OBJECTIVE: To explore the efficacy and adverse reactions of CAG regimen combined with venetoclax, chidamide, and azacitidine in the treatment of elderly patients with acute myeloid leukemia (AML). METHODS: 15 elderly AML patients aged≥60 years old who were admitted to the Hematology Department of our hospital from May 2022 to October 2023 were treated with the CAG regimen combined with venetoclax, chidamide and azacitidine, and the efficacy, treatment-related adverse events, overall survival (OS) and event-free survival (EFS) were analyzed. RESULTS: After one course of treatment, 11 out of 15 patients achieved complete response (CR), 3 patients achieved CR with incomplete hematologic recovery (CRi), and 1 patient died due to prior infection before efficacy evaluation, and the overall response rate (ORR) was 93.3% (14/15). The median follow-up time was 131 (19-275) days, with median OS and EFS both remaining unreached. Next-generation sequencing (NGS) analysis showed that among the 15 patients, 13 were detected with gene mutations, and there were 7 genes with mutation frequencies of more than 10%, including ASXL1 (4 cases), RUNX1 (4 cases), BCOR (3 cases), DNMT3A (3 cases), STAG2 (2 cases), IDH1/2 (2 cases), and TET (2 cases). Among the 13 patients with detectable mutations, 12 patients achieved composite response (CR+CRi). The average recovery time of white blood cell count was 14.6 days after chemotherapy, and the average recovery time of platelets was 7.7 days after chemotherapy. The main adverse event was myelosuppression, with 10 patients accompanied by infection. Except for 1 patient who died due to septic shock during chemotherapy, no patients experienced serious complications such as heart, liver, or kidney damage during the treatment process. CONCLUSION The CACAG+V regimen, which combines the CAG regimen with venetoclax, chidamide, and azacitidine, can be applied in the treatment of elderly AML patients, demonstrating good safety and induction remission rate.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Sulfonamides/therapeutic use* ; Aminopyridines/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Azacitidine/therapeutic use* ; Aged ; Benzamides/therapeutic use* ; Male ; Female ; Treatment Outcome ; Middle Aged ; Cytarabine ; Aclarubicin ; Granulocyte Colony-Stimulating Factor

Exploring the risk "time interval window" of sequential medication of Reduning injection (RDN) and penicillin G injection (PG) by detecting the correlation between serum biochemical indexes and plasma metabonomic characteristics, in order to reduce the risk of adverse reactions caused by the combination of RDN and PG. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). The changes of biochemical indexes in serum of rats were detected by enzyme-linked immunosorbent assay. It was determined that RDN combined with PG could cause pseudo-allergic reactions (PARs) activated by complement pathway. Further investigation was carried out at different time intervals (1.5, 2, 3.5, 4, 6, and 8 h PG+RDN). It was found that sequential administration within 3.5 h could cause significant PARs. However, PARs were significantly reduced after administration interval of more than 4 h. LC-MS was used for plasma metabolomics analysis, and the levels of serum biochemical indicators and plasma metabolic profile characteristics were compared in parallel. 22 differential metabolites showed similar or opposite trends to biochemical indicators before and after 3.5 h. And enriched to 10 PARs-related pathways such as arachidonic acid metabolism, steroid hormone biosynthesis, linoleic acid metabolism, glycerophospholipid metabolism, and tryptophan metabolism. In conclusion, there is a risk "time interval window" phenomenon in the adverse drug reactions caused by the sequential use of RDN and PG, and the interval medication after the "time interval window" can significantly reduce the risk of adverse reactions.

Objective To compare the pharmacokinetic behavior of two captopril tablets in Chinese healthy subjects,and evaluate the bioequivalence and safety of the tested and reference preparations.Methods This study was a single-center,random,open,double-cycle,double-cross design scheme.Twenty-four healthy subjects were randomized divided two groups and took single dose of 25 mg captopril of test tablet or reference tablet under fasting condition during each period.Plasma concentrations of captopril were determined by liquid chromatography-mass spectroscopy(LC-MS/MS)following administration of the oral single captopril tablet.The pharmacokinetic parameters were calculated by using non-atrioventricular model with WinNonlin 8.0 software to evaluate bioequivalence.The safety of clinical observation indexes of the subjects was evaluated during the trail.Results Main pharmacokinetic parameters of test preparation and reference preparation captopril in fasting group test:Cmax were(803.22±196.81)and(844.75±163.43)ng·mL-1;AUC0-t were(3 118.06±642.05)and(3 353.53±597.94)h·ng·mL-1;AUC0-∞ were(3 347.35±712.07)and(3 594.15±654.39)h·ng·mL-1.The 90％confidence intervals(CI)of geornetric mean ratio of Cmax,AUC0-t and AUC0-∞ were 87.15％-99.97％,89.54％-96.14％and 89.55％-96.26％,all in the range of 80.00％-125.00％,indicating that the bioequivalence of the two preparations could be determined.During the trial,the incidence rates of adverse events for the test preparation and the reference preparation were 30.43％and 33.33％,respectively,without any serious adverse events occurring.Conclusion The test tablet and reference tablet of captopril were equivalent and safe during the trial.

