The antidepressant activity and molecular mechanisms of Yueju Wan volatile oil were investigated. The Yueju Wan volatile oil was extracted by using supercritical CO_2. Gas chromatography-mass spectrometry(GC-MS) combined with network pharmacology identified 28 chemical constituents in Yueju Wan volatile oil, primarily terpenes and lactones. A total of 123 overlapping targets were associated with depression, including core targets of interleukin-1β(IL-1β), signal transducer and activator of transcription 3(STAT3), and caspase-3(CASP3). These targets were mainly involved in the prolactin, advanced glycation end products/receptor(AGE/RAGE), and phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) signaling pathways. A reserpine-induced depression mouse model was established to evaluate the therapeutic effects and mechanisms of Yueju Wan volatile oil. The effects of Yueju Wan volatile oil on depression-like behavior in mice were evaluated by analyzing body mass, body temperature index, tail suspension immobility time, forced swimming immobility time, and sucrose preference. Hematoxylin-eosin(HE) staining revealed neuronal protection of Yueju Wan volatile oil in the brain of mice. Enzyme-linked immunosorbent assay(ELISA) and Western blot were employed to detect the protein expression of AGEs, IL-1β, phosphorylated PI3K(p-PI3K), Akt, phosphorylated Akt(p-Akt), nuclear factor κB(NF-κB), and brain-derived neurotrophic factor(BDNF). Behavioral evaluation showed that Yueju Wan volatile oil could effectively control the decline of body mass and body temperature of depressed mice, reduce tail suspension and swimming immobility time, and enhance their preference for sucrose. Histopathological examination showed that Yueju Wan volatile oil could alleviate the neuronal damage in CA1 and dentate gyrus(DG) of the hippocampus of mice. ELISA and Western blot results showed that Yueju Wan volatile oil could significantly increase the protein expression levels of PI3K, Akt, and BDNF and significantly decrease the protein expression levels of AGEs, IL-1β, p-PI3K, p-Akt, and NF-κB in the hippocampus of mice. Furthermore, the p-PI3K/PI3K and p-Akt/Akt ratios were significantly decreased at medium and high doses. These findings suggest that the aromatherapy of Yueju Wan volatile oil can significantly improve reserpine-induced depression-like behavior in mice, which may be related to reducing the expression of neuronal membrane protein AGEs, reducing the phosphorylation levels of PI3K and Akt, inhibiting NF-κB entry into the nucleus, and alleviating the release of pro-inflammatory factors and nerve injury.
Animals ; Antidepressive Agents/chemistry* ; Mice ; Proto-Oncogene Proteins c-akt/immunology* ; Phosphatidylinositol 3-Kinases/immunology* ; Oils, Volatile/chemistry* ; Male ; Drugs, Chinese Herbal/chemistry* ; Signal Transduction/drug effects* ; Depression/metabolism* ; Glycation End Products, Advanced/immunology* ; Humans

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

BackgroundThe pathogenesis of postural tachycardia syndrome (POTS) remains unclear. This study aimed to explore the changes and significance of sulfur dioxide (SO) in patients with POTS.

MethodsThe study included 31 children with POTS and 27 healthy children from Peking University First Hospital between December 2013 and October 2015. A detailed medical history, physical examination results, and demographic characteristics were collected. Hemodynamics was recorded and the plasma SOwas determined.

ResultsThe plasma SOwas significantly higher in POTS children compared to healthy children (64.0 ± 20.8 μmol/L vs. 27.2 ± 9.6 μmol/L, respectively, P < 0.05). The symptom scores in POTS were positively correlated with plasma SOlevels (r = 0.398, P < 0.05). In all the study participants, the maximum heart rate (HR) was positively correlated with plasma levels of SO(r = 0.679, P < 0.01). The change in systolic blood pressure from the supine to upright (ΔSBP) in POTS group was smaller than that in the control group (P < 0.05). The ΔSBP was negatively correlated with baseline plasma SOlevels in all participants (r = -0.28, P < 0.05). In the control group, ΔSBP was positively correlated with the plasma levels of SO(r = 0.487, P < 0.01). The change in HR from the supine to upright in POTS was obvious compared to that of the control group. The area under curve was 0.967 (95% confidence interval: 0.928-1.000), and the cutoff value of plasma SOlevel >38.17 μmol/L yielded a sensitivity of 90.3% and a specificity of 92.6% for predicting the diagnosis of POTS.

ConclusionsIncreased endogenous SOlevels might be involved in the pathogenesis of POTS.

OBJECTIVE: To build the model of pharmaceutical industry space layout evaluation and explore the spatial layout of pharmaceutical industry. METHODS: Constructed the evaluation index system of the spatial distribution and designed the spatial layout model with the system cluster analysis method. RESULTS AND CONCLUSION: Based on clustering analysis of 31 provinces, with the region and objective reality, according to the principle of similar level of development region, pharmaceutical industry spatial layout is divided into innovative research and technology area, manufacturing area, industry development hot spot area and other areas of four levels of industrial level.

