To explore novel histone deacetylase (HDAC) inhibitors with anti-tumor activity, twelve target compounds were synthesized, and their structures were confirmed by 1H NMR, MS and elemental analyses. Evaluation results in vitro showed that compound Ia exhibited potent inhibition against HDAC and is worth for further investigation. And compounds IIa, IIb, IIIa-IIIi possessed moderate HDAC inhibitory activity.

Objective To evaluate the changes in the expression of spinal divalent metal transporter 1 (DMT1) during remifentanil-induced hyperalgesia in a rat model of incisional pain.Methods Thirtytwo male Sprague-Dawley rats,weighing 240-260 g,aged 2-3 months,were randomly divided into 4 groups (n =8 each) using a random number table:control group (group C),incisional pain group (group I),remifentanil group (group R),and incisional pain + remifentanil group (group I+R).In group C,normal saline was infused for 60 min at a rate of 0.1 ml · kg-1 · min-1.A 1-cm longitudinal incision was made through skin,fascia and muscle of the plantar aspect of the left hindpaw in sevoflurane-anesthetized rats,and normal saline was infused intravenously for 60 min at a rate of 1.0 μg · kg-1 · min-1 at the same time in group I.In group R,remifentanil was infused for 60 min at a rate of 1.0 μg · kg 1 · min-1 In group I+R,the model of incisional pain was established,and remifentanil was simultaneously infused for 60 min at a rate of 1.0 μg · kg-1 · min-1.At 24 h before normal saline or remifentanil infusion and 6,24 and 48 h after the end of infusion (T0-3),the mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured.All the rats wcrc sacrificed after the last measurement of pain thresholds,and the spinal cord was removed for determination of DMT1 with/without iron-responsive element [DMT1 (+)IRE and DMT1 (-)IRE] expression (by Western blot analysis and immunohistochemistry).Results Compared with group C,the MWT was significantly decreased,and the TWL was significantly shortened at T1-3,and the expression of spinal DMT1 (-) IRE was significantly up-regulated in I,R and I+R groups (P＜0.05).Compared with I and R groups,the MWT was significantly decreased,and TWL was significantly shortened at T1-3,and the expression of spinal DMT1 (-) IRE was significantly upregulated in group I+R (P＜0.05).There was no significant difference in the expression of spinal DMT1 (+) IRE between the four groups (P＞ 0.05).Conclusion Spinal DMT1 (-)IRE activation may be involved in the mechanism underlying remifentanil-induced hyperalgesia in a rat model of incisional pain.

Objective To investigate the effects and mechanisms of hydrogen inhalation on serum levels of pro-inflammatory factors and intestinal injury in severe septic mice. Methods 176 male ICR mice were randomly divided into four groups: sham operation group, hydrogen control group ( sham + hydrogen inhalation ), model group ( severe sepsis model ) and hydrogen treatment group ( severe sepsis model+hydrogen inhalation ), with 44 mice in each group. Severe sepsis model was reproduced by cecal ligation and puncture ( CLP ). 2%hydrogen inhalation was given for 1 hour at 1 hour and 6 hours after sham or CLP operation. Twenty animals in each group were selected and observed for 7-day survival rate. Six animals in each group were selected and sacrificed at 6, 12, 24 and 48 hours after sham or CLP, the concentrations of tumor necrosis factor-α ( TNF-α), interleukins ( IL-6, IL-10 ) and high mobility group box 1 ( HMGB1 ) in serum were determined, the intestinal histopathological changes and scores were evaluated by light microscopy, and the activities of myeloperoxidase ( MPO ) and caspase-3 were determined. Results The 7-day survival rate of severe sepsis mice was 0; the 7-day survival rate was increased to 60% in hydrogen treatment group, with statistical significance in variables compared with model group ( P<0.05 ). Compared with sham operation group, the serum concentrations of TNF-α, IL-6, IL-10 and HMGB1 were obviously increased, the intestine were heavily injured along with higher histopathological scores, and the intestinal MPO and caspase-3 activities were significantly enhanced at different time points after CLP in model group ( all P<0.05 ). Compared with model group, the serum concentrations of TNF-α, IL-6 and HMGB1 were significantly decreased [ TNF-α( ng/L ):6 hours:110.34±9.28 vs. 440.55±25.78, 12 hours: 82.29±8.43 vs. 448.36±32.54, 24 hours: 79.68±9.04 vs. 346.42±22.24, 48 hours: 80.79±10.06 vs. 368.94±31.58; IL-6 ( ng/L ): 12 hours: 58.68±8.55 vs. 158.28±16.73, 24 hours: 46.98±7.58 vs. 146.74±18.02, 48 hours: 38.67±8.22 vs. 136.45±15.45; HMGB1 (μg/L ): 6 hours: 15.75±4.32 vs. 55.56±10.04, 12 hours:32.02±9.33 vs. 89.65±15.65, 24 hours: 35.87±8.54 vs. 86.44±20.33, 48 hours: 23.85±9.83 vs. 98.33±18.88, all P<0.05 ], the serum concentrations of IL-10 ( ng/L ) at 24 hours and 48 hours after CLP were obviously increased ( 24 hours:135.44±16.43 vs. 79.22±12.03, 48 hours:110.92±12.54 vs. 74.47±11.18, both P<0.05 ), the intestinal injury were ameliorated with decreased histopathological scores ( 12 hours: 1.70±0.06 vs. 3.23±0.44, 24 hours:2.12±0.31 vs. 4.51±0.58, 48 hours:2.03±0.42 vs. 4.27±0.58, all P<0.05 ), and the intestinal MPO and caspase-3 activities were significantly decreased [ MPO ( U/g ):6 hours:13.75±4.21 vs. 25.56±5.34, 12 hours:14.72±4.22 vs. 30.53±6.87, 24 hours:11.62±3.14 vs. 33.58±7.24, 48 hours:11.33±4.03 vs. 38.57±8.12;caspase-3 ( fluorescence intensity ): 6 hours: 0.37±0.07 vs. 0.69±0.23, 12 hours: 0.42±0.07 vs. 0.86±0.13, 24 hours: 0.53±0.11 vs. 1.36±0.23, 48 hours:0.50±0.08 vs. 1.48±0.15, all P<0.05 ] in hydrogen treatment group. Conclusion Hydrogen inhalation can down-regulate the systemic inflammatory response to ameliorate the intestinal injury, and it may improve the septic process and increase the survival rate of mice with severe sepsis.

