Objective:To evaluate the prognostic value of 18F-fluorodeoxyglucose ( 18F-FDG) PET/CT metabolic parameters in small cell lung cancer (SCLC) . Methods:A retrospective analysis was conducted on the clinical and imaging data of 156 SCLC patients, who underwent 18F-FDG PET/CT imaging and were diagnosed by histopathological examination at Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from September 2013 to February 2024. The metabolic tumor volume (MTV), total lesion glycolysis (TLG), linear regression slope, area under the curve of cumulative standard uptake value (SUV) volume histogram (AUC-CSH), and coefficient of variation (CV) were calculated using LIFEx software with different SUV thresholds. Univariate and multivariate analyses were performed using Cox proportional hazards model. Patient stratification was based on the critical values determined by receiver operator characteristic (ROC) curve analysis. The survival curve was plotted using the Kaplan-Meier method and log-rank test was performed. Results:Univariate analysis showed that MTV 40% ( HR=2.91, 95% CI: 1.55-5.47, P=0.001), MTV 60% ( HR=2.31, 95% CI: 1.29-4.17, P=0.005), TLG 40% ( HR=2.07, 95% CI: 1.19-3.60, P=0.010), linear regression slope ( HR=0.45, 95% CI: 0.26-0.79, P=0.005), and CV 40% ( HR=0.27, 95% CI: 0.08-0.84, P=0.024) were factors affecting progression-free survival (PFS) in SCLC patients. MTV 40% ( HR=1.98, 95% CI: 1.22-3.22, P=0.005), MTV 60% ( HR=1.80, 95% CI: 1.12-2.88, P=0.015), MTV 80% ( HR=1.71, 95% CI: 1.08-2.74, P=0.024), TLG 40% ( HR=3.68, 95% CI: 1.59-8.49, P=0.002), linear regression slope ( HR=0.49, 95% CI: 0.30-0.80, P=0.004), and AUC-CSH 80% ( HR=0.44, 95% CI: 0.23-0.84, P=0.013) were found to be factors affecting overall survival (OS) in SCLC patients. Multivariate analysis revealed that MTV 40% ( HR=4.76, 95% CI: 1.11-20.50, P=0.036) was an independent factor influencing PFS, and TLG 40% ( HR=3.19, 95% CI: 1.02-9.92, P=0.046) was an independent factor influencing OS in SCLC patients. ROC curve analysis identified the optimal cutoff value for MTV 40% in predicting PFS as 5.5cm 3 and the optimal cutoff value for TLG 40% in predicting OS as 41.5 g in SCLC patients. Survival analysis showed that patients with MTV 40%≤5.5 cm 3 ( n=33) had a median PFS that was not reached, while patients with MTV 40%>5.5 cm 3 ( n=123) had a median PFS of 10.3 months, with a statistically significant difference ( χ2=12.09, P=0.001). For patients with TLG 40%≤41.5 g ( n=35), the median OS was not reached, whereas for TLG 40%>41.5 g ( n=121), the median OS was 31.6 months, with a statistically significant difference ( χ2=10.55, P=0.001) . Conclusions:The 18F-FDG PET/CT metabolic parameter MTV 40% is an independent factor influencing PFS, while TLG 40% is an independent factor influencing OS in SCLC patients. The above two parameters may serve as indicators for assessing the prognosis of SCLC patients.

