Objective To investigate the correlation between seasonal blood pressure （BP） variability and total burden score of cerebral small vessel disease （CSVD） with different severities. Methods The patients with CSVD who were consecutively admitted were enrolled， and according to the total burden score based on head MRI， they were divided into control group （CSVD 0 points）， mild group （CSVD 1‒2 points）， and moderate-to-severe group （CSVD 3‒4 points）.General information was collected from all patients， as well as 24-hour ambulatory blood pressure monitoring （ABPM） during warm and cold seasons. The correlation between ABPM parameters in different seasons and the imaging burden of different severities of CSVD was analyzed. Results A total of 145 patients were enrolled， with 29 patients in the control group，64 in the mild group， and 52 in the moderate-to-severe group.Compared with the control group， the mild group and the moderate-to-severe group had significantly higher age（F=9.721，P=0.001）， 24-hour systolic blood pressure （SBP） in hot season（F=6.572，P=0.002）， daytime SBP in hot season（F=6.460，P=0.002）， daytime diastolic blood pressure （DBP） in hot season（F=5.802，P=0.004）， nighttime SBP in hot season（F=8.508，P<0.001）. Compared with the control group， the moderate-to-severe group had significantly higher levels of 24-hour DBP in hot season（F=4.564，P=0.012）， nighttime DBP in hot season（F=6.294，P=0.002），24-hour SBP in cold season（F=7.012，P=0.001）， 24-hour DBP in cold season（F=4.527，P=0.012），daytime SBP in cold season（F=5.708，P=0.004），daytime DBP in cold season（F=3.138，P=0.046），nighttime SBP in cold season（F=9.154，P<0.001）， and nighttime DBP in cold season（F=8.006，P=0.001）. Compared with the control group， the mild group and the moderate-to-severe group had a significantly higher proportion of patients with abnormal BP circadian rhythm in hot season （χ2=13.059，P=0.001） and cold season （χ2=10.091，P=0.006）.The ordinal logistic regression analysis showed that age （OR=1.147， 95%CI 1.084‒1.214） was an independent risk factor for CSVD， and compared with the patients with dipper-type blood pressure in hot season， the patients with non-dipper blood pressure pattern had a risk of CSVD increased by 13.282 times （OR=13.282， 95% CI 2.379‒74.159）， while those with reverse-dipper blood pressure pattern had a risk of CSVD increased by 25.569 times（OR=25.569，95%CI 3.061‒213.551）. Conclusion The imaging burden score of CSVD increases with the increase in age and the proportion of abnormal circadian blood pressure pattern in hot season， and both age and abnormal circadian blood pressure pattern in hot season are independent risk factors for the imaging burden of CSVD.

Hepatocellular carcinoma （HCC） is a common malignant tumor with a high mortality rate， an insidious onset， and complex pathological mechanisms. In the tumor microenvironment， tumor-promoting immune cells protect tumor cells from immune attacks， while dysfunction of anti-tumor immune cells causes the inhibition of immune response， thereby leading to the continuous deterioration of cancer. In recent years， traditional Chinese medicine has shown good efficacy in the treatment of HCC， and it can inhibit the proliferation and metastasis of cancer cells by regulating immune cells. By analyzing related articles in China and globally， this article summarizes how immune cells affect the progression of HCC through the immunosuppressive pathway and how traditional Chinese medicine exerts an anti-HCC effect by regulating immune cells， in order to provide theoretical basis and reference for optimizing the treatment of HCC.

Abstract To analyzes the characteristics, problems and enlightenment of physical activity observation tools, so as to provide reference for researchers to quickly and accurately choose appropriate observation tools to evaluate children s and adolescents physical activity. Literature search is conducted in eight databases of Chinese and English, including CNKI, Wanfang, VIP, Web of Science, PubMed, Medline, ERIC, and SPORTDiscus. Ultimately, eight observation tools for assessing physical activity in children and adolescents are included. Through summarization and comparison, it is found that the applications of those tools cover multiple age groups, the observation indicators cover multiple dimensions for each with varying emphases, and the applicable contexts vary in their specific background information, and recording methods tend to be quantitative. However, several issues remain to be addressed in practical applications. First, the observation indicators need to be supplemented and improved; second, physical activity in community environments and academic classrooms requires further attention; third, physical activity intensity needs to be scientifically evaluated; fourth, observation and recording methods need to be integrated and innovated; fifth, the number of observation subjects needs to be expanded. Future research could focus on developing observation tools tailored to the characteristics of Chinese children and adolescents, while drawing on foreign observation tools to comprehensively assess physical activity among children and adolescents.

