Ying Wu

BACKGROUND AND PURPOSE: Ginsenoside-Rd is a receptor-operated calcium channel antagonist and has shown promise as a neuroprotectant in our phase II study. As an extended work, we sought to confirm its efficacy and safety of Ginsenoside-Rd in patients with acute ischaemic stroke. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 390 patients with acute ischaemic stroke in a 3:1 ratio to receive a 14-day intravenous infusion of Ginsenoside-Rd or placebo within 72 h after the onset of stroke. Our primary end-point was the distribution of disability scores on the modified Rankin scale (mRs) at 90 days. RESULTS: The efficacy analysis was based on 386 patients (Ginsenoside-Rd group: 290; placebo group: 96). Ginsenoside-Rd significantly improved the overall distribution of scores on the mRs, as compared with the placebo (P = 0.02; odds ratios [OR], 1.74; 95% confidence interval [CI], 1.08-2.78). There were significant differences between the two groups when we categorized the scores into 0-1 vs. 2-5 (P = 0.01; OR, 2.32; 95% CI, 1.23-4.38; 66.8% vs. 53.1%). It also improved the National Institutes of Health Stroke Scale (NIHSS) at 15 days [P < 0.01; least squares mean (LSM), -0.77; 95% CI, -1.31 to -0.24]. Mortality and rates of adverse events were similar in the two groups. CONCLUSIONS: Ginsenoside-Rd improved the primary outcome of acute ischaemic stroke and had an acceptable adverse-event profile.

BACKGROUND: Dexmedetomidine induces a sedative response that is associated with rapid arousal. To elucidate the underlying mechanisms, the authors hypothesized that dexmedetomidine increases the activity of dopaminergic neurons in the ventral tegmental area, and that this action contributes to the unique sedative properties of dexmedetomidine. METHODS: Only male mice were used. The activity of ventral tegmental area dopamine neurons was measured by a genetically encoded Ca indicator and patch-clamp recording. Dopamine neurotransmitter dynamics in the medial prefrontal cortex and nucleus accumbens were measured by a genetically encoded dopamine sensor. Ventral tegmental area dopamine neurons were inhibited or activated by a chemogenetic approach, and the depth of sedation was estimated by electroencephalography. RESULTS: Ca signals in dopamine neurons in the ventral tegmental area increased after intraperitoneal injection of dexmedetomidine (40 μg/kg; dexmedetomidine, 16.917 [14.882; 21.748], median [25%; 75%], vs. saline, -0.745 [-1.547; 0.359], normalized data, P = 0.001; n = 6 mice). Dopamine transmission increased in the medial prefrontal cortex after intraperitoneal injection of dexmedetomidine (40 μg/kg; dexmedetomidine, 10.812 [9.713; 15.104], median [25%; 75%], vs. saline, -0.498 [-0.664; -0.355], normalized data, P = 0.001; n = 6 mice) and in the nucleus accumbens (dexmedetomidine, 8.543 [7.135; 11.828], median [25%; 75%], vs. saline, -0.329 [-1.220; -0.047], normalized data, P = 0.001; n = 6 mice). Chemogenetic inhibition or activation of ventral tegmental area dopamine neurons increased or decreased slow waves, respectively, after intraperitoneal injection of dexmedetomidine (40 μg/kg; delta wave: two-way repeated measures ANOVA, F[2, 33] = 8.016, P = 0.002; n = 12 mice; theta wave: two-way repeated measures ANOVA, F[2, 33] = 22.800, P < 0.0001; n = 12 mice). CONCLUSIONS: Dexmedetomidine activates dopamine neurons in the ventral tegmental area and increases dopamine concentrations in the related forebrain projection areas. This mechanism may explain rapid arousability upon dexmedetomidine sedation.

