OBJECTIVE To investigate the effect and mechanism of modified Lichong decoction （MLCD） on the apoptosis of transplanted tumor cells in nude mice. METHODS Human gastric cancer AGS cells were cultured， and a nude mice transplanted tumor model was established. The nude mice were divided into the model group and MLCD low-， medium- and high-dose groups （150， 300， 600 mg/kg）. They were given distilled water or the corresponding drug solution by gavage once daily for four consecutive weeks. The size of transplanted tumors in nude mice was measured every six days， and the tumor volume was calculated. After the medication， the nude mice were sacrificed， and the transplanted tumor tissues were isolated. The contents of lactate dehydrogenase （LDH） and reactive oxygen species （ROS） in the transplanted tumor tissues were detected， and the changes in mitochondrial membrane potential were assessed. The pathological morphological changes were observed. The enzymatic activities of caspase-3， caspase-8， and caspase-9， as well as protein expressions of Fas and FasL and mRNA expressions of caspase-3， caspase-8， caspase-9， Fas and FasL in the transplanted tumor tissues， were detected. RESULTS Compared with the model group， the volume of transplanted tumors in nude mice from all MLCD dose groups was reduced to varying degrees. The contents of LDH and ROS， as well as the enzymatic activities of caspase-3， caspase-8 and caspase-9， were significantly increased/enhanced. The mitochondrial membrane potential was significantly decreased. The protein expressions of Fas and FasL， and the mRNA expressions of caspase-3， caspase-8， caspase-9， Fas and FasL were significantly up-regulated. Most of these differences were statistically significant （ P ＜0.05 or P ＜0.01）. Pathological results showed that with increasing doses of MLCD， the cellular density in the transplanted tumor tissues gradually decreased， and typical morphological features of apoptosis， such as loosening and increasing fragmentation， became more prominent. CONCLUSIONS MLCD can induce apoptosis in transplanted tumor cells of nude mice， and its mechanism may be related to the activation of the Fas/FasL pathway and the caspase apoptotic pathway.

Depression is a common mental disorder that falls under the category of "stagnation syndrome" in traditional Chinese medicine （TCM）. Its complex pathogenesis poses challenges for the development of novel therapeutic agents. Currently， clinically used antidepressants are often accompanied by significant side effects， and statistics show that about one-third of patients do not respond to these medications. TCM demonstrates advantages in the treatment of depression through multi-target， multi-pathway and multi-mechanistic approaches. Pinelliae Rhizoma， a phlegm-resolving herb， exhibits effects such as drying dampness and resolving phlegm， as well as eliminating stuffiness and reducing masses. The characteristics of harmonizing Yin and Yang and resolving stagnation in the middle energizer align precisely with the pathogenesis of depression syndrome， demonstrating therapeutic efficacy in affected patients. Literature studies have found that the active ingredients of Pinelliae Rhizoma， such as cavidine， baicalein， β-sitosterol， as well as Pinelliae Rhizoma herb pairs， such as Pinelliae Rhizoma-Magnoliae Officinalis Cortex， Pinelliae Rhizoma-husked sorghum， Pinelliae Rhizoma-Prunellae Spica， exhibit significant antidepressant effects. Furthermore， TCM formulas containing Pinelliae Rhizoma as the principal therapeutic agent， such as Banxia Xiexin Tang， Banxia Houpo Tang， and Wendan Tang， as well as formulas incorporating Pinelliae Rhizoma like compound Xiaochaihu Tang， Chaihu Jia Longgu Muli Tang， and Erchen Tang， have also demonstrated favorable antidepressant efficacy. The antidepressant mechanism of these agents may involve modulation of 5-hydroxytryptamine （5-HT） and dopamine （DA） levels， up-regulation of brain-derived neurotrophic factor （BDNF） expression， regulation of the hypothalamus-pituitary-adrenal （HPA） axis， reduction of oxidative stress， modulation of nuclear transcription factor-κB （NF-κB） signaling pathway， and inhibition of microglia-mediated inflammatory responses. This review summarized the antidepressant mechanisms and clinical applications of the active components， herb pairs， and TCM formulas containing Pinelliae Rhizoma， aiming to provide a reference for modern research on the use of Pinelliae Rhizoma in antidepressant therapy.

