Objective To study the effect and mechanism of Anchusa italica Retz on cerebral ischemia-reperfusion inju-ry in rats based on the target network of active compounds in Anchusa italica Retz.Methods The rat model of cerebral ische-mia-reperfusion injury was established by the thread occlusion method.After performing ischemia for 1.5 h and then reperfusion for 24 h,the neurological function of rats was scored and the volume of cerebral infarction was measured by the 2,3,5-triphenyltet-razolium chloride staining method.The molecular network analysis technique of network pharmacology,protein-protein interaction network,gene ontology(GO)enrichment analysis,KEGG signal pathway analysis,and molecular docking was used to study the mechanism of Anchusa italica Retz in the treatment of cerebral ischemia-reperfusion injury.Results The administration of An-chusa italica Retz could significantly improve the neurobehavioral dysfunction caused by cerebral ischemia-reperfusion injury and reduce the pathological injury of brain tissue.Anchusa italica Retz could regulate inflammation,apoptosis,protein phosphorylation,and other biological processes through 143 ischemic stroke-related targets,and interfere with the TNF signal pathway,VEGF signal pathway,HIF-1 signal pathway,and other pathways.Conclusion Network pharmacology and experimental verification had shown that Anchusa italica Retz could effectively reduce brain injury and protect neurological function through multi-target,multi-mechanism,and holistic treatment of cerebral ischemia-reperfusion injury.

Objective To explore and verify the protective and therapeutic effects and possible mechanisms of Zukamu granules on hypoxia alone and hypoxia+Su5416-induced hypoxic pulmonary hypertension(HPH)in mice.Methods Multiple databases and related literature were used to collect the active ingredients data in Zukamu granules and the HPH-related targets were predicted and obtained.The network construction and enrichment analysis were performed.The HPH mouse models were es-tablished by two-week hypoxia and four-week hypoxia+Su5416 induction,and the relevant indicators and the main pharmacodyna-mic indexes such as right ventricular pressure were tested.Masson staining was used to observe the pathological changes in lung tissues,and Western blotting was used to detect the expression levels of bax,bcl-2,PI3K,p-PI3K,eNOS,and HIF-1α in lung tis-sues.Results A total of 167 active ingredients of Zukamu granules were screened,with 179 intersecting targets with HPH,in-cluding targets like PIK3CA and HIF-1.The validation experimental results showed that Zukamu granules could significantly re-duce right ventricular systolic pressure and right ventricular hypertrophy in HPH mice,and down-regulate the expression of bcl-2 and HIF-1α and up-regulate the expression of bax,PI3K,p-PI3K and eNOS in mice lung tissues.Conclusion Zukamu gran-ules may act against HPH by modulating bax/bcl and PI3K-eNOS/HIF-1α signaling pathways.

Objective:To evaluate the role of lactate dehydrogenase in diabetic neuropathic pain (DNP) and the relationship with peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in mice.Methods:SPF-grade healthy male C57BL/6J mice, aged 6-8 weeks, weighing 18-22 g, were used to establish diabetes mellitus model by intraperitoneal injection of streptozotocin (STZ) 120 mg/kg. Twenty-four mice with diabetes mellitus were divided into 2 groups ( n=12 each) using a random number table method: DNP group and DNP + oxamate group (OXA group). Another 12 SPF-grade healthy male C57BL/6J mice were selected as control group (C group). In OXA group, oxamate 750 mg/kg was intraperitoneally injected once a day for 28 consecutive days. The equal volume of normal saline was given instead in C group and DNP group. The mechanical paw withdrawal threshold (MWT), blood glucose and body weight were measured at 3 days before STZ injection and at 1, 2, 3 and 4 weeks after STZ injection (T 0-4). After the last behavioural test was completed, blood samples were collected from the posterior orbits of anesthetized mice for determination of serum lactate concentrations. The animals were then sacrificed and the tissues from the prefrontal cortex of the brain were taken for determination of lactate content, mitochondrial membrane potential (by the JC-1), content of reactive oxygen species (ROS) (using dihydroethidium probes), and level of histone lactylation and expression of PGC-1α (by Western blot). Results:Compared with C group, the MWT was significantly decreased at T 2-4, the serum lactate concentrations, contents of lactate and ROS and level of histone lactylation were increased, the mitochondrial membrane potential was decreased, and the expression of PGC-1α was down-regulated in DNP and OXA groups ( P<0.05). Compared with DNP group, no significant change was found in blood glucose and body weight ( P>0.05), the MWT was significantly increased at T 2-4, the serum lactate concentrations, contents of lactate and ROS and level of histone lactylation were decreased, the mitochondrial membrane potential was increased, and the expression of PGC-1α was up-regulated in OXA group ( P<0.05). Conclusions:Lactate dehydrogenase promotes the development of DNP, and the mechanism is related to promotion of increase in histone lactfication and down-regulation of PGC-1α expression in the prefrontal cortex of mice.

