OBJECTIVE To investigate the effects of clopidogrel on the pharmacokinetics and pharmacodynamics of ciprofol in rats. METHODS Eighteen male SD rats were randomly divided into control group， clopidogrel normal-dose group and clopidogrel high-dose group， with 6 rats in each group. Among them， rats in the normal-dose group and high-dose group were given 7.5 mg/kg and 15 mg/kg clopidogrel by gavage， respectively， and rats in the control group were given the same volume of 0.5% sodium carboxymethyl cellulose solution， once a day， for 14 consecutive days. Afterward， 2.4 mg/kg ciprofol was injected by tailvein and blood samples were collected from the inner canthus of the eye at 2， 4， 8， 12， 16， 20， 30， 45 and 60 min after the end of the administration. During this period， the duration of the loss of righting reflex （LORR） in rats was counted. After the proteins were precipitated by acetonitrile， the rat plasma sample was analyzed by LC-MS/MS using deuterated ciprofol as the internal standard， Symmetry C18 as the chromatographic column， and acetonitrile-0.01% ammonia solution containing 5 mmol/L ammonium acetate （gradient elution） as the mobile phase to detect the concentration of ciprofol in the plasma. The pharmacokinetic parameters in rats were calculated by using DAS 2.0 software. RESULTS Compared with control group， area under the drug concentration-time curve and mean residence time of ciprofol increased or prolonged significantly， while plasma clearance decreased significantly in clopidogrel normal-dose and high-dose groups； the duration of LORR in rats was prolonged by 19.5% and 23.9%， with statistical difference （P＜0.05）. However， there was no statistically significant difference in the pharmacokinetic parameters or LORR duration of ciprofol between the different dose groups of clopidogrel （P＞0.05）. CONCLUSIONS Clopidogrel could inhibit the metabolism of ciprofol in rats and prolong the duration of LORR.

OBJECTIVE To investigate the effects of clopidogrel on the pharmacokinetics and pharmacodynamics of ciprofol in rats. METHODS Eighteen male SD rats were randomly divided into control group， clopidogrel normal-dose group and clopidogrel high-dose group， with 6 rats in each group. Among them， rats in the normal-dose group and high-dose group were given 7.5 mg/kg and 15 mg/kg clopidogrel by gavage， respectively， and rats in the control group were given the same volume of 0.5% sodium carboxymethyl cellulose solution， once a day， for 14 consecutive days. Afterward， 2.4 mg/kg ciprofol was injected by tailvein and blood samples were collected from the inner canthus of the eye at 2， 4， 8， 12， 16， 20， 30， 45 and 60 min after the end of the administration. During this period， the duration of the loss of righting reflex （LORR） in rats was counted. After the proteins were precipitated by acetonitrile， the rat plasma sample was analyzed by LC-MS/MS using deuterated ciprofol as the internal standard， Symmetry C18 as the chromatographic column， and acetonitrile-0.01% ammonia solution containing 5 mmol/L ammonium acetate （gradient elution） as the mobile phase to detect the concentration of ciprofol in the plasma. The pharmacokinetic parameters in rats were calculated by using DAS 2.0 software. RESULTS Compared with control group， area under the drug concentration-time curve and mean residence time of ciprofol increased or prolonged significantly， while plasma clearance decreased significantly in clopidogrel normal-dose and high-dose groups； the duration of LORR in rats was prolonged by 19.5% and 23.9%， with statistical difference （P＜0.05）. However， there was no statistically significant difference in the pharmacokinetic parameters or LORR duration of ciprofol between the different dose groups of clopidogrel （P＞0.05）. CONCLUSIONS Clopidogrel could inhibit the metabolism of ciprofol in rats and prolong the duration of LORR.

One case of knee infection after anterior cruciate ligament reconstruction caused by the gram-positive anaerobic bacterium Finegoldia magna was reported. The patient was admitted to hospital due to fever and knee joint swelling and pain after anterior cruciate ligament reconstruction. Through medical history, physical examination, imaging examination and next-generation sequencing, it was confirmed that the infection was caused by Finegoldia magna. Through literature review, 37 literatures on infectious diseases caused by Finegoldia magna was retrieved and analyzed, and the identification points of anaerobic bacteria, the application of second-generation sequencing technology and the treatment status of infection after anterior cruciate ligament reconstruction were reviewed. The incidence of infection after arthroscopic anterior cruciate ligament reconstruction is low, while anaerobic infection is even more rare and difficult to culture. The next-generation sequencing can be used to assist the diagnosis. On the basis of giving priority to the preservation of the reconstructed ligament, the combined use of arthroscopic debridement, irrigation and sensitive antibiotics is the main treatment method.