ObjectiveIn order to provide a reference for the optimization of preparation process of stir-fried Glycyrrhizae Radix et Rhizoma（sf-GRR）， the quality changes during the processing was studied. MethodsGlycyrrhizae Radix et Rhizoma was processed by stir-frying for 17 min， and samples were collected every 1 min during the processing. The appearance color of the samples was determined by visual analysis technology， the moisture and extract of the process samples were detected by the drying method and the hot extraction method of alcohol-soluble extract in the general rules of the 2020 edition of Chinese Pharmacopoeia（part Ⅳ）， and the contents of liquiritin apioside， liquiritin， isoliquiritin apioside， isoliquiritin， licoricesaponin G₂ and glycyrrhizic acid in the process samples were determined by high performance liquid chromatography（HPLC）. Then principal component analysis（PCA）， partial least squares-discriminant analysis（PLS-DA） and Spearman correlation analysis were used for clustering， discrimination and correlation analysis of the appearance color， moisture， extract and the contents of six internal components. Based on artificial neural network and random forest algorithm， the prediction model of processing degree of sf-GRR was established. On this basis， based on the five principles of quality marker（Q-Maker）， explore the monitoring Q-Maker of sf-GRR. ResultsThe color of Glycyrrhizae Radix et Rhizoma deepened after stir-frying， and the appearance color of the sample changed from light yellow to dark yellow during processing. During the stir-frying process， the moisture content showed a decreasing trend with the extension of processing time， while the extract content showed an increasing trend with the extension of processing time. After stir-frying， the contents of liquiritin apioside， liquiritin and licoricesaponin G₂ showed an overall decreasing trend， while the contents of isoliquiritin apioside and isoliquiritin increased， and the content of glycyrrhizic acid increased slightly. The correlation analysis showed that moisture was positively correlated with brightness（L^*） and red/green value（a^*）， and negatively correlated with yellow/blue value（b^*） and total color difference（E^*ab）. Isoliquiritin apioside and isoliquiritin had negative correlation with L^* and a^*， and positive correlation with b^* and E^*ab. The processing process of sf-GRR could be divided into two stages of the early stage（0-14 min） and the late stage（15-17 min）， and could be divided into three stages of the early stage（0-6 min）， the middle stage（7-14 min） and the late stage（15-17 min） by combining the moisture， extract， the contents of 6 components and color values. Based on artificial neural network analysis and random forest algorithm， isoliquiritin apioside， isoliquiritin， liquiritin and glycyrrhizic acid were selected as monitoring markers for sf-GRR. ConclusionBased on the analysis of the exterior-interior indicators of process samples of sf-GRR， this paper ultimately identifies four processing monitoring markers， which can provide a basis for optimizing the processing technology of sf-GRR.

BACKGROUND:Exosomes can be detected in synovial fluid and plasma at levels that vary with the progression of osteoarthritis in patients with osteoarthritis,and may play a relieving role in the local inflammation of osteoarthritis,cartilage calcification,and osteoarthritic joint degradation. OBJECTIVE:To comprehensively understand the function and mechanism of exosomes from different stem cells in the diagnosis and treatment of osteoarthritis,and to present the prospects and challenges of exosome therapy for osteoarthritis. METHODS:We searched the articles published from October 2003 to October 2023 included in PubMed and CNKI databases with the keywords of"exosomes,osteoarthritis,mesenchymal stem cells,stem cells"in Chinese and English,respectively.A total of 99 articles were finally included for review. RESULTS AND CONCLUSION:The appearance of exosomes brings hope to the diagnosis and treatment of osteoarthritis.The differences of RNA,protein,and lipid content in exosomes can be used as biomarkers for the diagnosis of osteoarthritis.At the same time,exosomes from various stem cells can effectively protect chondrocytes,relieve inflammation,maintain cartilage matrix metabolism,and regulate angiogenesis and subchondral bone remodeling,showing excellent potential in the treatment of osteoarthritis.The engineered exosomes break through the traditional limitations and enhance the specificity and efficiency of treatment by modulating the expression of specific non-coding RNA,providing a new strategy for the treatment of osteoarthritis.

