Objective To explore the mechanism of modified maimendong decoction (MMD) in inhibiting lung cancer metastasis from the perspective of immune regulation. Methods CTC-TJH-01 and LLC cells were intervened with different concentrations of modified maimendong decoction. The cell proliferation was detected with a CCK-8 kit, apoptosis was detected with an Annexin V-FITC/PI kit, and cell migration was detected through Transwell assays. A lung metastasis model was established through the tail vein injection of LLC cells into C57BL/6 mice, and body weight change and lung tumor metastasis in the mice were evaluated after continuous gavage intervention with MMD. HE staining, immunohistochemistry, and immunofluorescence were employed to observe the histomorphology, Ki-67 protein level, and NK and T cell levels of metastatic lesions. The levels of NK and T cells in the peripheral blood of mice were detected throughflow cytometry. Results MMD had no significant inhibitory effect on the proliferation, apoptosis, and migration of CTC-TJH-01 and LLC cells in vitro. In mice, MMD could significantly inhibit the lung metastasis of LLC cells, increase the proportion of NK and CD8⁺ T cells in peripheral blood and tumor microenvironment (P<0.05), and reduce the expression of Ki-67 protein in metastatic tumor tissues (P<0.05). Conclusion MMD may inhibit the growth of metastatic tumors by upregulating the expression levels of NK and CD8⁺ T cells in peripheral blood to promote the elimination of circulating tumor cells, and regulating the infiltration of NK and CD8⁺ T cells in the immune microenvironment of metastatic tumors, then play an antimetastatic role in lung cancer.

Palliative care is a way to help end-of-life populations improve their quality of life， and its development in practice cannot be separated from the level of education in palliative care. At present， some medical schools in palliative care education compared with western developed countries have problems such as imperfect construction of hospice curriculum system， lack of medical students’ hospice knowledge； insufficient interdisciplinary teaching faculty， weak palliative care awareness of medical students； single teaching evaluation mode； weak palliative care practice teaching links. To this end， it is necessary to improve the palliative care curriculum system， explore rich and diverse teaching methods； strengthen interdisciplinary teaching and faculty development， enhancing the awareness of palliative care among medical students；establish a scientific and effective evaluation method， carry out multi-dimensional dynamic assessment； expand the palliative care practice teaching base， and accurately improve the practical skills of medical students in palliative care， and other countermeasures to improve the level of palliative care education， and to help the strategy of Healthy China.

ObjectiveTo optimize the processing technology of honey bran-fried Rosae Laevigatae Fructus（h-RLF）， formulate relevant quality standards， and explore its improving effect and mechanism on mice with ulcerative colitis（UC） induced by dextran sodium sulfate（DSS）. MethodsTaking the content of polysaccharides and water-soluble extract as the indexes， L₉（3⁴） orthogonal test was used to optimize parameters of the amount of honey bran， frying time and frying temperature. The quality of 15 batches of h-RLF decoction pieces was evaluated according to the optimized process， and the inspection limit standard was preliminarily drawn up. Eighty SPF male Kunming mice were randomly divided into 8 groups， including the blank group， model group， mesalazine group（0.13 g·kg^-1）， RLF group（3.77 g·kg^-1）， bran-fried RLF group（3.77 g·kg^-1）， h-RLF low， medium and high dose groups（1.89， 3.77， 7.54 g·kg^-1）， with 10 mice in each group. The mice in the blank group were free to drink pure water， and the other groups were free to drink 3% DSS solution for 7 days to prepare UC mouse model. Each treatment group was given corresponding drugs by intragastric administration， and the blank and model groups were given equal volume of normal saline. The body weight of mice was recorded daily and the disease activity index（DAI） was calculated. After the administration， the colon tissues of mice were collected to observe the pathological changes by hematoxylin-eosin（HE） staining. The levels of tumor necrosis factor（TNF）-α， interleukin（IL）-1β， IL-6 and IL-10 in the colon of mice were detected by enzyme-linked immunosorbent assay（ELISA）. Western blot was used to detect the expression levels of phosphorylation nuclear transcription factor-κB p65（p-NF-κB