The chronic use of morphine and other opioids is associated with opioid-induced hypersensitivity (OIH) and analgesic tolerance. Among the different forms of OIH and tolerance, the opioid receptors and cell types mediating opioid-induced mechanical allodynia and anti-allodynic tolerance remain unresolved. Here we demonstrated that the loss of peripheral μ-opioid receptors (MORs) or MOR-expressing neurons attenuated thermal tolerance, but did not affect the expression and maintenance of morphine-induced mechanical allodynia and anti-allodynic tolerance. To confirm this result, we made dorsal root ganglia-dorsal roots-sagittal spinal cord slice preparations and recorded low-threshold Aβ-fiber stimulation-evoked inputs and outputs in superficial dorsal horn neurons. Consistent with the behavioral results, peripheral MOR loss did not prevent the opening of Aβ mechanical allodynia pathways in the spinal dorsal horn. Therefore, the peripheral MOR signaling pathway may not be an optimal target for preventing mechanical OIH and analgesic tolerance. Future studies should focus more on central mechanisms.
Humans ; Morphine/pharmacology* ; Hyperalgesia/metabolism* ; Analgesics, Opioid/pharmacology* ; Neurons/metabolism* ; Signal Transduction

Objective:To investigate the drug resistance factors in postoperative gemci-tabine chemotherapy after radical resection of pancreatic cancer.Methods:The retrospective case-control study was constructed. The clinicopathological data of 255 patients with pancreatic cancer who were firstly admitted to the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi ′an Jiaotong University from January 2018 to June 2021 were collected. There were 140 males and 115 females, aged (59±10)years. All patients underwent radical resection of pancreatic cancer and received postoperative gemcitabine-based adjuvant chemotherapy. Observation indicators: (1) follow-up; (2) postoperative chemotherapy; (3) drug resistance and changing of regimen; (4) factors influencing postoperative chemotherapy resistance. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and compari-son between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the Pearson chi-square test. Univariate analysis was conducted using the corresponding statistical methods based on data type. Multivariate analysis was conducted using the Logistic regression model with forward method. Kaplan-Meier method was used to draw survival curve, and Log-Rank test was used for survival analysis. Results:(1) Follow-up. All 255 patients were followed up for 18.6(16.7,21.4)months. The median survival time of 255 patients was 18.2[95% confidence interval ( CI) as 15.8-20.6]months. (2) Postoperative chemotherapy. Of the 255 patients, there were 5 cases receiving postoperative chemotherapy as gemcitabine monotherapy, 167 cases receiving postoperative chemotherapy as the AG combination (gemcitabine plus albumin-bound paclitaxel), 74 cases receiving postoperative chemotherapy as the GS combination (gemcitabine plus S-1) and 9 cases receiving postoperative chemotherapy as the GP combination (gemcitabine plus platinum). (3) Drug resistance and changing of regimen. Of the 255 patients, 81 cases completed the course of postoperative chemotherapy and evaluation. Of the 81 patients, there were 18 cases with no recurrence or metastasis of tumor, 10 cases with tumor local recurrence, 40 cases with tumor lymph node metastasis or distant metas-tasis, 3 cases with tumor local recurrence combined with distant metastasis, 10 cases with elevation of CA19-9. Of the 81 patients, 18 cases responded to chemotherapy, 63 cases underwent resistant to chemotherapy, including 11 cases with primary resistance and 52 cases with acquired resistance. The 63 patients with chemotherapy resistance underwent changing of regimen. (4) Factors influencing postoperative chemotherapy resistance. Results of multivariate analysis showed that chemotherapy cycle<6 is an independent risk factor for postoperative chemotherapy resistance in patients ( hazard ratio=17.18, 95% CI as 2.07-142.28, P<0.05). Conclusion:Adjuvant chemotherapy cycle <6 is an independent risk factor for postoperative chemotherapy resistance for gemcitabine based chemo-therapy in pancreatic cancer patients receiving radical resection.