Background The early lesions of pneumoconiosis that cannot be clearly shown by digital radiography (DR) chest films can be clearly displayed in high-resolution CT (HRCT). HRCT enables systematic observation of the evolution and progression of pneumoconiosis, providing reliable evidence for diagnosis. Objective To provide reliable evidences for the early screening of pneumoconiosis, By analyzing the imaging difference between HRCT and DR chestfilms in pneumoconiosis screening. Methods Six casting workers in a casting forging company suspected of early stage of pneumoconiosis through regular occupational health examination screening were recruited , and 64 rows of spiral CT thin layer were scanned and reconstructed by high-resolution bone algorithm. Compare the imaging findings of early stage of pneumoconiosis small shadow on DR chest film and HRCT and make diagnostic conclusion. Results All six subjects had Multiple small nodules and/or irregular shadows in the lungs were found in all six patients’ DR chest films, but the density and distribution of small shadows did not meet the diagnostic criteria of pneumoconiosis. The HRCT review showed that, dispersively distributed micro nodule shadows and/or short-thread shape thin shadows in the lung in four patients, the rest two patients' HRCT images showed multiple localized pleural thickening and partial calcification and multiple nodules like pleural uplift thickening. Other lesions were also identified, including lung multiple localized pleural thickening and calcification in 3 cases, lung multiple cystic bronchiectasis in 1 case, inflammatory nodules in 2 cases, of chronic lesions in 2 case. Through comprehensive analysis, early stage of pneumoconiosis were seen in 4 patients, among which 3 patients engaged in sand mixing and sand clearing presenting early stage of silicosis; 1 patient engaged in moulding sand manufacturing presenting early stage of foundry worker pneumoconiosis. Conclusion Compared with DR chest film, HRCT can more accurately show the morphology and distribution of lesions, and has significant advantages in identifying small shadows in early stage of pneumoconiosis and other lung diseases. The diffuse small nodules in the lung is not a characteristic manifestation of pneumoconiosis, and cannot be used as the basis for the diagnosis of early stage of pneumoconiosis alone. Even with a clear occupational dust exposure history, an early stage of pneumoconiosis diagnosis can be made after excluding other lung diseases. After dust work, especially silicon dust work workers showing abnormal changes in X-ray chest film, review of the HRCT should be conducted even if the small shadow distribution does not meet the diagnostic criteria of pneumoconiosis, so as to early detection of pneumoconiosis patients and high-risk groups.