Objective:To explore the deubiquitination modification of the deubiquitinase BRCC3 in rats with neuropathic pain (NPP) treated with meridian tuina of Zhuang medicine and its analgesic molecular mechanism.Methods:Rats were divided into normal group, sham-operation group, model group, sham-tuina group, and meridian tuina of Zhuang medicine group using a random number table method, with 9 rats in each group. Except for the normal and sham operation groups, spinal nerve ligation models were prepared in all other groups. On the first day after surgery, intervention was carried out on the meridian tuina of Zhuang medicine and sham-tuina groups for 14 days, while the other three groups were not intervened; the paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) of each group of rats were measured at 0 days before operation, 1, 7, and 14 days after operation. Western blot was used to detect the expressions of BRCC3 and NLRP3 proteins in spinal cord tissue, and ELISA was used to detect the level of IL-1β in serum.Results:On postoperative 7 and 14 d, compared with the model group, the meridian tuina of Zhuang medicine group showed an increase in PWMT and PWTL, a decrease in NLPR3 and BRCC3 expression in spinal cord tissue, and a decrease in serum IL-1β levels ( P<0.05). Compared with the sham-tuina group, the meridian tuina of Zhuang medicine group showed an increase in PWMT and PWTL, a decrease in NLRP3 protein expression in spinal cord tissue, and a decrease in IL-1β levels in serum ( P<0.05). Conclusion:Meridian tuina of Zhuang medicine can alleviate pain sensitivity in SNL model rats, and its mechanism is related to the inhibition of the expression of deubiquitinase BRCC3 by meridian massage of Zhuang medicine, which increases the ubiquitination level of NLRP3 and hinders its activation, thereby blocking the immune inflammatory response mediated by inflammatory factors.

Objective To investigate the protective effects of paeonol(PAE)on autophagy in human neuroblastoma cells(SH-SY5Y)induced by overexpression of α-synuclein(α-Syn),and to explore its related mechanism.Methods SH-SY5Y cells served as control group,while those induced with A53T-α-Syn mutation were used as model group.Additional groups included PAE(150 μg/ml)group,3-MA(1 mmol/L)group,and PAE(150 μg/ml)+3-MA(1 mmol/L)group.Cell viability was assessed using CCK-8 method,cell morphology was observed under an optical microscope,and protein expressions of α-Syn,LC3-Ⅱ,p62,Beclin-1,phosphorylated c-Jun N-terminal kinase(p-JNK),and p-Bcl-2 were determined by Western blotting.Results Compared with control group,model control exhibited decreased cell survival(P＜0.01),increased α-Syn expression(P＜0.001),reduced expression of autophagy-related proteins LC3-Ⅱ and Beclin-1(P＜0.01,P＜0.05),elevated autophagy substrate protein p62(P＜0.05),and decreased expression of autophagy pathway-related proteins p-JNK and Bcl-2(P＜0.05,P＜0.01).Compared with model group,PAE group showed increased cell survival(P＜0.01),decreased α-Syn and p62 protein expression(P＜0.01,P＜0.05),and increased expression of LC3-Ⅱ,Beclin-1,p-JNK and Bcl-2(P＜0.05).Compared with PAE group,3-MA+PAE group demonstrated increased α-Syn expression(P＜0.05).Conclusions PAE could attenuate the injury of SH-SY5Y cells induced by A53T-α-Syn and eliminate over-expressed α-Syn by activating autophagy pathway,which may be associated with the upregulation of JNK/Bcl-2 mediated autophagy pathway.

