of the control group， with no statistical significance between the two groups （P＞0.05）. ConclusionThe Uyghur medicine YDMHP can effectively improve symptoms of angina pectoris， reduce the number， duration， and intensity of attacks， decrease the dosage of nitrogly-cerin and improve the individual TCM symptoms and has good safety in the treatment of SAP patients of qi stagnation and blood stasis.

[Objective] To investigate the functional differences and potential effects of chromatin spatial structure in patients with normal karyotype and complex karyotype multiple myeloma. [Methods] High-throughput chromosome conformational capture (Hi-C) analysis was performed on plasma cells of 1 case with 1q21 complex karyotype and 1 case with normal karyotype multiple myeloma, and the differences in three-dimensional genome structure between the two patients were analyzed, and the transcriptome characteristics of plasma cells were combined to investigate the differential features through gene functional enrichment. [Results] A/B switch occurred in 36% of the chromatin compartments in two cases, and 1 041 genes in patient with complex karyotype had B/A switch. About 3 500 topological association domains (TADs) were identified in each sample, and there was no significant difference. The number of loops identified in complex karyotype sample was 1 069, which was 1/6 of the normal sample, and there were significant differences in the number of three different types of loops, which to some extent reflected the loss of genome stability. Transcriptome analysis showed significant differences in expression profiles between the two patients, and a total of 6 150 differentially expressed genes (3 303 up-regulated genes and 2 847 down-regulated genes) were identified. [Conclusion] Compared with patient with normal karyotype, patient with 1q21 complex karyotype multiple myeloma exhibit significant changes in the spatial structure of plasma cell chromatin at different levels, which leads to changes in gene expression and activation of pathways related to cancer progression.

Objective To investigate the incidence and severity of symptoms in patients with gastric cancer who received chemotherapy,we constructed a symptom network to explore core symptoms and bridge symptoms.Furthermore,the study explores the association between core symptoms and Traditional Chinese Medicine(TCM)constitutions.Methods Patients with gastric cancer who received chemotherapy in the medical oncology and surgical oncology department from March to August 2023 were selected for the study using a convenience sampling method.The MD Anderson Symptom Inventory Gastrointestinal Cancer was used for evaluating gastrointestinal symptoms and their severity among patients receiving chemotherapy for gastric cancer,as well as assessing the classification of TCM constitution among patients.The symptom network model was constructed using the R programming language,and the central index was analyzed to determine the core symptoms and bridge symptoms.Binary logistic regression analysis was employed to assess the association between different physical conditions and the occurrence of core symptoms.Results A total of 346 electronic questionnaires were collected,with 340 valid ones,and the effective recovery rate was 98.3％.The 3 most prevalent and severe symptoms among the 340 patients with gastric cancer were fatigue(85.59％),lack of appetite(82.35％),and taste alteration(81.18％).The centrality index results indicated that grief exhibited the highest intensity,medium,and compactness centrality values(rs=8.23,rb=2.00,rc=0.03),making it the core symptom of this condition.Sleep disorders,lack of appetite,drowsiness,and taste alteration were identified as bridging symptoms with bridge intensities of 0.74,0.76,0.99,and 0.94 respectively.The results of Spearman correlation analysis showed that there was a positive correlation between sadness and qi-deficiency constitution,phlegm-dampness constitution(P＜0.05).The phlegm-dampness constitution was positively correlated with the taste alterations(P＜0.05).Conclusion In patients with gastric cancer,fatigue emerges as the most prominent symptom,while sadness assumes the core symptom.Additionally,sleep disorder,lack of appetite,drowsiness,and taste alteration are bridge symptoms.According to the principles of TCM constitution,qi-deficiency and phlegm-dampness are constitutions associated with a higher risk of experiencing sadness,and phlegm-dampness is a constitution associated with a higher risk of taste changes.Nurses can integrate core symptoms and TCM constitutions characteristics to optimize the strategies for symptom intervention.

