As an important messenger molecule, NO exists in both peripheral and central nervous system (CNS). Recently, NO was proved to play a critical role in CNS, especially in synaptic plasticity. As a kind of retrograde messenger, it plays some roles in the induction and maintenance of LTP through activation of downstream pathway or molecules, such as NO-cGMP-PKG, ADPRT and C-FOS.

AIMTo further elucidate the role of agmatine on the pharmacological effects of opioids. METHODSThe effect of L-arginine and L-arginine decarboxylase(L-ADC) antibodies on pain threshold, morphine ntinociception and tolerance were investigated in mouse acetic acid writhing test, mouse radiant heat tail flick test and mouse hot plate test. RESULTSIn mouse acetic acid writhing test, intracerebroventricular injection of L-arginine dose-ependently inhibited the writhing of mice compared with saline control. L-arginine did not influence the tail flick latency itself in mouse radiant heat tail flick test, but enhanced antinociceptive effect of morphine in a dose-dependent manner. The possible maximal analgesia percentage of morphine 2.5 mg*kg-1 was increased from 23% to 71%. Furthermore, L-arginine inhibited acute tolerance induced by morphine 100 mg*kg-1in mouse radiant heat tail flick test. The effect of L-arginine as mentioned above could be antagonized by idazoxan (3 mg*kg-1, ip), which is a selective antagonist of imidazoline receptors. L-ADC specific antibodies inhibited morphine antinociception and promoted the development of tolerance to morphine in mouse radiant heat tail flick test and 55℃ hot plate test. CONCLUSIONL-Arginine and L-ADC play important roles in the formation of pain threshold, morphine antinociception and tolerance.

Objective To observe the analgesic effect of ultrasound-guided and nerve stimulator after artificial total knee athroplasty(TKA).Methods Forty elective cases receiving TKA under gen-eral anesthesia were randomly allocated into the ultrasound group (group C)and stimulator group (group S).The time for nerve block,onset time and complications were recorded in both groups. Results Compared to group S,the time for nerve block and onset time was significantly shortened in group C (P <0.05).There was no statistical difference in times of pressing analgesic pump and VAS score in postoperative 48 h.One patient suffered from nerve injury and two underwent vascular dam-age and hematoma in group S,while no complication was found in group C.Conclusion Compared to nerve stimulator,ultrasound-guided continuous femoral nerve block(CFNB)may reduce nerve block time and onset time and decrease complications,so that to increase safety of CFNB.

Aim To investigate the effects of Y-IP5 on morphine-induced behavioral sensitization and CPP in mice.Methods Locomotor activity was detected after Y-IP5 administration or co-administration of Y-IP5 with morphine in mice.Mice were treated with morphine to induce behavioral sensitization. Then the effects of Y-IP5 on the development, transfer and expression of morphine-induced behavioral sensitization were investigated. Mice were treated with morphine to induce CPP. Then the effect of Y-IP5 on the acquisition of morphine-induced CPP was studied.Results Y-IP5 itself didn′t influence locomotor activity of mice.Co-administration of Y-IP5 with morphine inhibited morphine-induced hyperactivity (P<0.05) and the development of morphine-induced behavioral sensitization in mice (P<0.05), however, did not influence the transfer and expression of morphine-induced behavioral sensitization.Co-administration of Y-IP5 with morphine also inhibited the acquisition of morphine-induced CPP (P<0.05).Conclusion Y-IP5 may inhibit the psychological dependence induced by morphine.

A 44-year-old male patient presented with a subcutaneous nodule in the left little finger for 3 years. Skin examination showed a subcutaneous nodule with rubber-like hardness but no tenderness on palpation, measuring 0.4 cm × 0.4 cm in size at the dorsal distal aspect of the left little finger, and the movement of the distal interphalangeal joint was unrestricted. Postoperative histopathological examination revealed that the tumor contained abundant stroma consisting of variable fiberous, chondroid and myxoid materials; tumor cells were oval to short spindle-shaped with inconspicuous nucleoli but no mitosis; cells were arranged haphazardly or in small clusters. Immunohistochemical study showed positive staining for vimentin, CD34 and transcription factors ERG and SOX9, but negative staining for S100, P63, broad-spectrum cytokeratin AE1/AE3, epithelial membrane antigen, smooth muscle actin and desmin in tumor cells, and the Ki67 labeling index was below 1%. Finally, the patient was diagnosed with acral fibrochondromyxoid tumor.

