Objective To provide a reference for medication therapy management(MTM)of diabetic patients complicated with abnormal blood pressure fluctuation.Methods A 71-year-old female diabetic patient with combined hypertension and abnormal blood pressure fluctuations was referred by the doctor to the pharmacy clinic.The pharmacists provided MTM services through pharmacy inquiry,medication evaluation,medication reconciliation,drug use education,and pharmacy follow-up.They reconciliated the medication regimen based on plasma glucose levels and dynamic blood pressure rhythms.Results Through twelve times MTM services for fourteen weeks,the atherosclerotic cardiovascular disease(ASCVD)risk factors,including morning peak blood pressure,fasting plasma glucose(FPG),plasma glucose two hours post breakfast(P2h PG)and glycosylated hemoglobin(HbA1c),reduced from 163/115 mmHg,7.54 mmol·L-1,12.87 mmol·L-1 and 7.2%before MTM to 137/84 mmHg,6.42 mmol·L-1,8.79 mmol·L-1 and 6.4%after MTM services,and the trough blood pressure post breakfast raised from 86/64mmHg to 115/76 mmHg.The patient's plasma glucose and blood pressure were effectively managed and controlled,and the abnormal non-spoon-shaped hypertension rhythm changed to the normal spoon-shaped diurnal blood pressure rhythm,and the patient's dizziness symptoms disappeared after breakfast.Conclusion The hospital develops pharmacy clinics,where pharmacists provide MTM services for patients with chronic diseases such as hypertension and diabetes,promote clinical rational drug use,and improve the level of patient health management.

Objective:To explore the death characteristics and disease burden of lung cancer in Chinese population from 2004 to 2021.Methods:A cross sectional study was conducted. The demographic data and lung cancer mortality surveillance data from 605 surveillance areas in the Chinese mortality surveillance dataset from 2004 to 2021 were used to calculate the crude death rate (CDR), potential years of life lost, average potential years of life lost, work years of potential life lost, and average work years of potential life lost for lung cancer in the population. Joinpoint model was used, and the trend of lung cancer mortality rates in different characteristic populations in the surveillance area was analyzed using average annual percentage change (AAPC) and annual percentage change (APC).Results:The CDR of lung cancer in the surveillance population of China from 2004 to 2021 was 42.94/100 000, with males having a higher CDR than females (58.94/100 000 vs. 26.92/100 000); the overall population, male and female lung cancer CDR showed an upward trend (AAPC were 2.70%, 3.20% and 1.85%, respectively), with a decreasing trend in the total population in 2004 and 2005 (APC = -1.04%), an increasing trend from 2006 to 2014 (APC = 4.46%), and an increasing trend from 2015 to 2021 (APC = 1.41%); the overall increase rate of lung cancer CDR in rural registered residence population (AAPC = 3.70%) was higher than that in urban registered residence population (AAPC = 1.30%). From 2004 to 2021, the age specific lung cancer CDR of the population in surveillance areas of China increased with age, reaching a peak of 437.77/100 000 in the population aged 85 years and above. From 2004 to 2021, the potential life loss caused by lung cancer in surveillance areas of China was 8 532 790.08 person years, with an average potential life loss of 6.55 years. Among them, females had a higher potential life loss than males (8.70 years vs. 4.30 years); the average potential work loss caused by lung cancer in males was 7.02 years, while in females it was 6.76 years. Conclusions:From 2004 to 2021, the overall mortality rate of lung cancer in China shows an upward trend, and the burden of lung cancer disease is relatively heavy. Male and elderly populations need to be given special attention.