Objective To investigate the plasma level of interleukin-31(IL-31)in patients with pulmonary arterial hypertension(PAH)and its clinical relevance.Methods The patients who were diagnosed as PAH in Zhongshan Hospital,Fudan University from January 1,2021 to December 30,2023(PAH group)and the healthy people in the same period(control group)were selected.The clinical data and follow-up records were collected.Plasma levels of IL-31,IL-1β,IL-6,IL-10,IL-12p70,monocyte chemoattractant protein-1(MCP-1),tumor necrosis factor-α(TNF-α)and transforming growth factor-β1(TGF-β1)were detected by enzyme-linked immunosorbent assay(ELISA).Pearson correlation test was used to evaluate the correlations between IL-31 and right cardiac catheterization parameters,echocardiography parameters and blood indices in patients with PAH.Cox proportional hazard model was used to analyze the prognostic factors of patients in PAH group.Results A total of 50 patients with PAH and 22 healthy controls were included.There was no significant difference in age,gender,body mass index and left ventricular ejection fraction between the two groups.Compared with the control group,the plasma level of IL-31 in the PAH group was significantly higher(168.82[149.14,177.26]pg/mL vs 152.76[145.58,159.41]pg/mL,P=0.001).Pearson correlation test showed that the plasma level of IL-31 in PAH patient was positively correlated with mean pulmonary artery pressure(r=0.652,P＜0.001)and pulmonary vascular resistance(r=0.651,P＜0.001),but was negatively correlated with tricuspid annular plane systolic excursion(r=-0.496,P＜0.001).Cox proportional hazard model showed that higher plasma level of IL-31 was an independent predictor of readmission for heart failure/all-cause mortality in patients with PAH(HR=1.130,95％CI 1.052-1.214,P=0.001).Conclusions Plasma level of IL-31 may be significantly increased in patients with PAH and be positively correlated with the severity of PAH,and elevated level of IL-31 is predictive of poor prognosis in PAH patients.

Osteoporosis， as a systemic bone disease with high incidence rate and high disability rate， has become a research hotspot in recent years. The daidzein in soybean isoflavones can bind with estrogen receptors， simulating the prevention and treatment of osteoporosis with estrogen-like effect. Its mechanism of action includes promoting osteoblast formation and differentiation by activating the Wnt signaling pathway， increasing bone density， and improving bone tissue health； inhibiting osteoclast differentiation and slowing down bone resorption by reducing receptor activator of nuclear factors κB ligand/ osteoprotegerin ratio， downregulating the expression of macrophage colony-stimulating factor （M-CSF）； collaborating antioxidant and immune regulation to achieve the goal of preventing and treating osteoporosis. In addition， different doses of daidzein have different effects on bone density and osteoporosis， which may be related to factors such as study design， sample selection， and individual differences.

Objective To investigate the influence of Nei endonuclease Ⅷ-like protein 1(NEIL1)on H2O2-induced apoptosis and autophagy in lens epithelial cells(LECs).Methods Reverse transcription polymerase chain reaction(RT-PCR)was used to detect the expression of NEIL1 messenger ribonucleic acid(mRNA)in the anterior lens capsule and LEC line SRA01/04 cells from age-related cataract(ARC)patients and macular epiretinal membrane patients who underwent the clear lens extraction.SRA01/04 cells were then divided into the control group,OE-Vector group and OE-NEIL1 group.RT-PCR and Western blot(WB)were used to detect the overexpression efficiency.Subsequently,the cells were divided into the control group,H2O2 group,OE-Vector H2O2 group and OE-NEIL1 H2O2 group;cell viability was detected by Cell Count-ing Kit-8,WB was used to evaluate the expression of autophagy-related proteins(ATG7,P62,Beclinl,LC3-Ⅰ and LC3-Ⅱ)and apoptosis-related proteins(Bax and Bcl-2),and fluorescent staining was adopted to measure cell apoptosis and mito-chondrial membrane potential.Results The expression of NEIL1 mRNA in the anterior lens capsule samples from ARC patients was significantly lower than that of macular epiretinal membrane patients,and the expression of NEIL1 mRNA in the SRA01/04 cells in the H2O2 group was also lower than that in the control group(both P＜0.05).The results of RT-PCR and WB revealed that the expressions of NEIL1 mRNA and protein in the SRA01/04 cells of the OE-NEIL1 group were signif-icantly higher than those in the OE-Vector group(both P=0.000).Compared with the control group,the viability of SRA01/04 cells in the H2O2 group decreased,the expression of the Bax protein was up-regulated,the Bcl-2 protein was down-regulated,viable cells labeled with Mito-Tracker decreased,and apoptotic cells labeled with Annexin V-FITC in-creased,with statistical significances(all P＜0.05).Compared with the OE-Vector H2O2 group,in the OE-NEIL1 H2O2 group,the viability of SRA01/04 cells significantly improved,the autophagy-related proteins(ATG7,P62,Beclin1,LC3-Ⅰand LC3-Ⅱ)and Bcl-2 protein were significantly up-regulated,the Bax protein was down-regulated,viable cells marked with Mito-Tracker increased,and apoptotic cells labeled with Annexin V-FITC decreased(all P＜0.05).Conclusion Under the oxidative stress induced by H2O2,NEIL1 can promote autophagy of LECs,maintain homeostasis of LECs,and then increase cell viability and reduce apoptosis of LECs,participating in the occurrence and development of ARC.