Ischemic stroke is one of the leading causes of death and disability worldwide. In Han dynasty， HUA Tuo proposed the original preventive medicine idea that "with good blood circulation， the disease cannot be born"， which opened a broad space for the cross-research of blood-related mechanical factors and pharmacology. In the pathogenesis of ischemic stroke， mechanical factors comprehensively affect the function and crosstalk of platelets and endothelial cells. In recent years， as the well-known effects on thrombosis and stroke， more attention has been paid to hemodynamic factors as the participants involved in pathological mechanisms and potential therapeutic targets of ischemic stroke. The mechanical force ion channel Piezo1 widely exists on the surface of many types of cells. Besides being regulated by chemical and endogenous substances， Piezo1 responds to different mechanical conditions， regulates the opening and closing of channels， and activates different downstream signaling pathways. Piezo1 is now regarded as an important connection between mechanical and biochemical signals. A variety of Chinese medicine can affect the activity of Piezo1 protein， which may prevent and treat thrombotic diseases such as ischemic stroke through Piezo1 protein. In this paper， the effects of Piezo1 protein on the physiological and pathological functions of endothelial cells and platelet under different mechanical conditions and the role of Piezo1 in the process of thrombosis were reviewed， as well as the effects of Chinese medicine， chemical medicine， and endogenous substances targeting Piezo1 channel. These could provide new ideas for further exploring the mechanisms of Chinese medicines in activating blood circulation， developing new drugs， and deepening biomechanical-pharmacology research.

Rutin,a flavonoid found in fruits and vegetables,is a potential anticancer compound with strong anti-cancer activity.Therefore,electrochemical sensor was developed for the detection of rutin.In this study,CoWO4 nanosheets were synthesized via a hydrothermal method,and porous carbon(PC)was prepared via high-temperature pyrolysis.Successful preparation of the materials was confirmed,and character-ization was performed by transmission electron microscopy,scanning electron microscopy,and X-ray photoelectron spectroscopy.A mixture of PC and CoWO4 nanosheets was used as an electrode modifier to fabricate the electrochemical sensor for the electrochemical determination of rutin.The 3D CoWO4 nanosheets exhibited high electrocatalytic activity and good stability.PC has a high surface-to-volume ratio and superior conductivity.Moreover,the hydrophobicity of PC allows large amounts of rutin to be adsorbed,thereby increasing the concentration of rutin at the electrode surface.Owing to the syn-ergistic effect of the 3D CoWO4 nanosheets and PC,the developed electrochemical sensor was employed to quantitively determine rutin with high stability and sensitivity.The sensor showed a good linear range(5-5000 ng/mL)with a detection limit of O.45 ng/mL.The developed sensor was successfully applied to the determination of rutin in crushed tablets and human serum samples.

Objective:To compare the effect of the new anterior cervical spine memory compression fixation device (GYZ memory alloy plate) and traditional titanium plate on the range of motion (ROM) and stress of the adjacent segment after anterior cervical discectomy and fusion.Methods:An adult male volunteer was recruited for a fee. After excluding cervical malformations, fractures, infections and other diseases, C 3-C 7 thin-layer CT scans were performed. Import the scanned data into the finite element modeling software to establish the finite element model of the physiological group and verify itseffectiveness. After C 5,6 discectomy, the intervertebral fusion device was inserted, and the anterior fixation was assisted by a conventional titanium plate or a new type of fixator. Thus, the finite element model of the traditional titanium plate group and the new fixer group was established. The three models were imported into the finite element analysis software ANSYS 16.0, and a vertical downward axial load of 73.6 N was loaded to simulate the head weight and the torque of 1.0 N·m to simulate the cervical spine flexion, extension, left lateral bending, right lateral bending, left rotation and right rotation.Compare the changes of intervertebral disc ROM and stress in adjacent segments of physiological group, traditional titanium plate group and new type fixator group. Results:The intervertebral disc ROM under six conditions was basically similar to the results of previous studies, and the model was effective. In the adjacent segment C 4,5, the three groups of activities in the flexion, extension, left lateral bending, right lateral bending, left rotation and right rotation conditions were: physiological group 3.9°, 4.2°, 3.7°, 3.7°, 2.2° and 2.2°, traditional titanium plate group 4.6°, 4.7°, 4.3°, 4.4°, 3.3° and 3.1°, and new fixture group 4.4°, 4.3°, 4.0°, 4.2°, 2.8° and 2.7°. The maximum stresses of the intervertebral discs under three different working conditions were: physiological group 1.81, 1.60, 3.99, 2.06, 3.63 and 3.41 MPa, traditional titanium plate group 1.86, 1.67, 4.21, 2.16, 3.82 and 3.63 MPa, and new fixture group 1.84, 1.64, 4.17, 2.14, 3.78 and 3.58 MPa. In the adjacent segment C 6,7, the activities of the three groups in six working conditions were: physiological group 3.1°, 3.2°, 2.5°, 2.5°, 1.2° and 1.3°, traditional titanium plate group 4.2°, 3.7°, 3.4°, 3.0°, 2.1° and 2.2°, and new fixture group 3.5°, 3.3°, 2.5°, 2.7°, 1.8° and 1.9°.The maximum stress of the intervertebral disc under three different working conditions was: physiological group 0.45, 0.66, 1.12, 0.85, 0.84 and 0.82 MPa, traditional titanium plate group 0.62, 0.93, 1.55, 1.24, 1.44 and 1.27 MPa, and new fixture group 0.61, 0.92, 1.54, 1.22, 1.07 and 1.24 MPa. The ROM and disc pressure of adjacent segments in the conventional titanium plate group were higher than those of the new fixator group. Conclusion:Compared with the traditional titanium plate, the new type of anterior cervical memory compression fixator has less effect on the ROM and stress of adjacent segments, which may slow down the process of adjacent segments degeneration to a certain extent.

