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.

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 explore the clinical effect of personalized pars plana vitrectomy(PPV)for proliferative di-abetic retinopathy(PDR).Methods In this retrospective case study,76 patients(86 eyes)diagnosed with PDR and re-ceiving PPV in the Department of Ophthalmology of Songjiang Hospital affiliated to Shanghai Jiao Tong University School of Medicine,from October 2019 to November 2022,were divided into the observation group(40 patients,46 eyes)and the control group(36 patients,40 eyes).Patients in the obseration group were treated with personalized PPV,while patients in the control group were treated with conventional PPV,After treatment,all patients were followed up for 12 months.The operation time,intraoperative use of heavy water and silicone oil,incidence of iatrogenic retinal tears and heavy water resi-dues,proportion of scleral buckling,preoperative and postoperative best corrected visual acuity(BCVA)and intraocular pressure(IOP),retinal reattachment rate at 12 months after surgery,and the incidence of post-vitrectomy vitreous hemor-rhage(PVH),diabetic macular edema(DME)and neovascular glaucoma(NVG)were compared between the two groups.Results The operation time of patients in the observation group was shorter than that in the control group(P＜0.05).Intraoperative use of heavy water and silicone oil in the observation group was lower than that in the control group(both P＜0.05).The incidence of iatrogenic retinal tears and heavy water residues and the proportion of scleral buckling showed no statistically significant difference between the two groups(all P＞0.05).There was no statistically significant difference between the two groups in BCVA preoperatively,3,6 and 12 months postoperatively(all P＞0.05).BCVA in the observa-tion group was better than that in the control group at 1 day,1 week and 1 month after surgery(all P＜0.05).Compared with the preoperative value,BCVA increased in the observation group at 1 day,1 week,1 month,3 months,6 months,and 12 months after surgery(all P＜0.05);in the control group,BCVA increased slightly at 1 day and 1 week(both P＞0.05)and then increased significantly at 1 month,3 months,6 months,and 12 months after surgery(all P＜0.05).The two groups showed no statistically significant difference in IOP at 1 day,1 week,1 month,3 months,6 months,and 12 months postoperatively(all P＞0.05).There was no statistically significant difference in the retinal reattachment rate and the inci-dence of complications such as PVH,DME,and NVG between the two groups at 12 months postoperatively(all P＞0.05).Conclusion Personalized PPV can shorten the operation time,reduce the intraoperative use of heavy water and silicone oil,enhance the efficiency of the operation,and rapidly improve the visual acuity of PDR patients.

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*

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 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.

The methamphetamine(METH)addiction is a compensatory adaptation of the central nervous system after the long-term exposure to METH in the molecular,cellular,neuronal loop function and brain structure.As a new type of post transcriptional regulatory molecules and regulatory factors,miRNAs are a large number of regulatory factors in the central nervous system.Studies have shown that miRNAs play an important role in the regulation of METH addiction.This paper is to review and summarize the expression features and the regulatory role of miRNAs in METH addiction,as well as the different expression of miRNAs in different tissues and organs.The aim of this paper is to provide a reference for further study on the role of miRNAs molecules in METH addiction and the discovery of new drug targets.

BACKGROUND:Anatomic medul ary locking (AML) femoral prosthesis is circular cylinder and has satisfactory efficacy. However, some scholars found the complications such as thigh pain, loss of bone at the proximal end of the femur, and wearing-related osteolysis. F2L femoral prosthesis is cone-shaped and also has satisfactory efficacy, but the thigh pain incidence is relatively low. ＜br> OBJECTIVE:To compare the intermediate-long term results of AML versus F2L in total hip arthroplasty. ＜br> METHODS:Between November 1997 and January 2005, we retrospectively reviewed 60 patients (66 hips) undergoing total hip arthroplasty using biological femoral prosthesis. At fol ow-up examination, 58 hips in 52 patients were available for clinical and roentgenographic review. 26 AML devices were placed in 24 patients, and 32 F2L devices were placed in 28 patients. The AML group were reviewed with an average of 12.7 years fol ow-up (range 10 years and 3 months to 15 years and 5 months), while the F2L group were reviewed with an average of 9.5 years fol ow-up (range 8 years and 3 months to 11 years and 1 month). The clinical results were evaluated with Harris methods and X-ray examination. Kaplan-Meier analysis was performed to evaluate the survival of femoral component. End point was radiographical loosening or revision of the femoral component for any reason. ＜br> RESULTS AND CONCLUSION:There were no significant difference between AML and F2L about Harris score in the latest fol ow-up (P>0.05). After surgery, the incidence of thigh pain was significantly lower in F2L group than that in AML group (P＜0.05). In AMKL group, the stress-shielding 1 level was observed in 21 hips (81%), and 2 level in five hips (19%);in F2L group, the stress shielding 0 level was observed in 20 hips (62%) and 1 level in 12 hips (38%). There were significant differences between the two groups (P＜0.05). The stress shielding showed significant differences between the two groups (P＜0.05). The incidence of osteolysis in F2L group was significantly lower than that in AML group (P＜0.05). Kaplan-Meier analysis showed that, the survival rate of both AML and F2L components were 1.0 (95%confidence interval:0.98-1.00). Experimental findings indicate that, both AML and F2L femoral prosthesis have a satisfactory long-term efficacy after total hip arthroplasty, and the incidence of thigh pain and osteolysis is significantly lower in F2L group.

