Objective To determine the 50%effective dose (ED 50) of dexmedetomidine for sedation in the brachial plexus block, so as to provide reference for clinical. Methods Twenty-three patients underwent the brachial plexus block using an ultrasound guided technique. After blocked for 30 min, the dexmedetomidine was infused by a intravenous continuous pump,and an observer' s assessment of alertness/sedation score (OAA/S) and auditory evoked potential index (AEPI) were used for monitoring the depth of sedation. The dexmedetomidine was adjusted according to the response of the previous patient using a up-and-down sequential method until the sequential response curve appeared seven fold points. The initial dexmedetomidine of the first patient was 1μg/kg. Each time the dosage increased/decreased by 0.1μg/kg. The OAA/S score of no more than 3 was defined an effective sedation. Results The ED50 of dexmedetomidine for sedation was 0.78μg/kg (95%CI 0.66-0.86μg/kg). The AAI was positively correlated to the OAA/S score, and linear regression equation was Y=-1.43+0.109 X, R2=0.919. Conclusion The ED50 of dexmedetomidine for sedation in the brachial plexus block is 0.78μg/kg (95%CI 0.66-0.86μg/kg).

Objective To study the median effective doses (ED50) of dexmedetomidine to induce adequate sedation in elderly patients undergoing epidural anaesthesia. Methods Seventy-five elderly patients undergoing lower extremity operation under epidural anesthesia were selected, and the patients were divided into 5 groups according to the random digits table method with 15 cases each: D1 group (dexmedetomidine 0.2 μg/kg), D2 group (dexmedetomidine 0.4 μg/kg), D3 group (dexmedetomidine 0.6 μg/kg), D4 group (dexmedetomidine 0.8μg/kg) and D5 group (dexmedetomidine 1.0μg/kg). After 20 min of dexmedetomidine injection, adequate sedation was defines as observer′s assessment of alertness/sedation score (OAA/S score) ≤ 3 scores. The ED50 and 95% effective dose (ED95) of dexmedetomidine and 95% CI in elderly patients undergoing epidural anaesthesia were calculated by probit regression method. The changes of mean arterial pressure (MAP), heart rate, pulse oxygen saturation (SpO2) and OAA/S score among 5 groups were compared. The incidences of adverse effects such as hypotension, bradycardia, hypoxemia and excessive sedation were compared. Results The ED50 in elderly patients was 0.36 μg/kg (95% CI 0.27 - 0.44 μg/kg); the ED95 was 0.94 μg/kg (95% CI 0.71 - 1.62 μg/kg). After dexmedetomidine injection, the MBP, heart rate, SpO2 and OAA/S scores in 5 groups were decreased, but in the D4 group and D5 group the decreases were more significant. The incidences of hypotension, bradycardia and excessive sedation in D1 group, D2 group and D3 group were significantly lower than those in D4 group and D5 group:2/15, 5/15 and 8/15 vs. 14/15 and 15/15;1/15, 6/15, 7/15 vs. 13/15 and 14/15;0, 0 and 1/15 vs. 5/15 and 7/15, the incidences of hypoxemia in D1 group, D2 group and D3 group were significantly lower than those in D5 group: 0, 0 and 0 vs. 3/15 and 4/15, and there were statistical differences (P<0.05). There were no statistical differences in incidences of adverse effects between D4 group and D5 group (P>0.05). Conclusions The ED50 of dexmedetomidine in elderly patients undergoing epidural anaesthesia is 0.36μg/kg, (CI 0.27-0.44μg/kg). The incidences of adverse effects are increased when single-dose dexmedetomidine is more than 0.8μg/kg.