Objective:To explore the spatiotemporal evolution and convergence trend of the level of health resource supply in the Yangtze River Delta Region,and to provide quantitative support for the formulation of health resource supply policies.Methods:Using Dagum Gini coefficient,kernel density estimation,Markov chain,and spatial β convergence model to analyze the regional differences,dynamic evolution,and convergence of health resource supply levels in the Yangtze River Delta.Results:From 2010 to 2022,the level of health resource supply in the Yangtze River Delta maintained an increasing trend,with overall differences,intra regional and inter regional differences all showing a narrowing trend.Inter regional differences contributed the most,and Anhui Province's development was relatively balanced.There is a weak polarization phenomenon in the Yangtze River Delta as a whole,and the balance in Zhejiang has improved in the later stage.The spatial factors significantly affect the dynamic evolution process of the supply level of health resources in the Yangtze River Delta,with obvious positive spillover effects,and the supply level has β convergence characteristics.Conclusion:It is needed to promote the comprehensive development of regional economy,accelerate the improvement of the supply level of health resources in underdeveloped areas,and narrow the gap.At the same time,it needs to enhance spatial interaction between regions and pay attention to the positive spillover effects in areas with higher supply levels.

Objective To investigate the optimal cutoff values of Kyoto gastritis score based on gastroscopy,pepsinogen(PG)combined with gastrin-17(G-17)for predicting Helicobacter pylori positive atrophic gastritis in middle-aged and elderly patients.Methods The subjects of this study were 120 middle-aged and elderly patients admitted,diagnosed with atrophic gastritis through gastroscopy examination and pathological biopsy and proved to be Hp positive via 14C urea breath test from August 2022 to June 2023.All patients were divided into atrophic gastritis group(AG group)with 68 cases and non atrophic gastritis group(non-AG group)with 52 cases according to atrophic gastritis results.The AG group was further divided per Kimura-Takemoto classification into mild AG group(n=12),moderate AG group(n=32)and severe AG group(n=24).Kyoto gastritis score based on gastroscopy was performed in all patients.And test their serum pepsinogen Ⅰ(PGⅠ),pepsinogen Ⅱ(PGⅡ),G-17 levels via chemiluminescence and calculate the PGR=PGⅠ/PGⅡ.Receiver operator characteristic curve(ROC curve)was adopted to assess the value of Kyoto gastritis score and serum PG and G-17 for predicting Hp positive atrophic gastritis in middle-aged and elderly patients.Results There were statistically significant differences in Kyoto gastritis score,serum PGⅠ,PGR and G-17 levels between AG group and non-AG group(t=13.38,P=0.000;t=50.84,P=0.000;t=26.44,P=0.000;t=9.44,P=0.000).The Kyoto score of gastritis in AG group was higher than that in non-AG group(P<0.05).The levels of serum PGⅠ,PGR and G-17 in AG group were lower than those in non-AG group(P<0.05).There was no significant difference in serum PGⅡ level between AG group and non-AG group(t=1.24,P=0.219).There were statistically significant differences in Kyoto gastritis score,serum PGⅠ,PGR and G-17 levels among mild AG group,moderate AG group and severe AG group(F=33.95,P=0.000;F=81.99,P=0.000;F=67.36,P=0.001;F=33.50,P=0.004).The mild AG group had a significantly lower Kyoto gastritis score than the moderate AG group and severe AG group(P<0.05),and the moderate AG group had a significantly lower Kyoto gastritis score than the severe AG group(P<0.05).The mild AG group and moderate AG group had significantly higher serum PGⅠ and PGR levels than the severe AG group(P<0.05),and the mild AG group was higher than moderate AG group(P<0.05).The mild AG group had a significantly lower serum G-17 level than the moderate AG group and severe AG group(P<0.05),and there was no significant difference between the moderate AG group and severe AG group(P>0.05).There was no significant difference in serum PGⅡ levels among mild AG group,moderate AG group and severe AG group(F=1.03,P=0.364).The optimal cutoff values of Kyoto gastritis score and serum PGⅠ,PGR and G-17 for predicting atrophic gastritis in middle-aged and elderly patients with Hp positive were 2.78,38.26 μg/L,1.92 and 9.54 pmol/L,respectively.The AUC of Kyoto gastritis score for predicting Hp positive atrophic gastritis in middle-aged and elderly patients was 0.780,the sensitivity was 71.42%,and the specificity was 78.62%.The AUC of PGⅠ for predicting Hp positive atrophic gastritis in middle-aged and elderly patients was 0.757,the sensitivity was 66.27%,and the specificity was 83.25%.The AUC of PGR for predicting Hp positive atrophic gastritis in middle-aged and elderly patients was 0.792,the sensitivity was 76.23%,and the specificity was 87.35%.The AUC of G-17 for predicting Hp positive atrophic gastritis in middle-aged and elderly patients was 0.672,the sensitivity was 60.24%,and the specificity was 74.28%.The AUC of the combination of the four markers for predicting Hp positive atrophic gastritis in middle-aged and elderly patients was 0.871,the sensitivity was 81.28%,and the specificity was 87.36%.Conclusion The Kyoto gastritis score based on gastroscopy,serum PGⅠ,PGR combined with G-17 have good predictive value for Hp positive atrophic gastritis in middle-aged and elderly patients,and the optimal cutoff values for the four markers are 2.78 points,38.26 μg/L,1.92 and 9.54 pmol/L in turn.