Objective To evaluate the effects of hydrogen-rich saline on incisional pain-remifentanil-induced hyperalgesia in rats.Methods Thirty-two male Sprague-Dawley rats,aged 2-3 months,weighing 240-260 g,in which the catheter was successfully inserted into the caudal vein,were randomly divided into 4 groups (n =8 each) using a random number table:control gourp (group C),remifentanil + incisional pain group (group R + I) and different doses of hydrogen-rich saline groups (H1 and H2 groups).A l-cm longitudinal incision was made through skin,fascia and muscle of the plantar aspect of the left hindpaw in chloral hydrate-anesthetized rats.Remifentanil 1 μg· kg-1 · min-1 was infused intravenously for 60 min sarting from beginning of establishment of incisional pain model in R + I,H1 and H2 groups.The equal volume of normal saline was infused intravenóusly for 60 rin instead of remifentanil group C.Hydrogen-rich saline 5 and 10 ml/kg were injected intraperitoneally at 10 min before establishment of incisional pain model in H1 and H2 groups,respectively.Paw withdrawal threshold (PWT) to yon Frey hair stimulation and paw withdrawal latency (PWL) to thermal stimulation were measured at 24 h before remifentanil infusion and 2,6,24 and 48 h after remifentanil infusion (T0-T4).The rats were sacrificed after measuremnt of pain threshold,and L4-6 segments of the spinal cord were removed for determination of the expression of R1 and 2B subunits-containing N-methyl-D-aspartate receptors (NR1 and NR2B) in total and membrane proteins by Western blot.The ratio between the expression of NR1 in membrane protein and in total protein (mNR1/tNR1) and NR2B in membrane protein and in total protein (mNR2B/tNR2B) was calculated.Results Compared with group C,PWT was significantly decreased,PWL was shortened,the expression of mNR1,mNR2B,tNR1 and tNR2B was up-regulated,and the ratios of mNR1/tNR1 and mNR2B/tNR2B were increased in R + I,H1 and H2 groups.Compared with group R + I,PWT was significantly increased,PWL was prolonged,the expression of mNR1 and mNR2B was down-regulated,and the ratios of mNR1/tNR1 and mNR2B/tNR2B were decreased in Ht and H2 groups.Compared with group H1,PWT was significantly increased,PWL was prolonged,the expression of mNR1 and mNR2B was down-regulated,and the ratios of mNR1/tNR1 and mNR2B/tNR2B were decreased in group H2.Conclusion Hydrogen-rich saline can attenuate incisional pain-remifentanil-induced hyperalgesia in rats and inhibition of trafficking of spinal neuronal NR1 and NR2B from cytoplasm to cell membrane may be involved in the mechanism.