A 24-year female with abdominal pain and fever for 4 days was admitted. The blood culture showed Leuconostoc growth, and sputum culture showed positive Acinetobacterbaumannii. The diagnosis Leuconostoclactis bacteremia following small intestinal perforation was confirmed; surgical treatment was performed and the infection was controlled by piperacillin sodium and tazobactam combined with tegacycline. Wanfang database, CNKI, PubMed and Embase database up to September 2020 were searched with the keywords of " Leuconostoc lactis" "infection" "bacteraemia" for relevant literature. A total of 32 cases were reported in the literature, of whom 13 (39.4%) were infants, 17 (51.5%) had catheter-related bloodstream infection, and one healthy adult male had bacteremia through gastrointestinal perforation. In 20 patients treated with penicillins-based antibiotics, 18 were cured with an effective rate of 90.0%. The results suggest that Leuconostoc infection is likely to occur in the infants, but adults can still get community-acquired Leuconostoc infection. Most β-lactams are susceptible to Leuconostoc, but some exhibit resistance, so it is recommended to select antimicrobial agents based on drug susceptibility.

Objective:To explore a new method for correcting the senile blepharochalasis and depression of the upper eyelid.Methods:Fourteen female patients with blepharochalasis and depression of upper eyelid were treated with subcutaneous tissue flap filling during eyebrow lifting. The under-eyebrow incision was used to remove the loose skin and lift the eyebrow, and a subcutaneous tissue flap was made to fill up the upper eyelid depression.Results:All the incisions were healed in one stage without complications such as infection and subcutaneous hematoma. 12 patients were followed up for more than 6 months. In the 3rd month after operation, 1 patient had obvious scar under the eyebrow, 1 patient had skin traction wrinkles at the eyebrow. After 6 months, the incision scar was not obvious in all patients, the appearance of eyebrow ptosis was eliminated, the upper eyelid was smooth and flat, and no absorption and further depression of the upper filler were observed; the effect was satisfactory.Conclusions:The eyebrow lifting combined with the subcutaneous tissue flap filling to correct the senile upper eyelid chalasis and depression is significantly effective with less trauma and complications, and it is worthy to be promoted.

Objective:To investigate the value of CT radiomics mode in differential diagnosis of benign and malignant thyroid nodules.Methods:The clinical and imaging data of 179 patients with thyroid nodules confirmed by pathology from May 2017 to August 2018 were retrospectively analyzed in the Affiliated Huaian First People′s Hospital of Nanjing Medical University. Among the patients, 89 cases were benign nodules and 90 cases were malignant nodules. All patients underwent unenhanced and enhanced CT scan before operation. The stratified random sampling method was used to divide patients into a training group (143 cases) and a testing group (36 cases) according to a ratio of 8∶2. The A.K software was used to extract 378 imaging omics features based on preoperative CT images, and then Spearman correlation analysis and least absolute shrinkage and selection operator regression analysis were used for feature selection and model construction. The receiver operating characteristic (ROC) curve was used to verify the model in the training group and the testing group, and the efficacy of imaging omics features to predict benign and malignant thyroid nodules was evaluated.Results:After feature screening, 16 radiomics features were used to construct an identification model between benign and malignant thyroid nodules. In the training group, the area under the ROC curve (AUC) was 0.92 [95% confidence interval (CI): 0.88-0.97], the sensitivity and specificity were 88.7%, 82.0%, and the diagnostic accuracy of the model was 91.1%. In the testing group, AUC was 0.90 (95 %CI: 0.81-0.98), sensitivity and specificity were 88.5%, 84.6%, and the diagnostic accuracy of the model was 88.2%. Conclusion:The CT radiomics mode has a good diagnostic performance in the identification of benign and malignant thyroid nodules.

Objective: To evaluate the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treatment of elderly patients with acute myeloid leukemia (AML). Methods: The clinical data of 53 elderly patients (≥55 years old) with AML who received allo-HSCT in the First Affiliated Hospital of Soochow University from June 2008 to March 2019 were retrospectively analyzed. All the patients included haplo-HSCT (26 cases), matched-sibling donors (MSD)-HSCT (18 cases), matched or mismatched unrelated donors (9 cases). The efficacy of allo-HSCT for elderly patients with AML was analyzed, and the efficacy and safety of haplo-HSCT and MSD-HSCT were compared. Results: There were 35 males and 18 females among 53 elderly AML patients. The median age was 57 years old (55-67 years old), and 45 patients received myeloablative conditioning (MAC) regimen while 8 patients received reduced intensity conditioning (RIC) regimen. There were 52 patients who were successfully implanted in granulocyte, and the median time for engraftment was 12 d (10-23 d). There were 50 patients who were successfully implanted in megakaryocyte and the median time for engraftment was 13 d (10-76 d). The incidence of acute graft-versus-host disease (GVHD) was 49.1% (26/53), and the incidence of grade Ⅲ-Ⅳ acute GVHD was 15.1% (8/53), respectively. The median follow-up time was 14.7 months (0.4-136.8 months), and 32 patients survived. The rate of 2-year overall survival (OS), disease-free survival (DFS) and graft-versus-host-free-relapse free survival (GRFS) was 63.1%, 59.5% and 46.1%, respectively. Multivariate analysis showed that non-complete remission (CR) state before transplantation was an independent prognostic factor for OS (HR = 3.600, 95% CI 1.213-10.684, P = 0.021), DFS (HR = 2.596, 95% CI 1.098-6.138, P = 0.030) and relapse (HR = 3.957, 95% CI 1.099-14.245, P = 0.035). Donor age > 45 years old was an independent risk factor for OS (HR = 3.687, 95% CI 1.343-10.215, P = 0.011). Time from diagnosis to transplantation ≥6 months was an independent risk factor for GRFS (HR = 2.308, 95%CI 1.083-4.918, P = 0.030). There were no statistical differences in OS rate, DFS rate, cumulative relapse rate, the incidence of grade Ⅲ-Ⅳ acute GVHD and moderate to severe chronic GVHD between haplo-HSCT and MSD-HSCT (all P > 0.05). Conclusions The preliminary results show that allo-HSCT is an effective and safe treatment for elderly AML patients. In addition, haplo-HSCT is similar to MSD-HSCT in the efficacy and safety, indicating that haplo-HSCT could be a better treatment option for elderly AML patients under the circumstance without non-identical donor.

