Objective To observe the effect and adverse reactions of iron sucrose injection in treating old patients with iron deficiency anemia(IDA). Methods Thirty-two old patients with IDA were divided into injection group(17 patients)and oral group(15 patients)by random digits table. The effects of improvement on IDA and their adverse reactions were observed. Results After treatment, hemoglobin(Hb)in the injection group and oral group was(100.18±8.71)g/L and(85.80 ± 6.92)g/L(P＜0.01), and serum iron was(23.84±5.34)μmol/L and(14.63±3.29)μmol/L(P＜0.01).There were no obvious adverse reactions in injection group, whereas there were 6 cases(40%)with gastric and colon adverse reaction in oral group. Conclusions The treatment of intravenous injection of iron sucrose can be effectively used to cure old patients with IDA. It has better effect and has lower rate of adverse reaction.

Objective To establish an animal model for study on early oral fluid resuscitation of burn shock so as to provide experimental basis for oral fluid resuscitation of burn shock in wars, accidents or disasters. Methods Male Beagle dogs weighing 11-13 kg were used in the study and the carotis, jugular and duodenum were cannulated respectively for measurement of homodynamics, tissue perfusion and gastrointestinal function. Dogs were subjected to a 35% TBSA full thickness flame injury with 10-mi-nute anesthesia by intravenous injection of propofol 24 hours later, and then randomly and equally divided into two groups(8 dogs in each group) : no fluid resuscitation group (NR group) undergoing no treatment in the first 24 hours post burn and oral fluid resuscitation group ( OR group) undergoing gastric infusion of glucose electrolyte solution (GES) according to Parkland formula. From the second 24 hours post burn, animals in two groups were given delayed Ⅳ fluid resuscitation, and then intravenous nutritional support was initiated at the 72nd hour. The mean arterial pressures (MAP), cardiac output (CO), dp/dt max of left ventricular contractility (dp/dtmax) and plasma volume (PV) were monitored continuously. The pa-rameters of gastrointestinal tissue peffusion, the rates of gastric emptying and intestinal absorption of GES were determined, the morbidity was also recorded at the end of 5-day experiment. Results After 35% TBSA burn injury, MAP, CO,dp/dt max and PV dropped markedly and gastrointestinal tissue perfusion reduced obviously. CO and PV in OR group were significantly higher than those in NG group at 4, 8 and 24 hours after burn. Homodynamic parameters and gastrointestinal tissue perfusion in OR group were pro-moted to pre-injury level at 48 and 72 hours respectively, while homodynamic parameters in NR group did not return to pre-injury level till 72 hours, and gastrointestinal tissue perfusion kept lower than pre-injury till 120 hours post burn. Rates of gastric emptying and intestinal absorption of GES significantly reduced to the lowest level (42% and 37% of pre-injury) at about 4 hours post bum, but did not return to pre-in-jury level till eight hours post bum. Over five days, two out of eight dogs (25%) died in NG group but none in OR group. Conclusions The animal model can exactly simulate the actual circumstance, where oral resuscitation is superior to Ⅳ resuscitation in some aspects in treating early bum shock in wars, accidents and disasters, and provide practical and reliable method for measurement of homodynamic parameters, tissue perfusion, gastric emptying and intestinal absorptive function.

Tyrosyl-DNA phosphodiesterase Ⅰ (TdpⅠ ) is a recently discovered proteinthat catalyzes the hydrolysis of 3′-phosphotyrosyl bonds .Such linkages form in vivo during the interaction of DNA and topoisomerase Ⅰ (TopⅠ) .TdpⅠ has been regarded as a potential therapeutic co-target of TopⅠ because it has the functions of repairing Top Ⅰ compound and coun-teracting the effects of Top Ⅰ inhibitors .TdpⅠ inhibitors can not only synergizing with Top Ⅰ-targeting drugs (camptoth-ecins) ,but also strength the function of bleomycin ,topoisomerase Ⅱ (TopⅡ ) inhibitors (etoposide ,doxorubicin) and DNA alkylating agents .We summarized the researching advance of TdpⅠ inhibitors and focused on the introduction of the mecha-nism ,bioactivity and structure-activity relationship .

With the development of science and the progress of age,medicinal chemistry is not only limited to the lead discovery and the structure-activity relationship studies,but also finding the target of bioactive small molecule drugs has be-come a tough issue to be solved.The identification and validation of bioactive small molecule targets has become the most criti-cal and difficult task,which plays a decisive role in academic and pharmaceutical research.Herein we summarize the current methods for target identification of small molecules,and mainly discuss about the target identification method by the chemical probes.Recent cases of successful application were also introduced to demonstrate the strategy of probe synthesis and design.

DNA topoisomerases (Tops) are essential enzymes that regulate the cellular processes such as replication , transcription ,recombination and repair .DNA Tops can be classified into two types ,topoisomerase Ⅰ (TopⅠ ) and topoi-somerase Ⅱ (TopⅡ) .They catalyze the breakage and religation of DNA ,maintaining the topological changes of DNA and va-rious DNA metabolic processes .Due to their important role in DNA metabolism ,the ability to interfere with the functions of Tops or generating Top-mediated DNA damage is an effective strategy for cancer chemotherapy .Tops have been considered as the most important targets for tumor chemotherapy .In this review ,we used examples to describe the development of dual to-poisomerase Ⅰ and Ⅱ inhibitors .