p65）， Toll-like receptor 4（TLR4）， p-p38 mitogen-activated protein kinase（p-p38 MAPK）， p-extracellular signal-regulated kinase（p-ERK） and p-c-Jun N-terminal kinase（p-JNK） proteins in colon tissues. ResultsThe optimum processing technology of h-RLF was 20 g honey bran per 100 g RLF， and stir-frying at 200 ℃ for 8 min. The limit standard under the examination of h-RLF was preliminarily formulated as follows：the polysaccharide content should not be less than 25% based on anhydrous glucose（C₆H₁₂O₆）， the content of water-soluble extract should not be less than 38%， the moisture content should not be more than 12.0%， the total ash content should not be more than 5.0%， and the acid-insoluble ash content should not be more than 1.0%. The cluster heat map analysis showed that the quality of RLF from Huanggang， Hubei province was better. Animal experiments showed that compared with the blank group， the DAI score of the model group was significantly increased， the levels of TNF-α， IL-1β and IL-6 in the colon tissue were significantly increased， the IL-10 level was significantly decreased， the colonic mucosa was seriously damaged， accompanied by a large number of inflammatory cell infiltration， tissue congestion and a significant reduction in glands， and the expression levels of p-NF-κB p65， TLR4， p-p38 MAPK， p-ERK and p-JNK proteins were significantly increased（P<0.01）. Compared with the model group， each administration group could alleviate the symptoms of colonic ulcer， the structure of colonic crypt was basically intact， and the glands were arranged in an orderly manner. Among them， the high-dose group of h-RLF had a better effect， which could significantly reduce the DAI score and the levels of TNF-α， IL-1β and IL-6 in colon tissue（P<0.01）， and significantly increase the level of IL-10（P<0.01）， alleviate the colonic mucosal injury， and effectively inhibit the expression levels of p-NF-κB p65， TLR4， p-p38 MAPK， p-ERK and p-JNK proteins（P<0.01）. ConclusionThe key parameters of the processing technology of h-RLF are determined， and the optimized technology is stable and feasible. The established quality standard is simple and reliable， and can be used for the quality control. h-RLF can effectively alleviate DSS-induced UC， and its mechanism may be related to inhibiting the activation of NF-κB/TLR4/MAPK pathway.

Objective: To explore the efficacy and surgical techniques of ultrasound-assisted transurethral flexible ureteroscopic holmium laser incision and internal drainage in the treatment of special renal cystic diseases，so as to provide reference for the diagnosis and treatment of such diseases. Methods: The clinical data of 48 patients with special renal cystic diseases treated during Jan.2019 and May 2023 were retrospectively analyzed.The diagnosis was made by computed tomography urography (CTU) and three dimensional urinary tract reconstruction before operation.All patients received the abovementioned surgery in semisupine lithotomy position.The general information，clinical data，and incidence of complications were analyzed. Results: There were 27 males and 21 females，with an average age of (48.0±7.5) years，including 22 cases of parapelvic cysts，6 cases of endogenic simple renal cysts with an average diameter of (5.0±1.0) cm，and 20 cases of renal calyceal diverticulum with stones，with an average diameter of (2.5±1.3) cm for the diverticulum and an average diameter of (1.5±1.0) cm for the stones，which were located in the upper or middle calyces.In 7 cases，ureteroscopic localization was difficult，and the surgery was completed with percutaneous renal puncture needle assisted localization.Ureteral stenosis was detected in 2 cases during surgery，and surgery was performed 4 weeks after double J tubes were placed.The remaining operations were successfully completed.The average operation time was (42.0±14.5) minutes，and average hospital stay was (2.0±0.5) days.During the follow-up of (12.0±8.5) months，lumbar pain improved in 27 cases (100%)，renal cysts disappeared in 23 cases (82.1%,23/28)，cysts significantly reduced by ≥50% in 4 cases (14.3%,4/28)，slightly reduced by <50% in 1 case (3.6%,1/28)，and the renal calyx diverticulum disappeared in 20 cases (100%).Gross hematuria and lower back pain occurred in 2 cases，and no other complications developed. Conclusion: Ultrasound-guided transurethral flexible ureteroscopic holmium laser incision and internal drainage is a safe and effective treatment for special benign renal cystic diseases.When ultrasound-guided flexible ureteroscope localization is difficult to perform，percutaneous renal puncture needle may be applied.