Objective:To evaluate the relationship between CCL21 and triggering receptor expressed on myeloid cells 2 (TREM2)/DNAX-activating protein of 12 kDa (DAP12) signaling pathways in the spinal dorsal horn in remifentanil-induced hyperalgesia in mice with incisional pain.Methods:Thirty-two SPF healthy male C57BL/6J mice, weighing 18-22 g, aged 8-10 weeks, were divided into 4 groups ( n=8 each) using a random number table method: control group (group C), CCL21 neutralizing antibody group (group anti-CCL21), remifentanil + incisional pain group (group R+ I), and CCL21 neutralizing antibody + remifentanil + incisional pain group (group anti-CCL21+ R+ I).A CCL21 neutralizing antibody 0.3 μg (diluted to 10 μl in normal saline) was intrathecally injected in anti-CCL21 and anti-CCL21+ R+ I groups twice a day.Normal saline 10 μl was intrathecally injected at the same time point twice a day in C and R+ I groups.Fifteen min after intrathecal injection, normal saline 0.1 ml was injected via the caudal vein for 4 consecutive times at an interval of 15 min in C and anti-CCL21 groups, and remifentanil 10 μg/kg (diluted to 0.1 ml in normal saline) was injected via the caudal vein for 4 consecutive times at an interval of 15 min in R+ I and anti-CCL21+ R+ I groups.The tail-flick latency (TFL) and mechanical paw withdrawal threshold (MWT) were measured at 24 h before remifentanil or normal saline injection (T 0) and 3, 6, 24 and 48 h after stopping injection of remifentanil or normal saline (T 1-4).The mice were sacrificed after the last measurement of pain threshold, and L 4-6 segments of the spinal cord were removed for determination of the expression of TREM2 and DAP12 protein and mRNA (by Western blot or quantitative real-time polymerase chain reaction). Results:Compared with group C, TFL was significantly shortened and MWT was decreased at T 1-4, and the expression of TREM2 and DAP12 protein and mRNA was up-regulated in group R+ I and R+ I+ anti-CCL21 ( P<0.05), and no significant change was found in the parameters mentioned above in group anti-CCL21 ( P>0.05).Compared with group R+ I, TFL was significantly prolonged and MWT was increased at T 1-4, and the expression of TREM2 and DAP12 protein and mRNA was down-regulated in group anti-CCL21+ R+ I ( P<0.05). Conclusions:CCL21 is involved in remifentanil-induced hyperalgesia by activating TREM2/DAP12 signaling pathways in the spinal dorsal horn of mice with incisional pain.

【Objective】 To introduce a modified microdot two-layer microsurgical vasovasostomy (MVV) and to analyze its effectiveness in patients with vas deferens obstruction caused by inguinal herniorrhaphy. 【Methods】 Clinical data of patients treated during Mar.2015 and Oct.2020 were retrospectively analyzed. According to different surgical methods, the patients were divided into the modified group and traditional group. The general data, intraoperative conditions, efficacies and complications of the two groups were compared. 【Results】 There were 59 cases in the modified group, 54(91.5%) of whom were successfully followed up, and 41 cases in the traditional group, 38(92.7%) of whom were successfully followed up. There were no significant differences in age, inguinal herniorrhaphy history, and unilateral/bilateral ratio between the two groups (P>0.05). The average operation time for unilateral lesions in the modified group was shorter than that in the traditional group [(89.44±24.86) vs. (112.04±43.40) min, P=0.032]. The postoperative patency rate (83.3% vs.73.7%, P>0.05) and natural pregnancy rate (33.3% vs.28.9%, P>0.05) of the modified group and traditional group were comparable. Incision fat liquefaction occurred in 2 cases (3.70%) in the modified group and in 1 case (2.63%) in the traditional group (P>0.05). 【Conclusion】 The modified microdot two-layer MVV is a safe surgical method with comparable effectiveness as the traditional approach. By adjusting the position of the marking points and the order of suturing, it helps the management of sutures, reduces the difficulty of vasovasostomy, shortens operation time, and can be applied to repair vas deferens obstruction caused by inguinal herniorrhaphy.

【Objective】 To analyze the application value of penile vibrating perception threshold measurement in the diagnosis of erectile dysfunction (ED) and provide reference for the seversity of ED patients. 【Methods】 The clinical data, Erectile Hardness Scale (EHS) score, International Index of Erectile Function Questionnaire-5 (IIEF-5) score, and the vibrating perception threshold (VPT) of the penis of 257 patients with decreased erectile function as the main complaint or accompanying symptoms treated during Jan. and Dec.2021 were retrospectively collected and analyzed.Patients with EHS=4 and IIEF-5≥22 were classified into the normal group, and the rest into the ED group.The differences in VPT in patients with different EHS scores were compared, and the correlation between IIEF-5 and VPT was analyzed.The diagnostic value of VPT for ED was evaluated with receiver operating characteristic (ROC) curve. 【Results】 The difference in penile VPT among patients with different EHS scores was statistically significant (P<0.05).With the decrease of EHS score, VPT showed an increasing trend.Glans VPT was negatively correlated with IIEF-5 score (ρ=-0.22, P<0.001), and penile shaft VPT was also negatively correlated with IIEF-5 score (ρ=-0.26, P<0.001).The VPT of glans penis [(4.17±1.37) V vs.(3.47±1.24) V, P=0.009] and the VPT of penis body [(3.73±1.41) V vs.(2.99±1.14)V, P=0.003] in the ED group were both higher than those in the normal group.The area under the ROC curve (AUC) of the glans VPT was 0.642.When the cut-off value was 3.537 V, the sensitivity was 63.4%, and the specificity was 63.6%.The AUC of the penile shaft VPT was 0.659.When the cut-off value was 2.775 V, the sensitivity was 72.3%, with a specificity of 54.5%. 【Conclusion】 The penile VPT of ED patients is higher than that of normal ones, and there is a correlation between VPT and the severity of ED.Severe ED is associated with higher VPT.The measurement of penile VPT is helpful for the clinical diagnosis of ED patients.