Objective To observe the clinical effect of traditional Chinese medicine bone-setting technique using spinal,pelvi-lower extremity line to treat patients with knee osteoarthritis(KOA).Methods 426 patients with KOA were all from the First Affiliated Hospital of Hebei University of Traditional Chinese Medicine.They were randomly divided into experimental group(384 cases,57 cases of elimination,shedding and termination)by computer generated sequence.Traditional Chinese bone setting techniques were applied with spinal-pelvic-lower limb force line(divided into three parts:lumbar fixed point reduction method,hip joint push-pull and extension method and knee peripheral tendon recovery method every 3 days.2 weeks)treatment;The control group was the waiting treatment group(48 cases,6 cases were eliminated,abscission,termination),which was only used for clinical observation for 2 weeks.The main outcome index was WOMAC pain score.Secondary outcome measures were WOMAC stiffness score,functional score,standardized score and quality of life score(SF-12).The test time points were baseline,2 weeks after enrollment,and follow-up(14 weeks after enrollment).The control group was at baseline and 2 weeks after enrollment.Results Compared with baseline,WOMAC pain score,stiffness score,functional score and standardized score were all decreased in 2 groups 2 weeks after enrollment(P<0.05),but the experimental group was significantly decreased compared with the control group(P<0.001).SF-12 quality of life scores were all higher than before(P<0.001),but the experimental group was significantly higher than the control group(P<0.001).At follow-up,compared with 2 weeks after enrollment,WOMAC pain scores were increased(P<0.001),WOMAC stiffness,joint function and standardized scores were decreased(P<0.001),and SF-12 scores were increased(P<0.001).Conclusion The use of spinal-pelvi-lower extremity line of traditional Chinese medicine bone-setting technique in the treatment of KOA is effective in improving the knee joint function and improving the quality of life of patients,but the short-term effect of pain relief is good,and the long-term effect is not good.Its safety is good,and it can be considered in clinical application for KOA patients with joint dysfunction as the main manifestation.

Objective:To evaluate the effect of berberine on acute kidney injury (AKI) in rats undergoing liver transplantation and the role of AMP-activated protein kinase (AMPK).Methods:Twenty-four SPF-grade adult male Sprague-Dawley rats, aged 12 weeks, weighing 210-230 g, were divided into 4 groups ( n=6 each) using the random number table method: sham operation group (S group), AKI group, berberine group (BBR group), and berberine + AMPK inhibitor Compound C group (BBR-Comp C group). In BBR group, berberine 200 mg/kg was given by gavage starting from 2 weeks before surgery, once a day for 14 consecutive days. In BBR-Comp C group, Compound C 1 mg/kg was injected into the tail vein at 30 min before surgery. The rat AKI model was prepared by in situ liver transplantation in AKI group, BBR group and BBR-Comp C group. Blood specimens were taken from the inferior vena cava at 24 h postoperatively, and serum BUN and Cr concentrations were determined by enzyme-linked immunosorbent assay. Then the rats were sacrificed, and the kidney tissues were taken for microscopic examination of the pathological changes (with the light microscope after HE staining) and for determination of the expression of phosphorylated AMPK (p-AMPK), receptor-interacting protein kinase-1 (RIPK-1), receptor-interacting protein kinase-3 (RIPK-3) and mixed lineage kinase domain-like protein (MLKL) (by Western blot). Results:Compared with S group, the serum BUN and Cr concentrations were significantly increased, the p-AMPK expression was down-regulated, the expression of RIPK-1, RIPK-3 and MLKL was up-regulated ( P<0.05), and the pathological damage to renal tissues occurred in AKI group. Compared with AKI group, the serum BUN and Cr concentrations were significantly decreased, the p-AMPK expression was up-regulated, the expression of RIPK-1, RIPK-3 and MLKL was down-regulated ( P<0.05), and the pathological changes of renal tissues were significantly attenuated in BBR group. Compared with BBR group, the serum BUN and Cr concentrations were significantly increased, the p-AMPK expression was down-regulated, and the expression of RIPK-1, RIPK-3 and MLKL was up-regulated in BBR-Comp C group ( P<0.05). Conclusions:Berberine can attenuate AKI in rats undergoing liver transplantation, and the mechanism may be related to the promotion of AMPK phosphorylation and inhibition of programmed necrosis.