Objective ToexploretheMRIfeaturesofthepseudoaneurysmsandarteriovenousmalformationsinuterus,andtoimprove ourunderstandingonthemforhigherdiagnosticaccuracy.Methods TheMRIfeaturesofthe4casesofuterinepseudoaneurysmsand the7casesofuterinearteriovenousmalformationswhichdiagnosedandcuredbyourhospitalwereanalyzedretrospetively.Results TheMRIofuterinepseudoaneurysms(n＝4)shownodular(n＝3)oroval(n＝1)abnormalsignalinthemyometriumsofuterus,low signalintensityonT1WI,highsignalintensityonT2WI.Thelesionenhancementissimilartotheuterinearterycommunicatingwiththe lesion.TheMRIofuterinearteriovenousmalformations(n＝7)showuterinepatchyabnormalsignal,andtheirboundaryarenotclear. Thereareanumberoftortuousbloodvessels.Thelesionsareobviouslyheterogenouslyenhanced,andthethickeneddrainagevessels couldalsobeseenoncontrastGenhancedimages.Thelesionsofuterinepseudoaneurysmsandarteriovenousmalformationsdon’tshow highsignalintensityonDWI,suggsetingnolimiteddiffusion.Conclusion The MRIcharacteristicsoftheuterinepseudoaneurysms showthattheuterinelesionenhancementissimilartotheuterinearterycommunicatingwiththelesion.The MRIcharacteristicsof theuterinearteriovenous malformationsarethatthereareanumberoftortuousbloodvesselsanddrainagevesselsintheuterus. Therearen’tlimiteddiffusioninthesetwodiseasesonDWI.

Objective To investigate the treatment measures of having trigeminocardiac reflex (TCR) for the primary trigeminal neuralgia via microvascular decompression.Methods From January 2016 to December 2016,the clinical data and anesthesia records of 79 consecutive patients with primary trigeminal neuralgia admitted to the Department of Neurosurgery,Xuanwu Hospital,Capital Medical University and treated the first craniotomy microvascular decompression were analyzed retrospectively.They were divided into a no TCR group (n=63) and a TCR group (n=16) according to the intraoperative anesthesia monitoring.The differences of baseline conditions,preoperative complications and pain involved the trigeminal nerve branches were compared between the two groups.The treatment measures and short-term prognosis of the patients with TCR during operation were summarized.Results (1) The proportion of hypertension in the TCR group was 31.2％ (n=5),it was higher than 7.9％ in the no TCR group (n=5).There was significant difference (χ2=6.273,P<0.05).(2) During the operation of microvascular decompression,16 patients in the TCR group had 19-time TCR.The baseline heart rate was 74±10/min before operation,and the heart rate decreased to 51±6/min at onset of TCR.The mean baseline arterial blood pressure was 102±13 mmHg,and the mean arterial blood pressure decreased to 74±8 mmHg at the onset of TCR.There was significant difference (P<0.05).(3) After the onset of TCR,the operation of was stopped,heart rate and the blood pressure recovered spontaneously (n=4).Fifteen patients were treated with medications,including using atropine (12 times,dose 0.2-0.5 mg) and ephedrine hydrochloride (3 times,dose 5-10 mg).Heart rate and blood pressure returned to the baseline level within 20 seconds or 20 seconds after administration of medications.There was no TCR-related cardiac complication or neurological deficit from after procedure to before discharge.Conclusions In microvascular decompression of primary trigeminal neuralgia,if TCR occurs,the selective use of anticholinergic agents or vasoactive agents is needed as early as possible.The risk factors for the occurrence of TCR need to be further verified.

