Chronic obstructive pulmonary disease （COPD） is a chronic respiratory disease that poses a significant threat to global health， exhibiting high morbidity， disability and mortality rate， with its prevention and treatment situation becoming increasingly critical. The pathogenesis of COPD is complex， and the underlying cellular and molecular biological mechanisms remain incompletely elucidated. Programmed cell death （PCD） is the process wherein cells actively undergo demise to maintain internal environmental stability in response to certain signals or specific stimuli. Contemporary medical research indicates that the dysregulation of PCD patterns such as apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis is closely related to the onset and progression of COPD. Clarifying the molecular mechanisms of PCD in COPD may provide novel perspectives for in-depth understanding and prevention of the disease. Traditional Chinese medicine （TCM） is characterized by holistic regulation. In recent years， extensive research has been conducted in the TCM field focusing on modulating apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis for the treatment of COPD， yielding remarkable achievements. Therefore， this study systematically explored the molecular mechanism of PCD in COPD and reviewed the potential mechanisms and intervention status of TCM targeting PCD in COPD， aiming to provide insights and references for the clinical prevention， treatment and in-depth research of COPD.

Chronic obstructive pulmonary disease （COPD） is a chronic respiratory disease that poses a significant threat to global health， exhibiting high morbidity， disability and mortality rate， with its prevention and treatment situation becoming increasingly critical. The pathogenesis of COPD is complex， and the underlying cellular and molecular biological mechanisms remain incompletely elucidated. Programmed cell death （PCD） is the process wherein cells actively undergo demise to maintain internal environmental stability in response to certain signals or specific stimuli. Contemporary medical research indicates that the dysregulation of PCD patterns such as apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis is closely related to the onset and progression of COPD. Clarifying the molecular mechanisms of PCD in COPD may provide novel perspectives for in-depth understanding and prevention of the disease. Traditional Chinese medicine （TCM） is characterized by holistic regulation. In recent years， extensive research has been conducted in the TCM field focusing on modulating apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis for the treatment of COPD， yielding remarkable achievements. Therefore， this study systematically explored the molecular mechanism of PCD in COPD and reviewed the potential mechanisms and intervention status of TCM targeting PCD in COPD， aiming to provide insights and references for the clinical prevention， treatment and in-depth research of COPD.

ObjectiveTo evaluate a novel nomogram based on contrast-enhanced MRI radiomics combined with clinical variables for the preoperative prediction of perineural invasion （PNI） in intrahepatic cholangiocarcinoma （ICC）. MethodsThe clinical data of 59 ICC patients were retrospectively collected. According to postoperative pathology reports， the patients were divided into the non-PNI group （n = 33） and the PNI group （n = 26）. Regions of interest （ROI） were delineated from five MRI sequences. Radiomics features were then extracted and filtered to select those with the strongest discriminative power for PNI identification. These selected features were used to construct a radiomics model， which subsequently generated a quantitative radiomics score （radiomics score， Radscore）. Univariate analysis was applied to identify clinical variables associated with PNI， and the glm function was subsequently used to construct clinical and combined models. Finally， the models were evaluated using receiver operating characteristic （ROC） curves， calibration curves， and decision curve analysis （DCA）. The combined model was then visualized as a nomogram. ResultsThe clinical model included age， carbohydrate antigen 19-9 （CA19-9）， red blood cell distribution width， and albumin， whereas the Radscore included five radiomic features. The areas under the ROC curves （AUCs） for the clinical and radiomics models were 0.717 （95%CI： 0.586-0.848） and 0.896 （95%CI： 0.820-0.973）， respectively， whereas the combined model further improved its AUC to 0.917 （95% CI：0.848-0.987）. The calibration curves and DCA showed that the nomogram was well calibrated and provided the greatest net clinical benefit. ConclusionThe novel nomogram may serve as a basis for preoperative prediction of PNI status， thereby assisting clinical decision-making and guiding personalized treatment.

