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In our previous study, we reported a series of N-(9,10-anthraquinone-2-carbonyl) amino acid derivatives as novel inhibitors of xanthine oxidase (XO). Recognizing the suboptimal drug-like properties associated with the anthraquinone moiety, we embarked on a nonanthraquinone medicinal chemistry exploration in the current investigation. Through systematic structure-activity relationship (SAR) studies, we identified a series of 4-(isopentyloxy)-3-nitrobenzamide derivatives exhibiting excellent in vitro potency against XO. The optimized compound, 4-isopentyloxy-N-(1H-pyrazol-3-yl)-3-nitrobenzamide (6k), demonstrated exceptional in vitro potency with an IC50 value of 0.13 µM. Compound 6k showed favorable drug-like characteristics with ligand efficiency (LE) and lipophilic ligand efficiency (LLE) values of 0.41 and 3.73, respectively. In comparison to the initial compound 1d, 6k exhibited a substantial 24-fold improvement in IC50, along with a 1.6-fold enhancement in LE and a 3.7-fold increase in LLE. Molecular modeling studies provided insights into the strong interactions of 6k with critical amino acid residues within the active site. Furthermore, in vivo hypouricemic investigations convincingly demonstrated that 6k significantly reduced serum uric acid levels in rats. The MTT results revealed that compound 6k is nontoxic to healthy cells. The gastric and intestinal stability assay demonstrated that compound 6k exhibits good stability in the gastric and intestinal environments. In conclusion, compound 6k emerges as a promising lead compound, showcasing both exceptional in vitro potency and favorable drug-like characteristics, thereby warranting further exploration.

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The occurrence and development of the tumor are very complex biological processes. In recent years, a large number of research data shows that CD73 is closely related to tumor growth and metastasis. It has been confirmed that the cascade hydrolysis of extracellular ATP to adenosine is one of the most important immunosuppressive regulatory pathways in the tumor microenvironment. The metabolite adenosine can mediate immunosuppression by activating adenosine receptor (such as A2A) on effector Immune cells and enable tumor cells to achieve immune escape. Therefore, attenuating or completely removing adenosine-mediated immunosuppression in the tumor microenvironment by inhibiting CD73 is a promising approach in the treatment of solid tumors. This paper focuses on the research progress of CD73 enzyme and CD73 small molecule inhibitors, and is expected to provide some insights into the development of small-molecule antitumor drugs targeting CD73.

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Our previous studies suggested that N-phenyl aromatic amides are a class of promising xanthine oxidase (XO) inhibitor chemotypes. In this effort, several series of N-phenyl aromatic amide derivatives (4a-h, 5-9, 12i-w, 13n, 13o, 13r, 13s, 13t and 13u) were designed and synthesized to carry out an extensive structure-activity relationship (SAR). The investigation provided some valuable SAR information and identified N-(3-(1H-imidazol-1-yl)-4-((2-methylbenzyl)oxy)phenyl)-1H-imidazole-4-carboxamide (12r, IC50 = 0.028 µM) as the most potent XO inhibitor with close in vitro potency to that of topiroxostat (IC50 = 0.017 µM). Molecular docking and molecular dynamics simulation rationalized the binding affinity through a series of strong interactions with the residues Glu1261, Asn768, Thr1010, Arg880, Glu802, etc. In vivo hypouricemic studies also suggested that the uric acid lowering effect of compound 12r was improved compared with the lead g25 (30.61 % vs 22.4 % reduction in uric acid levels at 1 h; 25.91 % vs 21.7 % reduction in AUC of uric acid) . Pharmacokinetic studies revealed that compound 12r presented a short t1/2 of 0.25 h after oral administration. In addition, 12r has non-cytotoxicity against normal cell HK-2. This work may provide some insights for further development of novel amide-based XO inhibitors.

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OBJECTIVE@#To compare the efficacy and safety of different doses of daunorubicin combined with a standard dose of cytarabine as induction chemotherapy in newly diagnosed primary acute myeloid leukemia (AML) patients.@*METHODS@#The clinical data and outcome were retrospectively analyzed in 86 newly diagnosed primary AML patients who were under 65 years old and treated with daunorubicin combined with cytarabine (DA regimen) at West China Hospital of Sichuan University from January 2017 to June 2019. Patients were divided into 2 groups based on the dose of daunorubicin they received, 35 cases in the escalated-dose group ［75 mg/(m@*RESULTS@#Median follow-up time of all the patients was 15 months. The CR rate and MRD@*CONCLUSION@#The escalated dose of daunorubicin can induce higher complete remission rate, deeper remission and longer duration of remission without increasing adverse events in newly diagnosed primary AML patients.

