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.

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.

Objective To investigate whether lidocaine can reverse Kupffer cell dysfunction in diabetic mice, as well as the mechanism of lidocaine in affecting liver abscess formation by improving the phagocytic function of Kupffer cells. Methods C57BLKS/J db/db mice were divided into diabetes control group and diabetes+lidocaine group, and C57BLKS/J db/m mice were divided into non-diabetes control group and non-diabetes+lidocaine group, with 5 mice in each group. All mice were fed with the suspension of Klebsiella pneumoniae . Kupffer cells were collected from each group and were cultured in vitro; an electron microscope was used to measure the change in ultrastructure, and Kupffer c ells were measured in terms of the levels of inflammatory mediators, the expression level of intercellular adhesion molecule-1 (ICAM-1), the chemotactic function of neutrophils, and phagocytic function; liver abscess formation was also observed. The Kruskal-Wallis H test was used for comparison of continuous data between multiple groups, and the Mann-Whitney U test was used for further comparison between two groups; the chi-square test was used for comparison of categorical data between groups. Results Compared with the non-diabetic mice, the diabetic mice had significant reductions in mitochondria and rough endoplasmic reticulum, endoplasmic reticulum dilation, mitochondrial swelling, and an increase in lipid droplets in Kupffer cells. Compared with the non-diabetes control group, the diabetes control group had significant increases in the levels of nitric oxide (NO) (4.95±0.06 μmol/L vs 1.34±0.13 μmol/L, P < 0.05), interleukin-6 (IL-6) (740.04±8.58 pg/mL vs 515.77±4.62 pg/mL, P < 0.05), tumor necrosis factor-α (TNFα) (774.23±7.98 pg/mL vs 461.51±1.76 pg/mL, P < 0.05), interferon gamma (IFNγ) (842.33±14.79 pg/mL vs 542.47±6.75 pg/mL, P < 0.05), and ICAM-1 (2.40±0.02 vs 1.33±0.01, P < 0.05) in Kupffer cells, a significant increase in neutrophil chemotaxis (100.80±10.18 vs 13.80±3.70, P < 0.05), and a significant reduction in phagocytic capacity (9.86±1.82 vs 60.00±3.54, P < 0.05), with no effect on liver abscess formation (40% vs 0, P > 0.05). Compared with the diabetes control group, the diabetes+lidocaine group had significant reductions in the levels of NO (3.35±0.28 μmol/L vs 4.95±0.06 μmol/L, P < 0.05), IL-6 (688.42±36.34 pg/mL vs 740.04±8.58 pg/mL, P < 0.05), TNFα (631.15±4.30 pg/mL vs 774.23±7.98 pg/mL, P < 0.05), IFNγ (704.56±3.64 pg/mL vs 842.33±14.79 pg/mL, P < 0.05), and ICAM-1 (1.50±0.02 vs 2.40±0.02, P < 0.05) in Kupffer cells, a significant reduction in neutrophil chemotaxis (33.40±5.60 vs 100.80±10.18, P < 0.05), and a significant increase in phagocytic capacity (49.20±2.59 vs 9.86±1.82, P < 0.05), with no effect on liver abscess formation (0 vs 40%, P > 0.05). Conclusion Lidocaine can inhibit Kupffer cell inflammatory response and improve the phagocytic function of Kupffer cells in diabetic mice, thereby exerting a protective effect on Kupffer cells, but it had no effect on liver abscess formation.

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.

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.

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.

Objective:To investigate the relationship between gallbladder carcinoma and gallbladder stones, and provide theoretical basis for the prevention and treatment of gallbladder carcinoma.Methods:A case-control study was used to retrospectively analyze the clinical data of 134 patients(study group) with gallbladder stones and gallbladder carcinoma treated in the Xinjiang Uygur Autonomous Region Corps Hospital of Chinese People′s Armed Police Forces from January 2010 to December 2012.Another 134 patients with gallbladder stones were selected as control group, and the clinical characteristics of the two groups were compared.Results:The average age of patients in the study group was (60.5±11.7)years, which was significantly older than that in the control group [(49.6±10.3)years], the difference was statistically significant ( t=7.916, P<0.05). The history of gallbladder stones in the study group and control group were (9.3±4.1)years and (4.6±2.5)years, respectively, and the difference between the two groups was statistically significant( t=11.682, P<0.01). The multiple stones, maximum stone diameter and maximum gallbladder wall thickness in the study group were 75 cases, (2.4±0.6)cm and (0.59±0.16)cm, respectively, which in the control group were 46 cases, (1.3±0.5)cm and (0.87±0.23)cm, respectively, the differences between the two groups were statistically significant(χ 2=3.978, t=6.217, 5.110, all P<0.05). The incidences of cholecystitis and jaundice in the study group were higher than those in the control group, and the differences were statistically significant(all P<0.05). Conclusion:Gallbladder stones are one of the causative factors of gallbladder carcinoma.Early diagnosis of gallbladder carcinoma is difficult.Patients with high-risk gallbladder stones who are old, have a long history of gallbladder stones, multiple stones, large stone diameters, and thick gallbladder walls should actively undergo surgical intervention.

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.