ObjectiveTo investigate the chemical constituents of Chuanxiong Rhizoma-Paeoniae Radix Rubra（CRPRR） that cross the blood-brain barrier in rats with ischemic stroke， their brain-protective effects， and their impact on inflammatory factors including tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） based on ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） and pharmacodynamic experiments. MethodsA focal cerebral ischemia-reperfusion injury model was established in rats via the middle cerebral artery occlusion/reperfusion （MCAO/R） method using intraluminal suture. Neurological function was evaluated using behavioral scoring. UPLC-Q-TOF-MS was employed to identify the chemical constituents of CRPRR that crossed the blood-brain barrier and entered the cerebrospinal fluid in MCAO/R model rats. Male Sprague-Dawley rats were randomly divided into six groups： sham operation group， model group， low-， medium-， and high-dose CRPRR groups （1.35， 2.7， 5.4 g·kg^-1， respectively）， and an edaravone group （5 mg·kg^-1）， with 12 rats in each group. The sham and model groups received normal saline， while the treatment groups received the respective doses of CRPRR once daily by gavage for three consecutive weeks. The brain-protective effects of CRPRR were assessed using the Longa five-point scoring method， open field test， Morris water maze， 2，3，5-triphenyltetrazolium chloride （TTC） staining， hematoxylin and eosin （HE） staining， and transmission electron microscopy. ResultsNine chemical constituents were identified in the cerebrospinal fluid containing CRPRR， namely paeoniflorin， senkyunolide F， senkyunolide G， paeonimetabolin Ⅰ， paeoniflorin derivative， senkyunolide H， benzoylpaeoniflorin， senkyunolide A， and ligustilide. Animal experiment results showed that compared with the sham operation group， the model group exhibited disordered neuronal arrangement， severe vacuolation， nuclear pyknosis， and evident mitochondrial swelling. Chromatin aggregation and peripheralization were also observed. Neurological scores and the number of crossings in the central region were significantly increased （P<0.01）， while platform crossings were significantly decreased （P<0.01）， and clear infarct areas were present （P<0.01）. Serum levels and protein expression of TNF-α， IL-1β， and IL-18 were significantly elevated （P<0.01）. Compared with the model group， all dose groups of CRPRR showed marked improvement in neuronal morphology which was close to the normal level， with mitochondrial swelling alleviated and chromatin distribution more uniform. The medium- and high-dose groups significantly reduced neurological scores （P<0.01）， while the low-， medium-， and high-dose groups significantly reduced the number of central crossings （P<0.01） and infarct volume （P<0.01）， and decreased TNF-α， IL-1β， and IL-18 levels （P<0.05， P<0.01） compared with the model group. Furthermore， the medium- and high-dose groups significantly reduced TNF-α protein expression （P<0.05，P<0.01）， and the high-dose group significantly reduced IL-1β and IL-18 protein expression （P<0.01）. ConclusionThis study confirmed that CRPRR improves neurological function and alleviates brain tissue damage in MCAO/R rats. Its mechanism may be associated with the downregulation of inflammatory factors TNF-α， IL-1β， and IL-18， as well as the presence of nine active chemical constituents in cerebrospinal fluid， namely paeoniflorin， senkyunolide F， senkyunolide G， paeonimetabolin Ⅰ， paeoniflorin derivative， senkyunolide H， benzoylpaeoniflorin， senkyunolide A， and ligustilide， which are closely related to their brain-protective effects.

ObjectiveTo investigate the chemical constituents of Chuanxiong Rhizoma-Paeoniae Radix Rubra（CRPRR） that cross the blood-brain barrier in rats with ischemic stroke， their brain-protective effects， and their impact on inflammatory factors including tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） based on ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） and pharmacodynamic experiments. MethodsA focal cerebral ischemia-reperfusion injury model was established in rats via the middle cerebral artery occlusion/reperfusion （MCAO/R） method using intraluminal suture. Neurological function was evaluated using behavioral scoring. UPLC-Q-TOF-MS was employed to identify the chemical constituents of CRPRR that crossed the blood-brain barrier and entered the cerebrospinal fluid in MCAO/R model rats. Male Sprague-Dawley rats were randomly divided into six groups： sham operation group， model group， low-， medium-， and high-dose CRPRR groups （1.35， 2.7， 5.4 g·kg^-1， respectively）， and an edaravone group （5 mg·kg^-1）， with 12 rats in each group. The sham and model groups received normal saline， while the treatment groups received the respective doses of CRPRR once daily by gavage for three consecutive weeks. The brain-protective effects of CRPRR were assessed using the Longa five-point scoring method， open field test， Morris water maze， 2，3，5-triphenyltetrazolium chloride （TTC） staining， hematoxylin and eosin （HE） staining， and transmission electron microscopy. ResultsNine chemical constituents were identified in the cerebrospinal fluid containing CRPRR， namely paeoniflorin， senkyunolide F， senkyunolide G， paeonimetabolin Ⅰ， paeoniflorin derivative， senkyunolide H， benzoylpaeoniflorin， senkyunolide A， and ligustilide. Animal experiment results showed that compared with the sham operation group， the model group exhibited disordered neuronal arrangement， severe vacuolation， nuclear pyknosis， and evident mitochondrial swelling. Chromatin aggregation and peripheralization were also observed. Neurological scores and the number of crossings in the central region were significantly increased （P<0.01）， while platform crossings were significantly decreased （P<0.01）， and clear infarct areas were present （P<0.01）. Serum levels and protein expression of TNF-α， IL-1β， and IL-18 were significantly elevated （P<0.01）. Compared with the model group， all dose groups of CRPRR showed marked improvement in neuronal morphology which was close to the normal level， with mitochondrial swelling alleviated and chromatin distribution more uniform. The medium- and high-dose groups significantly reduced neurological scores （P<0.01）， while the low-， medium-， and high-dose groups significantly reduced the number of central crossings （P<0.01） and infarct volume （P<0.01）， and decreased TNF-α， IL-1β， and IL-18 levels （P<0.05， P<0.01） compared with the model group. Furthermore， the medium- and high-dose groups significantly reduced TNF-α protein expression （P<0.05，P<0.01）， and the high-dose group significantly reduced IL-1β and IL-18 protein expression （P<0.01）. ConclusionThis study confirmed that CRPRR improves neurological function and alleviates brain tissue damage in MCAO/R rats. Its mechanism may be associated with the downregulation of inflammatory factors TNF-α， IL-1β， and IL-18， as well as the presence of nine active chemical constituents in cerebrospinal fluid， namely paeoniflorin， senkyunolide F， senkyunolide G， paeonimetabolin Ⅰ， paeoniflorin derivative， senkyunolide H， benzoylpaeoniflorin， senkyunolide A， and ligustilide， which are closely related to their brain-protective effects.