L-dopa (l-3,4-dihydroxyphenylalanine)-induced dyskinesia (LID) is a debilitating complication of dopamine replacement therapy for Parkinson's disease. The potential contribution of striatal D₂ receptor (D₂R)-positive neurons and downstream circuits in the pathophysiology of LID remains unclear. In this study, we investigated the role of striatal D₂R⁺ neurons and downstream globus pallidus externa (GPe) neurons in a rat model of LID. Intrastriatal administration of raclopride, a D₂R antagonist, significantly inhibited dyskinetic behavior, while intrastriatal administration of pramipexole, a D₂-like receptor agonist, yielded aggravation of dyskinesia in LID rats. Fiber photometry revealed the overinhibition of striatal D₂R⁺ neurons and hyperactivity of downstream GPe neurons during the dyskinetic phase of LID rats. In contrast, the striatal D₂R⁺ neurons showed intermittent synchronized overactivity in the decay phase of dyskinesia. Consistent with the above findings, optogenetic activation of striatal D₂R⁺ neurons or their projections in the GPe was adequate to suppress most of the dyskinetic behaviors of LID rats. Our data demonstrate that the aberrant activity of striatal D₂R⁺ neurons and downstream GPe neurons is a decisive mechanism mediating dyskinetic symptoms in LID rats.
Rats ; Animals ; Levodopa/toxicity* ; Dopamine ; Parkinsonian Disorders/drug therapy* ; Oxidopamine ; Dyskinesia, Drug-Induced ; Corpus Striatum/metabolism* ; Neurons/metabolism* ; Receptors, Dopamine D2/metabolism* ; Antiparkinson Agents/toxicity*

Objective:To evaluate the role of ferroptosis in lung injury in a rat model of autologous orthotopic liver transplantation.Methods:Twenty-four healthy adult SPF-grade male rats, aged 8-10 weeks, weighing 230-270 g, were divided into 3 groups ( n=8 each) using the random number table method: sham operation group (S group), autologous in situ liver transplantation group (LT group) and ferroptosis inhibitor Ferrostain-1 group (LT+ Fer-1 group). In LT group and LT+ Fer-1 group, an autologous in situ liver transplantation model was developed in anesthetized animals, and Ferrostain-1 5 mg/kg was intraperitoneally injected at 30 min before surgery in LT+ Fer-1 group. The inferior vena cava blood samples were obtained at 6 h of reperfusion, then animals were sacrificed, and lung tissues were obtained. The morphology of lung tissues was examined, and the lung injury was scored. The serum malondialdehyde (MDA) concentration and contents of MDA, reduced glutathione (GSH), glutathione peroxidase4 (GPX4), and Fe 2+ in lung tissues were measured by enzyme-linked immunosorbent assay. The expression of ferritin heavy chain 1 (FTH1) and solute carrier family 7 member 11 recombinant protein (SLC7A11) was determined by Western blot. Results:Compared with S group, the lung injury, serum MDA concentration, and contents of MDA and Fe 2+ were significantly increased, the contents of GSH and GPX4 were decreased, and the expression of FTH1 and SLC7A11 was down-regulated in LT group ( P<0.05). Compared with LT group, the lung injury, serum MDA concentration, and contents of MDA and Fe 2+ were significantly decreased, the contents of GSH and GPX4 were increased, and the expression of FTH1 and SLC7A11 was up-regulated in LT+ Fer-1 group ( P< 0.05). Conclusions:Ferroptosis is involved in the pathophysiology of lung injury in a rat model of autologous orthotopic liver transplantation.

