ObjectiveTo explore the mechanism of Shenmai injection in improving cisplatin resistance in non-small cell lung cancer （NSCLC） based on the endoplasmic reticulum stress through protein kinase R-like endoplasmic reticulum kinase （PERK）/activated transcription factor 4 （ATF4）/C/EBP homologous protein （CHOP） signaling pathway. MethodsBALB/c nude mice bearing cisplatin-resistant human lung cancer cell line （A549/cisplatin） were randomly divided into four groups： Blank control group （0.9% sodium chloride）， cisplatin group （5 µg·g^-1cisplatin）， Shenmai injection group （5.2 mg·g^-1 Shenmai injection）， and combination therapy group （5.2 mg·g^-1 Shenmai injection +5 µg·g^-1cisplatin）. The drug intervention lasted for 4 weeks， and the changes in body weight and tumor volume were monitored. Hematoxylin-eosin （HE） staining was performed to observe tumor tissue pathology. Transmission electron microscopy （TEM） was used to assess the morphology of the endoplasmic reticulum. Immunohistochemical assay was conducted to measure the positive expressions of PERK， ATF4， and CHOP in tumor tissues. Western blot quantified the protein expression of immunoglobulin heavy chain binding protein （BIP）， PERK， phosphorylated PERK （p-PERK）， eukaryotic translation initiation factor 2α （eIF2α）， phosphorylated eIF2α （p-eIF2α）， ATF4， CHOP， B-cell lymphoma -2 （Bcl-2）， and Bcl-2 Associated X protein （Bax）. A549/cis cells were divided into blank group： Blank control group （normal culture medium）， cisplatin group （23.3 µmol·L^-1 cisplatin）， Shenmai Injection group （20 g·L^-1 Shenmai injection）， and combination therapy group （20 g·L^-1 Shenmai injection+23.3 µmol·L^-1 cisplatin）. Cell counting kit-8 （CCK-8） method was used to detect cell viability， TEM was used to observe the morphology of endoplasmic reticulum， and Western blot was used to detect endoplasmic reticulum stress and apoptosis-related proteins. ResultsCompared with the cisplatin group， the combination therapy group showed increased body weight （P<0.05）， decreased tumor volume （P<0.05）， and expanded endoplasmic reticulum in tumor cells. The positive expressions of PERK， ATF4， and CHOP increased （P<0.05）. Western blot revealed elevated protein expression levels of BIP， p-PERK/PERK， p-eIF2α/eIF2α， ATF4， CHOP， and Bax （P<0.05）， while Bcl-2 expression decreased （P<0.05）. As shown in the in vitro experiment， compared with the cisplatin group， the combination therapy group exhibited a reduced cell survival rate （P<0.05）. TEM revealed increased endoplasmic reticulum dilation and vesicular degeneration. Western blotting showed increased protein levels of BIP， p-PERK/PERK， p-eIF2α/eIF2α， ATF4， CHOP and Bax （P<0.05）， with decreased Bcl-2 expression （P<0.05）. ConclusionShenmai injection combined with cisplatin has a synergistic antitumor effect in NSCLC， which may be attributed to the activation of endoplasmic reticulum stress response mediated by the PERK/eIF2α/ATF4/CHOP signaling pathway and the induction of tumor cell apoptosis.

Objective To investigate the epidemiological characteristics of patients with postcraniotomy meningitis(PM)caused by Gram-negative bacteria(GNB),and to evaluate the related risk factors for mortal-ity.Methods A total of 202 PM patients in Beijing Tiantan Hospital,Capital Medical University from May 2019 to December 2021 were retrospectively analyzed,including 54 cases in the death group and 148 cases in the survival group.The distribution of microorganisms in the two groups was analyzed,and Cox proportional hazards regression model was established to evaluate the risk factors of death.Results Among the 202 pa-tients with PM caused by GNB,with a mortality rate of 26.7%,Klebsiella pneumoniae(24.8%),Acinetobact-er baumannii(21.8%)and Escherichia coli(8.4%)were the top three isolated pathogens.The proportions of GNB distribution in the survival group and the death group were similar,but the bacteria distribution in the death group was more concentrate.Cox proportional hazards regression model results showed that hyperten-sion(HR=2.384,95%CI 1.229-4.626,P=0.010)and admission to ICU(HR=3.695,95%CI 1.412-9.670,P=0.008)were independent risk factors for death in patients with PM caused by GNB.Conclusion The mortality of PM caused by GNB is high.Hypertension and admission to ICU are independent risk factors for death of patients,and attention should be paid to prevention and treatment in clinical practice.

