Sonodynamic therapy （SDT） applies low-frequency ultrasound to activate sonosensitizers that have accumulated in tumor location， which induces cavitation effects and leads to the in-situ generation of reactive oxygen species （ROS）， thereby achieving precise and efficient tumor treatment. Owing to its advantages such as deep tissue penetration and controllable treatment range， SDT has attracted significant attention and has been widely used in the research on the treatment of various tumors. While conventional treatment modalities have achieved significant efficacy in the treatment of hepatocellular carcinoma （HCC）， there are still certain limitations. In this context， nanomedicine-based SDT leverages the targeting capabilities of nano-agents to realize specific killing of HCC cells， and furthermore， it can synergize with photodynamic therapy， chemotherapy， and immunotherapy to provide new opportunities for developing novel treatment modalities for HCC. This article reviews the mechanism of action of SDT and the advances in the research and application of SDT in the treatment of HCC， analyzes the shortcomings of existing studies， and proposes the directions for future development， in order to provide a theoretical foundation and scientific guidance for related research on HCC.

Objective To design and fabricate an integrated optoelectrical fiber to enable the simultaneous transmission of high-power laser and electrical current, thereby developing a novel tool for urological surgery.Methods A miniature metal sleeve was installed at the front end of a medical high-energy optical fiber, and corresponding conductive circuits were configured. The fiber was connected to a fiber thulium laser and a bipolar plasma generator simultaneously. Experiments of simulated vaporization were conducted on ex vivo porcine kidney tissues using thulium laser (50 W), plasma (100 W), and thulium laser + plasma (50 W+100 W), respectively. Tissue removal efficiency was calculated using the weighing method:tissue clearance rate (g/min)=[mass before vaporization (g) - mass after vaporization (g)]/vaporization time (min). Lateral tissue thermal damage was assessed with hematoxylin-eosin (HE) staining. One-way analysis of variance and least significant difference test were used for statistical analysis.Results The integrated optoelectrical fiber was successfully constructed, which could simultaneously and continuously transmit thulium laser and plasma electrocision current. The tissue clearance rate of the thulium laser+plasma group was significantly higher than that of the thulium laser group and plasma group [(0.49±0.13) g/min vs. (0.14±0.02) g/min vs. (0.11±0.04) g/min, P＜0.001]. The average lateral thermal damage depth of the thulium laser + plasma group showed no statistically significant difference compared to the thulium laser group [(985.5±178.5) μm vs.(957.5±197.4) μm, P＞0.05], but both were significantly higher than that of the simple plasma group [(499.6±78.0) μm] (P＜0.001). Conclusion The thulium laser + plasma energy transmitted simultaneously by the integrated optoelectrical fiber can vaporize kidney tissue more efficiently without additional thermal damage.

Objective: To analyze the implementation status of the “Three-Exemptions” policy for voluntary blood donation in China by taking Shandong Province as a case study, explore the sociodemographic characteristics of policy beneficiaries and the distribution differences in blood donation frequencies, so as to provide practical references for improving the honor incentive system of voluntary blood donation and stabilizing the blood donation team. Methods: Excel was used to sort out and summarize the policy documents from 31 provincial-level administrative regions of China (excluding Hong Kong, Macao and Taiwan), and its implementation models, temporal characteristics and implementation basis were analyzed. Using 238 193 policy beneficiaries in Shandong Province as the research objects, Stata was adopted for descriptive statistical analysis of sociodemographic characteristics including gender, age, educational background and occupation. The Mann-Whitney U test and Kruskal-Wallis H test were performed to compare the distribution differences of blood donation frequencies among populations with different characteristics. Results: The “Three Exemption” policy has been implemented in 29 provinces nationwide, forming five differentiated implementation models. Specifically, 45.16% of the regions adopted province-wide unified implementation, 32.26% adopted partial prefecture-level city implementation, 12.90% adopted partial clause implementation, 3.23% adopted encouraging implementation, and 6.45% had not implemented the policy. The period from 2023 to 2026 witnessed the concentrated promotion of the policy. In Shandong Province, the beneficiaries were mainly males (82.08%), middle-aged individuals aged 40-60 years (71.78%), groups with junior and senior high school education (56.57%), and staff employees (30.60%). The distribution of blood donation frequencies showed that nearly 60% (56.95%) of the beneficiaries had donated blood 20 to 29 times. Statistically significant differences in donation frequency distributions were observed across genders, age groups, educational backgrounds, and occupations (all P<0.05). Further analysis revealed that the proportion of males with 40 or more blood donations was higher than that of females (24.32% vs 15.60%), while females had a higher proportion of 20-29 blood donations than males (65.98% vs 54.99%). With the increase of age, the proportion of those with 20-29 blood donations gradually decreased, whereas the proportion of those with≥40 blood donations gradually increased. Conclusion: The coverage of the “Three Exemptions” policy for voluntary blood donation in China continues to expand. However, there is still room for optimization in terms of policy implementation standards, population structure adaptation and incentive gradient design. Future efforts should strengthen national top-level design to balance regional development gaps. Moreover, hierarchical and targeted incentive and publicity strategies combined with population structural characteristics should be implemented to enhance public enthusiasm for voluntary blood donation.

