Objective:To explore the correlation between ASXL1 gene mutation characteristics and clinical manifestations and prognosis in patients with myelodysplastic syndrome(MDS).Methods:The clinical date of 264 patients with MDS in Xuzhou Central Hospital,Southeast University from August 2010 to April 2024 was retrospectively analyzed.The patients were divided into ASXL1wt group and ASXL1mut group according to the presence of ASXL1 gene mutation,and the correlation between gene mutation characteristics and clinical manifestations and prognosis was analyzed.Results:Compared with ASXL1wt group,the ASXL1mut group had a higher age of onset(P＜0.05),a higher proportion of males(P＜0.05),while the incidence of del(5q)was lower(P＜0.01).The mutation frequency of ASXL1 in MDS patients was 21.97％,and most of them were frameshift mutations.The p.Gly646fs was the most common amino acid variant,with a mutation frequency of 20.69％.The median overall survival(OS)and leukemia-free survival of patients with this sequence variant was 18.1 and 23.8 months,respectively,while in those without this sequence variant was 30 months and not reached,and the differences were statistically significant(P＜0.05).The results of multivariate analysis showed that the mutation of NRAS,WT1,KIT gene and the p.Gly646fs sequence mutation of ASXL1 gene were independent prognostic factors for OS in ASXL1mut patients.The median OS of ASXL1wt and ASXL1mut patients was 27.9(21.3-40.4)and 23.7(18.6-NA)months,respectively(P＞0.05).Among 58 ASXL1mut patients,5 cases(8.6％)transformed to acute leukemia,including 3 cases with RUNX1 mutation and 3 cases with TET2 mutation.Among 206 ASXL1wt patients,28 cases(13.6％)transformed to acute leukemia.The difference in leukemia transformation rate between the two groups was not statistically significant(P＞0.05).The efficacy of different treatment regimens was similar in the ASXL1mut group,while in the ASXL1wt group,patients receiving allogeneic hematopoietic stem cell transplantation had a significantly better prognosis than those receiving other treatment regimens(P＜0.001).The overall response rate to demethylation therapy was 68.7％and 67.6％in ASXL1mut and ASXL1wt group,respectively,and the difference between the two groups was not significant(P＞0.05).Conclusion:The overall survival of MDS patients with ASXL1mut is poor.The patients with p.Gly646fs sequence mutation have a higher proportion of bone marrow blasts and a worse prognosis.There are no statistical differences in efficacy of different treatment strategies in ASXL1mut group.ASXL1 mutation shows no significant effect on the response of MDS to hypomethylating agent therapy.

Objective:To explore the correlation between ASXL1 gene mutation characteristics and clinical manifestations and prognosis in patients with myelodysplastic syndrome(MDS).Methods:The clinical date of 264 patients with MDS in Xuzhou Central Hospital,Southeast University from August 2010 to April 2024 was retrospectively analyzed.The patients were divided into ASXL1wt group and ASXL1mut group according to the presence of ASXL1 gene mutation,and the correlation between gene mutation characteristics and clinical manifestations and prognosis was analyzed.Results:Compared with ASXL1wt group,the ASXL1mut group had a higher age of onset(P＜0.05),a higher proportion of males(P＜0.05),while the incidence of del(5q)was lower(P＜0.01).The mutation frequency of ASXL1 in MDS patients was 21.97％,and most of them were frameshift mutations.The p.Gly646fs was the most common amino acid variant,with a mutation frequency of 20.69％.The median overall survival(OS)and leukemia-free survival of patients with this sequence variant was 18.1 and 23.8 months,respectively,while in those without this sequence variant was 30 months and not reached,and the differences were statistically significant(P＜0.05).The results of multivariate analysis showed that the mutation of NRAS,WT1,KIT gene and the p.Gly646fs sequence mutation of ASXL1 gene were independent prognostic factors for OS in ASXL1mut patients.The median OS of ASXL1wt and ASXL1mut patients was 27.9(21.3-40.4)and 23.7(18.6-NA)months,respectively(P＞0.05).Among 58 ASXL1mut patients,5 cases(8.6％)transformed to acute leukemia,including 3 cases with RUNX1 mutation and 3 cases with TET2 mutation.Among 206 ASXL1wt patients,28 cases(13.6％)transformed to acute leukemia.The difference in leukemia transformation rate between the two groups was not statistically significant(P＞0.05).The efficacy of different treatment regimens was similar in the ASXL1mut group,while in the ASXL1wt group,patients receiving allogeneic hematopoietic stem cell transplantation had a significantly better prognosis than those receiving other treatment regimens(P＜0.001).The overall response rate to demethylation therapy was 68.7％and 67.6％in ASXL1mut and ASXL1wt group,respectively,and the difference between the two groups was not significant(P＞0.05).Conclusion:The overall survival of MDS patients with ASXL1mut is poor.The patients with p.Gly646fs sequence mutation have a higher proportion of bone marrow blasts and a worse prognosis.There are no statistical differences in efficacy of different treatment strategies in ASXL1mut group.ASXL1 mutation shows no significant effect on the response of MDS to hypomethylating agent therapy.