To investigate the role of the angiotensin-converting enzyme gene (ACE) insertion (I)/deletion (D) polymorphism in hypertensive patients with different degrees of obstructive sleep apnea (OSA). A case-control study was performed. One hundred seventy four Chinese subjects were divided into four groups depending on the severity of OSA as follows: 1) normal control group (NC, n=68), 2) isolated hypertension group (HT, n=45), 3) hypertensive patients with mild OSA group (MO, n=27), and 4) hypertensive patients with moderate to severe OSA group (MSO, n=34). The distribution of ACE gene I/D allele and genotypes were analyzed in the subject population, as was an OSA pedigree. The study showed that the frequency of ACE gene I/D polymorphism differed significantly among the four groups. The frequency of I allele and II genotype were significantly higher in the MSO group than in the other groups (p<0.05). The distribution of I allele and II genotype showed no significant difference between any of the other groups (p>0.05, respectively). Meanwhile the higher frequency of I allele and II genotype was observed in the OSA pedigree. The higher frequency of ACE gene I allele and II genotype were closely associated with the hyptertensive patients with MSO. The inherited factors played an important role in the pathogenesis of hypertensive patients with MSO. (Hypertens Res 2000; 23: 407-411)

OBJECTIVE: To evaluate the usefulness of Hisense Computer Assisted Surgery System (Hisense CAS) in pre-operative surgical planning and intra-operative navigation for resection of pediatric giant hepatic mesenchymal hamartoma (HMH). METHODS: Five children with HMH underwent hepatectomy in our hospital. Pre-operative abdominal enhanced CT was performed for diagnosis and treatment planning. Using CT DICOM files, three-dimensional reconstruction was performed in three cases for operation planning and intra-operative navigation, with SID carrying out precise liver resection during the operation with Hisense CAS. RESULT: Two patients underwent right and left lobe hepatectomy, respectively, based only on enhanced CT. In 3 patients, by using the Hisense CAS system, three-dimensional reconstruction of the liver and tumors was successfully completed, and virtual hepatectomy performed successfully according to surgical plans. Hisense CAS could clearly and directly indicate the HMH location and shape, as well as its relationship with the intra-hepatic Glisson system, assisting safe hepatectomy. All five patients recovered well from surgery without any complications, and pathological examinations confirmed that all cases were HMH. No recurrence was observed during the follow-up period of 3 months to 5 years. CONCLUSION: Hisense CAS system is useful for preoperative planning and intra-operative navigation, assisting safer hepatectomy.

The role of FEN1 genetic variants on gallstone and gallbladder cancer susceptibility is unknown. FEN1 SNPs were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method in blood samples from 341 gallbladder cancer patients and 339 healthy controls. The distribution of FEN1-69G > A genotypes among controls (AA, 20.6%; GA, 47.2% and GG 32.2%) was significantly different from that among gallbladder cancer cases (AA, 11.1%; GA, 48.1% and GG, 40.8%), significantly increased association with gallbladder cancer was observed for subjects with both the FEN1-69G > A GA (OR = 1.73, 95% CI = 1.01-2.63) and the FEN1-69G > A GG (OR = 2.29, 95% CI = 1.31-3.9). The distribution of FEN1 -4150T genotypes among controls (TT, 21.8%;GT, 49.3% and GG 28.9%) was significantly different from that among gallbladder cancer cases (TT, 12.9%; GT, 48.4% and GG 38.7%), significantly increased association with gallbladder cancer was observed for subjects with both the FEN1-4150T GT(OR = 1.93, 95% CI = 1.04-2.91) and the FEN1-4150T GG(OR = 2.56, 95% CI = 1.37-5.39). A significant trend towards increased association with gallbladder cancer was observed with potentially higher-risk FEN1-69G > A genotypes (P < 0.001, χ2 trend test) and FEN14150G > T (P < 0.001, χ2 trend test) in gallstone presence but not in gallstone absence (P = 0.81, P = 0.89, respectively). In conclusion, this study revealed firstly that FEN1 polymorphisms and haplotypes are associated with gallbladder cancer risk.