OBJECTIVE: To investigate the therapeutic potential of pseudolaric acid B (PAB) on non-alcoholic fatty liver disease (NAFLD) and its underlying molecular mechanism in vitro and in vivo. METHODS: Eight-week-old male C57BL/6J mice (n=32) were fed either a normal chow diet (NCD) or a high-fat diet (HFD) for 8 weeks. The HFD mice were divided into 3 groups according to a simple random method, including HFD, PAB low-dose [10 mg/(kg·d), PAB-L], and PAB high-dose [20 mg/(kg·d), PAB-H] groups. After 8 weeks of treatment, glucose metabolism and insulin resistance were assessed by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). Biochemical assays were used to measure the serum and cellular levels of total cholesterol (TC), triglycerides (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). White adipose tissue (WAT), brown adipose tissue (BAT) and liver tissue were subjected to hematoxylin and eosin (H&E) staining or Oil Red O staining to observe the alterations in adipose tissue and liver injury. PharmMapper and DisGeNet were used to predict the NAFLD-related PAB targets. Peroxisome proliferator-activated receptor alpha (PPARα) pathway involvement was suggested by Kyoto Encyclopedia of Genes and Genomes (KEGG) and search tool Retrieval of Interacting Genes (STRING) analyses. Luciferase reporter assay, cellular thermal shift assay (CETSA), and drug affinity responsive target stability assay (DARTS) were conducted to confirm direct binding of PAB with PPARα. Molecular dynamics simulations were applied to further validate target engagement. RT-qPCR and Western blot were performed to assess the downstream genes and proteins expression, and validated by PPARα inhibitor MK886. RESULTS: PAB significantly reduced serum TC, TG, LDL-C, AST, and ALT levels, and increased HDL-C level in HFD mice (P<0.01). Target prediction analysis indicated a significant correlation between PAB and PPARα pathway. PAB direct target binding with PPARα was confirmed through luciferase reporter assay, CETSA, and DARTS (P<0.05 or P<0.01). The target engagement between PAB and PPARα protein was further confirmed by molecular dynamics simulations and the top 3 amino acid residues, LEU321, MET355, and PHE273 showed the most significant changes in mutational energy. Subsequently, PAB upregulated the genes expressions involved in lipid metabolism and mitochondrial biogenesis downstream of PPARα (P<0.05 or P<0.01). Significantly, the PPARα inhibitor MK886 effectively reversed the lipid-lowering and PPARα activation properties of PAB (P<0.05 or P<0.01). CONCLUSION PAB mitigates lipid accumulation, ameliorates liver damage, and improves mitochondrial biogenesis by binding with PPARα, thus presenting a potential candidate for pharmaceutical development in the treatment of NAFLD.
Animals ; PPAR alpha/metabolism* ; Non-alcoholic Fatty Liver Disease/pathology* ; Male ; Mice, Inbred C57BL ; Lipid Metabolism/drug effects* ; Diterpenes/therapeutic use* ; Organelle Biogenesis ; Diet, High-Fat ; Humans ; Mice ; Liver/metabolism* ; Insulin Resistance ; Mitochondria/metabolism* ; Molecular Docking Simulation