Objective To investigate the current situation and influencing factors of latent tuberculosis infection(LTBI)among close contacts of positive etiology pulmonary tuberculosis(PTB)patients,provide basis for formula-ting intervention measures for LTBI.Methods A multi-stage stratified cluster random sampling method was used to select close contacts of positive etiology PTB patients from 39 districts and counties in Chongqing City as the study objects.Demographic information was collected by questionnaire survey and the infection of Mycobacterium tuberculosis was detected by interferon gamma release assay(IGRA).The influencing factors of LTBI were analyzed by x2 test and binary logistic regression model.Results A total of 2 591 close contacts were included,the male to female ratio was 0.69∶1,with the mean age of(35.72±16.64)years.1 058 cases of LTBI were detected,Myco-bacterium tuberculosis latent infection rate was 40.83％.Univariate analysis showed that the infection rate was dif-ferent among peoples of different age,body mass index(BMI),occupation,education level,marital status,wheth-er they had chronic disease or major surgery history,whether they lived together with the indicator case,and whether the cumulative contact time with the indicator case ≥250 hours,difference were all statistically significant(all P＜0.05);infection rate presented increased trend with the increase of age and BMI(both P＜0.001),and decreased trend with the increase of education(P＜0.05).Logistic regression analysis showed that age 45-54 years old(OR=1.951,95％CI:1.031-3.693),age 55-64 years old(OR=2.473,95％CI:1.279-4.781),other occupations(OR=0.530,95％CI:0.292-0.964),teachers(OR=0.439,95％CI:0.242-0.794),students(OR=0.445,95％CI:0.233-0.851),junior high school education or below(OR=1.412,95％CI:1.025-1.944),BMI＜18.5 kg/m2(OR=0.762,95％CI:0.586-0.991),co-living with indicator cases(OR=1.621,95％CI1.316-1.997)and cumu-lative contact time with indicator cases ≥250 hours(OR=1.292,95％CI:1.083-1.540)were the influential fac-tors for LTBI(all P＜0.05).Conclusion The close contacts with positive etiology PTB have a high latent infection rate of Mycobacterium tuberculosis,and it is necessary to pay attention to close contacts of high age,farmers,and frequent contact with patients,and take timely targeted interventions to reduce the risk of occurrence of disease.

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

In recent years, with the policy reform of new drug review and approval, China has ushered in a surge of innovative drug development. Based on the Pharnexcloud database and the Pharmcube database, we analyzed the innovative drugs approved for marketing and entered clinical trials in China, sorted out the major research and development (R&D) institutions and enterprises, the distribution of innovative drug target types, and the primary therapeutic areas of the approved innovative drugs, and compared with the global innovative drug R&D landscape. Since 2020, China's innovative drug development has shown a rapid growth trend, with intense competition among biopharmaceutical companies, and the emergence of a number of leading biopharmaceutical enterprises. Popular targets for clinical-stage and approved drugs include protein tyrosine kinase, epidermal growth factor receptor, vascular endothelial growth factor receptor, and others. Oncological diseases are the most active domain for new drug R&D in China, followed by infectious diseases and neurological diseases. Suggestions for future development are proposed to increase policy support, enhance R&D innovation investment, optimize pipeline layout, strengthen international cooperation, and focus on innovative targets. This review provides a reference for pharmaceutical R&D enterprises, scientific researchers, and government administrators.
China ; Drug Development/trends* ; Drug Approval ; Pharmaceutical Research

OBJECTIVES: To compare the effect of different frequency of acupoint thread-embedding on weight loss in subjects with overweight/obesity of spleen deficiency and dampness retention. METHODS: A total of 126 subjects with overweight/obesity of spleen deficiency and dampness retention were randomized into a 2-week group(63 cases, 13 cases dropped out)and a 3-week group(63 cases, 11 cases dropped out, 1 case was eliminated). The two groups were treated with acupoint thread-embedding once every 2 weeks and once every 3 weeks respectively, Zhongwan(CV 12), Shuifen(CV 9), Qihai(CV 6), Guanyuan(CV 4) and bilateral Zhangmen(LR 13), Tianshu(ST 25), Liangmen(ST 21), Daheng(SP 15), Fujie(SP 14), Pishu(BL 20), Yinlingquan(SP 9)were selected. Four times were required in the two groups. Before and after treatment, follow-up after 2 months of treatment completion, the body mass index(BMI), body weight, waist circumference, hip circumference, waist-to-hip ratio, obesity degree, fat percentage(F%), skin fold thickness were observed in the two groups. RESULTS: After treatment and in follow-up, the BMI, body weight, waist circumference, hip circumference, waist-to-hip ratio, obesity degree, F%, skin fold thickness in the two groups were decreased compared with those before treatment (P<0.001, P<0.01), the changes of BMI, body weight, obesity degree, F%, skin fold thickness in the 2-week group were larger than those in the 3-week group(P<0.05, P<0.01, P<0.001). CONCLUSIONS The effect of acupoint thread-embedding once every 2 weeks on weight loss in subjects with overweight/obesity of spleen deficiency and dampness retention is superior to that once every 3 weeks.
Humans ; Acupuncture Points ; Overweight/therapy* ; Spleen ; Obesity/therapy* ; Body Weight ; Acupuncture Therapy ; Weight Loss