Objective:To investigate the correlation of peripheral blood 25-hydroxyvitamin D3 [25 (OH) D3] level with T cell subsets in multiple myeloma (MM).Methods:The clinical data of 11 newly diagnosed MM patients hospitalized in Heze Municipal Hospital and the First People's Hospital of Jining from June 2019 to June 2021 were retrospectively analyzed, and 8 healthy people were selected as the healthy control group. The patients achieved disease remission after 4 courses of BD (bortezomib + dexamethasone) regimen. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to measure the peripheral blood 25-(OH) D3 level in MM patients at initial diagnosis and after 4 courses of treatment, as well as people in the healthy control group. The proportion of peripheral blood helper T cell (Th) 1, Th2, Th17, and regulatory T cells (Treg cells) in CD3 + CD8 + T cells was measured by using flow cytometry. IgA, IgG, IgM, lactic dehydrogenase (LDH), β 2-microglobulin (β 2-MG) levels were analyzed by using fully automatic biochemical analyser. Cytoanalyze was used to detect the hemoglobin level in the peripheral blood. The differences of all indicators in MM patients at initial diagnosis, remission after treatment and the healthy control group were compared. Pearson method was used to analyze the correlation of the peripheral blood 25-(OH) D3 level with T cell subsets and other biochemical indicators in MM patients at initial diagnosis and remission after treatment. Results:Compared with the healthy control group, the peripheral blood 25-(OH) D3 level, Th1-to-Th2 ratio (Th1/Th2), the proportion of Treg cells were all decreased (all P < 0.01), and Th17-to-Treg cells ratio (Th17/Treg) was increased ( P = 0.002). The proportion of Th17 and Th17/Treg in MM patients achieving remission after treatment was higher than that in the healthy control group (all P < 0.05); the proportion of Treg cells in MM patients achieving remission after treatment was lower than that in the healthy control group ( P = 0.010); 25-(OH) D3 level in MM patients achieving remission after treatment was lower than that in the healthy control group, while the difference was not statistically significant ( P = 0.060). The peripheral blood IgM in MM patients at initial diagnosis and those achieving remission after treatment was lower than that in the healthy control group (all P < 0.01); the levels of LDH and β 2-MG in MM patients at initial diagnosis and those achieving remission after treatment was higher than that in the healthy control group (all P < 0.05). The peripheral blood 25-(OH) D3 level in MM patients at initial diagnosis was positively correlated with the proportion of Th1, Th1/Th2 ( r values 0.89, 0.60, all P < 0.05), and negatively correlated with the proportion of Th17 and Th17/Treg ( r values -0.61, -0.75, all P < 0.05). After treatment, there was no correlation of the proportion of Th1, Th2, Th17, Treg, Th1/Th2, Th17/Treg with peripheral blood 25- (OH) D3 level for patients achieving remission ( r values were -0.36, -0.45, -0.10, 0.10, 0.19, 0.03, all P > 0.05). IgM, LDH, β 2-MG was negatively correlated with 25- (OH) D3 level in the peripheral blood of MM patients at initial diagnosis ( r values were -0.76, -0.71, -0.62, all P < 0.05); while there was no correlation of 25-(OH) D3 level with IgA, IgG, IgM, LDH, β 2-MG, hemoglobin for patients achieving remission after treatment ( r values were -0.36, 0.19, -0.09, 0.47, 0.47, -0.11, all P > 0.05). Conclusions:MM patients show the decreased peripheral blood 25-(OH) D3 level, the increased Th17 and the decreased Treg cells; 25-(OH) D3 level is related to the imbalance of Th1/Th2/Th17/Treg, which suggests that 25-(OH) D3 may be related to the development, progression, prognosis and abnormal immune responses in the body of MM.