Objective:To investigate the efficacy of dexmedetomidine combined with transversus abdominis plane block in laparoscopic radical resection of colorectal cancer and its effect on serum CXCL8 level.Methods:A total of 72 patients who planned to undergo laparoscopic radical resection of colorectal cancer in Changzhou Hospital of Traditional Chinese Medicine from March 2017 to March 2021 were selected as the research subjects, and they were divided into transversus abdominis plane block anesthesia group (group A) and dexmedetomidine combined with transversus abdominis plane block anesthesia group (group B) by random number table method with 36 cases in each group. The operation time, intraoperative blood loss, fluid supplementation, visual analogue score (VAS) and Ramsay sedation score at different times after operation, and serum CXCL8 level after operation were compared between the two groups of patients. The adverse reactions of the two groups of patients were compared.Results:There was no significant difference in operation time and fluid supplementation between the two groups (both P > 0.05). The VAS scores of patients in group B at 4, 8 and 24 hours after operation were lower than those in group A [(2.8±0.6) points vs. (4.2±1.2) points, (2.1±1.0) points vs. (3.4±1.1) points, (1.8±0.4) points vs. (2.5±0.7) points, all P < 0.05], and the Ramsay sedation scores of patients in group B at 4, 8 and 24 hours after operation were higher than those in group A [(4.3±1.2) points vs. (2.7±0.7) points, (3.5±1.1) points vs. (2.2±1.0) points, (2.4±0.9) points vs. (1.6±0.6) points, all P<0.05]. Serum CXCL8 levels of patients in group B at 2, 24 and 48 hours after operation were lower than those in group A [(78±16) ng/ml vs. (87±19) ng/ml, (68±14) ng/ml vs. (75±15) ng/ml, (52±10) ng/ml vs. (61±13) ng/ml, all P<0.05]. The incidence rates of adverse reactions in group A and group B were 8.3% (3/36) and 13.9% (5/36), and the difference was not statistically significant ( P > 0.05). Conclusions:Dexmedetomidine infusion during laparoscopic radical resection of colorectal cancer under general anesthesia combined with transversus abdominis plane block can help reduce postoperative pain, increase sedative effect, and reduce serum CXCL8 level.

To report a case of cutaneous metaplastic synovial cyst. A 14-year-old male patient presented with a cystic mass on the forehead for more than 6 months. Histopathological findings revealed an intradermal cystic structure with multiple intraluminal broad band-like villiform protuberances, which was lined with a membrane resembling hyperplastic synovium and composed of a variety of cellular structures; some areas of the cystic wall were covered with fibrin-like hyaline connective tissues, and some areas were highly cellularized and lined with multiple layers of epithelioid cells and spindle cells. Immunohistochemical study revealed diffuse expression of vimentin and positive staining for the histocyte marker CD68, but negative staining for cytokeratin and smooth muscle actin in epithelioid cells and spindle cells. According to the clinical manifestations and histopathological findings, the diagnosis of cutaneous metaplastic synovial cyst was confirmed.