Objective To explore the effect of mangiferin(MF)on pyroptosis in an amyotrophic lateral sclerosis(ALS)cell model by regulating the nuclear factor erythroid 2-related factor 2/heme oxygenase-1(Nrf2/HO-1)signaling pathway.Methods(1)Mouse NSC-34 cell lines transfected with hSOD1WT and hSOD1G93A plasmids were randomly divided into blank group,model group,MF(100 μmol/L)group,MF(200 μmol/L)group.MF was added into the culture plate for 24 hours.Cell viability was assessed using CCK-8 kit.Lactate dehydrogenase(LDH)release was measured using LDH cytotoxicity detection kit.Levels of inflammatory factors interleukin(IL)-1β and IL-18 in cell supernatant were determined by enzyme-linked immunosorbent assay(ELISA).The expression of Nrf2,HO-1,NADPH quinone oxidoreductase-1(NQO-1),NOD-like receptor protein 3(NLRP3),gasdermin D(GSDMD)-N and caspase-1 was detected by Western blotting.(2)Mouse hSOD1G93A NSC-34 cells were randomly divided into model group,MF(200 μmol/L)group,Nrf2-siRNA group and Nrf2-siRNA+MF(200 μmol/L)group.The cells were transiently transfected with Nrf2-siRNA using LipofectamineTM 3000.Western blotting was used to detect the protein expression levels of Nrf2,HO-1,NQO-1,NLRP3,caspase-1 and GSDMD-N.Results(1)The results of the CCK-8 assay showed that after the hSOD1G93A NSC-34 cells were treated with MF at concentrations of 300 μmol/L and below for 24 hours,the changes in cell viability were not significant(P>0.05).Compared with blank group,the release of LDH,the contents of IL-1β and IL-18 in the cell culture supernatant of model group were increased(P<0.001);the protein expression levels of Nrf2,HO-1,and NQO-1 were decreased(P<0.05 or P<0.01);the protein expression levels of NLRP3,caspase-1,and GSDMD-N were increased(P<0.05 or P<0.01 or P<0.001).Compared with model group,the release of LDH,the contents of IL-18 and IL-1β in the culture supernatant in MF(100 μmol/L)and MF(200 μmol/L)groups were decreased(P<0.001);the protein expression levels of NLRP3,caspase-1 and GSDMD-N were decreased(P<0.05 or P<0.001),and the expression levels of Nrf2,HO-1 and NQO-1 were increased(P<0.05 or P<0.01).(2)Compared with model group,the protein expession levels of Nrf2,NO-1 and NQO-1 were increased(P<0.05 or P<0.001)in MF(200 μmol/L)group,while the protein expression levels of NLRP3,caspase-1 and GSDMD-N were decreased(P<0.001);the protein expression levels of Nrf2 and HO-1 were decreased in Nrf2-siRNA group(P<0.01 or P<0.001),while the protein expression levels of NLRP3,caspase-1 and GSDMD-N were increased(P<0.001).Compared with Nrf2-siRNA group,the protein expression levels of Nrf2,HO-1 and NQO-1 in Nrf2-siRNA+MF(200 μmol/L)group were increased(P<0.01 or P<0.001),and the protein expression levels of NLRP3,caspase-1 and GSDMD-N were decreased(P<0.001).Conclusion MF can inhibit pyroptosis in the ALS cell model through Nrf2/HO-1 signaling pathway,playing a protective role.

Objective To investigate the effects of short-term and long-term high-fructose diets on hippocampal neurometabolites and anxiety and depression-like behaviors in mice,revealing the potential mechanisms of high-fructose diets in mood disorders and providing a experimental basis for the prevention and treatment of related diseases.Methods C57BL/6J male mice were randomly divided into two groups,control group(standard diet,n=10)and experimental group(high-fructose diet,n=10).Four weeks(short-term)and eight weeks(long-term)later,each group of mice was examined for body weight and fasting blood glucose,and neurometabolites levels in the hippocampus were detected by hydrogen proton magnetic resonance spectroscopy(1H-MRS),followed by the open-field test,the forced-swimming test,and the tail-suspension test to evaluate anxiety-like and depression-like behaviors.Results High fructose diet for 4 weeks elevated glutamate levels and reduced glutathione and myo-inositol levels in mice,accompanied by shortened immobility time in the forced swim test.High fructose diet for 8 weeks not only led to abnormalities in body weight and glucose metabolism but also caused a reversal decrease in hippocampal glutamate levels and induced significant anxiety-like behaviors,and the decrease in hippocampal glutamate levels showed a significant negative correlation with the enhancement of anxiety-like behaviors.Conclusion Altered hippocampal glutamate levels may be a key contributing factor to the anxiety-like behaviors induced by long-term high-fructose diet.