Arrhythmia is an external manifestation of cardiac electrophysiological disorder. It exists in healthy people and patients with various heart diseases, which is often associated with other cardiovascular diseases. The contraction and diastole of myocardium are inseparable from the movement of ions. There are many ion channels in the membrane and organelle membrane of myocardium. The dynamic balance of myocardial ions is vital in maintaining myocardial electrical homeostasis. Potassium ion channels that have a complex variety and a wide distribution are involved in the whole process of resting potential and action potential of cardiomyocytes. Potassium ion channels play a vital role in maintaining normal electrophysiological activity of myocardium and is one of the pathogenesis of arrhythmia. Traditional Chinese medicine(TCM)has unique advantages in treating arrhythmia for its complex active components and diverse targets. A large number of TCM preparations have definite effect on treating arrhythmia-related diseases, whose antiarrhythmic mechanism may be related to the effect on potassium channel. This article mainly reviewed the relevant studies on the active components in TCM acting on different potassium channels to provide references for clinical drug use and development.
Humans ; Potassium Channels ; Medicine, Chinese Traditional ; Anti-Arrhythmia Agents/therapeutic use* ; Arrhythmias, Cardiac/drug therapy* ; Heart Diseases/drug therapy* ; Ions

Objective To determine the optimal dosage and intervention duration of reserpine to establish a rat model of hypotension.Methods According to the body weight and systolic blood pressure (SBP),60 male Wistar rats were assigned to six groups (n=10),including a control group and five observation groups with different doses.The control group was administrated with 10 ml/kg 0.5% sodium carboxymethyl cellulose solution,and the observation groups with 0.016,0.032,0.064,0.128,and 0.160 mg/kg reserpine suspensions,respectively.All the groups were administrated by gavage twice a day,and the body weights of rats were monitored daily.SBP and heart rate (HR) were measured before modeling and 1-6 weeks after administration.After 6 weeks of administration,the blood samples of inner canthus were collected.The levels of lactate dehydrogenase (LDH),creatine kinase MB isoenzyme (CK-MB),alanine aminotransferase,aspartate aminotransferase (AST),serum creatinine,and blood urea nitrogen (BUN) were measured by an autoanalyzer.Three rats in each group were randomly selected for observation of the changes in SBP after drug withdrawal and the rest rats were sacrificed for measurement of the levels of norepinephrine and dopamine in the brain.Results Compared with the control group,different doses of reserpine lowered the SBP of rats (F=28.492,P<0.001).The decline in SBP increased in a concentration-dependent manner.SBP reached the lowest value after 1 week,rose slightly later,and was stable after 3 weeks of administration.There was no significant difference in SBP between 0.016 mg/kg reserpine group and the control group after the 5th week (P>0.05).The SBP levels of rats in 0.032,0.064,0.128,and 0.160 mg/kg reserpine groups showed no significant difference between each other (P=0.204) and were lower than that in the control group (all P<0.001).One week after drug withdrawal,the SBP of rats in the observation groups rose to the baseline level and remained stable.HR showed similar changes among groups,first increasing and then decreasing.There was no significant difference in HR among different groups at the same time point (F=0.922,P=0.475).Compared with the control group,reserpine of different doses reduced the norepinephrine content in the hippocampus (all P<0.001),and 0.128 mg/kg (P=0.045) and 0.160 mg/kg (P=0.042) reserpine lowered the dopamine level in the striatum,which showed no significant differences between different reserpine groups(P=0.343,P=0.301).The levels of LDH,CK-MB,and BUN in the serum increased with the increase in reserpine concentration,and the levels of LDH (P=0.001),CK-MB (P=0.020),AST (P=0.007),and BUN (P=0.001) in the 0.160 mg/kg reserpine group were significantly different from those in the control group.Conclusions The rat model of hypotension can be induced by gavage with reserpine.The gavage with reserpine at a dose of 0.032 mg/kg,twice a day for three consecutive weeks is the optimal scheme for the modeling.After the model establishment,continuous administration is essential to maintain the hypotension.
Male ; Rats ; Animals ; Reserpine ; Dopamine ; Rats, Wistar ; Hypotension/chemically induced* ; Norepinephrine