Objective: To investigate the regional differences in the incidence of urothelial carcinoma among kidney transplant recipients between northern and southern China，so as to provide reference for early diagnosis of this disease. Methods: A comprehensive search was conducted across multiple databases，including CNKI，Wanfang，CBM，and PubMed，using the keywords “kidney transplantation” and “tumor” to collect clinical data from qualified kidney transplant centers.The latest and most complete literature data published by 17 transplant centers in northern China and 14 in southern China were included.Statistical analyses were performed to compare the incidence of post-transplant urothelial carcinoma and non-urothelial malignancies. Results: A total of 37 475 kidney transplant recipients were included，among whom 837 (2.23%) developed post-transplant malignancies，including urothelial carcinoma (366/837，43.73%)，non-urothelial carcinoma (444/837，53.05%)，and malignancies with unspecified pathology (27/837，3.23%).The incidence of malignancies was significantly higher in northern China than in southern China [(2.82±1.39)% vs. (1.67±0.83)%，P=0.011]，with a particularly pronounced difference in the incidence of urothelial carcinoma [(1.68±1.12)% vs. (0.32±0.32)%，P<0.001].No significant difference was observed in the incidence of non-urothelial carcinoma between the two regions [(1.11±0.56)% vs. (1.35±0.65)%，P=0.279].Additionally，female transplant recipients exhibited a higher incidence of malignancies than males in both regions (southern China：2.38% vs. 1.80%; northern China：8.93% vs. 2.52%). Conclusion: The incidence of urothelial carcinoma following kidney transplantation is significantly higher in northern China than in southern China，underscoring the importance of implementing regular tumor screening for kidney transplant recipients，particularly for female patients in northern China，to facilitate early diagnosis and timely intervention.

Objective To understand the application effect of early screening scale and behavioral intervention effect in children with autism spectrum disorder (ASD). Methods A total of 348 children with suspected ASD were selected and evaluated using the Modified Checklist for Autism in Toddlers (M-CHAT) and Autism Behavior Checklist (ABC). The evaluation results were compared with those from the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). Children enrolled were given Early start Denver model (ESDM) intervention. The evaluation results of Gesell Developmental Scale and Autism Treatment Evaluation Checklist (ATEC) scores were compared before and after intervention. Results The sensitivity, specificity, accuracy and Kappa value of M-CHAT for evaluating ASD in children aged 1-3 years were 89.53%, 90.70%, 89.92% and 0.78. The corresponding values of ABC were 78.49%, 81.40%, 79.46% and 0.56. The sensitivity, specificity, accuracy and Kappa value of M-CHAT for evaluating children aged >3-6 years were 87.30%, 77.78%, 84.44% and 0.64. The corresponding values of ABC were 85.71%, 77.78%, 83.33% and 0.62. The sensitivity and accuracy of M-CHAT were higher than ABC for evaluating ASD in children aged 1-3 years (P<0.05). There were no significant differences in sensitivity, specificity and accuracy between M-CHAT and ABC for evaluating ASD in children aged 3-6 years (P>0.05). After intervention, development quotients (DQ) of personal-social aspects, adaptability, language, gross motor, and fine motor of children with ASD were higher than those before intervention (P<0.05). ATEC scores for language, behavior, sensation, and social contact of children with ASD were lower than those before intervention (P<0.05). Conclusion M-CHAT and ABC both can be used for early screening of ASD in children, especially M-CHAT. Early behavioral intervention can effectively improve the condition and developmental level of children with ASD.

