Objective To analyze the correlation between lesion volume,lesion mass,and maximum lesion diameter in the assessment of advanced hepatocarcinoma with lung metastasis,and to evaluate the application value of total volume response and total mass response of lung metastatic lesions in efficacy assessment.Methods A retrospective analysis was conducted on the CT imaging data of 20 patients clinically confirmed with hepatocarcinoma and lung metastases,followed by subsequent follow-up to monitor their survival outcomes.Volume measurement software was used to measure the volume of lesions before and after treatment.We recored lesion diameter,volume measurements and CT values,calculated the mass of the lesions.The correlation between lesion volume,mass and diameter was analyzed,as well as the correlation between the change rates of volume,mass and lesion diameter.Additionally,the total volume and total mass of all lesions were calculated.The correlation between the change rates of total volume/total mass and the change rate of pulmonary lesion diameter under the RECIST 1.1 criteria,as well as the correlation with changes in patients'tumor markers,were analyzed.Furthermore,the overall volume response and overall mass response of lesions were evaluated based on changes in total volume and total mass,and their consistencies with the RECIST 1.1 criteria for efficacy evaluation were analyzed.Finally,univariate Cox regression analysis was performed to explore the association between these variables and patient survival outcomes.Results There was strong correlation between lesion volume,mass and tumor diameter(r=0.771,0.775),between the rate of change in mass and the rate of change in lesion diameter(r=0.846),and between the rates of change in total volume/total mass and the rate of change in pulmonary lesion diameter under the RECIST 1.1 criteria(r=0.800,0.896).The correlation between the rates of change in total volume/total mass and patients'tumor markers was not statistically significant.There was moderate correlation between the rate of change in volume and the rate of change in lesion diameter(r=0.692).The evaluation results of total volume response and total mass response for pulmonary lesions in advanced hepatocarcinoma with lung metastasis were generally consistent with the RECIST 1.1 criteria(Kappa=0.486,0.426).Univariate Cox regression analysis revealed that total lesion volume(P=0.047)and total lesion mass(P=0.049)were independent prognostic factors for survival outcomes.Conclusion Lesion volume,mass,and diameter,as well as their respective change rates,were found to be interrelated.Furthermore,total lesion volume and total lesion mass were identified as independent prognostic factors for survival outcomes.The total volume response and total mass response are promising evaluation methods in evaluating the efficacy of lung metastasis of hepatocarcinoma,which are different from the RECIST 1.1 evaluation criteria.

Objective To analyze the correlation between lesion volume,lesion mass,and maximum lesion diameter in the assessment of advanced hepatocarcinoma with lung metastasis,and to evaluate the application value of total volume response and total mass response of lung metastatic lesions in efficacy assessment.Methods A retrospective analysis was conducted on the CT imaging data of 20 patients clinically confirmed with hepatocarcinoma and lung metastases,followed by subsequent follow-up to monitor their survival outcomes.Volume measurement software was used to measure the volume of lesions before and after treatment.We recored lesion diameter,volume measurements and CT values,calculated the mass of the lesions.The correlation between lesion volume,mass and diameter was analyzed,as well as the correlation between the change rates of volume,mass and lesion diameter.Additionally,the total volume and total mass of all lesions were calculated.The correlation between the change rates of total volume/total mass and the change rate of pulmonary lesion diameter under the RECIST 1.1 criteria,as well as the correlation with changes in patients'tumor markers,were analyzed.Furthermore,the overall volume response and overall mass response of lesions were evaluated based on changes in total volume and total mass,and their consistencies with the RECIST 1.1 criteria for efficacy evaluation were analyzed.Finally,univariate Cox regression analysis was performed to explore the association between these variables and patient survival outcomes.Results There was strong correlation between lesion volume,mass and tumor diameter(r=0.771,0.775),between the rate of change in mass and the rate of change in lesion diameter(r=0.846),and between the rates of change in total volume/total mass and the rate of change in pulmonary lesion diameter under the RECIST 1.1 criteria(r=0.800,0.896).The correlation between the rates of change in total volume/total mass and patients'tumor markers was not statistically significant.There was moderate correlation between the rate of change in volume and the rate of change in lesion diameter(r=0.692).The evaluation results of total volume response and total mass response for pulmonary lesions in advanced hepatocarcinoma with lung metastasis were generally consistent with the RECIST 1.1 criteria(Kappa=0.486,0.426).Univariate Cox regression analysis revealed that total lesion volume(P=0.047)and total lesion mass(P=0.049)were independent prognostic factors for survival outcomes.Conclusion Lesion volume,mass,and diameter,as well as their respective change rates,were found to be interrelated.Furthermore,total lesion volume and total lesion mass were identified as independent prognostic factors for survival outcomes.The total volume response and total mass response are promising evaluation methods in evaluating the efficacy of lung metastasis of hepatocarcinoma,which are different from the RECIST 1.1 evaluation criteria.

