Objective To investigate the relationship between the levels of peripheral blood iri-sin,myostatin(MSTN),and 25-hydroxyvitamin D[25(OH)D]and the risk and predictive value of sarcopenia in elderly patients with type 2 diabetes mellitus(T2DM)complicated by heart failure.Methods Elderly patients with T2DM complicated by heart failure who visited Xingtai Central Hospi-tal from March 2023 to March 2024 were selected as the study subjects.The sample size was calculated based on the effect size.Patients were divided into modeling set(n=140)and validation set(n=60)at a ratio of 7 to 3 using a simple randomization method.Additionally,according to the occur-rence of sarcopenia,patients in the modeling set were divided into sarcopenia group and non-sar-copenia group.Clinical data and the levels of peripheral blood irisin,MSTN,and 25(OH)D were compared between the modeling and validation sets.The receiver operating characteristic(ROC)curve was used to analyze the predictive efficacy of peripheral blood irisin,MSTN,and 25(OH)D for sarcopenia.Multivariate logistic regression analysis was employed to identify the influencing fac-tors of sarcopenia in elderly patients with T2DM complicated by heart failure,and a relevant predic-tive model was constructed using R software.Results Among 200 elderly patients with T2DM com-plicated by heart failure,71 cases developed sarcopenia,with an incidence rate of 35.50％.The proportion of regular exercise,bone mineral content,and the levels of irisin and 25(OH)D in the sarcopenia group were lower than those in the non-sarcopenia group,while the MSTN level was high-er in the sarcopenia group,and the differences were statistically significant(P＜0.05).The areas under the curve(AUCs)for predicting sarcopenia by irisin,MSTN,and 25(OH)D were 0.878(95％CI,0.812 to 0.927),0.848(95％CI,0.778 to 0.903),and 0.826(95％CI,0.753 to 0.885),respectively.The sensitivities were 74.16％,79.78％,and 88.76％,and the specifici-ties were 74.16％,79.79％,and 88.76％,respectively.The results of multivariate logistic regres-sion analysis showed that lack of exercise habits(OR=2.489,95％CI,1.665 to 3.735),de-creased bone mineral content(OR=2.340,95％CI,1.596 to 3.595),irisin ≤105.44 ng/mL(OR=3.111,95％CI,2.004 to5.147),MSTN＞19.06 μg/L(OR=2.667,95％CI,2.015 to 4.693),and25(OH)D ≤12.23 ng/mL(OR=2.547,95％CI,1.285 to 4.492)were all inde-pendent risk factors for sarcopenia in these patients(P＜0.05).The results of ROC curve analysis showed that the AUCs of the nomogram model for predicting postoperative recurrence in the modeling and validation sets were 0.875 and 0.853,respectively.The Hosmer-Lemeshow test for the model-ing and validation sets showed the following results:x2=0.715,P=0.510;x2=0.651,P=0.568.The calibration curves were basically consistent with the standard curves.The threshold probability range of decision curve analysis(DCA)was 0.1 to 0.9.Within this range,both the modeling and validation sets showed good clinical net benefits.Conclusion Peripheral blood iri-sin,MSTN,and 25(OH)D all have certain predictive values for the occurrence of sarcopenia in elderly patients with T2DM complicated by heart failure.The nomogram model constructed based on irisin,MSTN,and 25(OH)D can provide a quantitative basis for the early screening of sarcopenia in these patients.

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.

In this paper, two cases of primary familial and congenital polycythemia (PFCP) were reported, and the literature was reviewed. PFCP is a rare autosomal dominant inherited disease caused by a gain-of-function mutation in the EPOR gene, resulting in a loss of negative regulation of erythrocyte proliferation. The two patients were young women with simple polycythemia and clear family history, and identified to carry the truncated mutation c.1316G>A (p.W439*) of EPOR gene. At present, there is no unified treatment plan for PFCP. Currently, there is no standardized treatment for PFCP; management primarily aligns with guidelines for polycythemia vera, focusing on preventing thrombotic complications. This article discusses the clinical features of PFCP, EPOR gene mutations, and their pathogenic mechanisms, while providing diagnostic and therapeutic recommendations based on existing literature.

In this paper, two cases of primary familial and congenital polycythemia (PFCP) were reported, and the literature was reviewed. PFCP is a rare autosomal dominant inherited disease caused by a gain-of-function mutation in the EPOR gene, resulting in a loss of negative regulation of erythrocyte proliferation. The two patients were young women with simple polycythemia and clear family history, and identified to carry the truncated mutation c.1316G>A (p.W439*) of EPOR gene. At present, there is no unified treatment plan for PFCP. Currently, there is no standardized treatment for PFCP; management primarily aligns with guidelines for polycythemia vera, focusing on preventing thrombotic complications. This article discusses the clinical features of PFCP, EPOR gene mutations, and their pathogenic mechanisms, while providing diagnostic and therapeutic recommendations based on existing literature.

Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*

Non-small cell lung cancer (NSCLC), as the predominant histological subtype of lung cancer, accounts for approximately 85% of all lung cancer cases. In recent years, immune checkpoint inhibitors (ICIs), represented by programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors, have achieved breakthrough advancements in patients with driver gene-negative NSCLC. They have been established as a key component of first-line treatment regimens and have significantly improved clinical outcomes. However, limited clinical evidence has emerged showing the phenomenon of histological transformation from NSCLC to small cell lung cancer (SCLC) in patients experiencing disease progression after ICIs monotherapy or combination therapy. Systematic research data on the clinical characteristics, molecular biological basis, and subsequent treatment strategies for such transformation events are currently lacking. This article reports a case of SCLC transformation occurring in a patient with KRAS-mutated lung adenocarcinoma after 16 months of ICIs combination therapy and provides a systematic review of 22 similar published cases. The study demonstrates that small cell transformation is a critical mechanism of immunotherapy resistance, and transformed patients exhibit poor prognosis. The research emphasizes the importance of dynamic monitoring of neuron-specific enolase (NSE) and standardized repeat biopsies during treatment, providing a basis for clinical practice. This aids in enhancing the recognition and management capabilities for this rare histological transformation, ultimately improving patient outcomes.
Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms/immunology* ; Carcinoma, Non-Small-Cell Lung/immunology* ; Small Cell Lung Carcinoma/genetics* ; Male ; Middle Aged ; Female

Objective To observe the clinical efficacy of modified Zhi Gancao Decoction combined with acupuncture in the treatment of ventricular arrhythmia with qi and yin deficiency type.Methods Sixty patients with ventricular arrhythmia of qi and yin deficiency type admitted to the wards and outpatient clinics of Hospital of Traditional Chinese Medicine of Qiqihar between January 2023 and January 2024 were selected,and the patients were randomly divided into the observation group and the control group according to the random number table method,with 30 patients in each group.The control group was treated with Mexiletine Hydrochloride Tablets,and the observation group was treated with modified Zhi Gancao Decoction combined with acupuncture on the basis of the treatment of the control group,the course of treatment covered two consecutive weeks.After two weeks of treatment,the efficacy of traditional Chinese medicine(TCM)syndrome and Lown grading were evaluated between the two groups,the changes of the number of ventricular premature beats,the total beat ratio,and TCM syndrome scores before and after treatment in the two groups were observed.The changes of QT interval and Tp-ec interval before and after treatment were compared between the two groups.Results(1)After treatment,the number of premature ventricular beats and the total beat ratio of the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(2)After treatment,the TCM syndrome scores of patients in the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(3)The total effective rate of TCM syndrome in the observation group was 90.00%(27/30),and 60.00%(18/30)in the control group.The efficacy of the observation group was superior to that of the control group,the difference being statistically significant(P<0.05).(4)The total effective rate of Lown grading efficacy was 93.33%(28/30)in the observation group and 76.67%(23/30)in the control group.The efficacy of the observation group was superior to that of the control group,the difference being statistically significant(P<0.05).(5)After treatment,the QT interval and Tp-ec interval of patients in the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,with a statistically significant difference(P<0.05).Conclusion Modified Zhi Gancao Decoction combined with acupuncture in the treatment of ventricular arrhythmia with qi and yin deficiency type can significantly improve the clinical symptoms of the patients.

With the process of China’s aging population intensifying， palliative care， as an important guarantee for improving the quality of life of terminally ill patients， is receiving more and more social attention， and the demand is constantly increasing. Palliative care needs versatile professionals， and general education can enhance people’s awareness and understanding of it， enabling more people to understand， accept， and participate in palliative care. With the advancement of knowledge and technology in palliative care， the traditional cramming education models are no longer able to meet the actual needs. Therefore， there is an urgent need to innovate palliative care education strategies. By analyzing the current problems in the general education of palliative care in China， this paper proposed thoughts and suggestions for general and innovative education of palliative care in several aspects， such as establishing general and innovative education systems and evaluation systems of palliative care， diversifying educational contents and methods， strengthening medical staffs training， promoting diversified student groups， and strengthening the popularization of palliative care knowledge among the public.

BACKGROUND:Plastic as a durable,inexpensive,easy to manufacture organic synthetic polymer materials are widely used.At the same time,plastic resistance to high temperatures,acid and alkali resistance,corrosion-resistant properties make it difficult to degrade in nature,and ultimately forming a huge number of microplastic pollution threatening human health. OBJECTIVE:To investigate the effects of microplastic exposure on growth and development and hepatic lipid metabolism in mice. METHODS:Twenty C57BL/6J male mice were adaptively fed for one week,and then randomly divided into normal and microplastic groups(n=10 per group).Mice in the normal group were given a normal diet and water,for 4 weeks.Mice in the microplastic group were given a normal diet and free drinking of microplastic(polystyrene)water with a concentration of 1 000 μg/L,for 4 weeks.At 2 and 4 weeks of drinking,body mass and grip strength,blood lipids and liver and kidney function,ultrasonic morphology and pathological morphology of liver and lipid deposition were detected. RESULTS AND CONCLUSION:(1)With the extension of time,the body mass of mice in the two groups gradually increased,and the body mass of mice in the microplastic group was greater than that in the normal group after 2,4 weeks of drinking water(P<0.05).With the extension of time,the grip strength of mice in the normal group gradually increased,and the grip strength of mice in the microplastic group first decreased and then increased,and the grip strength of mice in the microplastic group was lower than that in the normal group after drinking water for 4 weeks(P<0.05).(2)Liver ultrasound examination showed that compared with the normal group,the ultrasonic echo signal of the liver in the microplastic group was enhanced after 2 and 4 weeks of drinking water.(3)Hematoxylin-eosin staining showed that the morphology of liver cells in the microplastic group did not change significantly after 2 and 4 weeks of drinking water,but inflammatory cell infiltration could be seen.Oil red O staining showed that obvious lipid deposition was observed in the liver of microplastic group after 2 and 4 weeks of drinking water.(4)Compared with the normal group,the levels of serum high density lipoprotein cholesterol,triacylglycerol,and aspartate aminotransferase in the microplastic group were decreased after 2 weeks of drinking water(P<0.05),and the serum triacylglycerol concentration was decreased after 4 weeks of drinking water(P<0.05).(5)These findings confirm that microplastics may cause weight gain,loss of physical strength,and abnormal hepatic lipid metabolism in mice.