ObjectiveTo explore the effects of Kaixuan Jiedu core prescription （KXJD） on sphingolipid metabolism in the mouse model of imiquimod-induced psoriasis-like skin lesions. MethodsThirty-seven male C57BL/6J mice were randomly assigned into five groups： healthy control （n=11）， model （n=11）， methotrexate （MTX， n=5）， low-dose （15.21 g·kg^-1） KXJD （n=5）， and high-dose （30.42 g·kg^-1） KXJD （n=5）. Psoriasis-like skin lesions were induced in mice with 62.5 mg 5% imiquimod cream applied on the back. The KXJD groups and MTX group were treated with 0.2 mL corresponding decoction and MTX， respectively， by gavage daily， while the other groups were given an equal volume of normal saline by the same way. After 5 days of treatment， back skin lesions were collected. Firstly， healthy control and model mice were selected for tandem mass tag （TMT） quantitative proteomics （control vs model=3 vs 3） and targeted lipid metabolomics （control vs model=11 vs 11）. Then， the binding degree between core components and target proteins was predicted via network pharmacology and molecular docking. Finally， an animal experiment was performed to decipher the specific regulation mechanism of KXJD on sphingolipid metabolism. Immunohistochemistry was employed to determine the expression level of sphingosine-1-phosphate （S1P）， and Western blot was employed to determine the expression levels of sphingosine kinase 2 （SPHK2） and monocyte chemotactic protein-1 （MCP-1）. ResultsTMT proteomics and targeted lipid metabolomics suggested that sphingolipid metabolism was active in the psoriatic skin， and key proteases ［serine palmitoyltransferase， long chain base subunit 2 （SPTLC2）， SPHK2， delta（4）-desaturase sphingolipid 1 （Degs1）， and ceramide synthase 4 （CerS4）］ and 8 sphingolipid metabolites （including ceramides， sphingol， sphingomyelin， and glycosphingolipid） expressed abnormally （P<0.05） compared with those in the healthy skin. The molecular docking results indicated that the binding energy between the active components （quercetin， kaempferol， and luteolin） in KXJD and key proteins involved in sphingolipid metabolism was less than-8 kal·mol^-1. Further experimental verification showed elevated expression levels of SPHK2， S1P， and MCP-1 in psoriatic skin compared with healthy skin （P<0.05）， and KXJD down-regulated the expression levels of SPHK2， S1P， and MCP-1 compared with the model group （P<0.05）. ConclusionThis study indicates that there is an imbalance in sphingolipid metabolism in psoriatic skin lesions. KXJD may reduce psoriasis-like lesions in mice by regulating sphingolipid metabolism via the SPHK2/S1P/MCP-1 pathway.

ObjectiveTo investigate the efficacy and safety of Kaixuan Jiedu compatibility and the decomposed prescriptions in the treatment of psoriasis. MethodsThirty Balb/c mice were randomly grouped as follows （n=6）： normal， model， Kaixuan Jiedu （KXJD， 15.21 g·kg^-1）， Kaixuan （KX， 3.08 g·kg^-1）， and Jiedu （JD， 12.13 g·kg^-1）. Except the normal group， the rest groups were modeled for psoriasis-like skin lesions by topical application of imiquimod， and samples were collected after 7 days of continuous intervention. Mice were photographed at the lesion site during modeling and before sampling and the psoriasis area and severity index （PASI） was calculated. Hematoxylin-eosin （HE） staining was used to observe pathological changes in the lesions and measure the epidermal thickness. Mice were photographed and observed for the tortuous dilation of dermal capillaries. The expression of vascular endothelial growth factor （VEGF）， platelet-endothelial cell adhesion molecule （CD31）， proliferating cell nuclear antigen （Ki67）， and cytokeratin 10 （CK10） in the epidermal tissue was detected by immunohistochemistry. Immunofluorescence assay was employed to determine the expression of Claudin-1 and Occludin. Real-time PCR was employed to determine the mRNA levels of interleukin-17A （IL-17A） and interleukin-23 （IL-23）. The spleen and thymus were photographed and weighed， and the spleen and thymus indices were calculated. The safety of the treatment was assessed by automatic biochemistry testing of the serum， liver， and kidney functions and by HE staining of the liver， kidney and spleen. ResultsCompared with that of the normal group， the skin of the model group showed