Based on the theory of "sweet-flavored medicinals retaining and restoring body fluid"， this paper proposed that the core pathogenesis of hypercoagulable state in malignant tumors is qi deficiency and fluid consumption， blood stasis and vessels stagnation， which evolves dynamically according to the pattern "qi deficiency → fluid consumption → blood stasis". Accordingly， a staged treatment system is established with the general principle of "fortifying the middle jiao， restoring fluid and activating blood circulation". In the initial stage， invigorating the spleen and boosting qi to generate body fluid， targeting the onset of middle jiao deficiency and body fluid consumption； in the middle stage， nourishing yin and unblocking collaterals to facilitate body fluid circulation， addressing the disorder of body fluid transportation and collateral injury caused by internal dryness； in the late stage， consolidating yin and resolving blood stasis to retain body fluid， resolving yin impairment， fluid exhaustion， and binding of stasis and toxin. By regulating body fluid metabolism to improve the hypercoagulable state， this system is intended to provide insights for the prevention and treatment of hypercoagulable state in malignant tumors with traditional Chinese medicine.

This study aims to investigate the potential effect of the water extract of fresh Rehmanniae Radix on hypercholesterolemia in mice that was induced by a high-fat and high-cholesterol diet and explore its possible mechanism from bile acid reabsorption. Male C57BL/6 mice were randomly assigned into the following groups: control, model, low-and high-dose(4 and 8 g·kg~(-1), respectively) fresh Rehmanniae Radix, and positive drug(simvastatin, 0.05 g·kg~(-1)). Other groups except the control group were fed with a high-fat and high-cholesterol diet for 6 consecutive weeks to induce hypercholesterolemia. From the 6th week, mice were administrated with corresponding drugs daily via gavage for additional 6 weeks, while continuing to be fed with a high-fat and high-cholesterol diet. Serum levels of total cholesterol(TC), triglycerides(TG), low density lipoprotein-cholesterol(LDL-c), high density lipoprotein-cholesterol(HDL-c), and total bile acid(TBA), as well as liver TC and TG levels and fecal TBA level, were determined by commercial assay kits. Hematoxylin-eosin(HE) staining, oil red O staining, and transmission electron microscopy were performed to observe the pathological changes in the liver. Three livers samples were randomly selected from each of the control, model, and high-dose fresh Rehmanniae Radix groups for high-throughput transcriptome sequencing. Differentially expressed genes were mined and KEGG pathway enrichment analysis was performed to predict the key pathways and target genes of the water extract of fresh Rehmanniae Radix in the treatment of hypercholesterolemia. RT-qPCR was employed to measure the mRNA levels of cholesterol 7α-hydroxylase(CYP7A1) and cholesterol 27α-hydroxylase(CYP27A1) in the liver. Western blot was employed to determine the protein levels of CYP7A1 and CYP27A1 in the liver as well as farnesoid X receptor(FXR), apical sodium-dependent bile acid transporter(ASBT), and ileum bile acid-binding protein(I-BABP) in the ileum. The results showed that the water extract of fresh Rehmanniae Radix significantly lowered the levels of TC and TG in the serum and liver, as well as the level of LDL-c in the serum. Conversely, it elevated the level of HDL-c in the serum and TBA in feces. No significant difference was observed in the level of TBA in the serum among groups. HE staining, oil red O staining, and transmission electron microscopy showed that the water extract reduced the accumulation of lipid droplets in the liver. Further mechanism studies revealed that the water extract of fresh Rehmanniae Radix significantly down-regulated the protein levels of FXR and bile acid reabsorption-related proteins ASBT and I-BABP. Additionally, it enhanced CYP7A1 and CYP27A1, the key enzymes involved in bile acid synthesis. Therefore, it is hypothesized that the water extract of fresh Rehmanniae Radix may exert an anti-hypercholesterolemic effect by regulating FXR/ASBT/I-BABP signaling, inhibiting bile acid reabsorption, and increasing bile acid excretion, thus facilitating the conversion of cholesterol to bile acids.
Animals ; Male ; Bile Acids and Salts/metabolism* ; Mice, Inbred C57BL ; Mice ; Diet, High-Fat/adverse effects* ; Cholesterol/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Hypercholesterolemia/genetics* ; Receptors, Cytoplasmic and Nuclear/genetics* ; Rehmannia/chemistry* ; Liver/drug effects* ; Humans ; Cholesterol 7-alpha-Hydroxylase/genetics* ; Plant Extracts