Objective To investigate the effects of butorphanol pretreatment on myocardial injury induced by limb ischemia/reperfusion.Methods Forty patients with distal lower extremity orthopedic surgery (ASA Ⅰ or Ⅱ) were divided into two groups by random digits table method with 20 cases each:butorphanol group and control group.Epidural anesthesia was selected in all patients.In butorphanol group,patients were given butorphanol 0.04 mg/kg intravenously 15 min before tourniquet.In control group,equal volume of normal saline was infused at the same time.Blood samples were taken from jugular vein before tourniquet (T0),then 5 min(T1),2 h (T2),6 h (T3),12 h (T4) and 24 h (T5) after the second reperfusion of tourniquet.The serum creatine kinase isoenzyme MB (CK-MB),cardiac troponin Ⅰ (cTnI),tumor necrosis factor-α (TNF-α) and malondialdehyde (MDA) levels were determined.Results Compared with those at T0,the serum C K-MB levels were increased at T2-T5,the serum cTnI,MDA,TNF-α levels were increased at T1-T5 in control group,and there were significant differences (P ＜ 0.05).Compared with those at T0,the serum CK-MB levels were increased at T3,T4,the serum TNF-α levels were increased at T1-T3,the serum cTnI levels were increased at T1-T5 in butorphanol group,and there were significant differences (P ＜ 0.05).Compared with those in control group,the serum CK-MB levels were decreased at T2-T5 [(20.2 ± 5.0) U/L vs.(35.3 ±6.8) U/L,(32.3 ±3.7) U/L vs.(48.6 ±8.5) U/L,(29.5 ±5.4) U/L vs.(51.5 ±8.0) U/L,(22.2 ±4.8) U/L vs.(33.7 ±6.7) U/L],the serum cTnI,TNF-α levels were decreased at T1-T5 [(0.158 ± 0.016) μg/L vs.(0.278 ±0.021) μg/L,(0.169 ±0.036) μg/L vs.(0.332 ± 0.062) μg/L,(0.357 ±0.049) μg/L vs.(0.623 ±0.083) μg/L,(0.178 ±0.045) μg/L vs.(0.383 ±0.059) μg/L,(0.138 ±0.016) μg/L vs.(0.263 ±0.023) μg/L; (1.63 ±0.13) μg/L vs.(2.12 ±0.08) μg/L,(1.69 ± 0.08) μ g/L vs.(2.28 ± 0.09) μ g/L,(1.63 ± 0.09) μ g/L vs.(2.25 ± 0.07) μ g/L,(1.23 ± 0.14) μμg/Lvs.(1.93±0.12) μg/L,(1.13±0.15) μμg/Lvs.(1.79±0.07) μμg/L],theserumMDAlevelswere decreased at T1-T4 [(4.82 ±0.53) nmol/L vs.(6.68 ±0.67) nmol/L,(4.99 ±0.61) nmol/L vs.(7.59 ±0.72) nmol/L,(5.02 ±0.43) nmol/L vs.(7.54 ±0.63) nmol/L,(4.52 ±0.55) nmol/L vs.(6.52 ±0.47) nmol/L] in butorphanol group,and there were significant differences (P ＜0.05).Conclusion Butorphanol pretreatment can improve the serum CK-MB,cTnI levels,and has a protective role for myocardial injury induced by limb ischemia/reperfusion.

OBJECTIVETo investigate the clinical and laboratory features of very long chain acyl-CoA dehydrogenase deficiency ( VLCADD ) and the correlations between its genotype and phenotype.

METHODEleven patients diagnosed as VLCADD of Shanghai Jiaotong University School of Medicine seen from September 2006 to May 2014 were included. There were 9 boys and 2 girls, whose age was 2 d-17 years. Analysis was performed on clinical features, routine laboratory examination, and tandem mass spectrometry (MS-MS) , gas chromatography mass spectrometry (GC-MS) and genetic analysis were conducted.