OBJECTIVE: To investigate the application effect of sequential autologous hematopoietic stem cell transplantation (Auto-HSCT) with lenalidomide, bortezomib and dexamethasone (RVD) in the treatment of multiple myeloma (MM) evaluated by propensity score matching. METHODS: The clinical data of 49 MM patients treated with RVD scheme and followed-up for 36 months in the hospital from January 2015 to January 2021 were retrospectively analyzed and included in the control group, the clinical data of 54 MM patients who received RVD scheme and sequential Auto-HSCT scheme and completed 36 months of follow-up in the hospital during the same period were collected and included in the observation group. PSM method (1∶1, caliper value=0.01) was used to match the control group with the observation group based on baseline data and laboratory indexes, covariate equilibrium samples were obtained between groups (40 cases in each group). The clinical efficacy of patients in the two groups after 18 weeks of treatment was compared; the incidence of toxic and side effects during treatment of patients in the two groups was compared; the survival of patients in the two groups was compared after 36 months of follow-up. RESULTS: The ORR and DCR in the observation group were higher than those in the control group, the difference was statistically significant (P<0.05). Compared the incidence of fatigue, rash, thrombocytopenia, anemia and nausea of patients in the two groups, there was no statistical significant difference (P>0.05). After 36 months of follow-up (no loss during follow-up), 4 cases died from illness in the observation group, with a survival rate of 90% and an average survival time of 35.61 (95% CI: 35541-35.685) months, 10 cases died from illness in the control group, with a survival rate of 75% and an average survival time of 34.70 (95% CI: 34.559-34.832) months, the survival rate of the observation group was higher than that of the control group, the difference was statistically significant (P<0.05). CONCLUSION Sequential Auto-HSCT with RVD regimen in the treatment of MM can improve the short-term efficacy and increase the survival rate of patients, which will not increase toxic and side effects and has high safety.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Bortezomib/therapeutic use* ; Dexamethasone ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Humans ; Multiple Myeloma/drug therapy* ; Propensity Score ; Retrospective Studies ; Transplantation, Autologous/methods* ; Treatment Outcome