In the process of seeking new strategies to improve the efficacy of antidepressants,traditional Chinese medicine inter-vention has gradually revealed its unique prevention and treat-ment advantages.The dopamine reward system is closely in-volved in the pathological occurrence and development of depres-sion.Currently,research has mostly focused on the functional mechanism of a specific nucleus in the dopamine reward system,and there is less research focused on the functional mechanism of the neural circuit.In the current micro research on reward cir-cuits,the association between abnormal reward circuits and neg-ative emotions such as anxiety and depression has been widely recognized.Traditional Chinese medicine intervention can exert antidepressant effects by influencing reward circuits.This article provides a review on the loop mechanism of dopamine reward system involvement in depression and research on traditional Chinese medicine intervention.

OBJECTIVE: To explore clinical efficacy of Locking loop stitch with suture-bridge technique in repair of acute closed distal Achilles tendon rupture by using suture anchors. METHODS: From July 2019 to March 2021, 20 patients with acute closed distal Achilles tendon rupture were treated by minimally invasive suture anchor locking suture bridging repair technique. Among them, including 18 males and 2 females, aged from 19 to 52 years old with an average of(40.0±9.0) years old. Complications were observed, and recovery of ankle function was evaluated by American Orthopaedic Foot & Ankle Society(AOFAS) ankle and hindfoot function scoring system before operation and 1 year after operation. RESULTS: All patients followed up from 6 to 18 months with an average of (12.0±3.2) months. The incisions were healed at stageⅠwithout infection and skin necrosis occurred;no gastrocnemius nerve injury and deep vein thrombosis of the lower extremities occurred;and no heel pain and Achilles tendon re-rupture occurred. AOFAS scores of ankle and hindfoot increased from(59.0±4.3) before opertaion to(95.1±2.6) at 1 year after operation (t=-32.1, P<0.05). CONCLUSION The effect of locking suture bridging with suture anchor nails to repair acute distal Achilles tendon rupture is definite, and it could reduce incidence of complications such as Achilles tendon re-rupture, nerve injury, and skin necrosis, which has advantages of small surgical trauma, reliable anastomosis method and good functional recovery, and is an ideal method for treating acute closed distal Achilles tendon rupture.
Female ; Male ; Humans ; Young Adult ; Adult ; Middle Aged ; Suture Anchors ; Achilles Tendon/surgery* ; Ankle Injuries ; Tendon Injuries/surgery* ; Necrosis

Objective:To compare the changes of biliary microbiota after enteral extended biliary stents (EEBS) implantation with that of conventional plastic stents in animal experiment, and to preliminarily investigate its possible mechanism in preventing stents occlusion.Methods:A total of 12 healthy Bama minipigs were randomly assigned to the conventional plastic stent group ( n=6) and the EEBS group ( n=6) using simple random method. The bile samples of all pigs were collected before stents implantation and 4 weeks after stents placement. The biliary microbiota composition and diversity before and after different stents implantation were analyzed by 16S rRNA gene sequencing and compared. Results:No complications including acute cholangitis, perforation, bleeding, or death occurred in 12 pigs. Eight days after stents implantation, stents were out of bile duct in all pigs under endoscopy, while the bile samples were collected again for analysis. The main composition of biliary microbiota at the phylum level were Proteobacteria, Firmicutes and Bacteroidota. Alpha-diversities revealed the Shannon ( P=0.004) and Simpson index ( P=0.008) significantly decreased in the conventional stent group after stents placement, and Bata diversity analysis also showed a significant difference in microbial composition (Anosim: R=0.514 8, P=0.011). There was no significant difference in Observed species index ( P=0.095), Chao1 index ( P=0.136), Shannon index ( P=0.353), Simpson index ( P=0.227) or Bata diversity (Anosim: R=0.059 3, P=0.187) in the EEBS group before and after stents placement. LEfSe algorithm indicated Bacteroides_ fragilis and Proteobacteria- Gammaproteobacteria- Enterobacterales- Enterobacteriaceae- scherichia_ Shigella- Escherichia_ coli significantly increased in the conventional stent group, and Desulfobacterota- Desulfovibrionia- Desulfovibrionales- Desulfovibrionaceae- Bilophila significantly increased in the EEBS group after stents placement. Conclusion:The biliary microbiota change slightly after EEBS implantation in the short-term, and EEBS may prevent duodenobiliary reflux by prolonging the reflux path.