Background Diesel engines are widely used in transportation, agriculture, construction, industry, and other fields. Diesel exhaust, classified as a Group 1 carcinogen, emits particles (DEP) that can penetrate deep into the respiratory tract, posing significant health risks. DEP pollution is particularly severe in confined environments, necessitating effective control measures. Objective Under laboratory simulation conditions, to explore the spatiotemporal distribution characteristics of the mass and number concentrations of DEP as it diffuses indoors and to reveal the effects of ventilation and additional airflow on indoor DEP pollution levels. Methods A diesel engine was placed in a laboratory (length 3.39 m × width 2.85 m × height 2.4 m) with its exhaust emitted from east to west. An air purifier was installed 1 m south of the engine. Eight measurement points (1 m horizontal distance from the exhaust outlet, height: 1 m/1.5 m) were setup to monitor DEP concentrations using portable laser particle sizers. The effects of engine power (4.05 kW vs. 5.15 kW), ventilation (maximum airflow: 600 m³·h⁻¹), additional airflow intensity (low and high), and direction (forward/reverse) on DEP pollution were analyzed. DEP levels of 5 diesel vehicle models were also compared. Results The mass and number concentrations of DEP indoors increased immediately after the diesel engine started. The peak mass concentration time at the eastern measurement point (−1, 0) m opposite to the exhaust direction (17.70 min) was significantly longer than that at the western (1, 0) m (16.20 min), southern (0, -1) m (14.45 min), and northern (0, 1) m (12.70 min) points (P<0.05), with no significant differences between the other points (western, southern, and northern) (P>0.05). The northern point (0, 1) m exhibited the highest DEP mass and number concentration peaks (174.62 μg·m⁻³, 1319.85 p·cm⁻³), significantly exceeding those at the southern (0, −1) m (129.89 μg·m⁻³, 1175.24 p·cm⁻³), eastern (−1, 0) m (140.12 μg·m⁻³, 1120.53 p·cm⁻³), and western (1, 0) m (147.60 μg·m⁻³, 818.62 p·cm⁻³) points (P<0.05), and no significant differences were observed among other points (P>0.05). There were no significant differences in peak DEP mass and number concentrations by measurement heights (P>0.05). Diesel engine power, ventilation, airflow intensity, and airflow direction had no significant effect on the time of peak DEP concentration (P>0.05). However, higher engine power (5.15 kW) produced greater DEP peaks [(186.66±19.29) μg·m⁻³, (1382.79±122.56) p·cm⁻³] than the 4.05 kW engine power [(168.41±12.65) μg·m⁻³, (1284.45±71.30) p·cm⁻³] (P<0.05). The peak mass concentration [(342.04±35.03) μg·m⁻³] and number concentration [(1886.87±57.91) p·cm⁻³] of DEP in the non-ventilated group were significantly higher than those in the ventilated group [(186.66±19.29) μg·m⁻³, (1382.79±122.56) p·cm⁻³] (P<0.001). Forward airflow elevated DEP mass concentrations compared to reverse airflow (287.71 μg·m⁻³ vs. 243.74 μg·m⁻³, t=−2.592, P=0.009), but no effects on DEP number concentration (P>0.05). Significant differences in mass concentration were observed among selected 5 vehicle models (Z=38.109, P<0.001). Conclusion The operation of diesel engines will emit a large amount of particulate matter, causing pollution in enclosed spaces. Diesel engines with greater power have higher levels of DEP pollution emissions. Based on the spatiotemporal distribution characteristics, it is recommended to set the operation position in the reverse direction of exhaust emissions and close to air purifiers, while avoiding the use of additional air flow equipment.

Objective To explore function-structure covariant patterns in Alzheimer's disease(AD)and mild cognitive impairment(MCI),and to investigate their associations with cognitive function and activities of daily living.Methods three-way parallel group independent component analysis(three-way pGICA),was used to identify the covariant patterns of resting-state functional MRI temporal data,gray matter density maps,and fractional anisotropy(FA)maps,and the differences between different groups were compared.Furthermore,the associations of covariant patterns with the Montreal Cognitive Assessment-Basic(MoCA_B)Scale scores and Activities of Daily Living Scale scores were analyzed.Results The function-structure covariant patterns in AD and MCI were characterized by the enhanced negative functional connectivity between the left posterior salience network and the right default mode network,the decreased gray matter density in the bilateral dorsolateral prefrontal cortex,and the reduced FA values in the left superior corona radiata(correlations:P<0.001,FDR corrected).Compared with HC group,AD group showed significant abnormalities in all identified covariant patterns(P<0.01,FDR corrected),but MCI group only exhibited a significant decrease in gray matter density in the bilateral dorsolateral prefrontal cortex(P<0.05,FDR corrected).Additionally,AD group had significantly lower FA value in the left superior corona radiata than MCI group(P<0.05,FDR corrected).The loadings reflecting the degree of covariation were significantly correlated with the Activities of Daily Living Scale scores(P<0.05,FDR corrected)but not with MoCA_B Scale scores.Conclusion The function-structure covariant patterns in AD and MCI are consistent with the declines in activities of daily living.The multimodal fusion analysis(three-way pGICA)provides a novel approach to understand the brain damage mechanisms underlying the covariant evolution of MCI and AD.