The quality of traditional Chinese medicine(TCM) is a critical foundation for ensuring the stability of its efficacy, as well as the safety and effectiveness of its clinical use. The identification of critical quality attributes(CQAs) is one of the core components of TCM preparation quality control. This study focuses on Jianwei Xiaoshi Tablets and explores their CQAs related to property and flavor from the perspective of taste receptor proteins. Three taste receptor proteins, T1R2, T1R3, and TRPV1, were selected, and a biosensor based on high-electron-mobility transistor(HEMT) was constructed to detect the interactions between Jianwei Xiaoshi Tablets and taste receptor proteins. Simultaneously, liquid chromatography-mass spectrometry(LC-MS) technology was used to analyze the chemical composition of Jianwei Xiaoshi Tablets. In examining the interaction strength, the results indicated that the interaction between Jianwei Xiaoshi Tablets and TRPV1 protein was the strongest, followed by T1R3, with the interaction with T1R2 being relatively weaker. By combining biosensing technology with LC-MS, 16 chemical components were identified from Jianwei Xiaoshi Tablets, among which six were selected as CQAs for sweetness and seven for pungency. Further validation experiments demonstrated that CQAs such as hesperidin and hesperetin had strong interactions with their corresponding taste receptor proteins. Through the combined use of multiple technological approaches, this study successfully determined the property and flavor-related CQAs of Jianwei Xiaoshi Tablets. It provides novel ideas and approach for the identification of CQAs in TCM preparations and offers comprehensive theoretical support for TCM quality control, contributing to the improvement and development of TCM preparation quality control systems.
Drugs, Chinese Herbal/chemistry* ; Biosensing Techniques/methods* ; TRPV Cation Channels/chemistry* ; Tablets/chemistry* ; Receptors, G-Protein-Coupled/genetics* ; Quality Control ; Taste ; Humans ; Mass Spectrometry

In order to support the implementation of the Opinions on Improving the Quality of Traditional Chinese Medicine and Promoting the High-Quality Development of the Traditional Chinese Medicine Industry and fundamentally promote the high-quality development of Chinese materia medica(CMM) industry, this article analyzed the quality and safety issues arising during the transition of CMM from wild harvesting to cultivation. Root causes of these issues were identified, including changes in the habitats of medicinal plants caused by inappropriate field cultivation patterns, excessive use of chemical inputs such as fertilizers and pesticides, and shortened cultivation periods due to rising economic costs. To address the above issues, the following countermeasures and suggestions were proposed to advance the high-quality development of CMM:(1) comprehensively adjust the cultivation patterns, vigorously promote ecological cultivation of CMM, and ensure production quality and safety of CMM from the source;(2) strengthen the breeding of high-quality, stress-resistant CMM varieties, improve cultivation techniques to reduce the use of fertilizers and pesticides, and improve the quality and efficiency of ecological cultivation of CMM;(3) systematically design the production, operation, and supervision models for ecological cultivation of CMM, carry out demonstrations of "high quality with fair price", and ensure the sustainable development of ecological cultivation of CMM.
Drugs, Chinese Herbal/standards* ; Quality Control ; Plants, Medicinal/chemistry* ; Plant Roots/chemistry* ; China ; Fertilizers/analysis* ; Materia Medica/standards* ; Medicine, Chinese Traditional/standards*

In recent years, there have been frequent adverse reactions/events associated with traditional Chinese medicine(TCM), especially liver injury related to traditional non-toxic TCM, which requires adequate attention. Liver injury related to traditional non-toxic TCM is characterized by its sporadic and insidious nature and is influenced by various factors, making its detection and identification challenging. There is an urgent need to develop a strategy and method for early detection and recognition of traditional non-toxic TCM-related liver injury. This study was based on national adverse drug reaction monitoring center big data, integrating methodologies such as reporting odds ratio(ROR), network toxicology, and computational chemistry, so as to systematically research the risk signal identification and evaluation methods for TCM-related liver injury. The optimized ROR method was used to discover potential TCM with a risk of liver injury, and network toxicology and computational chemistry were used to identify potentially high-risk TCM. Additionally, typical clinical cases were analyzed for confirmation. An integrated strategy of "discovery via big data, identification via dry/wet method, confirmation via typical cases, and precise risk prevention and control" was developed to identify the risk of TCM-related liver injury. Corydalis Rhizoma was identified as a TCM with high risk, and its toxicity-related substances and potential toxicity mechanisms were analyzed. The results revealed that liver injury is associated with components such as tetrahydropalmatine and tetrahydroberberine, with potential mechanisms related to immune-inflammatory pathways such as the tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, and Th17 cell differentiation. This paper innovatively integrated real-world evidence and computational toxicology methods, offering insights and technical support for establishing a risk discovery and identification strategy for TCM-related liver injury based on real-world big data, providing innovative ideas and strategies for guiding the safe and rational use of medication in clinical practices.
Corydalis/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Chemical and Drug Induced Liver Injury/etiology* ; Medicine, Chinese Traditional/adverse effects* ; Rhizome/adverse effects* ; Male ; Female