ObjectiveTo explore the effects of different dosage forms of Kaixinsan （KXS） on the morphology and function of mitochondria in rat models of Alzheimer's disease （AD） and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group， model group， treatment groups receiving KXS decoction， powders， and granules （3.08 g·kg^-1）， as well as donepezil group （0.51×10^-3 g·kg^-1）， with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin （STZ）. After 30 days of administration， behavioral assessments were conducted， and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay （ELISA）. Changes in mitochondrial membrane potential were measured via JC-1 staining， and superoxide dismutase （SOD） activity and reactive oxygen species （ROS） levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， and silent information regulator 3 （SIRT3） was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， and Western blot was used to examine the protein expression levels of optic atrophy protein1 （OPA1）， mitochondrial fission protein 1 （FIS1）， AMPK， p-AMPK， PGC-1α， and SIRT3. ResultsCompared with the sham group， rats in the model group had significantly lower recognition index， spontaneous alternation rate， escape latency， number of platform crossings， time spent in the target quadrant， and percentage of distance traveled in the target quadrant distance （P<0.05， P<0.01）. Significant mitochondrial damage was observed in the hippocampal tissue， with a marked decrease in mitochondrial respiratory chain complex content （P<0.01） and reduced mitochondrial membrane potential （P<0.05）. Additionally， the SOD activity was reduced， while ROS levels were elevated （P<0.01）. The mRNA expression of PGC-1α and SIRT3 was significantly downregulated （P<0.01）， along with decreased protein expression levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， whereas FIS1 protein expression was significantly upregulated （P<0.05， P<0.01）. Compared with the model group， rats in KXS-treated groups （various dosage forms） showed significant improvement in behavioral indexes （P<0.05， P<0.01）， reduced hippocampal mitochondrial damage， and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased （P<0.05， P<0.01）， and mitochondrial membrane potentials were elevated （P<0.05）. SOD activity was elevated， and ROS levels were significantly reduced （P<0.05， P<0.01）. Furthermore， the mRNA expression of PGC-1α and SIRT3 was upregulated， with increased protein levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， while FIS1 protein expression levels were significantly reduced （P<0.05， P<0.01）. Across the KXS-treated groups， the granule group showed a higher spontaneous alternation rate than the decoction and powder groups （P<0.05）. ConclusionKXS decoction， powders， and granules can improve the learning and memory ability of rats， with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway， improvement of the mitochondrial function， and subsequent amelioration of the brain energy metabolism disorders.

ObjectiveTo explore the effects of different dosage forms of Kaixinsan （KXS） on the morphology and function of mitochondria in rat models of Alzheimer's disease （AD） and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group， model group， treatment groups receiving KXS decoction， powders， and granules （3.08 g·kg^-1）， as well as donepezil group （0.51×10^-3 g·kg^-1）， with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin （STZ）. After 30 days of administration， behavioral assessments were conducted， and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay （ELISA）. Changes in mitochondrial membrane potential were measured via JC-1 staining， and superoxide dismutase （SOD） activity and reactive oxygen species （ROS） levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， and silent information regulator 3 （SIRT3） was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， and Western blot was used to examine the protein expression levels of optic atrophy protein1 （OPA1）， mitochondrial fission protein 1 （FIS1）， AMPK， p-AMPK， PGC-1α， and SIRT3. ResultsCompared with the sham group， rats in the model group had significantly lower recognition index， spontaneous alternation rate， escape latency， number of platform crossings， time spent in the target quadrant， and percentage of distance traveled in the target quadrant distance （P<0.05， P<0.01）. Significant mitochondrial damage was observed in the hippocampal tissue， with a marked decrease in mitochondrial respiratory chain complex content （P<0.01） and reduced mitochondrial membrane potential （P<0.05）. Additionally， the SOD activity was reduced， while ROS levels were elevated （P<0.01）. The mRNA expression of PGC-1α and SIRT3 was significantly downregulated （P<0.01）， along with decreased protein expression levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， whereas FIS1 protein expression was significantly upregulated （P<0.05， P<0.01）. Compared with the model group， rats in KXS-treated groups （various dosage forms） showed significant improvement in behavioral indexes （P<0.05， P<0.01）， reduced hippocampal mitochondrial damage， and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased （P<0.05， P<0.01）， and mitochondrial membrane potentials were elevated （P<0.05）. SOD activity was elevated， and ROS levels were significantly reduced （P<0.05， P<0.01）. Furthermore， the mRNA expression of PGC-1α and SIRT3 was upregulated， with increased protein levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， while FIS1 protein expression levels were significantly reduced （P<0.05， P<0.01）. Across the KXS-treated groups， the granule group showed a higher spontaneous alternation rate than the decoction and powder groups （P<0.05）. ConclusionKXS decoction， powders， and granules can improve the learning and memory ability of rats， with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway， improvement of the mitochondrial function， and subsequent amelioration of the brain energy metabolism disorders.