Alzheimer's disease(AD) patients in China have been surging, and the resultant medical burden and care demand have a huge impact on the development of individuals, families, and the society. The active component compound of Epimedii Folium, Astragali Radix, and Puerariae Lobatae Radix(YHG) can regulate the expression of iron metabolism-related proteins to inhibit brain iron overload and relieve hypofunction of central nervous system in AD patients. Hepcidin is an important target regulating iron metabolism. This study investigated the effect of YHG on the expression of a disintegrin and metalloprotease-17(ADAM17), a key enzyme in the hydrolysis of β amyloid precursor protein(APP) in HT22 cells, by mediating hepcidin. To be specific, HT22 cells were cultured in vitro, followed by liposome-mediated siRNA transfection to silence the expression of hepcidin. Real-time PCR and Western blot were performed to examine the silencing result and the effect of YHG on hepcidin in AD cell model. HT22 cells were randomized into 7 groups: control group, Aβ25-35 induction(Aβ) group, hepcidin-siRNA(siRNA) group, Aβ25-35 + hepcidin-siRNA(Aβ + siRNA) group, Aβ25-35+YHG(Aβ+YHG) group, hepcidin-siRNA+YHG(siRNA+YHG) group, Aβ25-35+hepcidin-siRNA+YHG(Aβ+siRNA+YHG) group. The expression of ADAM17 mRNA in cells was detected by real-time PCR, and the expression of ADAM17 protein by immunofluorescence and Western blot. Immunofluorescence showed that the ADAM17 protein expression was lower in the Aβ group, siRNA group, and Aβ+siRNA group than in the control group(P<0.05) and the expression was lower in the Aβ+siRNA group(P<0.05) and higher in the Aβ+YHG group(P<0.05) than in the Aβ group. Moreover, the ADAM17 protein expression was lower in the Aβ+siRNA group(P<0.05) and higher in the siRNA+YHG group(P< 0.05) than in the siRNA group. The expression was higher in the Aβ+siRNA+YHG group than in the Aβ+siRNA group(P<0.05). The results of Western blot and real-time PCR were consistent with those of immunofluorescence. The experiment showed that YHG induced hepcidin to up-regulate the expression of ADAM17 in AD cell model and promote the activation of non-starch metabolic pathways, which might be the internal mechanism of YHG in preventing and treating AD.
ADAM17 Protein ; Alzheimer Disease/genetics* ; Amyloid beta-Peptides ; Drugs, Chinese Herbal/pharmacology* ; Hepcidins/genetics* ; Humans ; Pueraria

OBJECTIVE: Lung-toxin Dispelling Formula No. 1, referred to as Respiratory Detox Shot (RDS), was developed based on a classical prescription of traditional Chinese medicine (TCM) and the theoretical understanding of herbal properties within TCM. Therapeutic benefits of using RDS for both disease control and prevention, in the effort to contain the coronavirus disease 2019 (COVID-19), have been shown. However, the biochemically active constituents of RDS and their mechanisms of action are still unclear. The goal of the present study is to clarify the material foundation and action mechanism of RDS. METHODS: To conduct an analysis of RDS, an integrative analytical platform was constructed, including target prediction, protein-protein interaction (PPI) network, and cluster analysis; further, the hub genes involved in the disease-related pathways were identified, and the their corresponding compounds were used for in vitro validation of molecular docking predictions. The presence of these validated compounds was also measured in samples of the RDS formula to quantify the abundance of the biochemically active constituents. In our network pharmacological study, a total of 26 bioinformatic programs and databases were used, and six networks, covering the entire Zang-fu viscera, were constructed to comprehensively analyze the intricate connections among the compounds-targets-disease pathways-meridians of RDS. RESULTS: For all 1071 known chemical constituents of the nine ingredients in RDS, identified from established TCM databases, 157 passed drug-likeness screening and led to 339 predicted targets in the constituent-target network. Forty-two hub genes with core regulatory effects were extracted from the PPI network, and 134 compounds and 29 crucial disease pathways were implicated in the target-constituent-disease network. Twelve disease pathways attributed to the Lung-Large Intestine meridians, with six and five attributed to the Kidney-Urinary Bladder and Stomach-Spleen meridians, respectively. One-hundred and eighteen candidate constituents showed a high binding affinity with SARS-coronavirus-2 3-chymotrypsin-like protease (3CL), as indicated by molecular docking using computational pattern recognition. The in vitro activity of 22 chemical constituents of RDS was validated using the 3CL inhibition assay. Finally, using liquid chromatography mass spectrometry in data-independent analysis mode, the presence of seven out of these 22 constituents was confirmed and validated in an aqueous decoction of RDS, using reference standards in both non-targeted and targeted approaches. CONCLUSION RDS acts primarily in the Lung-Large Intestine, Kidney-Urinary Bladder and Stomach-Spleen meridians, with other Zang-fu viscera strategically covered by all nine ingredients. In the context of TCM meridian theory, the multiple components and targets of RDS contribute to RDS's dual effects of health-strengthening and pathogen-eliminating. This results in general therapeutic effects for early COVID-19 control and prevention.
Antiviral Agents ; chemistry ; therapeutic use ; Betacoronavirus ; chemistry ; enzymology ; Coronavirus Infections ; drug therapy ; prevention & control ; virology ; Cysteine Endopeptidases ; chemistry ; Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Humans ; Mass Spectrometry ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Pandemics ; prevention & control ; Pneumonia, Viral ; drug therapy ; prevention & control ; virology ; Protein Interaction Maps ; Viral Nonstructural Proteins ; chemistry