Objective To investigate the risk factors for identifying local tumor progression(LTP)in patients with hepatocellular carcinoma(HCC)after radiofrequency ablation(RFA)and to establish a predictive model.Methods The clinical data of 122 HCC patients treated by RFA were analyzed retrospectively,and then the patients were divided into positive and negative LTP groups according to that whether LTP occurred within 12 months after RFA.The risk factors of LTP were determined using univariate and multivari-ate analysis,and the predictive model was constructed based on these factors and the internal validation was conducted.Results The results of this study showed that multiple number,diameter＞2 cm,rough margin,and adjacent to large blood vessels of the tumor could be independent predictors of LTP,which were further incorporated into constructing the predictive model.Internal validation results showed that the area under the curve(AUC)of receiver operating characteristic(ROC)curve was 0.815[95％confidence interval(CI)0.735-0.895],indicating the model with high differentiation ability.The calibration curve was drawn and the Hosmer-Lemeshow goodness-fit test showed that the model had good stability(P＞0.05).The decision curve suggested that the model had good clinical application value.Conclusion The independent risk factors of LTP of HCC after RFA are multiple number,diameter＞2 cm,rough margin,and adjacent to large blood vessels of the tumor.When the predictive model is integrated with the above factors,it can poten-tially predict the risk of local tumor and may offer useful guidance for individual treatment and follow-up.

Objective:To evaluate the role of lactate-induced mitochondrial division of spinal cord neurons in diabetic neuropathic pain (DNP) in mice.Methods:Thirty-six SPF-grade healthy adult male C57BL/6 mice, aged 2 months, weighing 20-25 g, were divided into 3 groups ( n=12 each) using a random number table method: control group (CON group), DNP group, and DNP+ sodium oxalate group (OXA group). The diabetic model was established by intraperitoneal injection of streptozotocin 130 mg/kg. After the diabetic model was successfully established, sodium oxalate 750 mg/kg was intraperitoneally injected once a day for 4 consecutive weeks to inhibit lactate production in OXA group, while the equal volume of normal saline was given instead at the same time in C group and DNP group. The mechanical paw withdrawal threshold (MWT) of the left hindpaw was measured before developing the model and at 1, 2, 3 and 4 weeks after developing the model. After completing the last behavioral testing, the spinal cord tissue of the lumbar segment (L 4-6) was taken for determination of the levels of lactate in serum and spinal cord tissues (by the colorimetric method), expression of the mitochondrial membrane potential, reactive oxygen species (ROS) content (using JC-1 or DHE probes), expression of mitochondrial dynamin-related protein 1 (Drp1) and mitochondrial protein mitofusin 2 (Mfn2) (by Western blot), and co-expression of Drp1 and neuronal neuronal marker neuronal nuclear protein (NeuN) (by immunofluorescence double labeling) and for examination of the structure and the number of mitochondria (with a transmission electron microscope). Results:Compared with C group, the MWT was significantly decreased after developing the model, the levels of lactate in serum and spinal cord tissues and ROS content in the spinal cord were increased, the mitochondrial membrane potential was decreased, the Drp1 expression was up-regulated, the Mfn2 expression was down-regulated, the number of mitochondria was increased, the area was reduced ( P<0.05), and the co-expression of Drp 1 and NeuN was increased in DNP group and OXA group. Compared with DNP group, the MWT was significantly increased after developing the model, the levels of lactate in serum and spinal cord tissues and ROS content in the spinal cord were decreased, the mitochondrial membrane potential was increased, the Drp1 expression was down-regulated, the Mfn2 expression was up-regulated, the number of mitochondria was decreased, the area was increased ( P<0.05), and the co-expression of Drp 1 and NeuN was decreased in OXA group. Conclusions:Lactate-induced excessive mitochondrial division of spinal cord neurons can lead to mitochondrial dysfunction, which may be involved in the maintenance mechanism of DNP in mice.

Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorders (PTLD) are one of the most severe complications after hematopoietic stem cell transplantation (HSCT). This study includes 31 cases of aplastic anemia (AA) patients who developed PTLD after haploidentical transplantation, summarizing their clinical characteristics and categorizing them into either rituximab monotherapy group or combination therapy group based on whether their condition improved by 1 log after a single dose of rituximab. The incidence of PTLD after HSCT in children with AA was 10.16%, and the incidence of PTLD in patients with age >10 years was significantly increased ( χ2=11.336, P=0.010). Of the 31 patients, 27 were clinically diagnosed and 4 were pathologically confirmed. Finally, 15 patients were classified into the rituximab treatment group and 15 patients into the combination treatment groups. Finally three patients died, and the 2-year overall survival rate was (89.7±5.6) %. Standard pre-treatment protocols and EBV reactivation are risk factors affecting the prognosis of PTLD. There was no statistically significant difference in the impact of the two treatment schemes on prognosis.

Objective:To investigate the efficacy and safety of venetoclax combined with the decitabine, cytarabine, and homoharringtonine (HHT) regimen and donor lymphocyte infusion (DLI) for the preventive and salvage therapy of pediatric acute myeloid leukemia (AML) /myelodysplastic syndrome (MDS) after allogeneic hematopoietic stem cell transplantation (HSCT) .Methods:A total of 29 relapsed pediatric/minimal residual disease-positive AML after HSCT were recruited at the Peking University Institute of Hematology from January 1, 2021, to June 1, 2023. They were treated with the above combination regimen and administered with DLI after 24-48 hours at the end of chemotherapy, and the treatment response and adverse reactions were regularly assessed.Results:The overall response rate (ORR) was 75.8%, CR rate was 88.9% (8/9) in the hematologic relapse group, and MRD negativity rate was 61.1% (11/18) in the MRD-positive group. The incidence of agranulocytosis, anemia, and thrombocytopenia with a classification above grade 3 were 100%, 82.7%, and 100%, respectively. The median time of the granulocyte deficiency period was 15 days. Acute graft-versus-host diseases (aGVHD) with a classification of grades Ⅲ-Ⅳ occurred in 11.1% of the patients after DLI, while moderate or severe cGVHD occurred in 7.4% of the patients. The single risk factor for ORR was MNC counts of less than 10×10 8/kg, and the relapse occurred within 100 days. At a median follow-up of 406 days, the 1-year OS was 65%, and the 1-year OS was 57% in the group with no reaction ( P=0.164) compared with 71% in the group who had an overall reaction. Conclusion:The combined regimen based on the DAC, VEN, and modified HA regimen showed a high response rate in the salvage therapy for pediatric AML after the relapse of HSCT. However, bridging to transplantation should be performed immediately after remission to result in a long survival rate.

Bariatric surgery has been proven to be the most effective intervention for the treatment of obesity and obesity-related complications. In recent decades, medical experts as well as scholars in China have been actively promoting and pushing the development of bariatric surgery, and conducting a series of clinical and basic research. As a result of their unremitting efforts, research in the field of bariatric surgery in China has developed extremely rapidly. The authors examined the overview of literature research in the field of bariatric surgery in China through bibliometric analysis, and analyzed the current status, hot spots, trends, and frontiers of research in this field, with the aim of providing references for future research and development.