Objective:To evaluate the optimization efficacy of ropivacaine mixed with nalbuphine for epidural labor analgesia through comparison with ropivacaine mixed with sufentanil in primiparas.Methods:Four hundred and forty primiparas with a singleton fetus in vertex presentation without abnormal fetus, aged 19-36 yr, at 37-42 weeks of gestation, who were suitable and volunteered to receive epidural labor analgesia, were selected and randomly divided into observation group (NR group, n=220) and conventional group (C group, n=220).Epidural labor analgesia solution contained nalbuphine 40 mg and ropivacaine 120 mg in 150 ml of normal saline in group NR.Epidural labor analgesia solution contained sufentanil 50 μg and ropivacaine 120 mg in 150 ml of normal saline in group C. The analgesia pump was set up to deliver a 5 ml bolus dose with a 20-min lockout interval, programmed intermittent bolus 10-15 ml/h and background infusion at 2 ml/h after an initial dose of 15 ml to maintain VAS score <3.The length of labor, adverse reactions during labor analgesia, neonatal Apgar score, parameters of umbilical artery blood gas analysis and neonatal behavioral neurological assessment score were recorded. Results:Compared with group C, the incidence of urinary retention, pruritus, nausea and vomiting and fever at birth was significantly decreased in group NR ( P<0.05).The duration of the first and second stages of labor, neonatal Apgar score, pH value of umbilical artery blood, lactate concentrations, and neonatal behavioral neurological assessment score were within the normal range in both groups, and there was no significant difference between the two groups ( P>0.05). Conclusions:Compared with conventional medication, nalbuphine mixed with ropivacaine has the same efficacy when used for epidural labor analgesia in primiparas, but it has a certain optimization efficacy in terms of safety.

Oral immunosuppression caused by smoking creates a microenvironment to promote the occurrence and development of oral mucosa precancerous lesions. This study aimed to investigate the role of metabolism and macrophage polarization in cigarette-promoting oral leukoplakia. The effects of cigarette smoke extract (CSE) on macrophage polarization and metabolism were studied in vivo and in vitro. The polarity of macrophages was detected by flow cytometric analysis and qPCR. Liquid chromatography-mass spectrometry (LC-MS) was used to perform a metabolomic analysis of Raw cells stimulated with CSE. Immunofluorescence and flow cytometry were used to detect the polarity of macrophages in the condition of glutamine abundance and deficiency. Cell Counting Kit-8 (CCK-8), wound-healing assay, and Annexin V-FITC (fluorescein isothiocyanate)/PI (propidium iodide) double-staining flow cytometry were applied to detect the growth and transferability and apoptosis of Leuk-1 cells in the supernatant of Raw cells which were stimulated with CSE, glutamine abundance and deficiency. Hyperkeratosis and dysplasia of the epithelium were evident in smoking mice. M2 macrophages increased under CSE stimulation in vivo and in vitro. In total, 162 types of metabolites were detected in the CSE group. The metabolites of nicotine, glutamate, arachidic acid, and arginine changed significantly. The significant enrichment pathways were also selected, including nicotine addiction, glutamine and glutamate metabolism, and arginine biosynthesis. The results also showed that the supernatant of Raw cells stimulated by CSE could induce excessive proliferation of Leuk-1 and inhibit apoptosis. Glutamine abundance can facilitate this process. Cigarette smoke promotes oral leukoplakia via regulating glutamine metabolism and macrophage M2 polarization.
Animals ; Glutamine ; Leukoplakia, Oral ; Macrophages ; Mice ; Smoking ; Tumor Microenvironment