OBJECTIVE: Cigarette smoking exacerbates the progression of pulmonary tuberculosis (TB). The role of tertiary lymphoid structures (TLS) in chronic lung diseases has gained attention; however, it remains unclear whether smoking-exacerbated lung damage in TB is associated with TLS. This study aimed to analyze the characteristics of pulmonary TLS in smokers with TB and to explore the possible role of TLS in smoking-related lung injury in TB. METHODS: Lung tissues from 36 male patients (18 smokers and 18 non-smokers) who underwent surgical resection for pulmonary TB were included in this study. Pathological and immunohistological analyses were conducted to evaluate the quantity of TLS, and chest computed tomography (CT) was used to assess the severity of lung lesions. The correlation between the TLS quantity and TB lesion severity scores was analyzed. The immune cells and chemokines involved in TLS formation were also evaluated and compared between smokers and non-smokers. RESULTS: Smoker patients with TB had significantly higher TLS than non-smokers ( P < 0.001). The TLS quantity in both the lung parenchyma and peribronchial regions correlated with TB lesion severity on chest CT (parenchyma: r = 0.5767; peribronchial: r = 0.7373; both P < 0.001). Immunohistochemical analysis showed increased B cells, T cells, and C-X-C motif chemokine ligand 13 (CXCL13) expression in smoker patients with TB ( P < 0.001). CONCLUSION Smoker TB patients exhibited increased pulmonary TLS, which was associated with exacerbated lung lesions on chest CT, suggesting that cigarette smoking may exacerbate lung damage by promoting TLS formation.
Humans ; Male ; Tuberculosis, Pulmonary/immunology* ; Middle Aged ; Tertiary Lymphoid Structures/pathology* ; Adult ; Lung/pathology* ; Smoking/adverse effects* ; Smokers ; Aged ; Tomography, X-Ray Computed

Objective To propose an in vitro cytotoxicity evaluation method for novel iron-based biodegradable mateirals focusing on their degrading characteristics.Methods Half-finished scaffolds of nitrided iron tubes with a higher iron content of over 99％and a nitrogen content of 0.03％to 0.20％were selected as test samples,and based on the treatment mode were divided into an anaerobic treatment group,a non-anaerobic treatment group,a non-anaerobic treatment with removed iron particle group and a non-anaerobic treatment with plate-washing group.The anaerobic treatment group was processed in an anaerobic workstation;the conventional treatment group underwent standard handling in a biosafety cabinet;the conventional treatment with removed iron particle group was subjected to iron particle elimination using a Midimacs Starting Kit manual sorter after conventional treatment;and the conventional treatment with plate-washing group was rinsed with 0.9％sodium chloride injection before tetrazolium salt reagent treatment.Different extraction media(simulated body fluid,cell culture medium,phosphate buffer and 0.9％sodium chloride injection)were used for the immersion treatment of the test samples in each group to compare the effects of the degradation products on the survival rate of L929 cells.Results The anaerobic treatment group and the conventional treatment with removed iron particle group exhibited no detectable cytotoxicity.Trypan blue staining revealed significant cytotoxicity in the conventional treatment group,while false-negative results emerged due to interactions between the tetrazolium salt reagent and degradation products.In the non-anaerobic treatment with washing plate group,the false negative from iron particles was eliminated while potential cytotoxicity was showen,and the result accuracy was affected because some cells were washed out.Conclusion The proposed method can be used for the in vitro cytotoxicity evaluation,and facilitates the safety evaluation of the application of such materials.[Chinese Medical Equipment Journal,2025,46(3):35-41]