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Objective To investigate the effect of sarcopenia on the efficacy of percutaneous kyphoplasty(PKP)in the treatment of osteoporotic spinal compression fracture(OSCF)in elderly patients. Methods From February 2017 to June 2018,a total of 77 elderly patients who met the inclusion and exclusion criteria were included in this study.Grip strength of dominant hand was measured by an electronic grip dynamometer with cut-off values of 27 kg for males and 16 kg for females.The cross-sectional area of the pedicle level muscle of the 12th thoracic vertebra(T12)was measured by chest CT.The skeletal muscle index(SMI)was calculated by dividing the T12 pedicle level muscle cross-sectional area by the square of body height.The SMI cut-off value used to diagnose sarcopenia was 42.6 cm

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Objective To investigate the effect of sarcopenia on the efficiency of the treatment of femoral neck fracture in elderly patients.Methods A total of 65 elderly patients aged ≥65 years with femoral neck fractures meeting the inclusion and exclusion criteria were investigated in our hospital from February 2014 to February 2016.The muscle cross-sectional area(cm2) at the thoracic 12 pedicle level was measured by chest CT.The skeletal muscle index(SMI)is calculated by the formula that the muscle cross-sectional area(cm2)at T12 pedicle level was divided by m2 of the patient's body height(meter).SMI cutoff values of 42.6 cm2/m2 (males)and 30.6 cm2/m2 (females)were used to diagnose sarcopenia.Linear regression analysis was used to analyze the relationship of SMI with the length of hospital stay,blood transfusion during hospitalization and Harris score one month after surgery.The difference between the patients with and without sarcopenia in the length of hospital stay,the volume of blood transfusion,incidence rate of complications,Harris score,the mortality rate of perioperative period and on.year mortality rate were analyzed by ttest.Results Among 65 elderly patients,28 cases were diagnosed as sarcopenia.Their mean SMI was(30.3 ± 5.2)cm2/m2 in the sarcopenia group and (43.0±6.5)cm2/m2 in the non-sarcopenia group,the difference was statistically significant (t =-8.448,P ＜ 0.001).There were significant differences between the sarcopenia group and the non sarcopenia group in the mean hospital stay[(14.7 ± 5.8)d vs.(13.2±4.5)d,t =1.225,P =0.225],the transfusion volume during hospitalization[(1.7 ± 1.4) units vs.(0.92±1.0)units,t=2.621,P=0.011],Harris scores[(81.1±4.4) vs.(88.7±2.3),t=-8.219,P ＜0.001)],the incidence of complications(57.1 ％ vs.16.2 ％,x2 =11.923,P =0.001),the mortality of perioperative period(7.1％ vs.2.7％,P=0.573)and the one-year mortality(35.7％ vs.10.8％,x2 =4.468,P =0.035).Conclusions Sarcopenia can delay postoperative rehabilitation in elderly patients with femoral neck fracture and increase the incidence of complications and late mortality rate.

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Long non-coding RNA (lncRNA) refer to transcripts longer than 200 nucleotides that have a low coding potential. Autophagy,a unique life phenomenon of eukaryotic cells,removes excess or damaged organelles during cell growth and development and plays a key role in maintaining homeostasis. As a key regulator of cellular metabolism,lncRNA are involved in disease treatment by regulating autophagy. This article summarizes the role of lncRNA in the treatment of cancer,cardiovascular and cerebrovascular diseases,neurodegenerative diseases,and bacterial infections and analyzes the molecular mechanisms of lncRNA in regulating autophagy,along with prospects of its applications in other areas.