OBJECTIVE: To explore the incidence of Uigur patients with nonsyndromic hereditary hearing loss in Xinjiang, and to provide the basis for preventing deafness caused by aminoglycoside antibiotics. METHOD: The medical history of 51 Uigur deaf patients as the study group was collected in Xinjiang. Fifty-three Uigur normal people were selected as the control group in Xinjiang. Blood samples were obtained from them with informed consents. Genomic DNA was extracted from isolated leukocytes. The mitochondrial DNA fragments were amplified by polymerase chain reaction. mtDNA 12SrRNA A1555G mutation was detected using A1w26I restriction endonuclease digestion, followed by direct sequencing to identify the A1555G mutation. RESULT: The mtDNA A1555G mutation was detected in 2 Uigur patients, and both of them had used aminoglycoside antibiotics. CONCLUSION There is no statistically significant difference between patients and normal people in Xinjiang. The mtDNA A1555G mutation is related to aminoglycoside antibiotics-induced deafness, which can cause genetic stisceptibility to aminoglycoside antibiotics ototoxicity. The incidence of mtDNA A1555G is lower than the average level of the overall Chinese deaf population.
Adolescent ; Asian Continental Ancestry Group ; genetics ; Child ; Child, Preschool ; Connexins ; DNA, Mitochondrial ; genetics ; Hearing Loss ; genetics ; Humans ; Mitochondria ; genetics ; Mutation ; Pedigree ; RNA, Ribosomal ; genetics ; Young Adult

OBJECTIVETo compare the efficacy and toxicity of the chemotherapeutic regimen containing pirarubicin and mitoxantrone on the treatment of relapsed or refractory acute myeloid leukemia (AML) in adults.

METHODSIn this open prospective multicentre study, we randomly assigned patients with relapsed or refractory AML to receive TAE regimen (pirarubicin+cytarabine+etoposide) versus MAE regimen (mitoxantrone + cytarabine + etoposide). The efficacy and toxicity were compared between the two groups.

RESULTS56 patients entered this clinical trial. The complete remission (CR) rate on TAE arm was 79.0% versus 55.6% on MAE arm with the overall response (OR) rates of 86.8% versus 88.9%, respectively. The CR was higher on TAE arm (P=0.035) but with no significant difference between the two groups regarding the overall response (OR) rate. The regimens were well tolerated in both groups. Hematologic and non-hematologic toxicity were similar except relatively lower the mean dosage of G-CSF, red blood cells and platelets transfusion on TAE arm. No significant differences were seen between the two groups regarding the overall survival and relapse free survival rates.

CONCLUSIONTAE regimen might be an effective salvage therapy in patients with relapsed or refractory AML.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Dactinomycin ; administration & dosage ; Doxorubicin ; administration & dosage ; analogs & derivatives ; Etoposide ; administration & dosage ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Methotrexate ; administration & dosage ; Prospective Studies ; Recurrence ; Remission Induction

The trend toward designing large hydrophobic molecules for lead optimization is often associated with poor drug-likeness and high attrition rates in drug discovery and development. Structural simplification is a powerful strategy for improving the efficiency and success rate of drug design by avoiding "molecular obesity". The structural simplification of large or complex lead compounds by truncating unnecessary groups can not only improve their synthetic accessibility but also improve their pharmacokinetic profiles, reduce side effects and so on. This review will summarize the application of structural simplification in lead optimization. Numerous case studies, particularly those involving successful examples leading to marketed drugs or drug-like candidates, will be introduced and analyzed to illustrate the design strategies and guidelines for structural simplification.

The role of glial scar after intracerebral hemorrhage(ICH)remains unclear.This study aimed to inves-tigate whether microglia-astrocyte interaction affects glial scar formation and explore the specific function of glial scar.We used a pharmacologic approach to induce microglial depletion during different ICH stages and examine how ablating microglia affects astrocytic scar formation.Spatial transcriptomics(ST)analysis was performed to explore the potential ligand-receptor pair in the modulation of microglia-astrocyte interaction and to verify the functional changes of astrocytic scars at different periods.During the early stage,sustained microglial depletion induced disorganized astrocytic scar,enhanced neutrophil infiltration,and impaired tissue repair.ST analysis indicated that microglia-derived insulin like growth factor 1(IGF1)modulated astrocytic scar formation via mechanistic target of rapamycin(mTOR)signaling activation.Moreover,repopulating microglia(RM)more strongly activated mTOR signaling,facilitating a more protective scar formation.The combination of IGF1 and osteopontin(OPN)was necessary and sufficient for RM function,rather than IGF1 or OPN alone.At the chronic stage of ICH,the overall net effect of astrocytic scar changed from protective to destructive and delayed microglial depletion could partly reverse this.The vital insight gleaned from our data is that sustained microglial depletion may not be a reasonable treatment strategy for early-stage ICH.Inversely,early-stage IGF1/OPN treatment combined with late-stage PLX3397 treatment is a promising therapeutic strategy.This prompts us to consider the complex temporal dynamics and overall net effect of microglia and astrocytes,and develop elaborate treatment strategies at precise time points after ICH.

Natural product evodiamine and its derivatives represent a promising class of multi-target antitumor agents. However, the clinical development of these compounds has been hampered by a poor understanding of their antitumor mechanisms. To tackle this obstacle, herein, novel fluorescent probes were designed to elucidate the antitumor mode of action of 10-hydroxyevodiamine. This compound was proven to be distributed in the mitochondria and lysosomes and to act by autophagy and apoptosis mechanisms.