Objective:To investigate the correlation between carotid-femoral pulse wave velocity(cfPWV)and carotid artery structural,hemodynamic,and cardiac functional parameters.Methods:A total of 420 healthy volunteers who underwent neck ultrasound,cardiac ultrasound,and cfPWV examination at Kailuan General Hospital from June 2022 to February 2023 were selected,and they were divided into two groups based on the atherosclerosis threshold value of cfPWV>10 m/s,which included high cfPWV group(140 cases,cfPWV>10 m/s)and low cfPWV group(280 cases,cfPWV≤10 m/s).The demographic data(age,sex)of 420 persons were collected,and the common carotid artery diameter(CCAD),common carotid artery intima-media thickness(CIMT),plaque status,peak systolic velocity(PSV),end-diastolic velocity(EDV)and mean flow velocity(MFV)were compared between two groups.Then,the differences of interventricular septal thickness(IVST)of heart,left ventricular posterior wall thickness(LVPWT),the ratio of blood flow velocity at early stage to that at advanced stage in mitral valve(E/A)and stroke volume(SV)were analyzed.Multivariate logistic regression was adopted to analyze the independent influence factors of cfPWV enhancement.Results:The average age of high cfPWV group was(61.31±9.66)years old,which was significantly higher than(51.06±10.47)years old of low cfPWV group,and the difference of that was significant(t=-9.56,P<0.01).In the parameters of common carotid artery,63 persons(45.0%)occurred plaque in 140 persons of high cfPWV group,which was significantly lower than 50 persons(17.86%)in 280 persons of low cfPWV group,and the difference of that between two groups was significant(x2=34.97,P<0.05).The differences of CCAD,CIMT,PSV,EDV and MV of common carotid artery at right side of persons between two groups were significant(t=-2.16,-5.40,4.52,5.59,5.04,P<0.05),respectively.The parameters of heart showed that the LVPWT thickness increased(9.35±1.13)mm,and the ratio of E/A<1 increased 77.86%in high cfPWV group,which were significantly related to the increase of cfPWV(r=0.27,0.38,P<0.01).Multivariate logistic regression analysis indicated that age(OR=1.05,95%CI:1.02-1.08),CCAD(OR=1.63,95%CI:1.22-2.16),plaque presence(OR=1.84,95%CI:1.07-3.17),LVPWT(OR=1.35,95%CI:1.05-1.72),and the ratio of E/A<1(OR=2.37,95%CI:1.32-4.26)were independent predictors of cfPWV enhancement.Conclusion:The enhancement of cfPWV is closely related to high age,the reconstruction of common carotid artery(widening of inside diameter,and plaque formation),left ventricular hypertrophy,and diastolic abnormality,which indicates it is possible that atherosclerosis process accompanies by the change of interaction mechanism of blood vessels-heart.

Objective:To analyze the effect of routine ultrasound examination combined with computed tomography venous(CTV)angiography for lower extremity veins in assessing deep vein thrombosis(DVT)of lower extremity after ischemic stroke.Methods:The clinical data of 132 patients with ischemic stroke,who admitted to XiDian Group Hospital from January 2020 to May 2023,were retrospectively analyzed.All selected patients were suspected as DVT in lower extremity,so they underwent digital subtraction angiography(DSA),routine ultrasound and CTV examination for lower extremity veins.The result of DSA examination was used as the gold standard.The diagnostic efficacy of routine ultrasound examination combined with CTV for the DVT of lower extremity after stroke was further analyzed.Results:The results of DSA examination confirmed that a total of 128 cases of 132 patients with suspected DVT were diagnosed as DVT in lower extremity.The routine ultrasound on lower extremity found out about 102 cases with DVT on lower extremity,and the consistency between the results of ultrasound diagnosis and the results of DSA diagnosis was general(Kappa=0.461,P=0.000).The CTV found out about 111 cases with DVT on lower extremity,and the consistency between the results of CTV diagnosis and the results of DSA diagnosis also was general(Kappa=0.605,P=0.000).The diagnostic result of the combination of routine ultrasound and CTV for DVT in lower extremity had better consistency with DSA result(Kappa=0.752,P=0.000).The diagnostic accuracy(93.33%),sensitivity(94.53%)and negative predictive value(73.08%)of ultrasound combined with CTV were significantly higher than those of single diagnosis,and the differences of them were statistically significant(x2=10.727,12.463,6.313,P<0.05).Conclusion:The diagnosis of the routine ultrasound examination combined with CTV for DVT of lower extremity after ischemic stroke can improve the accuracy and diagnostic efficacy of clinical diagnosis,which is contribute to the assessment of patients'disease conditions.