Humans ; Induction Chemotherapy ; Benzamides ; Treatment Outcome ; Hematopoietic Stem Cell Transplantation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Remission Induction ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Glaucomatous optic neuropathy(GON)is the difficulty of glaucoma treatment. In recent years, a variety of theories have been put forward about the pathogenesis of GON, but none of them can explain the principle of optic neuropathy caused by all types of glaucoma, which makes the disease difficult to treat in clinical treatment and is not conducive to early intervention. The latest research found that the transient receptor potential channel vanillic acid subfamily 4(TRPV4)in the retina plays an important role in various pathogenesis of GON. This article will review TRPV4 and its role in the occurrence and development of GON in order to find a common “connection point” for the multiple mechanism theories of GON, which will contribute to further understanding and clinical treatment of the disease.

OBJECTIVE: To observe the effects of electroacupuncture (EA) pretreatment on cardiac function, sympathetic nerve activity, indexes of myocardial injury and GABA_A receptor in fastigial nucleus in rats with myocardial ischemia reperfusion injury (MIRI), and to explore the neuroregulatory mechanism of EA pretreatment in improving MIRI. METHODS: A total of 60 male SD rats were randomly divided into a sham operation group, a model group, an EA group, an agonist group and an agonist+EA group, 12 rats in each group. The MIRI model was established by ligation of the left anterior descending coronary artery. EA was applied at bilateral "Shenmen" (HT 7) and "Tongli" (HT 5) in the EA group and the agonist+EA group, with continuous wave, in frequency of 2 Hz and intensity of 1 mA, 30 min each time, once a day for 7 consecutive days. After intervention, the MIRI model was established. In the agonist group, the muscone (agonist of GABA_A receptor, 1 g/L) was injected in fastigial nucleus for 7 consecutive days before modeling, 150 μL each time, once a day. In the agonist+EA group, the muscone was injected in fastigial nucleus 30 min before EA intervention. The data of electrocardiogram was collected by PowerLab standard Ⅱ lead, and ST segment displacement and heart rate variability (HRV) were analyzed; the serum levels of norepinephrine (NE), creatine kinase isoenzyme MB (CK-MB) and cardiac troponin I (cTnI) were detected by ELISA; the myocardial infarction area was measured by TTC staining; the morphology of myocardial tissue was observed by HE staining; the positive expression and mRNA expression of GABA_A receptor in fastigial nucleus were detected by immunohistochemistry and real-time PCR. RESULTS: Compared with the sham operation group, in the model group, ST segment displacement and ratio of low frequency to high frequency (LF/HF) of HRV were increased (P<0.01), HRV frequency domain analysis showed enhanced sympathetic nerve excitability, the serum levels of NE, CK-MB and cTnI were increased (P<0.01), the percentage of myocardial infarction area was increased (P<0.01), myocardial fiber was broken and interstitial edema was serious, the positive expression and mRNA expression of GABA_A receptor in fastigial nucleus were increased (P<0.01). Compared with the model group, in the EA group, ST segment displacement and LF/HF ratio were decreased (P<0.01), HRV frequency domain analysis showed reduced sympathetic nerve excitability, the serum levels of NE, CK-MB and cTnI were decreased (P<0.01), the percentage of myocardial infarction area was decreased (P<0.01), myocardial fiber breakage and interstitial edema were lightened, the positive expression and mRNA expression of GABA_A receptor in fastigial nucleus were decreased (P<0.01). Compared with the EA group, in the agonist group and the agonist+EA group, ST segment displacement and LF/HF ratio were increased (P<0.01), HRV frequency domain analysis showed enhanced sympathetic nerve excitability, the serum levels of NE, CK-MB and cTnI were increased (P<0.01), the percentage of myocardial infarction area was increased (P<0.01), myocardial fiber breakage and interstitial edema were aggravated, the positive expression and mRNA expression of GABA_A receptor in fastigial nucleus were increased (P<0.01). CONCLUSION EA pretreatment can improve the myocardial injury in MIRI rats, and its mechanism may be related to the inhibition of GABA_A receptor expression in fastigial nucleus, thereby down-regulating the excitability of sympathetic nerve.
Male ; Animals ; Rats ; Rats, Sprague-Dawley ; Cerebellar Nuclei ; Electroacupuncture ; Myocardial Reperfusion Injury/therapy* ; Receptors, GABA-A/genetics* ; RNA, Messenger