BACKGROUND:Femoral offset reconstruction is significant for recovering strength of abductor and the balance of soft tissue tension surrounding hip joint, maintaining joint stabilization, restoring joint function, reducing limping after replacement, decreasing prosthetic abrasion, and the incidence of joint prosthesis dislocation.
OBJECTIVE:To discuss effect of femoral offset reconstruction on hip joint function in total hip arthroplasty.
METHODS:We comparatively analyzed 20 patients (20 hips) undergoing the modular prosthesis (S-ROM) total hip arthroplasty and 19 patients (20 hips) undergoing the one modular prosthesis (Corail) total hip arthroplasty at the same time. According to Harris hip score and radiography results, hip joint function and femoral offset reconstruction rate were comparatively studied in both groups.
RESULTS AND CONCLUSION:No infection, fracture, dislocation, deep venous thrombosis or neurovascular injury occurred in either group. Clinical fol ow-up results:In the modular prosthesis and one modular prosthesis groups, there was no significant difference in preoperative Harris hip score between the femoral offset reconstruction and non-reconstruction groups (P>0.05). At 12 months and the latest fol ow-up, the Harris hip score was higher in the patients with femoral offset reconstruction than those with femoral offset non-reconstruction (P<0.05). The range of abduction of hip joint was larger in patients with femoral offset reconstruction than those with femoral offset non-reconstruction (P<0.05). Radiographic fol ow-up results:significant differences in the rate of femoral offset reconstruction were detected between the modular prosthesis and one modular prosthesis groups (χ2=3.956, P<0.05). 39 (98%) femoral stems were in neutral position and one (2.5%) was in mild valgus. There was no significant difference in the abduction angle and the anteversion angle between patients with and without femoral offset reconstruction (P>0.05). These results indicated that functional recovery and the range of abduction were better in patients with femoral offset reconstruction than those without femoral offset reconstruction. Modular prosthesis has a high rate of femoral offset reconstruction.

Objective To investigate the effect of sevoflurane postconditioning on oxidative stress responses during focal cerebral ischemia-reperfusion (I/R) in rats.Methods Twenty-four male Wistar rats,weighing 240-280 g,were randomly assigned into 3 groups:sham operation group (group S),focal cerebral I/R group (group I/R) and sevoflurane postconditioning group (group SP).The animals were anesthetized with intraperitoneal 10％ chloral hydrate 350 mg/kg.Focal cerebral I/R was produced by middle cerebral artery occlusion.In group SP,3.9％ sevoflurane (1.5 MAC) was inhaled starting from 20 min before reperfusion until 10 min after reperfusion.While 100％ O2 and air were given instead of sevoflurane in groups I/R and S,respectively.Six rats chosen from each group at 24 h of reperfusion were sacrificed and brains were removed for determination of malondialdehyde (MDA),glutathione (GSH),superoxide dismutase (SOD),catalase (CAT),glutathione peroxidase (GSH-Px) and glutathione reductase (GR) levels and for microscopic examination.The cerebral infarct size was measured by TTC staining.Results Compared with group S,MDA level and cerebral infarct size were significantly increased in groups I/R and SP,and GSH,SOD,CAT,GSH-Px and GR levels were decreased in group I/R,and GSH-Px level was decreased in group SP (P ＜ 0.05).Compared with group I/R,cerebral infarct size and MDA level were decreased,and GSH,SOD,CAT,GSH-Px and GR levels were decreased in group SP (P ＜ 0.05).The pathological changes were significantly attenuated in group SP compared with group I/R.Conclusion The mechanism by which sevoflurane postconditioning mitigates focal cerebral I/R injury in rats is related to enhanced antioxidase activity and inhibition of oxidative stress responses.