Objective:To explore the death characteristics and disease burden of lung cancer in Chinese population from 2004 to 2021.Methods:A cross sectional study was conducted. The demographic data and lung cancer mortality surveillance data from 605 surveillance areas in the Chinese mortality surveillance dataset from 2004 to 2021 were used to calculate the crude death rate (CDR), potential years of life lost, average potential years of life lost, work years of potential life lost, and average work years of potential life lost for lung cancer in the population. Joinpoint model was used, and the trend of lung cancer mortality rates in different characteristic populations in the surveillance area was analyzed using average annual percentage change (AAPC) and annual percentage change (APC).Results:The CDR of lung cancer in the surveillance population of China from 2004 to 2021 was 42.94/100 000, with males having a higher CDR than females (58.94/100 000 vs. 26.92/100 000); the overall population, male and female lung cancer CDR showed an upward trend (AAPC were 2.70%, 3.20% and 1.85%, respectively), with a decreasing trend in the total population in 2004 and 2005 (APC = -1.04%), an increasing trend from 2006 to 2014 (APC = 4.46%), and an increasing trend from 2015 to 2021 (APC = 1.41%); the overall increase rate of lung cancer CDR in rural registered residence population (AAPC = 3.70%) was higher than that in urban registered residence population (AAPC = 1.30%). From 2004 to 2021, the age specific lung cancer CDR of the population in surveillance areas of China increased with age, reaching a peak of 437.77/100 000 in the population aged 85 years and above. From 2004 to 2021, the potential life loss caused by lung cancer in surveillance areas of China was 8 532 790.08 person years, with an average potential life loss of 6.55 years. Among them, females had a higher potential life loss than males (8.70 years vs. 4.30 years); the average potential work loss caused by lung cancer in males was 7.02 years, while in females it was 6.76 years. Conclusions:From 2004 to 2021, the overall mortality rate of lung cancer in China shows an upward trend, and the burden of lung cancer disease is relatively heavy. Male and elderly populations need to be given special attention.

Objective To provide a reference for medication therapy management(MTM)of diabetic patients complicated with abnormal blood pressure fluctuation.Methods A 71-year-old female diabetic patient with combined hypertension and abnormal blood pressure fluctuations was referred by the doctor to the pharmacy clinic.The pharmacists provided MTM services through pharmacy inquiry,medication evaluation,medication reconciliation,drug use education,and pharmacy follow-up.They reconciliated the medication regimen based on plasma glucose levels and dynamic blood pressure rhythms.Results Through twelve times MTM services for fourteen weeks,the atherosclerotic cardiovascular disease(ASCVD)risk factors,including morning peak blood pressure,fasting plasma glucose(FPG),plasma glucose two hours post breakfast(P2h PG)and glycosylated hemoglobin(HbA1c),reduced from 163/115 mmHg,7.54 mmol·L-1,12.87 mmol·L-1 and 7.2%before MTM to 137/84 mmHg,6.42 mmol·L-1,8.79 mmol·L-1 and 6.4%after MTM services,and the trough blood pressure post breakfast raised from 86/64mmHg to 115/76 mmHg.The patient's plasma glucose and blood pressure were effectively managed and controlled,and the abnormal non-spoon-shaped hypertension rhythm changed to the normal spoon-shaped diurnal blood pressure rhythm,and the patient's dizziness symptoms disappeared after breakfast.Conclusion The hospital develops pharmacy clinics,where pharmacists provide MTM services for patients with chronic diseases such as hypertension and diabetes,promote clinical rational drug use,and improve the level of patient health management.