BACKGROUND:Hydroxy safflower yellow A has anti-ischemia,anti-oxidation,anti-thrombotic and anti-inflammatory effects.Whether it affects neuronal pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation is still unclear. OBJECTIVE:To investigate the protective effect of hydroxy safflower yellow A on neuronal pyroptosis and its mechanism. METHODS:HT22 cells in logarithmic growth phase were randomly divided into five groups:normal group,model group,hydroxy safflower yellow A group,colivelin group,and colivelin+hydroxy safflower yellow A group.HT22 cells were treated with glucose-oxygen deprivation/reglucose-reoxygenation to establish neuronal pyroptosis model,and then treated with STAT3 agonist Colivelin and hydroxy safflower yellow A.JC-1 probe was employed to assess changes in mitochondrial membrane potential.Reactive oxygen species kit was used to determine the content of reactive oxygen species in cells.GSDMD/TUNEL staining was conducted to observe cell pyroptosis.Immunofluorescence analysis was performed to detect STAT3 and GSDMD protein expression.RT-PCR was utilized for assessing mRNA expression levels of STAT3,NLRP3,and Caspase-1.Western blot assay was utilized to measure the protein expression levels of p-STAT3,NLRP3,GSDMD,Cleaved-caspase-1,and interleukin-1β. RESULTS AND CONCLUSION:(1)Compared with the normal group,the number of pyroptotic cells increased in HT22 cells in the model group along with a significant increase in protein expression levels of p-STAT3,NLRP3,Cleaved-caspase-1,GSDMD,and interleukin-1β.Compared with the model group,the number of pyroptotic cells reduced,and the expression of pyroptosis-related proteins significantly decreased in the hydroxy safflower yellow A group.(2)In comparison with the model group,pyroptosis worsened in the colivelin group where mitochondrial membrane potential decreased along with elevated reactive oxygen species content and increased mRNA expression levels of STAT3,NLRP3,and Caspase-1,as well as increased protein expression levels of p-STAT3,NLRP3,GSDMD,Cleaved-caspase-1,and interleukin-1β.Compared with the Colivelin group,above indexes were improved in the colivelin+hydroxy safflower yellow A group.These results suggest that hydroxy safflower yellow A plays a neuroprotective role through STAT3 signaling pathway to inhibit HT22 pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation treatment.

OBJECTIVE To provide a reference for pharmaceutical care in patients with ulcerative colitis （UC） and ankylosing spondylitis （AS） who developed pustular psoriasis induced by infliximab. METHODS Clinical pharmacists participated in the pharmaceutical care process of a patient with UC and AS who developed pustular psoriasis after using infliximab. The clinical pharmacists determined， using Naranjo’s Scale， that the correlation between the patient’s pustular psoriasis and infliximab was “likely”. Regarding the patient’s development of pustular psoriasis after using infliximab， the clinical pharmacists recommended discontinuing infliximab and switching to Upadacitinib extended-release tablets. For the patient’s skin allergic reaction after using upadacitinib， the clinical pharmacists advised continuing the use of upadacitinib and closely monitoring any potential adverse reactions during the treatment period. RESULTS The clinicians adopted the clinical pharmacists’ recommendation. Following the treatment， the patient’s symptoms were significantly alleviated， and the patient was discharged with medication. The follow-up after discharge showed that the treatment was effective and well-tolerated. CONCLUSIONS The clinical pharmacists analyzed the causal relationship between infliximab and pustular psoriasis. Through pharmaceutical care measures such as dynamic monitoring of skin lesions， evaluation of treatment responses， and optimization of drug regimens， they assisted the physicians in formulating an individualized medication plan， ensuring the safety and efficacy of the patient’s medication use.