Objective:To determine if preoperative 68Ga-fibroblast activation protein inhibitor (FAPI)-04 PET/MR could contribute to predicting pathological complete response (pCR) in patients with gastrointestinal cancer undergoing neoadjuvant immunotherapy. Methods:In this retrospective study, 35 patients (23 males, 12 females, age (59.1±7.9) years) with gastrointestinal cancer who underwent 68Ga-FAPI-04 PET/MR after receiving neoadjuvant immunotherapy between February 2021 and January 2024 were enrolled. Clinical data, PET imaging parameters including SUV, peak of SUV normalized by lean body mass (SUL peak), FAPI-positive tumor volume (FTV), and total FAPI-positive lesion burden (TLF), and pathological data were collected and analyzed. Patients were divided into pCR group and non-pCR group, and the independent-sample t test or Mann-Whitney U test was performed to compare those parameters between the 2 groups. ROC curve analysis (Delong test) was performed to evaluate the diagnostic efficiency of each parameter to predict pCR. Results:The overall pCR rate of the neoadjuvant therapy was 40.0%(14/35). In the visual evaluation, 68Ga-FAPI-04 PET was limited in predicting pCR, showing false positivity in 12 patients and false negative in 1 patent. While SUV max( t=2.50, P=0.018), SUL peak( t=3.11, P=0.004), FTV( U=3.00, P=0.030) and TLF( U=2.96, P=0.042) in non-pCR group were all higher than those in pCR group. The predictive efficiency of FTV <1.925cm 3 for pCR was better than the efficiency of PET visual evaluation ( Z=3.61, P<0.001), with the prediction accuracy of 82.86%(29/35). Conclusions:68Ga-FAPI-04 PET/MR may provide an effective clinical tool for guiding further treatment of patients with gastrointestinal cancer undergoing neoadjuvant immunotherapy. The quantitative features derived from 68Ga-FAPI-04 PET appear promising in predicting pCR, which are expected to provide a reference for avoiding surgery.

Objective To investigate the expression levels of class Ⅰ histone deacetylases(HDAC)in the serum of patients with newly diagnosed psoriatic arthritis(PsA)and screen out serological indicators that are of significance for early diagnosis and assessment of disease activity.Methods A total of 49 PsA patients newly diagnosed in Shanxi Provincial People's Hospital from August 2022 to February 2024 and 30 healthy individuals(control group)were enrolled in this study.Demographic data were collected,and disease severity was assessed.Serum samples were collected,and the expression levels of class Ⅰ HDAC(HDAC1,HDAC2,HDAC3,and HDAC8)in the serum of each group were determined by ELISA.The correlations between the expression levels of class Ⅰ HDAC and clinical assessment indicators in each group were evaluated.Multivariate Logistic regression was adopted to analyze the risk factors affecting the disease activity of PsA patients.The receiver operating characteristic curve was used to evaluate the diagnostic efficacy of the risk factors affecting the disease activity of PsA patients.Results Compared with the control group,PsA patients showed up-regulated expression levels of HDAC1(P=0.003),HDAC2(P=0.010),HDAC3(P=0.003),and HDAC8(P=0.018)in the serum.The serum HDAC1 level of PsA patients was positively correlated with erythrocyte sedimentation rate(r=0.344,P=0.028).The serum HDAC2 level was positively correlated with the overall assessment of disease activity(r=0.468,P=0.001),the disease activity index of arthritis(r=0.401,P=0.007),the number of swollen joints(r=0.308,P=0.042),hospital anxiety and depression scale(HADS)score of anxiety(r=0.360,P=0.018),and HADS score of depression(r=0.302,P=0.047).The serum HDAC3 level was correlated with erythrocyte sedimentation rate(r=0.542,P<0.001),C-reactive protein(CRP)level(r=0.440,P<0.001),HADS score of anxiety(r=0.420,P=0.005),interleukin-6 level(r=0.397,P=0.004),the overall assessment of disease activity(r=0.318,P=0.036),and the course of psoriatic arthritis(r=0.330,P=0.028).The serum HDAC8 level was positively correlated with HADS score of anxiety(r=0.477,P=0.008)and erythrocyte sedimentation rate(r=0.385,P=0.039).Compared with the patients with low disease activity,those with moderate to high disease activity presented up-regulated expression of HDAC3(P=0.041).HDAC2(P=0.028)and CRP(P=0.034)were risk factors for moderate to high disease activity in PsA patients.HDAC2(area under the curve=0.802,P=0.003)and CRP(area under the curve=0.718,P=0.033)had diagnostic value for the progression of PsA.Conclusions The expression levels of class Ⅰ HDAC in the serum of patients with newly diagnosed PsA were significantly different.The serum levels of HDAC2 and CRP are expected to become serological indicators for the early diagnosis and disease activity assessment of PsA.
Humans ; Histone Deacetylases/blood* ; Arthritis, Psoriatic/diagnosis* ; Male ; Female ; Histone Deacetylase 1/blood* ; Histone Deacetylase 2/blood* ; Adult ; Middle Aged ; Clinical Relevance ; Repressor Proteins