Objective: To investigate the clinical features and short-term prognosis of patients with SARS-CoV-2 infection associated acute encephalopathy (AE). Methods: Retrospective cohort study. The clinical data, radiological features and short-term follow-up of 22 cases diagnosed with SARS-CoV-2 infection associated AE in the Department of Neurology, Beijing Children's Hospital from December 2022 to January 2023 were retrospectively analyzed. The patients were divided into cytokine storm group, excitotoxic brain damage group and unclassified encephalopathy group according to the the clinicopathological features and the imaging features. The clinical characteristics of each group were analyzed descriptively. Patients were divided into good prognosis group (≤2 scores) and poor prognosis group (>2 scores) based on the modified Rankin scale (mRS) score of the last follow-up. Fisher exact test or Mann-Whitney U test was used to compare the two groups. Results: A total of 22 cases (12 females, 10 males) were included. The age of onset was 3.3 (1.7, 8.6) years. There were 11 cases (50%) with abnormal medical history, and 4 cases with abnormal family history. All the enrolled patients had fever as the initial clinical symptom, and 21 cases (95%) developed neurological symptoms within 24 hours after fever. The onset of neurological symptoms included convulsions (17 cases) and disturbance of consciousness (5 cases). There were 22 cases of encephalopathy, 20 cases of convulsions, 14 cases of speech disorders, 8 cases of involuntary movements and 3 cases of ataxia during the course of the disease. Clinical classification included 3 cases in the cytokine storm group, all with acute necrotizing encephalopathy (ANE); 9 cases in the excitotoxicity group, 8 cases with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and 1 case with hemiconvulsion-hemiplegia syndrome; and 10 cases of unclassified encephalopathy. Laboratory studies revealed elevated glutathione transaminase in 9 cases, elevated glutamic alanine transaminase in 4 cases, elevated blood glucose in 3 cases, and elevated D-dimer in 3 cases. Serum ferritin was elevated in 3 of 5 cases, serum and cerebrospinal fluid (CSF) neurofilament light chain protein was elevated in 5 of 9 cases, serum cytokines were elevated in 7 of 18 cases, and CSF cytokines were elevated in 7 of 8 cases. Cranial imaging abnormalities were noted in 18 cases, including bilateral symmetric lesions in 3 ANE cases and "bright tree appearance" in 8 AESD cases. All 22 cases received symptomatic treatment and immunotherapy (intravenous immunoglobulin or glucocorticosteroids), and 1 ANE patient received tocilizumab. The follow-up time was 50 (43, 53) d, and 10 patients had a good prognosis and 12 patients had a poor prognosis. No statistically significant differences were found between the two groups in terms of epidemiology, clinical manifestations, biochemical indices, and duration of illness to initiate immunotherapy (all P>0.05). Conclusions: SARS-CoV-2 infection is also a major cause of AE. AESD and ANE are the common AE syndromes. Therefore, it is crucial to identify AE patients with fever, convulsions, and impaired consciousness, and apply aggressive therapy as early as possible.
Child ; Female ; Male ; Humans ; Retrospective Studies ; Cytokine Release Syndrome ; COVID-19/complications* ; SARS-CoV-2 ; Brain Diseases/etiology* ; Prognosis ; Seizures ; Cytokines