Objective:To construct a thyroid nodule segmentation model using ultrasound dynamic images and explore its potential for assisting in the screening of thyroid nodules.Methods:A total of 126 patients with thyroid nodules（comprising 150 nodules）who were diagnosed and treated at Xuzhou Cancer Hospital from April 2024 to December 2024 were prospectively enrolled. Two-dimensional ultrasound was performed to capture short-axis and long-axis video images of thyroid nodules，forming a dynamic ultrasound image dataset. The dataset was divided into training，validation，and test sets in a ratio of 6∶1∶3. After the training loss curve converged，the model that performed well on the validation set was selected for testing. Three-fold cross-validation was employed for training and testing. All 300 ultrasound videos were divided into three subsets. In each experiment，two subsets were used as the training set，and one subset was used as the test set to evaluate the model's generalization ability. A collaborative spatiotemporal diffusion model was established based on the dynamic trends and tissue texture details of thyroid nodules. Six widely used segmentation metrics were employed to evaluate the model's application capabilities.Results:The study included 126 patients with 150 thyroid nodules，300 dynamic ultrasound images，and video lengths of 3-4 seconds per nodule，resulting in 12 312 segmented images. The size of the thyroid nodules was（10.7 ± 10.6）mm（transverse diameter）×（8.4 ± 6.3）mm（anteroposterior diameter）. Among the nodules，62（41.3%）had clear boundaries，while 88（58.7%）had indistinct boundaries；61（40.7%）exhibited regular shapes，while 89（59.3%）were irregular；66（44.0%）had a taller-than-wide aspect ratio；and 70（46.7%）showed microcalcifications. The collaborative diffusion model based on dynamic ultrasound image segmentation achieved the following scores：a Jaccard score of（69.22 ± 0.03）%，a Dice score of（79.16 ± 0.18）%，a Precision score of（86.70 ± 0.17）%，a Recall score of（77.82 ± 0.04）%，an Sα score of（85.26 ± 0.01）%，and an Eθmn score of（90.58 ± 0.17）%. Compared to other models，this model demonstrated significant improvements across all evaluation metrics，achieving the highest values in each metric with increments of over 8% and 1%，respectively. Conclusions:The collaborative diffusion model with a dynamic controller，constructed based on dynamic ultrasound images of thyroid nodules，demonstrates excellent performance in ultrasound image segmentation. It improves the accuracy of thyroid nodule screening，thereby providing a valuable auxiliary diagnostic tool for clinical practice.