Objective To investigate the effects of edaravone-dexborneol combined with intravenous thrombolysis on cerebrovascular reserve capacity and inflammatory factors in patients with acute cerebral infarction.Methods From January 2023 to June 2024,100 patients diagnosed with acute cerebral infarction in our hospital were divided into research group(n=50)and conventional group(n=50)by random number table method.The conventional group received intravenous thrombolysis,while the research group was treated with edaravone-dexborneol in addition to intravenous thrombolysis.The efficacy was evaluated after 2 weeks of treatment;the neurological function scores(mRS and NIHSS),cerebrovascular reserve indicators[pulsatility index(PI),cerebrovascular reserve(CVR)],hemorheological indicators(platelet aggregation rate,red blood cell aggregation index),levels of inflammatory factors[matrix metalloproteinase(MMP)-9,monocyte chemoattractant protein(MCP)-1,intercellular adhesion molecule(ICAM)-1],and levels of neurological functional factors[neuron specific enolase(NSE),nerve growth factor(NGF),central nervous system specific protein(S100)β]before and after treatment were compared.Results After 2 weeks of treatment,the efficacy of the conventional group was 80.00％,the efficacy of the research group was 94.00％.And the therapeutic effect of research group was significantly higher than the conventional group(x2=4.332,P=0.037).After 4 weeks of treatment,the mRS score,NIHSS score,PI,platelet aggregation rate,red blood cell aggregation index,and serum levels of MCP-1,MMP-9,ICAM-1,NSE and S100β were significantly lower than those before treatment in the two groups,while the CVR and serum NGF levels were significantly higher than those before treatment(all P＜0.05).After 4 weeks of treatment,the mRS score,NIHSS score,PI,platelet aggregation rate,red blood cell aggregation index,and serum levels of MCP-1,MMP-9,ICAM-1,NSE and S100β were significantly lower in the research group than those in the conventional group(all P＜0.05),while the CVR and serum NGF level were significantly higher in the research group than those in the conventional group(all P＜0.05).Conclusion The combination of edaravone-dexborneol with intravenous thrombolysis can improve clinical efficacy,restore neurological function,enhance cerebrovascular reserve capacity,improve hemorheology,and reduce inflammatory factors in patients with acute cerebral infarction.

Objective To investigate the effects of edaravone-dexborneol combined with intravenous thrombolysis on cerebrovascular reserve capacity and inflammatory factors in patients with acute cerebral infarction.Methods From January 2023 to June 2024,100 patients diagnosed with acute cerebral infarction in our hospital were divided into research group(n=50)and conventional group(n=50)by random number table method.The conventional group received intravenous thrombolysis,while the research group was treated with edaravone-dexborneol in addition to intravenous thrombolysis.The efficacy was evaluated after 2 weeks of treatment;the neurological function scores(mRS and NIHSS),cerebrovascular reserve indicators[pulsatility index(PI),cerebrovascular reserve(CVR)],hemorheological indicators(platelet aggregation rate,red blood cell aggregation index),levels of inflammatory factors[matrix metalloproteinase(MMP)-9,monocyte chemoattractant protein(MCP)-1,intercellular adhesion molecule(ICAM)-1],and levels of neurological functional factors[neuron specific enolase(NSE),nerve growth factor(NGF),central nervous system specific protein(S100)β]before and after treatment were compared.Results After 2 weeks of treatment,the efficacy of the conventional group was 80.00％,the efficacy of the research group was 94.00％.And the therapeutic effect of research group was significantly higher than the conventional group(x2=4.332,P=0.037).After 4 weeks of treatment,the mRS score,NIHSS score,PI,platelet aggregation rate,red blood cell aggregation index,and serum levels of MCP-1,MMP-9,ICAM-1,NSE and S100β were significantly lower than those before treatment in the two groups,while the CVR and serum NGF levels were significantly higher than those before treatment(all P＜0.05).After 4 weeks of treatment,the mRS score,NIHSS score,PI,platelet aggregation rate,red blood cell aggregation index,and serum levels of MCP-1,MMP-9,ICAM-1,NSE and S100β were significantly lower in the research group than those in the conventional group(all P＜0.05),while the CVR and serum NGF level were significantly higher in the research group than those in the conventional group(all P＜0.05).Conclusion The combination of edaravone-dexborneol with intravenous thrombolysis can improve clinical efficacy,restore neurological function,enhance cerebrovascular reserve capacity,improve hemorheology,and reduce inflammatory factors in patients with acute cerebral infarction.