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Objective The proportion of multiple drugs and the irrational use of drugs increased significantly in the elderly patients (over 80 years). This study aimed to investigate the occurrence of potentially inappropriate medication (PIM) and analyzed the possible reasons related to PIM in elderly patients. Methods In this study,918 cases from Cadre Ward I of Research Center for Geriatrics of Nanjing General Hospital of Nanjing Military Region were selected from January to December in 2016. According to the Beers Criteria (Version 2015),we evaluated PIM in four subtypes,type 1 that is not related to the state of disease in elderly patients, type 2 that is related to the state of disease in elderly patients,type 3 which should be used carefully,and type 4 which is the inappropriate combination of non-anti-infective Drugs. The PIM influence factors were analyzed by logistic regression analysis. Results There are 521 cases (56.75%) of type 1 PIM. The first 3 drugs are Short and medium acting benzodiazepams,PPI and long acting benzodiazepams. There are 206 cases (22.4%) of type 2 PIM. The first 2 drugs are drugs associated with insomnia (oral hyperemia, stimulants, theo-phylline and caffeine) and drugs associated with dementia or cognitive impairment (anti-cholinergic drugs and H2 receptor antago-nists). There are 834 cases (90.85%) of type 3 PIM,which should be used carefully and 45 cases(4.90%) of type 4 PIM.45 cases (4.90%) of non-anti-infective drugs should be avoid or reduced as much as possible in consideration of renal function. The number of combined drug use(OR=5.331,95% CI:3.549-8.009),the age(OR=1.171,95% CI:1.093-1.249),the Chalson's comorbidity index (OR=1.964,95% CI:1.477-2.450) are risk factors of PIM. Conclusion The incidence of potentially inappropriate use of drugs is high among the elderly patients. Reducing the number of combined drugs is an important measure to avoid the occurrence of PIM in elderly patients.

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BACKGROUND/AIMS: The p22phox C242T gene polymorphism (rs4673) may be linked to an increased susceptibility for overt diabetic nephropathy (ODN), but the study results are still inconclusive. METHODS: To explore the relationship between p22phox C242T gene polymorphism and ODN, the current meta-analysis of 707 ODN patients and 745 controls from five individual studies was conducted. The pooled odds ratio (OR) and its corresponding 95% confidence interval (CI) were evaluated by either a random or fixed effect model. RESULTS: In our meta-analysis, a significant relationship between the p22phox C242T gene polymorphism and ODN was found under allelic (OR, 2.760; 95% CI, 1.400 to 5.450; p = 0.004), recessive (OR, 5.080; 95% CI, 1.020 to 25.430; p = 0.05), dominant (OR, 1.700; 95% CI, 1.167 to 2.477; p = 0.006), homozygous (OR, 3.900; 95% CI, 1.022 to 14.889; p = 0.046), heterozygous (OR, 1.523; 95% CI, 1.167 to 1.986; p = 0.002), and additive genetic models (OR, 2.019; 95% CI, 1.232 to 3.309; p = 0.005). CONCLUSIONS: A positive correlation between p22phox C242T gene polymorphism and ODN risk was found. The T allele carriers of p22phox C242T gene polymorphism might be predisposed to ODN.

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BACKGROUND/AIMS: Although lipoprotein lipase (LPL) gene Pvu II polymorphism has been associated with an increased risk of hypertriglyceridemia (HT), there is no clear consensus within the scientific community. METHODS: A meta-analysis of 1,640 subjects from six individual studies was conducted to better elucidate the potential relationship between the LPL gene Pvu II polymorphism and HT within the Chinese population. Pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were evaluated by using fixed effect models. RESULTS: Our analysis indicated a significant association between LPL gene Pvu II polymorphism and HT within the Chinese population under allelic (OR, 1.550; 95% CI, 1.320 to 1.830; p = 1.158 × 10-7), recessive (OR, 0.540; 95% CI, 0.390 to 0.750; p = 0.0002), dominant (OR, 1.889; 95% CI, 1.501 to 2.377; p = 5.960 × 10-8), homozygous (OR, 2.167; 95% CI, 1.531 to 3.067; p = 1.242 × 10-5), heterozygous (OR, 1.810; 95% CI, 1.419 to 2.309; p = 1.842 × 10-6), and additive genetic models (OR, 1.553; 95% CI, 1.320 to 1.828; p = 1.158 × 10-7). CONCLUSIONS: Because LPL gene Pvu II restriction fragment length polymorphism polymorphism was associated with an elevated risk of HT, the P+ allele carriers of the LPL gene might be predisposed to HT.

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