Objective To explore the mechanism of Lidan Huatan Huoxue Decoction improving cognitive impairment caused by obesity based on metabolomics.Methods Twenty-four 6-week-old male SD rats were randomly divided into a normal group fed with regular diet(Con,n=6)and a modeling group fed with high-fat and high-sugar diet(n=18).Rats with a body mass that is 20%higher than the standard body mass of their age-matched peers fed with ordinary diet were considered to have a successful obese model established.The presence of cognitive impairment was assessed by Morris water maze and Barnes maze tests.After the obese-induced cognitive impairment(OICI)model was established,the modeling rats were randomly divided into a model group(Model,n=6),a donepezil group(Donepezil,n=6),and a Lidan Huatan Huoxue Decoction group(LHH,n=6).Drugs were administered to the donepezil and LHH groups by gastric intubation.The donepezil group was administered with a dose of 0.45 mg·(kg·d)-1,while the LHH group was administered with a dose of 25 g·(kg·d)-1.The normal and model groups were given the same volume of normal saline by gastric intubation for 8 weeks.Before the rats were sacrificed,water maze and Barnes maze experiments were conducted to assess cognitive function.After sacrifice,specimens were collected for biochemical and histological examination of liver tissue and brain tissue.Non-targeted metabolomic analysis using liquid chromatography-mass spectrometry(LC-MS)was performed on feces,serum,and brain tissue to analyze changes in differential metabolites in rats.Results Compared with the model group,the intervention of Donepezil and LHH effectively improved the learning and memory ability of OICI rats(P<0.05 or P<0.01),inhibited the overactivation of hippocampal microglia,and increased the number of hippocampal synaptic proteins.LHH improved metabolic-related indicators in OICI rats(P<0.05 or P<0.01).Metabolomic analysis showed significant differences in metabolites in feces,serum,and brain tissue between the model group and the normal group.The main affected pathways in fecal metabolites included steroid biosynthesis,caffeine metabolism,lysosome,vitamin B6 metabolism,phenylalanine,tyrosine,and tryptophan biosynthesis.The main affected pathways in serum metabolites included central carbon metabolism in cancer,pentose phosphate pathway,mineral absorption,protein digestion and absorption,and aminoacyl-tRNA biosynthesis.The main affected pathways in brain tissue metabolites included glycerophospholipid metabolism,β-alanine metabolism,propionic acid metabolism,niacin and nicotinamide metabolism,and caffeine metabolism.After LHH intervention,fecal metabolites showed the most significant changes,mainly involving vitamin B6 metabolism,vitamin digestion and absorption,histidine metabolism,fructose and mannose metabolism,and steroid biosynthesis.Conclusion LHH can improve cognitive impairment in obese rats mainly by regulating fecal metabolites.The main pathways involved include vitamin B6 metabolism,vitamin digestion and absorption,histidine metabolism,fructose and mannose metabolism,and steroid biosynthesis.Among them,vitamin B6 metabolism and vitamin digestion and absorption may be the most important pathways.

Objective To explore the mechanism of Lidan Huatan Huoxue Decoction improving cognitive impairment caused by obesity based on metabolomics.Methods Twenty-four 6-week-old male SD rats were randomly divided into a normal group fed with regular diet(Con,n=6)and a modeling group fed with high-fat and high-sugar diet(n=18).Rats with a body mass that is 20%higher than the standard body mass of their age-matched peers fed with ordinary diet were considered to have a successful obese model established.The presence of cognitive impairment was assessed by Morris water maze and Barnes maze tests.After the obese-induced cognitive impairment(OICI)model was established,the modeling rats were randomly divided into a model group(Model,n=6),a donepezil group(Donepezil,n=6),and a Lidan Huatan Huoxue Decoction group(LHH,n=6).Drugs were administered to the donepezil and LHH groups by gastric intubation.The donepezil group was administered with a dose of 0.45 mg·(kg·d)-1,while the LHH group was administered with a dose of 25 g·(kg·d)-1.The normal and model groups were given the same volume of normal saline by gastric intubation for 8 weeks.Before the rats were sacrificed,water maze and Barnes maze experiments were conducted to assess cognitive function.After sacrifice,specimens were collected for biochemical and histological examination of liver tissue and brain tissue.Non-targeted metabolomic analysis using liquid chromatography-mass spectrometry(LC-MS)was performed on feces,serum,and brain tissue to analyze changes in differential metabolites in rats.Results Compared with the model group,the intervention of Donepezil and LHH effectively improved the learning and memory ability of OICI rats(P<0.05 or P<0.01),inhibited the overactivation of hippocampal microglia,and increased the number of hippocampal synaptic proteins.LHH improved metabolic-related indicators in OICI rats(P<0.05 or P<0.01).Metabolomic analysis showed significant differences in metabolites in feces,serum,and brain tissue between the model group and the normal group.The main affected pathways in fecal metabolites included steroid biosynthesis,caffeine metabolism,lysosome,vitamin B6 metabolism,phenylalanine,tyrosine,and tryptophan biosynthesis.The main affected pathways in serum metabolites included central carbon metabolism in cancer,pentose phosphate pathway,mineral absorption,protein digestion and absorption,and aminoacyl-tRNA biosynthesis.The main affected pathways in brain tissue metabolites included glycerophospholipid metabolism,β-alanine metabolism,propionic acid metabolism,niacin and nicotinamide metabolism,and caffeine metabolism.After LHH intervention,fecal metabolites showed the most significant changes,mainly involving vitamin B6 metabolism,vitamin digestion and absorption,histidine metabolism,fructose and mannose metabolism,and steroid biosynthesis.Conclusion LHH can improve cognitive impairment in obese rats mainly by regulating fecal metabolites.The main pathways involved include vitamin B6 metabolism,vitamin digestion and absorption,histidine metabolism,fructose and mannose metabolism,and steroid biosynthesis.Among them,vitamin B6 metabolism and vitamin digestion and absorption may be the most important pathways.