Objective To explore function-structure covariant patterns in Alzheimer's disease(AD)and mild cognitive impairment(MCI),and to investigate their associations with cognitive function and activities of daily living.Methods three-way parallel group independent component analysis(three-way pGICA),was used to identify the covariant patterns of resting-state functional MRI temporal data,gray matter density maps,and fractional anisotropy(FA)maps,and the differences between different groups were compared.Furthermore,the associations of covariant patterns with the Montreal Cognitive Assessment-Basic(MoCA_B)Scale scores and Activities of Daily Living Scale scores were analyzed.Results The function-structure covariant patterns in AD and MCI were characterized by the enhanced negative functional connectivity between the left posterior salience network and the right default mode network,the decreased gray matter density in the bilateral dorsolateral prefrontal cortex,and the reduced FA values in the left superior corona radiata(correlations:P<0.001,FDR corrected).Compared with HC group,AD group showed significant abnormalities in all identified covariant patterns(P<0.01,FDR corrected),but MCI group only exhibited a significant decrease in gray matter density in the bilateral dorsolateral prefrontal cortex(P<0.05,FDR corrected).Additionally,AD group had significantly lower FA value in the left superior corona radiata than MCI group(P<0.05,FDR corrected).The loadings reflecting the degree of covariation were significantly correlated with the Activities of Daily Living Scale scores(P<0.05,FDR corrected)but not with MoCA_B Scale scores.Conclusion The function-structure covariant patterns in AD and MCI are consistent with the declines in activities of daily living.The multimodal fusion analysis(three-way pGICA)provides a novel approach to understand the brain damage mechanisms underlying the covariant evolution of MCI and AD.

Objective To investigate the association of liver radiodensity with the degree and progression of liver fibrosis in patients with chronic hepatitis B(CHB).Methods A retrospective cohort study was conducted among 114 CHB patients who were hospitalized in The First Hospital of Lanzhou University from January to December 2019,and related clinical data were collected,including laboratory tests and abdominal CT.The metabolic characteristics of the patients were assessed,and liver radiodensity was measured.An analysis of variance was used for comparison of normally distributed continuous data between three groups,and the Kruskal-Wallis H rank sum test was used for comparison of continuous data with skewed distribution between three groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between three groups.A logistic regression analysis was used to investigate the influencing factors for the degree of liver fibrosis,and the Cox proportional-hazards regression model analysis was used to investigate the influencing factors for the progression of liver fibrosis in CHB.Results Among the 114 patients enrolled,43(37.72％)had no liver cirrhosis,30(26.32％)were suspected of liver cirrhosis,and 41(35.96％)had liver cirrhosis,with a median follow-up time of 538.5(322.75-1 031.50)days.Liver radiodensity on plain scan(odds ratio[OR]=0.81,95％confidence interval[CI]:0.68-0.97,P=0.025),liver radiodensity on contrast-enhanced scan(OR=0.95,95％CI:0.90-0.99,P=0.037),and liver volume(OR=0.99,95％CI:0.98-0.99,P<0.001)were independent influencing factors for the degree of liver fibrosis.The univariate Cox regression analysis showed that the low level of HDL(hazard ratio=2.81,95％CI:1.04-7.54,P=0.041)was associated with the progression of liver fibrosis in CHB patients,and the degree of liver fibrosis,liver volume,and liver radiodensity showed no significant association with the progression of liver fibrosis(all P>0.05).Conclusion In CHB patients,liver radiodensity is an independent influencing factor for the degree of liver fibrosis,and low HDL has a marked influence on the progression of liver fibrosis.

Objective To investigate alterations in interhemispheric functional connectivity(FC)in the cerebral cortices connected via the corpus callosum in patients with Alzheimer's disease(AD),and to explore their relationships with cognitive function and activities of daily living.Methods Resting-state functional magnetic resonance imaging data were collected from 28 patients with Alzheimer's dementia(d-AD),47 patients with mild cognitive impairment(MCI),and 37 healthy controls(HC).Using a trancallosal tract template,32 pairs of homologous cortical brain regions directly connected to 32 subregions of the corpus callosum were selected as regions of interest for interhemispheric FC analysis.Further correlation analyses were performed between FC values in patient groups and their scores on the Montreal Cognitive Assessment-Basic(MoCA-B)Scale and the Activities of Daily Living(ADL)Scale.Results Compared with HC group,both MCI and d-AD groups exhibited hyperconnectivity(significantly increased FC)in interhemispheric non-homologous brain regions.Specifically,hyperconnectivity in the MCI group was scattered across the frontal,parietal,temporal,and occipital lobes,while in the d-AD group,it was concentrated within the precentral and postcentral gyri.Notably,hyperconnectivity involving the prefrontal and occipital lobes in the MCI group showed significant declines in the d-AD group.The interhemispheric homologous FC in the d-AD group reduced more significantly than the MCI group.Additionally,in the d-AD group,2 interhemispheric FC within the prefrontal lobe(between the bilateral orbital parts of the inferior frontal gyrus,and between the left medial frontal gyrus and the right middle frontal gyrus)were correlated with MoCA-B scores,and 2 FC(between the bilateral middle occipital gyri,and between the left inferior parietal lobule and the right middle frontal gyrus)were correlated with ADL scores.Conclusion MCI and d-AD exhibit distinct patterns of interhemispheric FC alterations,and the interhemispheric FC changes in AD patients are non-progressive.The close relationships between interhemispheric homologous/non-homologous FC and MoCA-B/ADL scores in d-AD patients provide an objective basis and reference for clinical neuromodulation.