Objective:To compare the efficacy differences between the combination therapy of Callicarpa nudiflora and dexamethasone versus dexamethasone monotherapy via retention enema in the treatment of acute radiation proctitis.Methods:A total of 100 patients with pelvic malignancies who developed acute radiation proctitis during radiotherapy at Jiangxi Provincial People's Hospital from November 2021 to June 2023 were enrolled,and randomly divided into two groups:a control group(50 cases)vs a treatment group(50 cases).Based on the acute radiation injury scoring criteria established by the Radiation Therapy Oncology Group(RTOG),patients with injury severity scores≤1 were excluded.Subsequently,the remaining patients received the following interventions:the control group(45 cases)underwent single-agent dexamethasone retention enema,while the treatment group(47 cases)received a combined regimen of Callicarpa nudiflora combined with dexamethasone retention enema.Clinical symptoms,defecation frequency,and routine fecal parameters(leukocyte and erythrocyte counts)were recorded before and at 2 weeks of retention enema,to compare the efficacy differences between the two regimens.Results:A statistically significant difference in therapeutic efficacy was observed between the treatment and control groups(χ2=11.37,P=0.003,P<0.05),with the regimen of Callicarpa nudiflora combined with dexamethasone retention enema in the treatment group demonstrating a markedly higher efficacy rate compared to the regimen of single-agent dexamethasone retention enema in the control group(82.2%vs 62.2%).Conclusion:Callicarpa nudiflora combined with dexamethasone retention enema in the treatment of acute radiation proctitis,can significantly alleviates clinical symptoms and improves life quality of patients with acute radiation proctitis.This approach provides novel insights for optimizing clinical treatment strategies for acute radiation proctitis.

Objective:To compare the efficacy differences between the combination therapy of Callicarpa nudiflora and dexamethasone versus dexamethasone monotherapy via retention enema in the treatment of acute radiation proctitis.Methods:A total of 100 patients with pelvic malignancies who developed acute radiation proctitis during radiotherapy at Jiangxi Provincial People's Hospital from November 2021 to June 2023 were enrolled,and randomly divided into two groups:a control group(50 cases)vs a treatment group(50 cases).Based on the acute radiation injury scoring criteria established by the Radiation Therapy Oncology Group(RTOG),patients with injury severity scores≤1 were excluded.Subsequently,the remaining patients received the following interventions:the control group(45 cases)underwent single-agent dexamethasone retention enema,while the treatment group(47 cases)received a combined regimen of Callicarpa nudiflora combined with dexamethasone retention enema.Clinical symptoms,defecation frequency,and routine fecal parameters(leukocyte and erythrocyte counts)were recorded before and at 2 weeks of retention enema,to compare the efficacy differences between the two regimens.Results:A statistically significant difference in therapeutic efficacy was observed between the treatment and control groups(χ2=11.37,P=0.003,P<0.05),with the regimen of Callicarpa nudiflora combined with dexamethasone retention enema in the treatment group demonstrating a markedly higher efficacy rate compared to the regimen of single-agent dexamethasone retention enema in the control group(82.2%vs 62.2%).Conclusion:Callicarpa nudiflora combined with dexamethasone retention enema in the treatment of acute radiation proctitis,can significantly alleviates clinical symptoms and improves life quality of patients with acute radiation proctitis.This approach provides novel insights for optimizing clinical treatment strategies for acute radiation proctitis.