Objective:To construct a thyroid nodule segmentation model using ultrasound dynamic images and explore its potential for assisting in the screening of thyroid nodules.Methods:A total of 126 patients with thyroid nodules（comprising 150 nodules）who were diagnosed and treated at Xuzhou Cancer Hospital from April 2024 to December 2024 were prospectively enrolled. Two-dimensional ultrasound was performed to capture short-axis and long-axis video images of thyroid nodules，forming a dynamic ultrasound image dataset. The dataset was divided into training，validation，and test sets in a ratio of 6∶1∶3. After the training loss curve converged，the model that performed well on the validation set was selected for testing. Three-fold cross-validation was employed for training and testing. All 300 ultrasound videos were divided into three subsets. In each experiment，two subsets were used as the training set，and one subset was used as the test set to evaluate the model's generalization ability. A collaborative spatiotemporal diffusion model was established based on the dynamic trends and tissue texture details of thyroid nodules. Six widely used segmentation metrics were employed to evaluate the model's application capabilities.Results:The study included 126 patients with 150 thyroid nodules，300 dynamic ultrasound images，and video lengths of 3-4 seconds per nodule，resulting in 12 312 segmented images. The size of the thyroid nodules was（10.7 ± 10.6）mm（transverse diameter）×（8.4 ± 6.3）mm（anteroposterior diameter）. Among the nodules，62（41.3%）had clear boundaries，while 88（58.7%）had indistinct boundaries；61（40.7%）exhibited regular shapes，while 89（59.3%）were irregular；66（44.0%）had a taller-than-wide aspect ratio；and 70（46.7%）showed microcalcifications. The collaborative diffusion model based on dynamic ultrasound image segmentation achieved the following scores：a Jaccard score of（69.22 ± 0.03）%，a Dice score of（79.16 ± 0.18）%，a Precision score of（86.70 ± 0.17）%，a Recall score of（77.82 ± 0.04）%，an Sα score of（85.26 ± 0.01）%，and an Eθmn score of（90.58 ± 0.17）%. Compared to other models，this model demonstrated significant improvements across all evaluation metrics，achieving the highest values in each metric with increments of over 8% and 1%，respectively. Conclusions:The collaborative diffusion model with a dynamic controller，constructed based on dynamic ultrasound images of thyroid nodules，demonstrates excellent performance in ultrasound image segmentation. It improves the accuracy of thyroid nodule screening，thereby providing a valuable auxiliary diagnostic tool for clinical practice.

Objective Targeting the cell cycle and autophagy,Kangai injection(KAI)was investigated through PI3K/Akt/mTOR Signaling pathways improve the molecular mechanism of cisplatin resistance in human lung adenocarcinoma A549/DDP cells.Methods A549/DDP cells were randomly divided into control group,cisplatin group(20 μmol·L-1 cisplatin),low concentration KAI combined with cisplatin(15 mg·mL-1 KAI+20 μmol·L-1 cisplatin),medium concentration KAI combined with cisplatin(25 mg·mL-1 KAI+20 μmol·L-1 cisplatin)and high concentration KAI combined with cisplatin(50 mg·mL-1 KAI+20 μmol·L-1 cisplatin).The survival rate of cells was detected by CCK-8 method,the cell cycle distribution was detected by flow cytometry,the expression of p53 protein was detected by immunocytochemistry,and the expression levels of protein p53、autophagy-related protein LC3 and key molecules of autophagy pathway(mTOR,p-mTOR,Akt and p-Akt)were detected by Western blotting.Besides,the inhibitor of PI3K/Akt signaling pathway was used to further verify the molecular mechanism of KAI in reversing cisplatin in A549/DDP cells.Results Compared with the control group,cisplatin group and different concentrations of KAI combined with cisplatin groups effectively inhibited cell viability(P<0.05);compared with the cisplatin group,increased the cell proportion in S+G2/M phase(P<0.05),the mean integral absorbance of p53 protein(P<0.05),and the expression level of autophagy-related protein LC3Ⅱ(P<0.05),but decreased the expression levels of p-mTOR and p-Akt(both P<0.01).Moreover,LY294002,the inhibitor of PI3K/Akt signaling pathway,could effectively inhibit the up-regulation of LC3Ⅱ expression and cell death induced by KAI combined with cisplatin(both P<0.05).Conclusion KAI combined with cisplatin can induce cell cycle arrest and autophagic death by inhibiting PI3K/Akt/mTOR signaling pathway,and improve cisplatin resistance in NSCLC.