Objective: To summarize the clinical and imaging features of linear scleroderma en coup de saber (LSCS) with central nervous system involvement in children. Methods: The clinical data(clinical manifestations and imaging features) of 6 children diagnosed with LSCS with central nervous system involvement who were admitted to Beijing Children's Hospital Affiliated to Capital Medical University from May 2019 to November 2021 were retrospectively analyzed. Results: The 6 patients were all female, aged 6.8 (3.3, 11.0) years at the time of diagnosis, and aged 3.0 (1.7, 4.1) years at the time of discovery of facial skin lesions. Facial skin lesions appeared before neurological symptoms in 5 cases, and neurological symptoms appeared 2 months before skin lesions in 1 case. All the patients had "sword wound" skin lesions on the forehead with alopecia. Neurological manifestations included epileptic seizures in 6 cases, focal neurological defects in 5 cases, and headaches in 2 cases. The intracranial lesions were all ipsilateral to the skin lesions. The magnetic resonance imaging (MRI) of 6 cases showed abnormal signals mainly involving white matter in 1 hemisphere, and 3 cases showed local encephalomalacia. The scattered low signal was observed in 5 cases on susceptibility weighted imaging. Localized brain parenchyma or leptomeninges enhancement was seen on Gadolinium-enhanced sequences in 5 cases. Scattered foci of calcification on the affected side were seen on cranial CT in 4 cases. Skin biopsy was performed in 2 cases. Part of the lesion of the brain was removed in 1 case, and the pathological findings suggested small vasculitis, which was consistent with skin pathological changes. All patients received symptomatic treatment with antiepileptic drugs. Oral prednisone combined with methotrexate was given in 4 cases, and 1 case was given oral prednisone only. One case was presumed to be in the resting stage of the disease due to significant cerebral atrophy in half of the brain, and only antiepileptic drugs were added. The patients were followed up for 6-36 months. The skin lesions of scleroderma and alopecia did not progress in 5 cases, and hemifacial atrophy was developed in 1 case, which was considered to be combined with Parry-Romberg syndrome. The seizures were controlled in 4 cases. One case had reduced seizure frequency but left hemiplegia. One patient still had intractable epilepsy and paroxysmal headache. Conclusions: LSCS with central nervous system involvement is more common in girls, with seizures and neurological defects as the main manifestations. Intracranial lesions are mostly ipsilateral to the skin lesions. Cerebral microbleeds, calcification, and encephalomalacia foci are common, and the pathological changes in skin and intracranial lesions are consistent with small-vessel vasculitis. Prednisone combined with methotrexate treatment has shown some efficacy, but some children remain with refractory epilepsy and neurological deficit symptoms.
Child ; Humans ; Female ; Scleroderma, Localized ; Anticonvulsants ; Methotrexate ; Prednisone ; Retrospective Studies ; Seizures ; Drug Resistant Epilepsy ; Calcinosis ; Alopecia ; Brain ; Encephalomalacia ; Headache

There are certain limitations in the application of liver transplantation， resection and radiofrequency ablation for liver cancer. Therefore，specific and selective new drugs are needed to provide better treatment. Curcumin is a hydrophobic polyphenol with a wide range of activities，such as anti-inflammatory，antibacterial，anti-oxidant and anti-tumor properties. Its nano-preparation has stronger growth inhibition and pro-apoptosis effects on tumor cells. Literature retrieval found that curcumin's anti-liver cancer molecular mechanisms include inhibiting cell proliferation by regulating the expressions of relevant miR，glyoxalase 1（GLO1），CD133 and vascular endothelial growth factor （VEGF），inhibiting signal transducer and activator of transcription （STAT3） and YAP expression to induce cell apoptosis，regulating the heat shock protein 70 （HSP70）-Toll-like receptor 4 （TLR4） signaling pathway，Wnt/β-catenin and transforming growth factor（TGF）/epithelial-mesenchymal transition（EMT） pathways，nuclear factor-κB （NF-κB） signaling pathway and nuclear factor E₂-related factor 2（Nrf2）/ Kelch-like ECH-related protein 1（Keap1） signaling pathway，inhibiting p38 mitogen-activated protein kinase （MAPK） phosphorylation，to reduce Lin28B expression，regulating phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway and inhibiting G protein-coupled receptors （GPR81）/hydroxycarboxylic acid receptor-1 （HCAR-1） expression to reverse transformation therapy resistance. Curcumin nano-preparation mainly includes polymer micelles，liposomes，loaded microbubbles，nanocapsules and nanoparticles. Curcumin is mainly delivered to liver cancer cells to rapidly release the drug，enhance the anti-liver cancer effect and reduce toxic and side effects in normal liver cells. The mechanisms include activation of DR5/Caspase-mediated exogenous apoptosis pathway and VEGF/VEGF receptors （VEGFRs） signaling pathway，loss of mitochondrial membrane potential and increase of intracellular reactive oxygen species （ROS）. This paper summarizes the molecular mechanism of curcumin and its nano-preparation against liver cancer，in order to further define the molecular mechanism of liver cancer and provide a new reference for its clinical diagnosis and treatment.