Patients with brain metastases from non-small cell lung cancer (NSCLC) generally have a poor prognosis. Tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of patients with sensitizing mutations in the epidermal growth factor receptor (EGFR) gene. Combining TKIs with other treatments such as radiotherapy, chemotherapy, and anti-angiogenic therapy can improve survival of patients with EGFR-mutant NSCLC brain metastases. However, more in-depth clinical studies are needed to determine the best combination strategies and to identify which patient groups will benefit the most from these approaches.

Objective To investigate the effect of Danshen Baoxin Cha (DBC) on a rat model of coronary heart disease combined with cognitive impairment. Methods Male Sprague-Dawley(SD) rats were randomly assigned to two groups:normal group and model group. Streptozotocin was injected into the bilateral ventricles of rats in the model group to establish cognitive impairment model,then isoproterenol hydrochloride was injected subcutaneously to model myocardial ischemia. Behavioral experiments were conducted to verify the success of the model of cognitive dysfunction. The rats of the model group were randomly divided into five groups:model control group,Tongxinluo Capsule group (TXL group,1.6 g·kg-1),and low-(4 g·kg-1),medium-(8 g·kg-1),and high-(16 g·kg-1) dose DBC groups. These groups were received the respective treatments continuously for two weeks. Subsequently,the Y-maze,novel object recognition and Morris water maze experiment were employed to assess the learning and memory abilities of rats. A kit was utilized to quantify the level of oxidative stress in the brain and the adenosine triphosphate (ATP) content in the brain and mitochondria. Hematoxylin-eosin (HE) staining and Nissl staining were employed to observe the pathological changes of neurons in hippocampus CA1 region. Electron microscopy was utilized to observe the pathological changes of mitochondria in hippocampal CA1 region. The expression levels of peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α),glucose transporter type 4(GLUT4),and optic atrophy 1(OPA1) were quantified by real-time fluorescence quantitative polymerase chain reaction (PCR),and the expression of proteins related to the AMPK/OPA1 signaling pathway was determined by Western Blot analysis. Results Compared with the normal group,the spontaneous alternating reaction rate,the novel object recognition index,number of crossing the original platform,and distance ratio in the model group were obviously decreased (P<0.01). Neuronal density in the CA1 region of the hippocampus was decreased,Nissl bodies were decreased,and nucleus consolidation was increased. The ATP level in mitochondria,and the levels of ATP,SOD,and GSH-PX in brain were significantly decreased(P<0.05,P<0.01),as well as the content of ROS and MDA were significantly increased (P<0.05,P<0.01). The mitochondria of hippocampus in CA1 region were swollen,with sparse and vacuolated cristae. The mRNA expression levels of GLUT4,PGC-1α,and OPA1 were significantly decreased (P<0.01). The protein expression levels of GLUT4,SIRT1,PGC-1α and OPA1,and p-AMPK/AMPK ratio were significantly decreased (P<0.05,P<0.01). Compared with the model group,the behavioral indexes of rats in the DBC groups were significantly improved (P<0.05,P<0.01),the number of neurons in the hippocampal CA1 area,Nissl bodies and nucleus consolidation were improved. The ATP level in mitochondria and the levels of ATP,SOD,and GSH-PX in brain were significantly increased (P<0.05,P<0.01). The levels of ROS and MDA were significantly decreased (P<0.05,P<0.01). The structure of mitochondrial cristae in hippocampal CA1 region were relatively intact. The mRNA expression levels of GLUT4,PGC-1α and OPA1 were increased (P<0.05,P<0.01),and the expression of proteins related to the AMPK/OPA1 signaling pathway was significantly increased(P<0.05,P<0.01). Conclusion DBC can enhance learning and memory abilities,reduce neuronal damage in a rat model of coronary heart disease combined with cognitive impairment. The mechanism may be related to the reduction of oxidative stress damage in the brain,the activation of the AMPK/OPA1 signaling pathway,and the restoration of energy levels.

