OBJECTIVE To study the sedative and hypnotic effects of zolpidem and the content of amino acid neurotransmitters in the thalamus and hypothalamus after treatment with zolpidem.METHODS Experiments on the loss of righting reflex(LORR)induced by the upper-threshold dose pentobarbital sodium(50 mg·kg-1,ip)were conducted to establish a hypoxic insomnia model in mice by simulating an altitude of 5500 m.Based on this model,the synergistic effect of zolpidem(0.33,1,3,9 and 27 mg·kg-1,ip)and the subthreshold(20 mg·kg-1,ip)and upper-threshold pentobarbital sodium,as well as the sedative hypnotic effect of zolpidem(10,13,17,20,23,30 and 40 mg·kg-1,ip)were evaluated via the LORR in normoxic and hypoxic environments.One hour after ip given zolpidem,the levels of glutamic acid(Glu)and γ-aminobutyric acid(GABA)in the thalamus and hypothalamus of mice in either environment were determined by the high-performance liquid chromatography(HPLC)with fluorescence detection.RESULTS One-day treatment with hypoxia significantly shortened the duration of LORR induced by the upper-threshold dose pentobarbital sodium.Compared with normoxia vehicle and hypoxia induced insomnia vehicle groups,zolpidem 9 and 27 mg·kg-1 significantly shortened the latency to LORR(P<0.01,P<0.05)and prolonged duration of LORR induced by subthreshold and upper-threshold pentobarbital sodi-um(P<0.01,P<0.05).The median effective dose(ED50)of LORR induced by zolpidem was 16.21 and 20.55 mg·kg-1 in normoxic and hypoxic environments,respectively.The results of neurotransmitter level detection showed that Glu contents in the thalamus and hypothalamus and the ratio of Glu/GABA in the hypothalamus were decreased after treatment with zolpidem 40 mg·kg-1 in a normoxic environment(P<0.01,P<0.05).Compared with the normoxia control group,Glu content and the ratio of Glu/GABA in the hypothalamus were significantly increased after treatment with hypoxia(P<0.01,P<0.05),and zolpidem 40 mg·kg-1 could reverse their elevation.CONCLUSION The sedative-hypnotic effect of zolpidem is weakened in a hypoxic environment,and the effect of zolpidem on the levels of Glu and GABA in the hypothalamus may play an important role in the sedative-hypnotic effect of zolpidem.

Objective This study aims to compare the accuracy of self-developed universal implant guide(SDG),3D printed digital guide(DG),and free hand(FH)simulated implantation in the posterior tooth area of dental models.Methods Ten junior dentists were selected to place three implants in the 35,37,and 46 tooth sites of the mandibular models(35,36,37,and 46 missing teeth)by using SDG,DG,and FH,and the process was repeated again to take the av-erage value.Cone beam computed tomography(CBCT)was used to evaluate the global coronal deviation,global apical deviation,depth deviation,and angular deviation between the actual position and preoperative planned position.Re-sults The coronal deviation and apical deviation of the three implant sites in the SDG group were not significantly dif-ferent from those in the two other groups(P>0.05).The depth deviation and angular deviation in the SDG group were smaller than those in the DG group(P<0.05)and FH group(P<0.05),respectively.All deviations at site 37 in the SDG group were not different from those at site 35(P>0.05),while the depth and angular deviation at site 37 in the DG group were higher than those at site 35(P<0.05).Conclusion The precision of the self-developed universal dental im-plant guide can meet the requirements of clinical posteri-or implantation.

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.

Objective:To explore the clinical effect of free transplantation of thoracodorsal artery perforator flap in reconstructing large scar on the facial subunit.Methods:From April 2014 to March 2018, 7 patients with large facial scar were admitted to Ningbo NO.6 Hospital, including 3 males and 4 females, aged from 31 to 49 years, 4 with frontal involvement and 3 with chin and neck. Color Doppler ultrasound was used for the positioning of the thoracodorsal artery perforating vessel, and scar resection was performed according to the principle of facial subunit repair. The wound area was 8 cm×6 cm-21 cm×8 cm, and the wound was repaired with the free thoracodorsal artery perforator flap in the area of 9 cm×7 cm-22 cm×9 cm. The donor site was closed directly by suturing. The consistency of the location of the perforating vessel explored during the operation with its preoperative positioning and the flap survival were recorded. The color, texture, and appearance of the flap and the healing condition, scar formation, and function of the donor area were observed during follow-up.Results:The locations of the perforating vessels of 7 patients explored during the operation were consistent with those positioned by color Doppler ultrasound before the operation. All the flaps of the 7 cases survived successfully after operation. Postoperative follow-up of 12-18 months showed that the flap color was similar to the surrounding skin of the recipient area, with soft texture and no obvious contracture. Slight bloated appearance was observed in the flaps of 4 cases. All the 7 patients had postoperative healing of the flap donor site without obvious scar hyperplasia or influence on shoulder joint function.Conclusions:The anatomy of the perforating vessel of the thoracodorsal artery perforator flap is relatively constant and the flap can be cut in large area with soft texture, good appearance, and concealed donor area, which is a good choice for reconstructing large scar on the facial subunit.