RESULTAll cases had elevated levels of blood tetradecanoylcarnitine (C14:1) recognized as the characteristic biomarker for VLCADD. The eleven patients were classified into three groups: six cases in neonatal onset group, three in infancy onset group form patients and two in late onset group. Neonatal onset patients were characterized by hypoactivity, hypoglycemia shortly after birth. Infancy onset patients presented hepatomegaly and hypoglycemia in infancy. The two adolescent patients showed initial manifestations of exercise intolerance or rhabdomyolysis. Six of the eleven patients died at the age of 2-8 months, including four neonatal onset and two infant onset patients, with one or two null mutations. The other two neonatal onset patients were diagnosed since early birth through neonatal screening and their clinical manifestation are almost normal after treatments. Among 11 patients, seventeen different mutations in the ACADVL gene were identified, with a total mutation detection rate of 95.45% (21/22 alleles), including eleven reported mutations ( p. S22X, p. G43D, p. R511Q, p. W427X, p. A213T, p. C215R, p. G222R, p. R450H, p. R456H, c. 296-297delCA, c. 1605 + 1G > T) and six novel mutations (p. S72F, p. Q100X, p. M437T, p. D466Y, c. 1315delG insAC, IVS7 + 4 A > G). The p. R450H was the most frequent mutation identified in three alleles (13.63%, 3/22 alleles), followed by p. S22X and p. D466Y mutations which were detected in two alleles (9.09%, 2/22 alleles).

CONCLUSIONThe ACADVL gene mutations were heterozygous in our patients. The mortality of neonatal onset form and infant onset form is much higher than the late onset form patients, suggesting a certain correlation between the genotype and phenotype was found. The earlier diagnosis and treatment of VLCADD are of vital importance for the improvement of the prognosis of the patients.

Acyl-CoA Dehydrogenase, Long-Chain ; deficiency ; genetics ; Adolescent ; Age of Onset ; Alleles ; Asian Continental Ancestry Group ; Child ; Child, Preschool ; China ; Female ; Genetic Testing ; Genotype ; Heterozygote ; Humans ; Infant ; Infant, Newborn ; Lipid Metabolism, Inborn Errors ; complications ; genetics ; Male ; Mitochondrial Diseases ; complications ; genetics ; Muscular Diseases ; complications ; genetics ; Mutation ; Neonatal Screening ; Phenotype ; Prognosis ; Rhabdomyolysis ; etiology ; Spectrum Analysis ; Tandem Mass Spectrometry

Objective To investigate the effect of quadratus lumborum block on postoperative analgesia and T lympho-cyte subsets in patients receiving transabdominal radical resection of rectal cancer, so as to provide clinical references. Methods From May 2016 to November 2017, 30 patients receiving selective radical resection of rectal cancer in our hospital were selected. The random number table was used to divide the patients into quadratus lumborum block group(experimental group) and incision partial infiltration block group (control group), with 15 patients in each group. After induction of general anesthesia, the experimental group underwent ultrasound-guided bilateral anterior lateral quadratus lumborum block. Each side was injected with 0. 375％ ropivacaine of 20 mL. The control group was induced by general anesthesia and 0. 375％ ropivacaine of 40 mL was injected for local infiltration block. The surgery time, volume of blood loss, total infusion volume of propofol, effective analgesia time, the amount of sufentanil infusion every 12 hours after surgery and resting VAS scores at postoperative different time points (2, 6, 12, 24, 36, 48 hours postoperatively) were observed and recorded. Venous blood (1 mL) was drawn 30 minutes before anesthesia(TO), 2 hours after surgery(T1), 1 day after surgery(T2) and 3 days after surgery(T3). T lymphocyte subsets were detected by flow cytometry(CD3+, CD4+, CD8+, CD4+/CD8+). Results Compared with the control group, the dosage of propofol in the experimental group was significantly less than that in the control group (P＜0. 05); the effective analgesia time in the experimental group was significantly longer than that in the control group (P＜0. 0l); the amount of sufentanil in the experimental group was significantly less than that in the control group at 0-12 h and 12-24 h after surgery (P＜0. 05); the resting VAS scores in the experimental group at 6 h and 12 h after the surgery were significantly lower than those in the control group (P＜0. 05); the levels of CD3+, CD4+, CD4+/CD8+ in the experimental group were significantly higher than those in control group at T2 (P＜0. 05). Compared with TO, CD3+, CD4+, CD4+/CD8+ at T1 and T2 in the two groups were significantly lower than those at TO(P＜0. 05); at T2, CD8+ in the control group was significantly lower than that at TO(P＜0. 05). Conclusion Bilateral quadratus lumborum block can significantly improve postoperative analgesia effect in patients receiving radical resection of rectal cancer and reduce the inhibition of T lymphocytes by surgical stress.