Objective:To investigate the feasibility and safety of high-speed railway (HSR) transport for critically ill pediatric patients.Methods:A single-center retrospective analysis was conducted.A total of 39 children transported via HSR (HSR group) and 420 children transported via ambulance (ambulance group) from May 2019 to December 2024 at the Seventh Medical Center of the PLA General Hospital were included.Demographic data,disease types,transport distances,and outcomes were compared between the two groups,and the vital signs,blood gas analysis,mechanical ventilation parameters,and vasoactive drug usage before and after HSR transport were also compared.Results:Over the five-year period,39 HSR transports and 420 ambulance transports were completed.No significant differences were observed in gender,age,or weight between HSR group and ambulance group( P>0.05).The proportion of circulatory system diseases was significantly higher in the HSR group (74.4% vs.55.1%, P = 0.020).HSR transports covered longer distances [855(855,1 075)km vs.84(23,273) km, P<0.001] and achieved faster speeds [150(150,216) vs.80(79,80)km/h, P<0.001].No significant differences were found in heart rate,body temperature,or diastolic pressure before and after HSR transport ( P>0.05).However,systolic blood pressure and partial pressure of oxygen increased slightly post-HSR transport [(82.97±15.44) vs.(85.15 ± 14.82)mmHg, P=0.003；(84.22±25.45)mmHg vs.(88.95±28.70)mmHg, P=0.029].Mechanical ventilation parameters remained stable during HSR transport ( P>0.05). Conclusion:HSR transport is feasible and safe for critically ill children and represents a promising option for long-distance interhospital transfers of pediatric patients.

Objective:To investigate the value of biparametric-MRI (bpMRI) based peritumoral radiomics for preoperative prediction of extraprostatic extension (EPE) in prostate cancer (PCa).Methods:In this cross-sectional study, consecutive bpMRI of patients undergoing prostatectomy for PCa were retrospectively collected from the First Medical Center (center 1) and the Third Medical Center (center 2) of Chinese PLA General Hospital. A total of 274 patients were finally enrolled. Patients at center 1 from January 2020 to December 2022 were randomly divided into a training set (149 cases) and an internal validation set (63 cases) by stratified random sampling. Patients at center 2 from January 2023 to March 2024 were assigned to the external test set (62 cases). Patients were categorized into EPE-positive group and EPE-negative group according to pathological assessment postoperatively. In the training set, there were 49 cases in EPE-positive group and 100 cases in EPE-negative group. In the internal validation set, there were 26 cases in EPE-positive group and 37 cases in EPE-negative group. In the external test set, there were 22 cases in EPE-positive group and 40 cases in EPE-negative group. Axial T 2WI and apparent diffusion coefficient (ADC) images were manually annotated to obtain index lesion regions of interest (ROIs), with the peritumoral ROIs subsequently delineated by semi-automatic segmentation technique. Radiomics features were extracted from intra-tumoral, peri-tumoral, and intra-tumoral plus peri-tumoral ROIs. The training set data was employed to select and optimize features to build the radiomics models. The logistic regression analysis was used to develop radiomics, clinical, and integrated models. The predictive performance was assessed by the area under the receiver operating characteristic curve (AUC) in the external test set, and compared by the DeLong test. The sensitivity and specificity were compared by the exact McNemar test. Results:In the external test set, the peri-tumoral radiomics model based on bpMRI showed the highest performance in evaluating EPE, with an AUC of 0.739 (95% CI 0.611-0.842), which was identified as the optimal radiomics model. EPE grade ( OR=6.151, 95% CI 3.371-11.226, P<0.001) was incorporated into the clinical model, with an AUC of 0.780 (95% CI 0.657-0.875) in the external test set. The integrated model had an AUC of 0.817 (95% CI 0.698-0.904) in the external test set. There was no statistically significant difference in comparisons of AUCs among the three models (all P>0.05). The sensitivity of the integrated model (68.2%) showed no significant difference from those of the clinical model and the optimal radiomics model (77.3% and 86.4%, respectively; P=0.500 and P=0.289). However, the specificity of the integrated model (85.0%) was significantly higher than those of the clinical model (67.5%, P=0.016) and the optimal radiomics model (50.0%, P<0.001). Conclusion:A bpMRI-based peritumoral radiomics integrating clinical model demonstrates high performance for preoperative prediction of EPE in PCa.