Objective To investigate the correlation between TYMS gene mRNA expression level and EGFR mutation in stage Ⅲ A-N2 non-small-cell lung cancer tissue (NSCLC).Methods The branched DNA-liquidchip technology (bDNA-LCT) and mutant-enriched liquidchip (MEL) technology were used to detect the TYMS mRNA expression and EGFR mutations at exon 19 and 21 in NSCLC tissues from 30 patients with stages Ⅲ A-N2 NSCLC,and the results were analyzed.Results Among 30 cases,low TYMS mRNA expression was in 14 cases (46.7 ％),middle to low TYMS mRNA expression in 7 cases (23.3 ％),middle mRNA expression in 7 cases (23.3 ％),middle to high TYMS mRNA expression in 0 case and high TYMS mRNA expression in 2 cases (6.7％);12 cases of EGFR mutation were detected out with the mutation rate of 40.0％,including 6 cases of exon 19 deletion and 6 cases of exon 21 missense mutation.The TYMS mRNA expression level was correlated with the EGFR mutation.The EGFR mutation commonly occurred in the tumor tissue of the patients with TYMS mRNA low expression (Z=-2.604,P=0.009).Conclusion The TYMS mRNA expression in NSCLC tissue is correlated with the EGFR gene mutation,which can provide references for the drug selection aiming at the patients with different conditions.

OBJECTIVE To explore the antidepressant effect and the underlying mechanisms of schisandrin (SCH), a component of the fruits of Schizandra chinesis. METHODS The forced swimming test (FST) and tail suspension test (TST) in mice were used to evaluate the antidepressant activity of SCH (5, 10, and 30 mg · kg-1) following single administration intragastrically, and the locomotor activity was investigated to exclude its neural excitatory effects. Effects of SCH on neural monoamine systems were studied in two pharmacological models, including reserpine induced monoamine depletion test and yohimbine toxicity potentiation test. RESULTS In behavioral despair models, SCH (30 mg·kg-1) signif?icantly decreased the immobility time in the TST and FST (P<0.05) compared with normal control group. Results of the locomotor activity experiment showed that SCH had no excitatory or inhibitory actions on the central nervous system. In the reserpine reversal experiment, SCH (30 mg · kg-1) antagonized thepalpebral ptosis and akinesia symptoms caused by reserpine(2.5 mg · kg-1) treatment (P<0.05) compared with model group, but had little effect on the drop of the anal temperature. Moreover, SCH did not increase the lethality caused by subcutaneous injection of yohimbine (30 mg · kg-1)at the threshold lethal dosage. CONCLUSION SCH exerts potential antidepressant-like effect in mice.

Objective To evaluate the diagnostic performance of a point-of-care testing for sensitive cardiac troponin Ⅰ (POCT-cTnI) in early diagnosis of chest pain patients who had a high pretest probability of acute myocardial infarction (AMI).Methods Total of 127 patients with new-onset chest pain at the emergency department were enrolled.Blood samples were drawn for the routine blood test,and determined POCT-cTnI and central laboratory testing for high sensitive cardiac troponin T (CLT-hscTnT) at admission,three and then at six hours after admission.All patients were divided into AMI group and non-AMI group according to the final diagnosis,which was adjudicated independently by two physicians who reviewed all available medical records for the 90-day follow-up period,and they were unaware of the results of the investigational assays of cardiac troponins.The receiver operating characteristic (ROC) curves were constructed to assess and compare the diagnostic performance of AMI of two cardiac troponin assays.The comparison of areas under the ROC curves (AUC) was performed by DeLong test,and the sensitivity,specificity,negative predictive values (NPV) and positive predictive values (PPV) for the target markers were calculated by applying a maker-specific cutoff value.Results The final diagnosis of AMI was made in 40 of 127 patients (31.5 ％).The diagnostic accuracy of the two assays oBtained at presentation,as quantified by AUC,was no statistically differences (AUC for POCT-cTnⅠ,0.901,95％ CI,0.901 to 0.947;and for CLT-hscTnT,0.907,95％ CI,0.842 to 0.951;Z =0.235,P =0.745).The AUC for POCT-cTnI at 3 hours after admission was significantly higher than that on admission (0.931 vs.0.858;Z =-2.038,P =0.042),while there was on further improvement at 6 hours after admission (0.931 vs.0.949;Z =-1.435,P =0.151).With use of POCT-cTnI (cutoff value 0.023 ng/mL,which was the 99th percentile upper reference limit) on adimission,the clinical sensitivity was 77.5％,and the specificity was 94.2％.A single sample of POCT-cTnI at 3 hours after admission improved the diagnostic accuracy,with a sensitivity of 96.4％,a specificity of 92.0％,and a NPV of 98.6％,a PPV of 81.8％.While,with use of CLT-hscTnT (cutoff value 0.014 ng/mL,was the 99th percentile upper reference limit) at 3 hours after admission,the NPV reached to 100％.Conclusions The use of a POCT-cTnI assay in chest pain patients can identify and exclude the AMI rapidly and exactly at three hours after admission,and the diagnostic performance is equivalent to CLT-hscTnT.