Objective:To systematically review the qualitative research on the care experience of caregivers of palliative care for minors, in order to provide a reference for formulating a care plan that is more in line with the needs of palliative care for minors and their families.Methods:The Cochrane Library, Australia Joanna Briggs Institute Evidence-based Health Care Center Library, Embase, PubMed and Web of Science, CINAHL, China National Knowledge Infrastructure, Wanfang Database, VIP Database and China Biology Medicine Disc were searched by computer for literature on qualitative research on care experience of underage hospice care caregivers from the establishment of the database to December 30, 2023.Results:A total of 11 articles were included and 70 research results were extracted, which were summarized into 7 new categories and formed 2 integrated results: professional caregivers and relative caregivers had multiple care burden, and need multiple care support; professional caregivers and relative caregivers can shoulder the care responsibility of children together, actively respond to the difficulties in care, gain personal care experience and growth.Conclusions:Hospice care for minors has its own characteristics, and caregivers have various care burdens and needs. Special attention should be paid to the emotional experience and care demands of caregivers, and targeted support and protection should be provided to promote the construction of hospice care team for minors in China and improve the level of hospice care for minors in China.

Objective Targeting the cell cycle and autophagy,Kangai injection(KAI)was investigated through PI3K/Akt/mTOR Signaling pathways improve the molecular mechanism of cisplatin resistance in human lung adenocarcinoma A549/DDP cells.Methods A549/DDP cells were randomly divided into control group,cisplatin group(20 μmol·L-1 cisplatin),low concentration KAI combined with cisplatin(15 mg·mL-1 KAI+20 μmol·L-1 cisplatin),medium concentration KAI combined with cisplatin(25 mg·mL-1 KAI+20 μmol·L-1 cisplatin)and high concentration KAI combined with cisplatin(50 mg·mL-1 KAI+20 μmol·L-1 cisplatin).The survival rate of cells was detected by CCK-8 method,the cell cycle distribution was detected by flow cytometry,the expression of p53 protein was detected by immunocytochemistry,and the expression levels of protein p53、autophagy-related protein LC3 and key molecules of autophagy pathway(mTOR,p-mTOR,Akt and p-Akt)were detected by Western blotting.Besides,the inhibitor of PI3K/Akt signaling pathway was used to further verify the molecular mechanism of KAI in reversing cisplatin in A549/DDP cells.Results Compared with the control group,cisplatin group and different concentrations of KAI combined with cisplatin groups effectively inhibited cell viability(P<0.05);compared with the cisplatin group,increased the cell proportion in S+G2/M phase(P<0.05),the mean integral absorbance of p53 protein(P<0.05),and the expression level of autophagy-related protein LC3Ⅱ(P<0.05),but decreased the expression levels of p-mTOR and p-Akt(both P<0.01).Moreover,LY294002,the inhibitor of PI3K/Akt signaling pathway,could effectively inhibit the up-regulation of LC3Ⅱ expression and cell death induced by KAI combined with cisplatin(both P<0.05).Conclusion KAI combined with cisplatin can induce cell cycle arrest and autophagic death by inhibiting PI3K/Akt/mTOR signaling pathway,and improve cisplatin resistance in NSCLC.