Objective To investigate gene-gene interactions of suicidal behavior with single-nucleotide-polymorphism (SNP) in MAOA ,GAD1 and 5-HTR2C by multifactor dimensionality reduction .Methods For this case-control study ,six SNPs were captured in related genes and detected in blood samples obtained from 21 patients with suicidal behavior and 50 healthy individuals .The genotype frequency and allele frequency as well as the Hardy-Weinberg equilibrium (HWE) ,tests were performed and compared by plink software .The gene-gene interactions models were built by the MDR software .Results The HWE test for case group showed that rs3813928 rs518147 of 5-HTR2C gene was not in line with HWE ( P< 0 .05) .However ,the additive model analysis after adjustment by gender indicated that the polymorphism had a positive correlation with suicidal behavior in case group .The case and control groups differed significantly only in genotype frequencies of 5-HTR2C gene (χ2 =6 .18 , P=0 .04) .There was no significant difference in allele and genotype frequencies of the other genes ( P>0 .05) .The best combination model of MDR was rs5953210-rs769391 OR=20 .19 ,95% CI 4 .19-97 .38 , P<0 .01 ,with significant interaction . Conclusion The 5-HTR2C gene rs3813928 and rs518147 polymorphisms may play an important role in the susceptibility to suicidal behavior .The combination of MAOA with GAD1 has a significant interaction which may increase the risk of suicidal behavior .

OBJECTIVETo characterize carbapenem (CPM)-non-susceptible Klebsiella pneumoniae (K. pneumoniae) and carbape-nemase produced by these strains isolated from Beijing Children's Hospital based on a five-year surveillance.

METHODSThe Minimal Inhibition Concentration values for 15 antibiotics were assessed using the Phonix100 compact system. PCR amplification and DNA sequencing were used to detect genes encoding carbapenemases. WHONET 5.6 was finally used for resistance analysis.

RESULTSIn total, 179 strains of CPM-non-susceptible K. pneumoniae were isolated from January, 2010 to December, 2014. The rates of non-susceptible to imipenem and meropenem were 95.0% and 95.6%, respectively. In the 179 strains, 95 (53.1%) strains carried the blaIMP gene, and IMP-4 and IMP-8 were detected in 92 (96.8%) and 3 (3.2%) IMP-producing isolates, respectively. 65 (36.3%) strains carried the blaNDM-1 gene. 6 (3.4%) strains carried the blaKPC gene, and KPC-2 were detected in 6 KPC-producing isolates. In addition, New Delhi-Metallo-1 (NDM-1) producing isolates increased from 7.1% to 63.0% in five years and IMP-4 producing isolates decreased from 75.0% to 28.3%.

CONCLUSIONHigh frequencies of multiple resistances to antibiotics were observed in the CPM-non-susceptible K. pneumoniae strains isolated from Beijing Children's Hospital. The production of IMP-4 and NDM-1 metallo-β-lactamases appears to be an important mechanism for CPM-non- susceptible in K. pneumoniae.

Anti-Bacterial Agents ; pharmacology ; Bacterial Proteins ; genetics ; metabolism ; Child ; China ; epidemiology ; Drug Resistance ; Gene Expression Regulation, Bacterial ; physiology ; Gene Expression Regulation, Enzymologic ; physiology ; Hospitals, Pediatric ; Humans ; Klebsiella Infections ; epidemiology ; microbiology ; Klebsiella pneumoniae ; drug effects ; enzymology ; genetics ; Microbial Sensitivity Tests ; Population Surveillance ; Time Factors ; beta-Lactamases ; genetics ; metabolism

Based on the stakeholder theory,externalities theory and marginal utility theory,this paper analyzes the behavioral needs of stakeholders in the process of market access of innovative drugs.It also draws out the core of the government and the pharmaceutical enterprises in the policy of access to innovative drug market and supply to the community,the patients,and the medical institutions enter the mechanism of the interaction of the various stakeholders in the innovative drug market for the demand community and construct the above-mentioned stakeholder perspective Innovative Drug Market Access Policy Environment Model.Based on the status quo of China's innovative drug market access,the present study puts forward to encourage innovative drug market access to the interests of the main body,to optimize the existing innovative drug market access policy environment to make reference recommendations.