The aim of this experiment was to study the effects of different feeding modes on growth performance,blood biochemical indexes and intestinal flora of lactating Holstein male calves.Twenty-four newborn Holstein male calves with body mass of(40.00±1.01)kg and similar day old were selected and randomly divided into four groups of six calves each.The subgroups were low-milk group(LM),high-milk group(HM),high-milk milk replacer feeding group(HMR),and low-milk switching to high-milk milk replacer feeding group(CMR).The results showed that:At 45 d,the body mass of calves in the HM group was significantly higher than that of calves in the other groups(P＜0.05),and at 60 d,the body mass of calves in the HM group was significantly higher than that of calves in the LM &.CMR groups(P＜0.05).At 90 d,the body mass of calves in the LM group was significantly higher than that of calves in the HM group.Throughout the ex-perimental period,the average daily weight gain and average pellet feed intake of calves in the LM group were significantly higher than that of calves in the HM group(P＜0.05).The calf globulin level in the HMR group was significantly higher than that in the LM and HM groups(P＜0.05);the plasma immunoglobulin A level of calves in the HM group was significantly lower than that of calves in the LM and HMR groups(P＜0.05);and the plasma immunoglobulin M level of calves in the HM group was significantly higher than that of calves in the LM and CMR groups(P＜0.05),and HMR group was also significantly higher than that of LM group(P＜0.05);plasma glutathione peroxidase level of calves in HMR group was significantly higher than that of LM group(P＜0.05);plasma malondialdehyde level of calves in LM group was significantly higher than that of calves in HMR and HM groups(P＜0.05),and CMR group was also significantly higher than that of HM group(P＜0.05).Relative abundance of Thermodesulfovibrio was higher in the HM group(P＜0.05),relative abundance of Bacteroidetes in the LM group was significantly higher than that in the HMR and HM groups(P＜0.05),relative abundance of Blautia in the HM group(P＜0.05),and relative abundance of Corynebacterium in the CMR group was significantly higher than that in the LM and HM groups(P＜0.05).In summary,calves in the LM group had better weaning weights and pellet feed intake;calves in the CMR group could compensate for growth by supplemental feeding of milk replacer to obtain more optimal weaning weights and pel-let feed intake;the HMR group proved that milk-free feeding could ensure stable growth of calves;and calves in the HM group had a better pre-lactation growth performance,lower levels of oxida-tive stress,and a healthier fecal flora.

Alzheimer's disease(AD)is the leading cause of dementia,and no effective treatment has been devel-oped for it thus far.Recently,the use of natural compounds in the treatment of neurodegenerative diseases has garnered significant attention owing to their minimal adverse reactions.Accordingly,the potential therapeutic effect of pterostilbene(PTS)on AD has been demonstrated in multiple in vivo and in vitro experiments.In this study,we systematically reviewed and summarized the results of these studies investigating the use of PTS for treating AD.Analysis of the literature revealed that PTS may play a role in AD treatment through various mechanisms,including anti-oxidative damage,anti-neuroinflammation,anti-apoptosis,cholinesterase activity inhibition,attenuation of β-amyloid deposi-tion,and tau protein hyperphosphorylation.Moreover,PTS interferes with the progression of AD by regulating the activities of peroxisome proliferator-activated receptor alpha(PPAR-α),monoamine oxi-dase B(MAO-B),silent information regulator sirtuin 1(SIRT1),and phosphodiesterase 4A(PDE4A).Furthermore,to further elucidate the potential therapeutic mechanisms of PTS in AD,we employed network pharmacology and molecular docking technology to perform molecular docking of related proteins,and the obtained binding energies ranged from-2.83 to-5.14 kj/mol,indicating that these proteins exhibit good binding ability with PTS.Network pharmacology analysis revealed multiple po-tential mechanisms of action for PTS in AD.In summary,by systematically collating and summarizing the relevant studies on the role of PTS in treatment of AD,it is anticipated that this will serve as a reference for the precise targeted prevention and treatment of AD,either using PTS or other developed drug interventions.