A retrospective analysis was conducted on the clinical course of two children with PICALM-MLLT10-positive acute leukemia treated at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, between July 2021 and July 2023. The patients were diagnosed with acute T-lymphoblastic leukemia with central nervous system involvement and high-risk acute myeloid leukemia, respectively. Both achieved bone marrow complete remission after conventional chemotherapy combined with venetoclax. Following conversion to molecular negativity, they underwent sequential allogeneic hematopoietic stem cell transplantation. At the latest follow-up, both patients were alive and in good clinical condition. These observations suggest that proceeding to hematopoietic stem cell transplantation after venetoclax-based chemotherapy may improve the long-term survival of children with PICALM-MLLT10-positive leukemia.
Humans ; Hematopoietic Stem Cell Transplantation ; Male ; Female ; Child, Preschool ; Transplantation, Homologous ; Child ; Leukemia, Myeloid, Acute/genetics* ; Oncogene Proteins, Fusion/genetics*

OBJECTIVE: To elucidate the modulation mechanism of Suanzaoren Decoction (SZRD) on basolateral amygdala (BLA) neuronal activity to alleviate chronic restraint stress (CRS)-related behavioral deficits. METHODS: The male C57BL/6J mice were assigned to 4 groups using the complete randomization method, including control (CON, n=19), CRS (n=19), SZRD (n=21), and fluoxetine (Flu, n=22) groups. Mice were restrained for 6 h per day, over a 21-d period to establish CRS models. The CON group remained in their cages without food or water during the 6-h matching period. SZRD and Flu groups received intragastric administration of SZRD (4.68 g/kg) and Flu (20 mg/kg) daily, respectively, 30 min before restraint for 21 consecutive days. The therapeutic effects of SZRD were evaluated using behavioral tests including the tail suspension test, elevated plus maze test, and forced swimming test. The cellular Fletcher B. Judson murine osteosarcoma proto-oncogene (c-Fos) expression in the BLA was measured using immunofluorescence, while action potential (AP) firing and synaptic transmission in BLA pyramidal neurons were evaluated using whole-cell patch-clamp recordings. RESULTS: SZRD administration significantly increased time spent in the open arms and open-arm entries while reducing immobility time (P<0.05 or P<0.01). It downregulated CRS-induced c-Fos expression and AP firing of pyramidal neurons in the BLA (P<0.01). Additionally, SZRD selectively attenuated excitatory (P<0.01), but not inhibitory, synaptic transmission onto BLA pyramidal neurons. CONCLUSION SZRD alleviated CRS-induced anxiety- and depression-like behaviors in mice by modulating the excitability and synaptic transmission of BLA pyramidal neurons.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Depression/complications* ; Pyramidal Cells/pathology* ; Male ; Mice, Inbred C57BL ; Basolateral Nuclear Complex/pathology* ; Restraint, Physical ; Anxiety/complications* ; Behavior, Animal/drug effects* ; Stress, Psychological/physiopathology* ; Mice ; Proto-Oncogene Proteins c-fos/metabolism* ; Action Potentials/drug effects* ; Synaptic Transmission/drug effects*