Viral pneumonia is an infectious disease caused by virus invading the lung parenchyma and interstitial tissue and causing lung inflammation， with the incidence rising year by year. Traditional Chinese medicine （TCM） can treat viral pneumonia in a multi-component， multi-target， and holistic manner by targeting the core pathogenesis of pneumonia caused by different respiratory viruses， demonstrating minimal side effects and significant advantages. According to the theory of healthy Qi and pathogenic Qi in TCM， the struggle between healthy Qi and pathogenic Qi and the imbalance between immunity and inflammation run through the entire process of viral pneumonia， and the immunity-inflammation status at different stages of the disease reflects different relationships between healthy Qi and pathogenic Qi. Immune dysfunction leads to the deficiency of healthy Qi， causing viral infections. The struggle between healthy Qi and pathogenic Qi causes immunity-inflammation imbalance， leading to the onset of viral pneumonia. Inflammatory damage causes persistent accumulation of phlegm and stasis， leading to the progression of viral pneumonia. The cytokine storm causes immunodepletion， leading to the excess of pathogenic Qi and diminution of healthy Qi and the deterioration of viral pneumonia. After the recovery from viral pneumonia， there is a long-term imbalance between immunity and micro-inflammation， which results in healthy Qi deficiency and pathogenic Qi lingering. Healthy Qi deficiency and pathogenic Qi excess act as common core causes of pneumonia caused by different respiratory viruses. Clinical treatment should emphasize both replenishing healthy Qi and eliminating pathogenic Qi， helping to restore the balance between healthy Qi and pathogenic Qi as well as between immunity and inflammation， thus promoting the recovery of patients from viral pneumonia. According to the TCM theory of healthy Qi and pathogenic Qi， this article summarizes the immunity-inflammation mechanisms at different stages of viral pneumonia， and explores the application of the method of replenishing healthy Qi and eliminating pathogenic Qi in viral pneumonia. The aim is to probe into the scientific connotation of the TCM theory of healthy Qi and pathogenic Qi in viral pneumonia and provide ideas for the clinical application of the method of replenishing healthy Qi and eliminating pathogenic Qi to assist in the treatment of viral pneumonia.

Objective This study aims to investigate the effects of transcatheter arterial chemoembolization(TACE)using EqualSpheres,CalliSpheres,and Lipiodol loaded with idarubicin on VX2 liver cancer in rabbits.Methods Twelve New Zealand white rabbits were randomly assigned to three groups:EqualSpheres group,CalliSpheres group,and Lipiodol group(n=4 per group).The VX2 liver cancer animal model was successfully established through ultrasound-guided percutaneous puncture.EqualSpheres,CalliSpheres,and Lipiodol were employed as embolization agents loaded with idarubicin for the embolization procedure.Peripheral blood samples were collected at intervals of 5 minutes,0.5,1,4,12 and 24 hours following embolization and were centrifuged to obtain serum.At 24 hours post-TACE treatment,the rabbits in both the experimental and control groups were euthanized,and both liver cancer tissues and normal liver tissues were collected.UPLC-MS/MS was used to measure the drug concentration of idarubicin in peripheral blood and tissue samples,and Graphpad software was used to construct drug concentration-time curves in peripheral blood.The pharmacokinetic curves were constructed to evaluate the dynamic in vivo distribution characteristics.Results The average drug concentration in the EqualSpheres group(920.06 ng/mL)was significantly higher than that in both the CalliSpheres group(79.47 ng/mL)and the Lipiodol group(118.71 ng/mL).However,the average drug concentration in normal liver tissue of all the three groups was lower,and the difference was not statistically significant.The peripheral blood drug concentration of the three groups decreased at 5 minutes post-TACE and increased over the next 24 hours.The average blood concentration curve of EqualSpheres group increased more steadily compared to the CalliSpheres group and the Lipiodol group.The Cmax of the Lipiodol group was reached at 0.5 hours,measuring 11.54 ng/mL.Both the CalliSpheres group and the EqualSpheres group achieved their Cmax at 5 minutes,with values of 7.82 and 8.36 ng/mL,respectively.Conclusion EqualSpheres loaded with idarubicin achieve a high drug concentration at the tumor site while maintaining a low concentration in peripheral blood over 24 hours.This study demonstrates the stable drug release capability of idarubicin-loaded EqualSpheres.