Temporary prescription preparation is the preparation processed into different dosage forms by relevant pharmacist according to the temporary preparation requirement and the personalized prescription made by the doctor in accordance with the syndrome differentiation and drug performance.It is an important part in personalized pharmaceutical services.Rational design of process route,production equipment and quality control method for the temporary prescription preparation,and establishment of technology research strategy and mode in accordance with the characteristics of traditional Chinese medicine temporary prescription preparations play an important role in promoting the development of the temporary prescription preparations.To promote the normalization,standardization and intelligent development of temporary prescription preparations,we would comprehensively summarize the significance,policy,technology characteristics,technology research status quo and existing problems in this paper,and put forward the research direction of temporary prescription preparation technology based on the physical properties of raw materials,equipment research strategy,and intelligent manufacturing technology.Thus it will push the inheritance and innovation of temporary prescription preparation.
Medicine, Chinese Traditional ; Prescriptions ; standards ; Quality Control ; Research Design

Objective The level of lactic acid in blood can reflect the degree of ischemia and hypoxia of brain tissue and cerebral perfusion pressure. The aim of this paper is to explore the value of blood lactate and lactate clearance in evaluating the survival rate and neurological outcome of patients with craniocerebral trauma. Methods The clinical data of 497 craniocerebral trauma patients admitted to our hospital from September 2017 to July 2018 were collected and retrospectively analyzed. Patients were divided into groups with different 6 h lactate clearance rates and admission lactate levels, and the differences in mortality and outcome of neurological function in each group were compared. Results The serum admission lactate levels、serum lactate levels at 6 hours, 28-day mortality and 28-day poor nerve function prognosis rate of patients with different 6h lactate clearance rates were statistically significant differences(P < 0. 05). The efficacy of 6h lactic acid to predict the mortality rate of patients was better than that of admission lactic acid and 6h lactate clearance rate (Z=3.71、Z=3.95,P<0.05). However, in predicting the neurological function of patients, the lactate clearance rate is not better than blood lactate level at any time(Z=1.30，Z=0.81，P>0.05). Conclusion 6h lactic acid has the best ability to judge the mortality of patients while lactic acid clearance rate is not better than the blood lactate level at any time in predicting the neurological function of patients.

BACKGROUNDConventional high ligation and stripping of the great saphenous vein (GSV) has a good curative effect but is highly traumatic with a considerable relapse rate. Subfascial endoscopic perforator surgery (SEPS) plus endovenous laser treatment (EVLT) could be applied as individual therapy. This study aimed to evaluate the feasibility of performing combined SEPS and EVLT without impacting GSV in the management of valvular insufficiency of the lower-limb venous perforators.

METHODSPlacement of lower-limb venous perforator insufficiency was marked by ascending phlebography in 83 affected limbs from September 2010 to June 2011. After randomization, SEPS was performed on 41 limbs to address the insufficiency of the venous perforators under the deep fascia, in combination with EVLT to close the superficial varicose veins without impacting the GSV. The remaining 42 limbs were treated using traditional GSV phlebectomy as controls.

RESULTSPostoperatively, all varicose veins were resolved, with lightening of the pigmentation and healing of the ulcer. Within a follow-up period of 5 - 11 months, no symptoms had recurred. Compared with the control group, the operation time, the number of incisions sutured, and the in-hospital time decreased on average by 1.5 hours, 4.7, and 6.8 days, respectively (P < 0.01 in all cases).

CONCLUSIONCombined SEPS and EVLT for treatment of valvular insufficiency of the lower-limb venous perforators offer the advantages of microtrauma and rapid cure.

Adult ; Aged ; Endovascular Procedures ; methods ; Female ; Humans ; Male ; Middle Aged ; Saphenous Vein ; surgery ; Varicose Ulcer ; surgery ; Varicose Veins ; surgery ; Vascular Surgical Procedures ; methods