Quality marker(Q-marker) is a new concept and pattern for quality control of traditional Chinese medicine(TCM),which will lead the development direction for quality control of TCM.Among them,how to characterize the overall quality attribute of TCM and its biological effect,is a critical scientific problem in the study of Q-marker.In this paper,integrated pharmacology is utilized to screen out and confirm the Q-marker from the complex system of TCM,so as to solve the critical scientific problem.System biology in vivo is firstly applied to establish the correlation of chemical fingerprints of TCM,their metabolic fingerprints,network targets,biological effects and efficacy of TCM,which is used to preliminary screen out Q-marker of TCM.Following that,a pharmacological method in vitro,including intestinal absorption in vitro coupled with bioactivity assessment,is employed to simultaneously determine the absorbed doses of TCM and evaluate their biological activity.Furthermore,data mining is utilized to establish the exact quantitative mathematic model between Q-marker of TCM and bioactivity.Meanwhile,two representative examples,including Yuanhu Zhitong tablets,Xinsuning capsules,are introduced to identify Q-marker of TCM and establish their quality standards related with bioactivity,which will be beneficial to improve the level of quality control of TCM and ensure the effectiveness and safety of clinical applications.

Antifungal drug resistance is a significant clinical problem, and antifungal agents that can evade resistance are urgently needed. In infective niches, resistant organisms often co-existed with sensitive ones, or a subpopulation of antibiotic-susceptible organisms may evolve into resistant ones during antibiotic treatment and eventually dominate the whole population. In this study, we established a co-culture assay in which an azole-resistant Candida albicans strain was mixed with a susceptible strain labeled with green fluorescent protein to mimic in vivo conditions and screen for antifungal drugs. Fluconazole was used as a positive control to verify the validity of this co-culture assay. Five natural molecules exhibited antifungal activity against both susceptible and resistant C. albicans. Two of these compounds, retigeric acid B (RAB) and riccardin D (RD), preferentially inhibited C. albicans strains in which the efflux pump MDR1 was activated. This selectivity was attributed to greater intracellular accumulation of the drugs in the resistant strains. Changes in sterol and lipid compositions were observed in the resistant strains compared to the susceptible strain, and might increase cell permeability to RAB and RD. In addition, RAB and RD interfered with the sterol pathway, further aggregating the decrease in ergosterol in the sterol synthesis pathway in the MDR1-activated strains. Our findings here provide an alternative for combating resistant pathogenic fungi.
ATP-Binding Cassette Transporters ; genetics ; metabolism ; Antifungal Agents ; chemistry ; metabolism ; pharmacology ; Azoles ; pharmacology ; Biosynthetic Pathways ; drug effects ; genetics ; Candida albicans ; chemistry ; drug effects ; metabolism ; Cell Membrane ; chemistry ; metabolism ; Coculture Techniques ; Drug Resistance, Fungal ; drug effects ; Ergosterol ; metabolism ; Fungal Proteins ; genetics ; metabolism ; Lipids ; chemistry ; Molecular Structure ; Permeability ; Phenyl Ethers ; chemistry ; metabolism ; pharmacology ; Sterols ; chemistry ; metabolism ; Stilbenes ; chemistry ; metabolism ; pharmacology ; Triterpenes ; chemistry ; metabolism ; pharmacology