Objective:To explore the predictive value of N-terminal pro-brain natriuretic peptide (NT-proBNP) combined with coronary CT in the final diagnosis of coronary artery disease.Methods:A total of 168 patients who were admitted to Dalian Friendship Hospital from August 2016 to August 2017 were randomly selected. The demographic data, clinical data and Gensini score of each selected patient were recorded. The patients were divided into coronary heart disease group (71 cases )and non coronary heart disease group (97 cases) according to the final results of coronary angiography. The demographic, clinical data and Gensini scores of the two groups were compared. The variables with significant differences were analyzed by multiple factors. The receptor working characteristic (ROC) curve of NT-proBNP for predicting patients with coronary heart disease was made.Results:The age, body mass index (BMI) , white blood cell count (WBC), Gensini score, the number of coronary artery lesions and the level of NT-proBNP of coronary heart disease group and non coronary heart disease group had significant differences [(65.8 ± 8.8) years vs. (58.8 ± 10.5) years, (27.5 ± 4.2) kg/m 2 vs. (23.3 ± 5.3) kg/m 2, (8.4 ± 2.6) × 10 9/L vs. (5.7 ± 2.2) × 10 9/L, (88.2 ± 12.0) scores vs. (43.3 ± 10.5) scores, 2.2 ± 1.1 vs. 1.1 ± 0.8, 72.1(28.0, 87.2) ng/L vs. 27.2(13.5, 34.6) ng/L, t=4.56, 2.43, 2.54, 7.89, 5.97, U=3 407.76, P<0.05]. Thirty-six patients (50.7%, 36/71) had diabetes history in coronary heart disease group and 24 patients (24.7%, 24/97) had diabetes history in non coronary heart disease group, and there was significant difference ( χ2= 12.04, P<0.05). Logistic analysis showed that coronary CT combined with NT-proBNP, age, history of diabetes mellitus and Gensini scores significantly increased the risk of final diagnosis of coronary artery disease, especially NT-proBNP ( OR = 14.57, 1.05, 2.48, 3.47, P<0.05). The results of ROC curve of NT -proBNP for predicting patients with coronary heart disease showed that the area under the curve was 0.899, with a sensitivity of 55.6% and a specificity of 82.6%, and critical value of the maximum Yoden index was 71.5 ng/L. Conclusions:NT-proBNP combined with coronary CT has predictive value for the final diagnosis of coronary heart disease, especially for patients with NT-proBNP over 71.5 ng/L. The patients who are initially diagnosed as coronary heart disease by coronary CT should be actively mobilized for coronary angiography.

Objective:To evaluate the effect of adductor canal block(ACB)and local infiltration anesthesia(LIA)around the knee joint on inflammatory responses in the patients undergoing total knee arthroplasty(TKA).Methods:Sixty American Society of Anesthesiologists physical status Ⅱor Ⅲ patients of both sexes, aged 54-76 yr, scheduled for elective TKA, were divided into 2 groups ( n=30 each) using a random number table method: ACB group (group A) and ACB combined with LIA around knee joint group (group AL). ACB was performed with 0.5% ropivacaine 15 ml after endotracheal intubation in group A and group AL, and in addition LIA was performed around the knee joint after the osteotomy was completed during surgery in group AL.The patient-controlled ACB analgesia was applied at the end of surgery in both groups.The analgesic solution contained ropivacaine 400 ml (in 0.9% normal saline 200 ml), and the analgesic pump was set up to deliver a 5 ml bolus dose with a 30-min lockout interval and background infusion at 5 ml/h.When visual analog scale score>4, and pain was still not relived at 30 min after pressing by patients, pethidine hydrochloride 100 mg was intramuscularly injected as rescue analgesic.Peripheral venous blood samples were collected immediately before surgery (T 0) and at 24, 48 and 72 h after surgery (T 1-3) for determination of serum interleukin-6 (IL-6) and IL-10 concentrations by enzyme-linked immunosorbent assay.The muscle strength on the affected side was assessed at T 1-3.The patients′ satisfaction score, requirement for rescue analgesia, and adverse effects were recorded. Results:Compare with group A, the serum IL-6 concentrations were significantly decreased and serum IL-10 concentrations were increased at each time point after surgery, postoperative patients′ satisfaction scores were increased, the requirement for rescue analgesia was decreased ( P<0.05), and no significant change was found in the quadriceps strength of the affected limb and incidence of adverse reactions after surgery in group AL ( P>0.05). Conclusion:ACB and LIA around the knee joint can mitigate postoperative inflammatory responses in the patients undergoing TKA.