erythema， infiltration， and typical psoriasis-like changes， tortuous dilation of dermal capillaries， hyperkeratosis in epidermal cells， acanthosis， massive lymphocytic infiltration in the dermis， impaired barrier function， increased expression of VEGF， CD31， Ki67， and CK10 （P<0.01）， reduced expression of Claudin-1 and Occludin （P<0.01） in the epidermis， and up-regulated mRNA levels of IL-17A and IL-23 （P<0.01）. In addition， the mice in the model group showed spleen enlargement， thymus atrophy， increased spleen index， and decreased thymus index （P<0.01）. Compared with the model group， KXJD and JD reduced psoriasis-like skin lesions， inhibited the tortuous dilation of dermal capillaries， reduced the expression of VEGF， CD31， Ki67， and CK10 （P<0.01）， increased the expression of claudin-1 （P<0.01）， and down-regulated the mRNA levels of inflammatory factors （P<0.01）. Moreover， the KXJD group outperformed the JD group. The JD group showed no significant difference from the model group regarding the spleen index， thymus index， and Occludin expression. The psoriasis indicators in the KX group were not significantly different from those in the model group. ConclusionKXJD and JD can reduce the symptoms of local skin lesions of psoriasis， which is manifested as different inhibition degrees of the proliferation and differentiation of keratin-forming cells， tortuous dilation of dermal capillaries， and inflammatory reactions， as well as the protection of the skin barrier. Moreover， KXJD outperformed JD. KX alone did not significantly reduce psoriasis lesions in mice. KXJD and the decomposed prescriptions are safe and effective， causing no obvious liver and kidney injuries.

ObjectiveTo explore the effects of Kaixuan Jiedu core prescription （KXJD） on sphingolipid metabolism in the mouse model of imiquimod-induced psoriasis-like skin lesions. MethodsThirty-seven male C57BL/6J mice were randomly assigned into five groups： healthy control （n=11）， model （n=11）， methotrexate （MTX， n=5）， low-dose （15.21 g·kg^-1） KXJD （n=5）， and high-dose （30.42 g·kg^-1） KXJD （n=5）. Psoriasis-like skin lesions were induced in mice with 62.5 mg 5% imiquimod cream applied on the back. The KXJD groups and MTX group were treated with 0.2 mL corresponding decoction and MTX， respectively， by gavage daily， while the other groups were given an equal volume of normal saline by the same way. After 5 days of treatment， back skin lesions were collected. Firstly， healthy control and model mice were selected for tandem mass tag （TMT） quantitative proteomics （control vs model=3 vs 3） and targeted lipid metabolomics （control vs model=11 vs 11）. Then， the binding degree between core components and target proteins was predicted via network pharmacology and molecular docking. Finally， an animal experiment was performed to decipher the specific regulation mechanism of KXJD on sphingolipid metabolism. Immunohistochemistry was employed to determine the expression level of sphingosine-1-phosphate （S1P）， and Western blot was employed to determine the expression levels of sphingosine kinase 2 （SPHK2） and monocyte chemotactic protein-1 （MCP-1）. ResultsTMT proteomics and targeted lipid metabolomics suggested that sphingolipid metabolism was active in the psoriatic skin， and key proteases ［serine palmitoyltransferase， long chain base subunit 2 （SPTLC2）， SPHK2， delta（4）-desaturase sphingolipid 1 （Degs1）， and ceramide synthase 4 （CerS4）］ and 8 sphingolipid metabolites （including ceramides， sphingol， sphingomyelin， and glycosphingolipid） expressed abnormally （P<0.05） compared with those in the healthy skin. The molecular docking results indicated that the binding energy between the active components （quercetin， kaempferol， and luteolin） in KXJD and key proteins involved in sphingolipid metabolism was less than-8 kal·mol^-1. Further experimental verification showed elevated expression levels of SPHK2， S1P， and MCP-1 in psoriatic skin compared with healthy skin （P<0.05）， and KXJD down-regulated the expression levels of SPHK2， S1P， and MCP-1 compared with the model group （P<0.05）. ConclusionThis study indicates that there is an imbalance in sphingolipid metabolism in psoriatic skin lesions. KXJD may reduce psoriasis-like lesions in mice by regulating sphingolipid metabolism via the SPHK2/S1P/MCP-1 pathway.