Objective:To study the clinical characteristics and management strategies of late bleeding after laparoscopic pancreaticoduodenectomy (LPD).Methods:The clinical data of 58 patients with post-pancreaticoduodenectomy hemorrhage (PPH) admitted to the Department of Hepatobiliary Surgery of the Second Hospital of Hebei Medical University from March 2018 to March 2022 were retrospectively analyzed, including 42 males and 16 females, aged (61.88±11.02) years old. According to the occurrence of intra-abdominal erosion factors (e.g., pancreatic fistula, biliary fistula, gastrointestinal anastomotic fistula, intra-abdominal abscess), patients were divided into the erosion group ( n=42) and non-erosion group ( n=16). All patients underwent standard lymphadenectomy. Clinical data including the PPH time-point, occurrence of rebleeding, and treatment outcomes were accessed. The management strategies of PPH in the two groups of patients were analyzed. Results:The PPH time-point in the erosion group and non-erosion patients was 8.00 (5.00, 19.25) d and 21.50 (12.75, 26.75) d, respectively ( P=0.001). PPH can occurred within one month after surgery in both erosion and non-erosion groups. In the erosion group, 31 cases (73.81%, 31/42) were treated by re-operation, two (4.76%, 2/42) by interventional radiology and nine (21.43%, 9/42) with conservative protocol, respectively. In the non-erosion group, five cases (31.25%, 5/16) were treated by re-operation, seven (43.75%, 7/16) by interventional radiology and four (25.00%, 4/16) with conservative protocol, respectively. The incidence of re-bleeding is higher in the erosion group [47.6% (20/42) vs 12.5% (2/16), P<0.05]. Clinical manifestations, sites and severity of bleeding, and treatment outcomes were also different in the erosion and non-erosion groups (all P<0.05). Conclusions:The occurrence of intra-abdominal erosion factors can affect the clinical characteristics and treatment strategy of late bleeding after laparoscopic pancreaticoduodenectomy. Surgery remains the treatment of choice for post-pancreaticoduodenectomy hemorrhage either as an urgent or last resort.

Most α2-AR agonists derived from dexme-detomidine have few structure differences between them and have no selectivity for α2A/2B-AR or Gi/Gs,that can lead to the side effect of drugs.To get novel and potent α2A-AR agonists,we built the homology model for human α 2A-AR and α2B-AR to find α2A-AR agonists with higher selectivity.Compound P300-2342 and its 3 analogs sig-nificantly decreased the locomotor activity of mice(P＜0.05).Furthermore,P300-2342 and its 3 analogs inhibited the binding of[3H]rauwolscine to α 2A-AR and α 2B-AR respectively.In α2A-AR-HEK293 cells,P300-2342 decre-ased forskolinstimulatedcAMPpruductionwithoutincreas-ing cAMP pruduction,that indicated the P300-2342 acti-vating α2A-AR coupling with Gαi/o pathway without Gαs coupling.P300-2342 had no agonistic and antagonistic activities on α 2B-AR.Similar results were shown in 3 analogs of P300-2342.The docking results showed that P300-2342 formed the π-hydrogen bonds with Y394,V114 of α2A-AR,and with V93 of α2B-AR.3 analogs of P300-2342 formed several π-hydrogen bonds with V114,Y196,F390 of α 2A-AR and with V93 of α 2B-AR.We believe that these molecules can serve as leads for fur-ther optimization of α2A-AR agonists with potentially few side effects.

AIM: To investigate the possible use of anti-FGF-2 nanobody for the treatment of pathological neovascularization. METHODS: SD rats were divided into a sham operation group, a control group (3 mm diameter circular filter paper soaked with 1 mol/L NaOH solution was applied to the central part of the cornea of rats for 30 s to prepare the rat model of alkali-burn angiogenesis) and a treatment group (treated with a drop of 3 mg/mL anti-FGF-2 nanobody 7 days after the operation. Repeat application 3x/day for 14 days). Corneal angiogenesis was measured by stereoscopic microscopy and CD31 immunohistochemical staining. The mRNA and protein expression levels of VEGF and FGF-2 were detected by quantitative fluorescence PCR (qPCR), enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry.RESULTS: (1) Blood vessel: The area of the treatment group was significantly reduced compared with the model group, and the vascular lumen was narrower (P<0.05). The difference was the most significant after 14 days of drug intervention; (2) Expression level of FGF-2 mRNA and protein: the model group had similar results to the treatment group (P>0.05); (3) Expression levels of VEGF mRNA and protein: The treatment group was significantly higher than the model group (P<0.05). In addition, the expression of VEGF also increased significantly in the continuous administration of the sham operation group. CONCLUSION: Anti-FGF-2 nanobody can be used for the treatment of angiogenesis. However, the expressions of VEGF will compensatorily increase after blocking FGF-2 in normal or pathological rats.