Objective To analyze the epidemiological distribution characteristics and influencing factors of treat-ment outcome of pulmonary tuberculosis(PTB)patients complicated with diabetes mellitus(DM)in Bijie City from 2017 to 2022,and provide reference for formulating prevention and control measures of PTB-DM.Methods The registered management cases of PTB patients combined with DM from the tuberculosis surveillance report informa-tion management system in Bijie City in 2017-2022 were collected.Changing trends in annual registration rates and successful treatment rates were analyzed with Joint-point regression models.Different characteristics between pa-tients with PTB-DM and PTB alone were conducted comparative analysis;the influencing factors of treatment out-come were analyzed by x2 test and binary logistic regression analysis.Results A total of 679 PTB-DM patients were registered in Bijie City from 2017 to 2022,accounting for 1.53％of total PTB patients,the annual registration rate increased from 1.11/100 000 in 2017 to 3.08/100 000 in 2022,with an increasing trend in the annual percentage change(APC=26.67％,95％CI:5.36％-52.29％,t=3.564,P=0.024).In the analysis on characteristics,the proportion of PTB-DM male patients,age ≥45 years and farmers,the ratio of direct consultation to transfer treat-ment,the pathogenicity positive rate,the proportion re-treatment,and rate of delay in consultation were all higher than those of PTB alone;successful treatment rate and proportion of floating population were all lower than PTB alone,difference were all statistically significant(all P＜0.05).The successful treatment rate of PTB-DM patients in Bijie City from 2017 to 2022 was 87.80％.Age,occupation,pathogenicity diagnosis results were influencing fac-tors for treatment outcome in patients with PTB-DM,with farmers(OR=3.68,95％CI:1.22-11.09),with pathogenicity positivity(OR=2.84,95％CI:1.24-6.50),and without pathogenic detection result+tuberculous pleurisy(OR=11.35,95％CI:2.16-59.74)being risk factors for successful treatment.Conclusion Although the proportion of PTB-DM in the total PTB patients in Bijie City from 2017 to 2022 was not high,it showed an up-ward trend;it is necessary to attach great importance to male,re-treated,farmer,and pathogenicity positivity co-morbid patients in Bijie City,and strengthen the two-way screening of PTB-DM in high-risk populations.

Objective Using event-related potentials(ERPs)technology to study the effect of long term emotional distress on selective attention distraction inhibition function in college students and its neuroelectrophysiological mechanism.Methods The Eysenck personality questionnaire(EPQ)adult version was used to screen the high and low neuroticism groups among college students,and 35 subjects in each group were included in the long term emotional distress group and the emotional smoothness control group,respectively,and the response time,correct rate,N2 and P3 amplitude and latency results of the participants to complete the negative priming paradigm task were collected and analyzed.Results Compared with the control group,① the long term emotional distress group showed a prolonged response trend(P=0.072).② the long term emotional distress group had a prolonged N2 and P3 latency(P<0.05).Conclusion Selective attention distraction inhibition in college students with long term emotional distress decreased,and the decline mechanism may be related to the decline of inhibition processing and attention resource allocation ability.

Objective To investigate the effect of Qi stagnation on inhibitory control function and its neuroelectrophysiological mechanism in college students.Methods The population of peace and Qi depression was screened from college students through the scale of"Classification and Judgment Criteria of Traditional Chinese Medicine Constitution",and 35 subjects were included in each group.Combined with event-related potential technology,the two groups were collected to complete the Flanker paradigm behavioral indicators(accuracy,response time)and EEG data indicators(amplitude and latency of N2 and P3 components),and the behavioral differences and neuroelectrophysiological mechanisms between the two groups under the Flanker paradigm were explored.Results Compared with the flat group,the reaction time of the gas depression group was longer(P=0.07).Compared with the consistent dondition,the reaction time was longer under the inconsistent condition(P<0.001),and the accuracy rate was lower under the inconsistent condition significantly(P<0.001).Compared with the peaceful group,the N2 amplitude of the air depression group was higher(P<0.05).There was a statistically significant difference in the main effect of brain regions in the N2 latency period(P<0.001).Frontal lobe zero(Fz)in frontal region was greater than Frontal lobe central zero(FCz)in frontal region and greater than Central zero(Cz)in central region(P<0.05).There was a statistically significant difference in the main effect of brain region(P<0.001).FCz in the frontal central region was significantly greater than that in the frontal region Fz(P<0.001),and the difference was statistically significant in the central region Cz was significantly greater than that in the frontal region(P<0.001).The incubation period of P3 component was significantly smaller than that of inconsistent stimulation(P<0.001).Conclusion Qi stagnation has a negative effect on the inhibitory control function of college students,and the decline of conflict monitoring and control ability is one of the possible mechanisms.

