Hydrogen sulfide (H₂S) is a gas signaling molecule with versatile bioactivities; however, its exploitation for disease treatment appears challenging. This study describes the design and characterization of a novel type of H₂S donor-drug conjugate (DDC) based on the thio-ProTide scaffold, an evolution of the ProTide strategy successfully used in drug discovery. The new H₂S DDCs achieved hepatic co-delivery of H₂S and an anti-fibrotic drug candidate named hydronidone, which synergistically attenuated liver injury and resulted in more sufficient intracellular drug exposure. The potent hepatoprotective effects were also attributed to the H₂S-mediated multipronged intervention in lipid peroxidation both at the whole cellular and lysosomal levels. Lysosomal H₂S accumulation and H₂S DDC activation were facilitated by the hydrolysis through the specific lysosomal hydrolase, representing a distinct mechanism for lysosomal targeting independent of the classical basic moieties. These findings provided a novel pattern for the design of optimally therapeutic H₂S DDC and organelle-targeting functional molecules.

Objective To investigate the optimal dose of remifentanil combined with dexmedetomidine for awake tracheal intubation.Methods 60 cases with difficult airway general anesthesia surgery from March 2014 to August 2016 in Jinhua People's Hospital were selected and divided into group R1,R2,R3,20 cases in each group.0.6μg/kg dexmedetomidine 10 minutes micro pump intravenously,Simultaneous target-controlled infusion effect of the chamber concentration of remifentanil.2.0ng/mL remifentanil in group R1,2.3ng/mL remifentanil in group R2,2.5ng/mL remifentanil in group R3.All patients underwent full surface anesthesia with 2％lidocaine under visual soft mirror guidance.The heart rate(HR),mean arterial pressure(MAP)and Ramsay sedation score at before anesthesia(T0),at the end of the administration(T1),intubation(T2),immediately after intubation(T3),tracheal catheter placement reaction score and record tracheal intubation during respiratory depression,cardiovascular adverse events,postoperative follow-up of tracheal intubation process satisfaction.Results MAP,HR and RR at T2,T3 in group R1 were significantly higher than those in group R2 and R3,the difference was statistically significant(P<0.05).The incidence of hypertension in the group R3 was significantly lower than that in group R1,while the incidence of respiratory depression and tachycardia was significantly higher than that in group R1,the difference was statistically significant(P<0.05),RSS score and satisfaction scores in group R3 were significantly higher than those in group R1,the reaction score in group R3 was significantly lower than the group R1,the difference was statistically significant(P<0.05).Within group comparison,the mean arterial pressure and heart rate and respiratory rate at T2 and T3 in group R1 was significantly higher than those at T1,heart rate was significantly faster than T1,the respiratory rate was significantly faster than T1,the difference was statistically significant(P<0.05),T2 and T3 in group R3 were significantly slower than those at T0,the difference was statistically significant(P<0.05).Conclusion Remifentanil combined with dexmedetomidine can be safely and effectively used for awake intubation under glidescope guiding in difficult airway patients.In the full airway surface anesthesia,dexmedetomidine micropump 0.6μg/kg simultaneous target transfusion effect of the concentration of remifentanil 2.3ng/mL is a more reasonable medication.

From November 2003 to May 2010, intrathecal drug delivery system (IDDS) was implanted in 18 patients with chronic intractable pain. Analgesia was provided with morphine. Thirteen patients suffered from late stage cancer and 5 from diseases other than cancer. VAS score was used to measure intensity of pain in all 18patients. QLQ-C30 score was used to evaluate quality of life in cancer patients. The patients were followed up for 3-62 months in 5 non-cancer patients. All 13 cancer patients died at 57 days-10 months after operation. VAS scores were significantly decreased and QLQ-C30 scores increased by intrathecal administration of morphine. Side effects developed in all patients to some extent including nausea, vomiting, constipation, urinary retention, pruritus and over-sedation and vanished in a week. Intrathecal catheter was cut while being pulled out of the needle in 1 patient. Two patients developed low intracranial pressure after operation. Cerebrospinal fluid leakage occurred in 1 patient. One patient developed neuropathic pain in the posterolateral side of right leg.

Seventy-four patients aged 26-63 yr who had suffered cervicogenic headache for 3 months-21 yr were treated with puked radiofrequency applied to C2 dorsal root ganglion, which is located in the middle of the posterior side of lateral atlantoaxial joint. A trochar was introduced percutaneously under the guidance of X-ray aiming at the target point. As it was inserted through the deep fascia, the stylet was withdrawn and a 10 cm long 22 gauge curved blunt electrode was inserted into the trochar and advanced until the patients felt radiating pain from the point of puncture to occiput. Lateral radiograph was obtained to verify the placement of electrode. The tip of the electrode was usually located in front of spinal canal at the atlantoaxial joint level. Sensory stimulation was performed with 50 Hz and 0.1-0.5 V and the patients could feel radiating pain at occiput. Motor stimulation was performed with 2 Hz and 0.4-1.0 V and regular pulsation of the patient's muscle of occiput could occur. Pulsed radiofrequency was applied at 42 ℃7 for 240 s and was performed twice on each side. VAS scores and disturbances of daily activity, mood and sleep were recorded before operation and at 1 week and 1, 3, 6, 12 and 18 months after pulsed radiofrequency treatment. Complications and recurrence within 12 and 18 months were recorded. Follow-up was lost in 22 patients. VAS scores and disturbances of daily activity, mood and sleep significantly decreased after procedure. All of the patients responded without complications like infection, spinal cord and vertebral artery injury. Some patients had transient occipital neuralgia which was usually relieved within 24 h. The recurrence rate in 12 and 18 months after operation was 19% and 31% respectively.

Objective To explore the relationship between tumor necrosis factor (TNF) gene polymorphisms in donors and recipients and the incidence and severity of acute graft-versus-host diseases (aGVHD) after unrelated allogeneic hematopoietic stem cell transplantation (alIo-HSCT). Methods Single nucleotide polymorphisms (SNPs) of TNFα-238 (G/A), TNFα-857 (C/T), TNFα-863 (C/A), TNFα-1031 (T/C), TNFβ + 252 (A/G) were analyzed by Multiplex SNaPshot analysis in 76 pairs of donors and recipients. Results Transplantation involving donors with TNFα-857 CC genotype resulted in a higher incidence of grade Ⅱ-Ⅳ aGVHD than donors with CT genotype (91.3% vs 8. 7% , P =0. 039). In the 23 patients with grade Ⅱ-Ⅳ aGVHD, no patients had TNFβ +252 AA genotype, 19 (82.6%) had GA genotype and 4 (17.4%) had GG genotype. There was a significant difference in the distribution pattern of the TNFβ +252 (AA, GA and GG) genotypes in these patients (P =0.03). There was no significant association of TNFα-238 (G/A), TNFα-863 (C/A) and TNFα-1031 (T/C) polymorphisms with the risk of aGVHD. Conclusion These results suggest donor TNFα-857 CC genotype is related to a higher incidence of grade Ⅱ -Ⅳ aGVHD, and patients with TNFβ +252 AA genotype have protection against the risk of grade Ⅱ -Ⅳ aGVHD.