Objective:Mutations in epidermal growth factor receptor (EGFR) can predict tumor response to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). However, not all cases of NSCLC with EGFR mutations can respond well;thus, discovering the heterogeneity of NSCLC at the molecular level is necessary. This study aimed to determine the discrepancy in EGFR mutations in primary tumors, N2 lymph nodes, and plasma samples. Methods:Primary tumors, N2 lymph nodes, and plasma samples obtained from 49 patients with stageⅢA-N2 NSCLC were analyzed for EGFR mutations in exons 19 and 21 by using mutant-enriched liquidchip technology. Results:In 49 patients, we detected 18 (36.7%) EGFR mutations in primary tumors, 11 (22.4%) mutations in N2 lymph nodes, and 2 (4.1%) mutations in plasma samples. Eleven (22.4%) cases showed discordance in EGFR mutations between primary tu-mors and N2 lymph nodes. In nine cases, EGFR mutations were detected only in primary tumors, whereas EGFR mutations were de-tected only in N2 lymph nodes in two cases. In addition, EGFR mutations were detected in the plasma samples of two patients, who al-so carry mutations in their primary tumors. Conclusion:A considerable proportion of NSCLC cases showed discrepancy in EGFR muta-tions between primary tumors and N2 lymph nodes. In addition, the detection rate of EGFR mutations was lower in plasma samples obtained from patients with stage IIIA-N2 NSCLC. All of the results indicated tumor heterogeneity at the molecular level during metas-tasis, and this heterogeneity may have implications during treatment with TKIs.

Objective To investigate the impact of purinergic receptors P2Y12 gene inhibited by small interference RNA (siRNA) on the angiogenesis of hepatocellular carcinoma (HCC). Methods Human HCC cell line MHCC97H was infected using P2Y12-siRNA lentiviral expression vector and empty negative control vector to establish siRNA group and control group. The expression of P2Y12 protein in two groups was detected by Western blot assay. angiogenesis assay was used to deifne the angiogenesis potential of HCC cell. The microvessel density (MVD) of nude mice subcutaneous tumors was observed. The experimental data between two groups were compared using t test. Results The average relative expression of P2Y12 protein were 0.07±0.01 and 0.26±0.02 respectively in siRNA group and control group. The expression of P2Y12 protein in siRNA group decreased significantly compared with that in control group (t=-35.64, P<0.05). No continuous closed small tubular structure was observed in the human umbilical vein endothelial cell (HUVEC) stimulated by the supernatant of siRNA group, while large number of closed tubules was observed in the HUVEC stimulated by the supernatant of control group. A few microvessels of nude mice subcutaneous tumors were observed in siRNA group. The MVD was 5±1, which was signiifcantly lower than that in control group (23±6) (t=-17.01, P<0.05). Conclusion Purinergic receptors P2Y12 gene inhibited by siRNA can suppress the angiogenesis of HCC.

Objective:This study aimed to achieve the early diagnosis and active treatment of adult hemophagocytic syndrome (HPS) and investigate the clinical characteristics and prognostic factors of this syndrome. Methods:A single-center retrospective analysis was performed to analyze clinical characteristics, laboratory findings, and survival data. Results:In 58 patients, the most common clinical manifestations were fever (100%) and splenomegaly (89.7%). The most common laboratory parameters were serum ferritin 500 g/L (100%) and peripheral cytopenia in two or more lineages (96.6%). platelet count, fibrinogen, and lactate dehydrogenase in the death group were significantly lower than in the survival group (P=0.000, 0.001, and 0.000). Survival analysis results showed that infections in the rheu-matological group exhibited good prognosis [the overall survival (OS) time was not reached in 190 d]. Patients with unexplained causes had moderate prognosis (OS time was 60 d);tumor-associated HPS patients had poor prognosis (the OS time was only 30 d). Univariate analysis results showed that patients with Fbg<1.5 g/L, PLT<40×109/L, and LDH≥2000 U/L also exhibited poor prognosis (P=0.000). Multivariate analysis results showed that PLT<40 × 109/L was an independent adverse factor (HR=6.472, 95%CI:1.526-26.065, P=0.011). Conclusion:HPS exhibits complex clinical manifestations and varied etiology. Patients with infection and rheumatism-related HPS had good prognosiss compared with those manifesting tumor-associated HPS. Fbg<1.5 g/L, PLT<40×109/L, and LDH≥2 000 U/L were the univariate factors that affected the survival time of patients. PLT<40×109/L is an independent adverse factor. These patients need systemic treatments as early as possible.