Objective:To prepare a peptide fluorescent probe based on aggregation-induced emission and to investigate its application in the detection of early caries.Methods:Eight aspartate-serine-serine (DSS) were combined with aggregation-induced emission material to prepare peptide fluorescent probes, and an artificial demineralization model was established in vitro. The samples were immersed in the peptide fluorescent probe solution for 1 min, and a fluorescence imaging system was applied to examine the tooth samples and collect images and fluorescence data. Scanning electron microscopy was also applied to observe the phenotype of the teeth, and electron microscopy was applied to detect the calcium-phosphorus ratio on the enamel surface of the teeth. Polarized light microscopy was also applied to observe the enamel area of the teeth. Results:The fluorescence intensity of demineralized teeth was clearly observed to be lower than that of normal teeth in the peptide fluorescent probe-treated area, and the difference was statistically significant ( P < 0.05). The results of scanning electron microscopy showed that the enamel surface of the demineralized group had more irregular pores, while the enamel surface of the undemineralized group was flatter with only some irregular accumulation of flakes. The results of polarized light microscopy showed that a clear birefringence could be observed in the enamel region of normal teeth, while a black area or the disappearance of the birefringence effect accompanied by a partial black dark shadow could be observed in the enamel region of demineralized teeth. Conclusions:An aggregation-induced luminescence-based peptide fluorescent probe was successfully prepared, which can precisely localize the enamel and show some application value in early caries detection.

Objective:To investigate the level change of serum total n-terminal propeptide of type Ⅰ precollagen (t-PINP) /type Ⅰ collagen carboxy-terminal peptide (beta-CTX) ratio, 25-hydroxyvitamin D (25-hydroxyvitamin D, 25 (OH) ) ratio, and 25-hydroxyvitamin D in elderly women with differentiated thyroid cancer (DTC) after surgery and its value in the prevention and treatment of osteoporosis (OP) .Methods:From Jan. 2020 to May. 2021, 112 elderly female postoperative DTC patients treated with thyroid stimulating hormone (TSH) suppression in Department of Endocrinology of Wenzhou Hospital of Integrative Medicine were collected for a prospective study, and the incidence of OP after 1 year of treatment was counted, and according to the incidence of OP, they were divided into incidence group ( n=78) and non-incidence group ( n=34). The general information, thyroid parameters [TSH, free triiodothyronine (FT3), free thyroxine (FT4) ], bone mineral density (BMD), and serum t-titrosine (BMD) were compared between the two groups. SPSS22.0 software was used, and the counting data was described by examples χ2 test. Grade data was expressed in u, Ridit test was used, measurement data was described in mean±standard deviation ( ±s), t test was used, Pearson correlation coefficient model was used to analyze postoperative thyroid index and serum t-PINP/β- Correlation between CTX ratio and 25 (OH) D level, and serum t-PINP after 1 year of treatment was analyzed through interaction/β- The role of CTX ratio and 25 (OH) D level in OP occurrence. Results:The incidence of OP after 1 year of TSH suppression treatment in 112 elderly female post-DTC patients in this study was 69.64% (78/112) ; serum TSH levels (0.63±0.19) mIU/ml after 1 year of treatment in patients who developed OP were lower than those in patients who did not develop OP (0.81±0.22) mIU/ml, and serum FT3 (6.15±1.71) pmol/ml and FT4 levels (24.63±4.28) pmol/ml were higher than those of patients without OP (4.32±1.29) pmol/ml and (20.36±3.70) pmol/ml ( t1=4.391, t2=5.581, t3=5.050,all P<0.05) .Serum t-PINP/β-CTX ratio (130.27±18.09) and 25 (OH) D level (20.18±4.15) ng/ml after 1 year of treatment in patients with OP were lower than those in patients without OP (148.56±20.37) and (23.36±4.36) ng/ml ( t1=4.733, t2=3.672, both P<0.05) ; serum TSH levels were positively correlated with serum t-PINP/β-CTX ratio and 25 (OH) D levels, and serum FT3 and FT4 levels were negatively correlated with serum t-PINP/β-CTX ratio and 25 (OH) D levels after 1 year of treatment in patients with OP ( P<0.05) ; low serum t-PINP/β-CTX ratio after 1 year of treatment expression, and low 25 (OH) D levels showed a positive interaction in OP occurrence in a superphase multiplicative model ( P<0.05) . Conclusion:Serum t-PINP/β-CTX ratio and 25 (OH) D level are closely associated with the occurrence of OP after DTC in elderly women, and postoperative monitoring can help prevent and treat OP.