Objective To evaluate the miRNA change between hypothermia circulatory arrest at different temperature and its impact on intestinal protection.Methods Sixteen piglets were randomly(n =4) divided into four groups:deep hypothermia circulatory arrest (DHCA,18℃) group,moderate hypothermia circulatory arrest(MHCA,24℃) group,cardiopulmonary bypass(CPB) group and sham operation(SO) group.They were subjected to 80 min hypothermia circulatory arrest,305 min CPB or thoracotomy,respectively.Pick-and-mix custom miRNA real-time PCR panels were utilized to detect intestinal samples.miRNA expression between DHCA and MHCA were compared directly(DHCA vs.MHCA) and indirectly(DHCA/SO vs.MHCA/SO,DHCA/CPB vs.MHCA/CPB).Results Exposure to DHCA caused less intestinal miRNA dysregulation than MHCA.Besides,seven miRNAs(miR-122,miR-145-5p,miR-421-5p,miR-99a,miR-365-5p,miR-31 and miR-192)were differentially expressed between the two hypothermia circulatory arrest groups.Conclusion Better intestinal miRNA protection was provided by DHCA than MHCA.Intestinal miRNA were differentially expressed between hypothermia circulatory arrest at different temperature.

Objective To evaluate the effects of β1 adrenergic receptor (β1-AR) autoantibodies on the micro-mechanics of a single rat ventricular myocyte and the concentration of intracellular calcium for investigating the pathogenic mechanism of heart disease caused by β1-AR autoantibody on both cellular and molecular levels .Methods The micro-mechanics of an acutely isolated single myocardial cell from rat was detected by using the atomic force microscopy ( AFM) in combination with laser scanning confocal micro-scope (LSCM) before and after binding to β1-AR autoantibodies.The ventricular myocyte contraction and the intracellular calcium concentration were observed as well .Results The micro-mechanics of a single ventricular myocyte was increased from (44-51) nN to (76-82) nN after binding to β1-AR autoantibodies. Its contraction frequency was also increased from (0.17±0.04) Hz to (0.40±0.03) Hz (P<0.05).More-over, the intracellular calcium fluorescence intensity was increased significantly during contraction in com -parison with that before binding to β1-AR autoantibodies [ ( 102.1 ±12.3 ) % vs ( 154.3 ±16.7 ) %, P<0.01 ] .Conclusion β1-AR autoantibody could affect the contraction and the micro-mechanics of ventricu-lar myocytes and the intracellular calcium concentration in ventricular myocytes .

Objective To evaluate the molluscicidal effect of 2 kinds of shamingdan in lab. Methods Under constant temperature (25?1) ℃, the studies were carried out by using different concentrations(dosages) of molluscicide, shamingdan, in various methods of immersing, spraying and dusting power, and the molluscicidal effects were compared with 50% wettable powder of niclosamide ethanolamine salt(WPN). Results The 48-hour's LC_ 50(s) of 4% shamingdan granular formulation and 50% shamingdan soluble powder were 0.1752 mg/L and 0.2713 mg/L, respectively, which were similar to that of 50% WPN. In spraying and dusting powder experiment, the 7-day's LC_ 50(s) were 3.0418, 0.1623 g/m~2 and 2.8752, 1.1101 g/m~2, respectively, and the 50% shamingdan soluble powder was better than 4% shamingdan granular formulation and 50% WPN. Conclusions The molluscicidal effect of 2 kinds of shamingdan using immersing is better than that using spraying and dusting. The molluscicidal effect of the 50% shamingdan soluble powder is remarkably better than that of the 4% shamingdan granular formulation and 50% WPN.