Objective To investigate the influence of the liver failing to convey and disperse on space navigation aging.Methods High and low neuroticism subjects screened by Eysenck personality questionnaire were included in liver failing to convey and disperse group and liver controlling conveyance and dispersion group,respectively.The two groups were then divided into youth and elderly groups based on age.Finally,spatial navigation task was conducted to record and analyze behavioral(reaction time and accuracy)and EEG data(amplitude and latency of P2 and N2 components)of all the four groups(30 subjects each group).Results Compared with liver controlling conveyance and dispersion group,the accuracy in subjects with liver failing to convey and disperse decreased significantly(P<0.001)and reaction time was prolonged significantly(P<0.05).The interaction effect between age and liver regulation status showed a marginal significant difference(P=0.078).The accuracy of elderly people was lower than that of youth people(P=0.002)for liver failing to convey and disperse subjects,while there was no significant difference between the two groups for subjects with liver controlling conveyance and dispersion.The P2 amplitude in the elderly group was significantly smaller than that in the youth group(P=0.027).The amplitude of P2 in group of liver failing to convey and disperse was significantly smaller than that in group of liver controlling conveyance and dispersion(P=0.042).The interaction effect of P2 amplitude between age and liver regulation status showed a marginal significance(P=0.073).For youth subjects,the P2 amplitude in group of liver controlling conveyance and dispersion was significantly larger than that in group of liver failing to convey and disperse(P=0.007),while there was no significant difference in P2 amplitude between the two groups for the elderly subjects.The N2 amplitude for tasks of allocentric frames of reference was significantly greater than that of egocentric frames of reference(P=0.024).Conclusion Liver failing to convey and disperse caused by long-term emotional disturbance accelerates spatial navigation aging,and selective attention feature inhibition disorder may be the underlying ERPs neuroelectrophysiological mechanism.

Objective To investigate the influence of the and mechanism of liver failing to convey and disperse on age-related changes in attentional search based on ERPs.Methods oddball attention search task was administrated to record and analyze behavioral and EEG data(N2pc、SPCN、N2pc-Ptc components)of 120 subjects.Results Compared with liver controlling conveyance and dispersion group,the accuracy in subjects with liver failing to convey and disperse decreased significantly(P<0.05).The elderly group had a lower accuracy(P<0.001)and a longer reaction time(P<0.001)compared to the young group.The N2pc amplitude in subjects with liver failing to convey and disperse was significantly greater than that in subjects with liver controlling conveyance and dispersion(P<0.05).The interaction effect of SPCN amplitude between age and liver failing to convey and disperse status was significant(P=0.024).And in the elderly group,SPCN amplitude in subjects with liver dysregulation was significantly smaller than that of liver controlling conveyance and dispersion(P=0.042).The N2pc-Ptc peak to peak amplitude interaction effect between age and liver regulation status was marginal significant(P=0.087),and in liver failing to convey and disperse group,N2pc-Ptc peak to peak amplitude of the elderly was significantly smaller than that of the young(P=0.008).Conclusion Attention search ability is impaired in the elderly with liver failing to convey and disperse,and the electrophysiological abnormalities,such as directed attention allocation,spatiotemporal dynamic cohesion and short-term memory maintenance,may be part of the mechanism.

The rise of nanomedicine has opened up new avenues for drug delivery and tumor treatment.Nanocarriers,in particular,have become core tools in the field of drug delivery.Anti-cancer peptides(ACPs)can achieve anti-tumor effects by inducing tumor cell apoptosis,inhibiting angiogenesis,and regulating the immune microenvironment.Their low toxic side effects and drug resistance make them im-portant in the field of cancer treatment.However,ACPs face limitations such as poor stability,short in vivo half-life,and low targeted delivery efficiency,which seriously limit their therapeutic effects and fur-ther development.Nanocarriers provide an efficient,flexible and precise solution for the delivery of ACPs due to their advantages of increasing drug solubility,changing drug distribution in the body and improving drug targeting.This review systematically summarizes the structural characteristics and biological proper-ties of four types of nanocarriers,including liposome nanocarriers,polymer nanocarriers,inorganic nano-carriers,and self-assembled peptides,and focuses on analyzing the application examples of nanocarriers in enhancing the stability of ACPs,improving targeted delivery efficiency,improving bioavailability,and overcoming drug-resistant tumor treatment.We also summarize in detail the structural pros and cons of these four carriers.Finally,we look forward to the development direction of research on the combination of nanocarriers and ACPs,in order to provide a theoretical basis for the clinical application of ACPs.