Objective To evaluate the role of necroptosis in intestinal injury induced by autologous orthotopic liver transplantation ( AOLT) in rats. Methods Twenty-four SPF adult male Sprague-Dawley rats, aged 10-12 weeks, weighing 250-280 g, were divided into 3 groups ( n=8 each) using a random number table method: sham operation group ( group S) , AOLT group ( group T) and necroptosis inhibitor necrostatin-1 group ( group N) . Necrostatin-11. 0 mg∕kg and the equal volume of dimethyl sulfoxide ( DM-SO) were intraperitoneally injected at 30 min before surgery in N and T groups, respectively. Blood samples were collected from the inferior vena cava at 6 h after opening the portal vein ( at 6 h after the end of surgery in group S) for determination of serum diamine oxidase ( DAO) , D-lactic acid ( D-LA) and intestinal fatty acid binding protein ( I-FABP ) concentrations by enzyme-linked immunosorbent assay. Rats were sacrificed after blood sampling, and the intestine was removed for examination of the pathological changes ( with a light microscope ) and for determination of malondialdehyde ( MDA ) contents and superoxide dismutase ( SOD) activities ( using a spectrophotometer) , and the expression of receptor-interacting protein kinase-1 ( RIPK1) , RIPK3 and mixed lineage kinase domain-like protein ( MLKL) in intestinal tissues ( by Western blot) . Intestinal damage was assessed and scored using Chiu' s scoring system. Results Compared with group S, the serum DAO, D-LA and I-FABP concentrations, MDA content and Chiu's score were signifi-cantly increased, SOD activity was decreased, and the expression of RIPK1, RIPK3 and MLKL was up-regulated in group T ( P<0. 05) . Compared with group T, the serum DAO, D-LA and I-FABP concentra-tions, MDA content and Chiu's score were significantly decreased, the SOD activity was increased, and the expression of RIPK1, RIPK3 and MLKL was down-regulated in group N ( P<0. 05) . Conclusion Ne-croptosis is involved in the pathophysiological process of intestinal injury induced by AOLT in rats.

Objective To evaluate the role of necroptosis in liver injury in rats undergoing autolo-gous orthotopic liver transplantation ( AOLT). Methods Twenty-four SPF adult male Sprague-Dawley rats, weighing 250-280 g, were divided into 3 groups ( n=8 each) using a random number table method:sham operation group ( group S ) , AOLT group ( group T ) and necroptosis inhibitor necrostatin-1 group ( group N) . Rats were anesthetized using intraperitoneal 5％ chloral hydrate 0. 5 ml∕100 g. A standard mod-el of OALT was established as previously described by Yao et al. in T and N groups. Necrostatin-11. 0 mg∕kg and the equal volume of dimethyl sulfoxide were intraperitoneally injected at 30 min before surgery in N and T groups, respectively. Blood samples were collected from the inferior vena cava at 6 h after opening the portal vein ( at 6 h after operation in group S) for determination of serum aspartate amino-transferase(AST) and alanine amino-transferase (ALT) concentrations. The livers were removed for examination of the pathological changes (with a light microscope) and for determination of the malondialdehyde (MDA) contents and superoxide dismutase ( SOD) activity ( using a spectrophotometer) and expression of receptor-interacting protein kinase-1 ( RIPK1) , RIPK3 and mixed lineage kinase domain-like ( MLKL) in liver tis-sues ( by Western blot) . The damage to livers was evaluated using Suzuki′s scoring system. Results Com-pared with group S, the serum AST and ALT concentrations, Suzuki′s score of liver tissues and MDA con-tent were significantly increased, the SOD activity was decreased, and the expression of RIPK1, RIPK3 and MLKL was up-regulated in group T ( P<0. 05) . Compared with group T, the serum AST and ALT con-centrations, Suzuki′s score of liver tissues and MDA content were significantly decreased, the SOD activity was increased, and the expression of RIPK1, RIPK3 and MLKL was down-regulated in group N ( P<0. 05) . Conclusion Necroptosis is involved in liver injury in rats undergoing AOLT.