Objective ToexplorethediagnosticvalueofenhancedCTandGd-EOB-DTPA-enhanced MRIinthedetectionofhepatocellular carcinoma (HCC).Methods 41patientswith52HCCsunderwentenhancedCTandGd-EOB-DTPA-enhancedMRIrespectively.The imagingmanifestationswereanalyzed,andthelesionsweregrouped.Theimagingdiagnositicresultswerecomparedwiththepathologicalresults, andtheefficacyofthetwomodalitieswasevaluatedusingtheaccuracyindex.Results Ofthetotal52HCCs,42lesionswereidentifiedexactlyby enhancedCT,and51byGd-EOB-DTPA-enhancedMRI.Foralllesions,includingsmalllesions(≤2cm),theaccuracyratioofGd-EOB-DTPA-enhancedMRIwashigherthanthatofenhancedCT withastatisticallysignificantdifference(P<0.05),however,therewasnosignificant differenceforthelesionsbiggerthan2cm (P>0.05).Conclusion EnhancedCTislimitedindiagnosisoftheHCCssmallerthanor equalto2cm.ThediagnosticefficacyofGd-EOB-DTPA-enhanced MRIishigherthanthatofenhancedCT,anditcansignificantly improvethediagnosisofsmallHCC.

Orthodontic pain that is induced by tooth movement is an important sequela of orthodontic treatment and has a significant effect on patient quality of life. Studies have shown that the high expression of transient receptor potential vanilloid 1 (TRPV1) in trigeminal ganglions plays a vital role in the transmission and modulation of orofacial pain. However, little is known about the role of TRPV1 in orthodontic pain. In this study, male Sprague-Dawley rats were randomly assigned to six groups to study the role of TRPV1 in the modulation of tooth-movement pain. The expression levels of TRPV1 mRNA and protein were determined by real-time PCR and western blot, respectively. Moreover, pain levels were assessed using the rat grimace scale (RGS). The role of TRPV1 in modulating tooth-movement pain was examined by injecting a TRPV1 antagonist into the trigeminal ganglia of rats. A lentivirus containing a TRPV1 shRNA sequence was constructed and transduced into the rats' trigeminal ganglia. The results showed that the expression levels of TRPV1 protein and mRNA were elevated following tooth-movement pain. Pain levels increased rapidly on the 1 day, peaked on the 3 day and returned to baseline on the 14 day. The TRPV1 antagonist significantly reduced tooth-movement pain. The lentivirus containing a TRPV1 shRNA sequence was able to inhibit the expression of TRPV1 and relieved tooth-movement pain. In conclusion, TRPV1-based gene therapy may be a treatment strategy for the relief of orthodontic pain.
Animals ; Calcitonin Gene-Related Peptide ; Genetic Therapy ; Male ; Molar ; Pain ; Quality of Life ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; TRPV Cation Channels ; Tooth Movement Techniques ; Trigeminal Ganglion

Orthodontic pain that is induced by tooth movement is an important sequela of orthodontic treatment and has a significant effect on patient quality of life.Studies have shown that the high expression of transient receptor potential vanilloid 1 (TRPV1) in trigeminal ganglions plays a vital role in the transmission and modulation of orofacial pain.However,little is known about the role of TRPV1 in orthodontic pain.in this study,male Sprague-Dawley rats were randomly assigned to six groups to study the role of TRPV1 in the modulation of tooth-movement pain.The expression levels of TRPV1 mRNA and protein were determined by real-time PCR and western blot,respectively.Moreover,pain levels were assessed using the rat grimace scale (RGS).The role of TRPV1 in modulating tooth-movement pain was examined by injecting a TRPV1 antagonist into the trigeminal ganglia of rats.A lentivirus containing a TRPV1 shRNA sequence was constructed and transduced into the rats' trigeminal ganglia.The results showed that the expression levels of TRPV1 protein and mRNA were elevated following tooth-movement pain.Pain levels increased rapidly on the 1st day,peaked on the 3rd day and returned to baseline on the 14th day.The TRPV1 antagonist significantly reduced tooth-movement pain.The lentivirus containing a TRPV1 shRNA sequence was able to inhibit the expression of TRPV1 and relieved tooth-movement pain.In conclusion,TRPV1-based gene therapy may be a treatment strategy for the relief of orthodontic pain.