Objective To explore the intervention effect and mechanism of sitagliptin on renal injury in type 1 diabetic (T1DM) mice.Methods The modeling group was intraperitoneally injected with streptozotocin (150 mg· kg-1) once and blood glucose ≥ 16.7 mmol · L-1 was considered as diabetes mellitus (DM).DM mice were randomly divided into two groups:model group and experimental group.Experimental group was treated with sitagliptin (15 mg · kg-1 · d-1) via intragastric administration for 4 weeks while the mice in model group and normal group treated with equal volume of ultrapure water.The 24 h microalbuminuria(ALB) was determined after administration.At the end of the experiment,urea nitrogen (BUN) and creatinine (SCr) in serum was detected.The protein expression levels of transforming growth factor-β1 (TGF-β1),Smad2,Smad3 were measured by Western blot.Results After administration sitagliptin for 4 weeks,the contents of ALB in model group and experimental group were (11.96 ± 3.36) (2.46 ±0.97) mg/24 h with significantly(P ＜0.001).The index of kidney weight/body weight(KW/BW) in normal group,model group and experimental group were 15.20 ±2.24,21.43 ±2.16,15.14 ±4.14;compared with normal group,the difference was significantly increased (P ＜ 0.05);compared with model group,the difference was significantly increased (P ＜0.05).The SCr in model group and experimental group were (352.58 ±47.09),(238.51 ± 53.03) μmol · L-1;the BUN in the two groups were(26.08 ±4.65),(10.40 ±2.47)mmol · L-1;compared with model group,the difference was significantly increased (P ＜0.01,P ＜0.001).The expression levels of TGF-β1,Smad2/3 and p-Smad2/3 in normal group,model group and experimental group were 0.19 ±0.02,0.12 ±0.02,0.07 ±0.01;0.23 ±0.02,0.27 ±0.04,0.13 ±0.01;0.18 ±0.01,0.14 ±0.01,0.11 ±0.00,compared with normal group,the difference was significantly increased (P＜0.05,P＜0.01);compared with model group,the difference was significantly increased (P ＜0.05,P ＜0.01).Conclusion Experimental delaying the progression of T1DM nephropathy without not decreasing blood glucose can effect partly through inhibiting TGF-β1/Smad2/3 pathway.

Objective To study the tolerability and safety of single and multiple doses of Picika oral solution in healthy volunteers.Methods A single center, randomized, single -blind, placebo -controlled, dose -escalation study was designed.50 patients were given single dose, and 10 cases were given multiple doses.All of them had half male and fe-male.Single -dose group: 20 mL(4 subjects), 40 mL(6 subjects), 60 mL(10 subjects; 2 using placebo), 90 mL(10 subjects; 2 using place-bo), 120 mL (10 subjects ; 2 using placebo), 160 mL (10 subjects; 2 using placebo); multiple doses group: 10 subjects(2 using placebo), 40 mL? times-1 , tid, continuous medication for 10 days.Results Of the sixty healthy subjects enrolled , 58 finally completed the trial, and two shed.One case (female) of adverse event in single -dose 160 mL group was reported: her ctivated partial thromboplastin time (APTT) was ab-normal with clinical significance.It may not be associated with the medi-cation.In multiple doses group, one case of abdominal pain (female) was reported, may not be associated with the medication.Conclusion Single and multiple doses of Picika oral solution are safe and well tolera -ted in healthy subjects.

OBJECTIVETo study the clinical effects of Achillon for the treatment of acute Achilles tendon rupture (AATR).

METHODSFrom April 2009 to April 2010, 19 patients with AATR who were treated with Achillon were retrospectively analyzed. There were 17 males and 2 females, with an average age of 40.2 years (30 to 58 years). There were 9 cases of sports injury, and 2 case of fall injury. The time from injury to surgery ranged from 0 to 8 days (2.2 days on average). The results of Thompson test and single heel rise test were positive in 19 cases. Clinical data were assessed with the patient satisfaction and the AOFAS hindfoot score during follow-up.

RESULTSAll the patients were followed up, and the duration ranged from 12 to 28 months (19.9 months on average). The average operation time was 41 minutes. There were no wound infections, recurrent rupture, or sural nerve complications. At the latest follow-up, 18 patients were totally satisfied with the surgical result, 1 patient feel generally due to mild pain when running. None of the patients were dissatisfied with the final results the latest follow-up. At the latest follow-up, the AOFAS score was 98.42 +/- 3.29 (89 to 100). All the patients regained normal range of motion and were able to resume their previous activities at six months after operation, with a high rate of satisfaction. Average decreased of mid-calf circumference was (0.82 +/- 0.85) cm (ranged from 0 to 3 cm).

CONCLUSIONTreatment with Achillon is safe, effective for AATR with low incidence of complications and early active rehabilitation can be carried out. It is a good method to treat AATR.

Achilles Tendon ; injuries ; surgery ; Acute Disease ; Adult ; Female ; Humans ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures ; instrumentation ; Retrospective Studies ; Rupture ; Suture Techniques ; instrumentation ; Tendon Injuries ; surgery