Objective To explore the mechanism of action of Danshen Baoxin Cha(DBC) on depressed mice with coronary heart disease (CHD) based on network pharmacology and NLRP3 inflammatory pathway. Methods (1) TCMSP and BATMAN-TICAM databases were used to screen the DBC active ingredients and targets. The targets of CHD with depression were screened using the OMIM and Genecards databases. The targets of DBC active ingredients and related targets of CHD with depression were imported into Venny 2.1 online platform to obtain the intersection targets,which was the potential target of DBC in the treatment of CHD with depression. Protein-protein interaction (PPI) analysis was performed on the intersection targets using the STRING platform to screen the key targets. A "drug-active ingredients-disease-targets" network was created to select the main active ingredients and core targets of DBC for the treatment of CHD with depression. Thereafter,the primary targets were examined by GO function and KEGG pathway enrichment using the Metascape database.(2)Kunming mice were split into six groups of eight mice each at random:the control group,the model group,the positive control group (metoprolol tartrate 5.14 mg·kg-1+sertraline hydrochloride 10.3 mg·kg-1),and the DBC high-,middle-,and low-dose groups (30.8,15.4 and 7.7 g·kg-1·d-1). Chronic unpredictable mild stimulation (CUMS)and subcutaneous injection of isoprenaline hydrochloride (ISO) were used to induce a mice model of CHD with depression. Mice were treated orally with the corresponding drug once a day for 18 consecutive days. Behavioral experiments involving forced swimming test,tail suspension test,and open-field test were applied to detect depression levels of mice. Histopathological alterations in hippocampus tissues were noted using HE and Nissl staining. qPCR was used to determine the mRNA expression levels of IL-6,TNF-α,NLRP3,IL-1β,IL-10,and Caspase-1 in hippocampus tissues. Results(1) Sixty-five active components in Salvia and seven active components in green tea were screened out. A total of 1042 potential targets and 2116 CHD complicated with depression-related targets were obtained. The intersection of the targets of active components and disease-related targets was performed by Venny 2.1.0 platform to obtain 299 potential targets (common targets) of DBC in the treatment of CHD with depression. The core targets including IL-1β,AKT1,TNF-α,IL-6,VEGFA,CASP3 and IL-10 were screened through PPI network analysis of potential targets. Key active ingredients including vitamin B,luteolin,salvianolic acid,tanshinone ⅡA and catechin,as well as key targets,such as PTGS2、IL-1β、IL-6、TNF-α and IL-10,were obtained by network analysis of "drugs-active ingredients-disease-targets". The potential targets were correlated with biological processes such as inflammation response,regulation of tumour necrosis factor (TNF),glucocorticoid regulation,regulation of nuclear factor kappa B(NF-κB) transcription factor,as well as major pathways including PI3K-Akt signaling pathway,TNF signaling pathway,apoptosis signaling pathway,and NF-κB signaling pathway.(2) Compared with the control group,mice in the model group showed a significant decrease in the total and center distance of the open field (P<0.01) and a significant increase in the time of forced swimming and immobility time of tail suspension test (P<0.01). The mRNA expression of IL-6,TNF-α,NLRP3,IL-1β,and Caspase-1 was significantly up-regulated(P<0.01) in the hippocampus tissues,but IL-10 mRNA expression was down-regulated (P<0.05). Compared with the model group,the total and center distance in DBC high-,middle-,and low-dose groups were significantly up-regulated(P<0.05,P<0.01),and the time of forced swimming and immobility time of tail suspension test were significantly down-regulated (P<0.01). The mRNA expression of IL-6,TNF-α,NLRP3,IL-1β and Caspase-1 of the DBC high-,middle-,and low-dose groups were significantly down-regulated(P<0.01),IL-10 mRNA expression in mice hippocampus tissue of DBC high-and middle-dose groups was up-regulated (P<0.01). Conclusion The intervention effect of DBC on depressed mice with CHD may be achieved by active ingredients including luteolin,tanshinone,salvianolic acid and catechin acting on the key targets,such as IL-6,TNF-α,IL-1β and IL-10,to regulate the NLRP3 inflammatory signaling pathway.