ObjectiveTo investigate the efficacy and safety of Kaixuan Jiedu compatibility and the decomposed prescriptions in the treatment of psoriasis. MethodsThirty Balb/c mice were randomly grouped as follows （n=6）： normal， model， Kaixuan Jiedu （KXJD， 15.21 g·kg^-1）， Kaixuan （KX， 3.08 g·kg^-1）， and Jiedu （JD， 12.13 g·kg^-1）. Except the normal group， the rest groups were modeled for psoriasis-like skin lesions by topical application of imiquimod， and samples were collected after 7 days of continuous intervention. Mice were photographed at the lesion site during modeling and before sampling and the psoriasis area and severity index （PASI） was calculated. Hematoxylin-eosin （HE） staining was used to observe pathological changes in the lesions and measure the epidermal thickness. Mice were photographed and observed for the tortuous dilation of dermal capillaries. The expression of vascular endothelial growth factor （VEGF）， platelet-endothelial cell adhesion molecule （CD31）， proliferating cell nuclear antigen （Ki67）， and cytokeratin 10 （CK10） in the epidermal tissue was detected by immunohistochemistry. Immunofluorescence assay was employed to determine the expression of Claudin-1 and Occludin. Real-time PCR was employed to determine the mRNA levels of interleukin-17A （IL-17A） and interleukin-23 （IL-23）. The spleen and thymus were photographed and weighed， and the spleen and thymus indices were calculated. The safety of the treatment was assessed by automatic biochemistry testing of the serum， liver， and kidney functions and by HE staining of the liver， kidney and spleen. ResultsCompared with that of the normal group， the skin of the model group showed erythema， infiltration， and typical psoriasis-like changes， tortuous dilation of dermal capillaries， hyperkeratosis in epidermal cells， acanthosis， massive lymphocytic infiltration in the dermis， impaired barrier function， increased expression of VEGF， CD31， Ki67， and CK10 （P<0.01）， reduced expression of Claudin-1 and Occludin （P<0.01） in the epidermis， and up-regulated mRNA levels of IL-17A and IL-23 （P<0.01）. In addition， the mice in the model group showed spleen enlargement， thymus atrophy， increased spleen index， and decreased thymus index （P<0.01）. Compared with the model group， KXJD and JD reduced psoriasis-like skin lesions， inhibited the tortuous dilation of dermal capillaries， reduced the expression of VEGF， CD31， Ki67， and CK10 （P<0.01）， increased the expression of claudin-1 （P<0.01）， and down-regulated the mRNA levels of inflammatory factors （P<0.01）. Moreover， the KXJD group outperformed the JD group. The JD group showed no significant difference from the model group regarding the spleen index， thymus index， and Occludin expression. The psoriasis indicators in the KX group were not significantly different from those in the model group. ConclusionKXJD and JD can reduce the symptoms of local skin lesions of psoriasis， which is manifested as different inhibition degrees of the proliferation and differentiation of keratin-forming cells， tortuous dilation of dermal capillaries， and inflammatory reactions， as well as the protection of the skin barrier. Moreover， KXJD outperformed JD. KX alone did not significantly reduce psoriasis lesions in mice. KXJD and the decomposed prescriptions are safe and effective， causing no obvious liver and kidney injuries.