Substances addiction is one of the important factors that deeply affect human health.At present, there is still lack of effective treatment drugs in the clinic.Exploring mechanisms of substances addiction, finding new therapeutic targets and developing effective therapeutic drugs are important issues to be solved.Hyperpolarization-activated cyclic nucleotide gated cation channels (HCN channels) participate in many advanced brain activities and are closely related to the occurrence and progression of various brain diseases.Among them, the researches on the role and mechanism of HCN channels in substances addiction are gradually gaining attention.Reviewing the researches regarding substances addiction, abnormal function and abnormal expression of HCN channels were observed in many brain regions under the condition of psychoactive substances addiction.However, it has not yet been able to fully understand the mechanism and the behavioral consequences of this change.Therefore, we review the neurobiological mechanisms of HCN channels in substances addiction induced by opioids, cocaine, cannabis, amphetamines, alcohol and tobacco, in order to provide new ideas for the mechanism researches and treatment of substance addiction.

Objective:To delineate the histomorphological disparities of subchondral bone between hemophilic arthritis (HA) and osteoarthritis (OA) and to explore the mechanisms underpinning aberrant bone remodeling in HA.Methods:Fifteen male HA patients, aged 32.60±7.58 years (range 22-45), who underwent total knee arthroplasty at the Second Affiliated Hospital of Anhui Medical University from January 2021 to June 2023, were included. All patients had hemophilia A and tested negative for coagulation factor VIII antibodies. Simultaneously, fifteen male OA patients, aged 75.67±5.09 years (range 71-87), also underwent arthroplasty. Tibial plateau bones were extracted for micro-CT, which assessed morphological parameters. Histological changes in the subchondral bone plate (SBP) and trabecular bone were evaluated with HE and Safranin O-Fast Green staining. TRAP staining determined osteoclast differentiation levels, and VEGF-A and Osterix immunohistochemistry gauged angiogenesis and osteoblast differentiation.Results:Micro-CT revealed that HA patients had a BV/TV of 25.14%±0.70% (medial) and 22.31%±0.53% (lateral), Conn.D. of 4.20±0.10 1/mm 3 (medial) and 3.27±0.08 1/mm 3 (lateral), BMD of 0.288±0.006 g/cm 3 (medial) and 0.285±0.004 g/cm 3 (lateral), Tb.Th of 0.257±0.008 mm (medial) and 0.206±0.008 mm (lateral), Tb.N of 0.984±0.043 1/mm (medial) and 0.908±0.026 1/mm (lateral), and Tb.Sp of 0.683±0.008 mm (medial) and 0.808±0.010 mm (lateral). These parameters were significantly lower than those in the OA group except for Tb.Sp, which was higher ( P<0.001). Histological staining indicated that the HA group's SBP thickness was 177.43±6.42 μm (medial) and 117.96±5.08 μm (lateral) with significant differences observed ( P<0.001). TRAP staining showed that TRAP + osteoclasts accounted for 33.4%±3.1% (medial) and 25.1%±2.3% (lateral) in HA subchondral bone, again significantly different ( P<0.001). Immunohistochemical staining revealed VEGFA + cells at 34.1%±5.9% (medial) and 25.9%±3.7% (lateral), and Osterix + cells at 14.6%±1.4% (medial) and 5.8%±1.1% (lateral) in HA patients, differing significantly from the OA group ( P<0.001). Conclusion:The HA group exhibited more extensive subchondral bone destruction, thinner trabeculae, a nearly absent tidemark, higher osteoclast differentiation, increased angiogenesis, and reduced osteoblast differentiation, indicating severe osteoporosis, despite thicker SBP. These findings suggest that targeting abnormal bone remodeling and angiogenesis in HA could retard its progression and provide therapeutic benefits.