Enteropathy-associated T cell lymphoma(EATL)is a rare subtype of mature T cell lymphoma,formerly known as EATL type Ⅰ.EATL is closely linked to celiac disease.Risk factors for EATL include a history of celiac disease,human leukocyte antigen-DQ2(HLA-DQ2)gene susceptibility,aberrant intestinal intraepithelial lymphocytes(IELs)accumulation and ulcerative jejunitis.The pathogenesis is related to HLA-DQ2 allele variation,mutational events of Janus kinase(JAK)-signal transducer and activator of transcription(STAT)pathway and nuclear factor kappa-B(NF-κ B),as well as functional changes of microRNA(miRNA).Commonly involved sites in EATL are the small intestine,followed by the stomach and colon.EATL usually presents with dyspepsia,gluten-insensitive malabsorption,intestinal obstruction,hemorrhage and perforation.EATL is an aggressive disease,with a poor prognosis.Misdiagnosis is common during the early stage of the disease.Anthracycline-based combination chemotherapy is the dominant treatment for EATL.Surgical resection is used to alleviate obstruction,hemorrhage,or perforation in some patients.Stem cell transplantation for consolidation after remission of first-line chemotherapy can prolong patients'survival time.Monoclonal antibody brentuximab vedotin targeting CD30,anti-CD52 antibody alemtuzumab,immune checkpoint inhibitors,and drugs used to treat refractory celiac disease(RCD)type Ⅱ and peripheral T cell lymphomas(PTCL)may be effective against EATL.This paper summarizes the epidemiology,genetic and molecular characteristics,clinicopathological characteristics,immunophenotypic characteristics and new advances in the treatment of EATL.

Objective: To systematically evaluate the efficacy and safety of CT-guided percutaneous lung puncture biopsy versus ultrasound-guided percutaneous lung puncture biopsy. Methods: Relevant domestic and foreign related databases such as PubMed, Web of Science, Cochrane Library, OVID, China Biology Medicine, VIP, Wanfang and CNKI databases were searched, the randomized controlled trial about the applications of CT-guided and ultrasound-guided percutaneous lung puncture biopsy were collected. After extracting the relevant data, a Meta-analysis was performed using RevMan 5.2 and Stata softwares. Results: Ten studies met the inclusion criteria, with a total sample size of 1 158 cases, of which 635 were CT-guided puncture biopsy and 523 were ultrasound-guided puncture biopsy. Meta-analysis showed that the difference of the success rate between the CT-guided group and the ultrasound-guided group was not statistically significant [97.48% (619/635) vs. 96.56% (505/523), RR= 1.01, 95% CI 0.99-1.03, P= 0.360]; the puncture diagnosis rate in the CT-guided group was lower than in the ultrasound-guided group, and the difference was statistically significant [92.44% (619/635) vs. 96.56% (505/523), RR= 0.97, 95% CI 0.94-0.99, P= 0.007]. The total incidence of complications after puncture in the CT-guided group was higher than that in the ultrasound-guided group, and the difference was statistically significant [14.49% (92/635) vs. 9.56% (50/523), RR= 1.56, 95% CI 1.11-2.19, P= 0.010]; the incidence of pneumothorax after puncture in the CT-guided group was higher than that in the ultrasound-guided group, and the difference was statistically significant [11.50%(73/635) vs. 6.31% (33/523), RR= 1.77, 95% CI 1.17-2.68, P= 0.007]; the difference of the incidence of bleeding after puncture between the CT-guided group and the ultrasound-guided group was not statistically significant [2.99% (19/635) vs. 3.25% (17/523), RR= 1.08, 95% CI 0.59-1.98, P= 0.800]. Conclusions Both CT-guided and ultrasound-guided percutaneous lung puncture biopsy have good clinical diagnostic value. However, for the intrapulmonary masses shown by ultrasound, the ultrasound-guided lung puncture biopsy has a shorter operation time, lower cost, and higher safety.

Gastric cancer is one of the most common malignant tumors of digestive system, which has the characteristics of strong heterogeneity, rapid progress and poor prognosis. Liver metastasis of gastric cancer is the main cause of death of advanced gastric cancer. At present, the clinical treatment of gastric cancer mainly includes systematic treatment (systemic chemotherapy, targeted treatment, immunotherapy), surgical resection, interventional treatment and radiotherapy, but the therapeutic effects are not good, and liver metastasis of gastric cancer is lack of standardized treatment strategy. At present, the multi-disciplinary comprehensive treatment mode has been widely used in the diagnosis and treatment of malignant tumors, and has achieved good results. According to the clinical characteristics and surgical accessibility of liver metastasis of gastric cancer, the Chinese Gastrointestinal Surgery Expert Group divides it into three clinical types: resectable type, potential resectable type and non-resectable type. All kinds of clinical types of patients need multidisciplinary comprehensive treatment cooperation group experts to discuss and formulate individualized treatment plan.