Myelodysplastic syndrome (MDS), a myeloid tumor derived from the malignant clones of hematopoietic stem cells, has an annually increasing incidence. The contemporary research direction has shifted to analyzing the synergistic effect of immune surveillance collapse and abnormal bone marrow microenvironment in the pathological process of MDS. Against this backdrop, the immune checkpoint molecule TIM3 has emerged as a key target because of its persistently high expression on the surface of important immune cells such as T and NK cells. The abnormal activation of the TIM3 pathway is the mechanism by which solid tumors and hematological malignancies achieve immune escape and is a key hub in the formation of immune exhaustion phenotypes. This work integrates the original discoveries of our team with the latest international progress, systematically demonstrating the bidirectional regulatory network of TIM3 between the malignant clone proliferation of MDS and the immunosuppressive microenvironment. Integrating the evidence from emerging clinical trials allows us to consider the clinical significance of TIM3-targeted blocking for MDS, providing a transformative path to overcome the resistance of traditional treatments and marking a new chapter in the active immune reconstitution of MDS treatment.

Objective To investigate the role of cytochrome P450 2E1 (CYP2E1) in trichloroethylene (TCE)-induced skin sensitization and liver damage in guinea pigs, using diallyl sulfide (DAS), a CYP2E1 inhibitor, as an intervention. Methods Specific pathogen-free female guinea pigs were randomly divided into blank control group, solvent control group, positive control (2,4-dinitrochlorobenzene) group, TCE-exposure group, and DAS-intervention group. Skin sensitization experiments were conducted using the guinea pig TCE maximal dose-skin sensitization test. Urinary trichloroacetic acid levels were determined following TCE induction and challenge. At 48 hours after the final challenge, serum liver function markers and inflammatory cytokines levels were detected. Histopathological examination on skin and liver tissues was performed, and hepatic CYP2E1 protein expression and oxidative stress indicators were assessed. Results The sensitization rates of guinea pigs were 100.0%, 75.0%, and 33.3% in the positive control, TCE-exposure, and DAS-intervention groups, respectively, while the blank control and solvent control groups were both 0.0%. Compared with the guinea pigs in TCE-exposure group, those in the DAS-intervention group had lower urinary trichloroacetic acid levels at intradermal induction, local induction, first challenge, and 24 hours after the final challenge time point (all P<0.05). Histopathology of guinea pigs showed dermal inflammatory infiltration and basal keratinocyte necrosis in the TCE-exposure group, whereas only mild dermal inflammation was observed in the DAS-intervention group. The guinea pigs in TCE-exposure group exhibited diffuse hepatocellular necrosis, while hepatic damage in the DAS-intervention group was alleviated, characterized by only mild hepatocellular steatosis and hepatocyte swelling around the central vein. The skin sensitization rate of guinea pigs in the TCE-exposure group increased (all P<0.01), the serum alanine aminotransferase (ALT )activity, the levels of interleukin (IL)-2, IL-17, and tumor necrosis factor-α (TNF- α) increased (all P<0.05), the relative expression of CYP2E1 protein, the activity of superoxide dismutase (SOD), and the level of malondialdehyde in liver tissue increased (all P<0.05), while the activity of catalase decreased (P<0.05), compared with the blank control and solvent control groups. The serum ALT activity and the levels of IL-2, IL-17, and TNF-α of guinea pigs in DAS-intervention group reduced (all P<0.05), as well as CYP2E1 protein expression, SOD activity, and malondialdehyde level in liver tissue reduced (all P<0.05), compared with the TCE-exposure group. Conclusion TCE can induce hepatic CYP2E1 expression, thereby promoting oxidative stress and inflammatory responses, which contributes to skin sensitization and liver damage. DAS alleviates TCE-induced toxic effects on skin and liver by inhibiting CYP2E1 expression.