Humans ; Consensus ; Pancreatic Neoplasms/therapy* ; Neuroendocrine Tumors/therapy*

Aim To investigate the effect of lactate dehydrogenase inhibitor on LPS/D-Gal-induced acute liver injury in mice. Methods BALB/ C mice were divided into four groups:solvent control group, lactate dehydrogenase inhibitor NHI-2 group, lipopolysaccharide(LPS)/ D-galactosamine(D-Gal)group and LPS/D-Gal+NHI-2 group. To induce acute liver injury, mice were injected intraperitoneally with LPS(10 μg·kg-1)and D-Gal(700 mg·kg-1), NHI-2 was intraperitoneally injected 30 min before LPS/D-Gal exposure. Liver tissue and serum were harvested 1.5 or 6 h after LPS/D-Gal exposure, serum lactate, serum aspartate aminotransferase(ALT), serum alanine aminotransferase(AST), serum tumor necrosis factor alpha(TNF-α)liver malondialdehyde(MDA)and liver caspase-3/8/9 levels were determined. HE staining was used to evaluate the degree of liver injury. TUNEL staining was used to evaluate hepatocyte apoptosis. Survival curve was used to record survival situation of tested mice. Results Serum lactate level of model mice was significantly reduced after treatment with NHI-2. Compared with LPS/D-Gal group, level of serum TNF-α showed no significant difference, but serum ALT and AST level of LPS/D-Gal+NHI-2 group significantly decreased, injury of liver structure was remarkably attenuated, level of MDA and activity of caspase-3/8/9 in liver were significantly down-regulated, and the number of TUNEL-positive cells was significantly reduced. Treatment with NHI-2 also significantly improved the survival rate of LPS/D-Gal-insulted mice. Conclusion Lactate dehydrogenase inhibitor alleviates LPS/D-Gal-induced acute liver injury in mice.

Eight sesquiterpenoids were isolated from petroleum ether extract of Aquilariae Lignum Resinatum by various column chromatography techniques including silica gel, ODS, and semi-preparative HPLC. Their structures were identified on the basis of physicochemical properties, UV, IR, MS, and NMR spectroscopic data as(4S,5S,7R,10S)-5,7-dihydroxy-11-en-eudesmane(1),(7R,10S)-eudesma-4-en-11,15-diol(2),(2R,4S,5R,7R)-2-hydroxyeremophila-9,11-dien-8-one(3), 7α-H-9(10)-ene-11,12-epoxy-8-oxoeremophilane(4),(+)-9β,10β-epoxyeremophila-11(13)-en(5), 4(14)-eudesmene-8α,11-diol(6), 12,15-dioxo-selina-4,11-dien(7), and 2β,8 aα-dihydroxy-11-en-eremophilane(8). Compounds 1 and 2 are new compounds, and their absolute configurations were determined by calculating ECD. Compounds 1, 4, and 6-8 could significantly improve taurocholic acid(TCA)-induced gastric mucosal GES-1 cell injury at a concentration of 20 μmol·L~(-1), and the cell protection rates were 23.51%±2.79%, 16.10%±1.25%, 24.45%±4.89%, 17.48%±2.93%, and 21.44%±2.39%, respectively.
Chromatography, High Pressure Liquid ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Sesquiterpenes/chemistry*

Scaffold hopping refers to computer-aided screening for active compounds with different structures against the same receptor to enrich privileged scaffolds, which is a topic of high interest in organic and medicinal chemistry. However, most approaches cannot efficiently predict the potency level of candidates after scaffold hopping. Herein, we identified potent PDE5 inhibitors with a novel scaffold via a free energy perturbation (FEP)-guided scaffold-hopping strategy, and FEP shows great advantages to precisely predict the theoretical binding potencies ΔG _FEP between ligands and their target, which were more consistent with the experimental binding potencies ΔG _EXP (the mean absolute deviations | Δ G FEP - Δ G EXP |  < 2 kcal/mol) than those ΔG _MM-PBSA or ΔG _MM-GBSA predicted by the MM-PBSA or MM-GBSA method. Lead L12 had an IC₅₀ of 8.7 nmol/L and exhibited a different binding pattern in its crystal structure with PDE5 from the famous starting drug tadalafil. Our work provides the first report via the FEP-guided scaffold hopping strategy for potent inhibitor discovery with a novel scaffold, implying that it will have a variety of future applications in rational molecular design and drug discovery.