Objective To evaluate the role of α2 adrenergic receptors in dexmedetomidine-induced inhibition of lipid peroxidation during lung ischemia-reperfusion (I/R) injury in rats.Methods Thirty-two isolated rat lungs in which the model of isolated lung perfusion was successfully established,were divided into 4 groups (n=8 each) using a random number table:control group (C group),I/R group,dexmedetomidine group (D group) and dexmedetomidine plus yohimbine group (DY group).The isolated lungs were subjected to 60 min of ischemia and apnea followed by 75 min of reperfusion and ventilation to establish the model of isolated lung I/R injury.From the beginning of reperfusion,2.3 ng/ml dexmedetomidine was added to the perfusion fluid in D group,and 2.3 ng/ml dexmedetomidine and 0.4 μg/ml yohimbine (an α2 adrenergic receptor blocker) were added to the perfusion fluid in DY group.Lung specimens were obtained immediately after the end of reperfusion for determination of the wet/dry weight ratio (W/D ratio),superoxide dismutase (SOD) activity (by using modified pyrogallol autoxidation method) and malondialdehyde (MDA) content (by thiobarbituric acid method) and for examination of the pathological changes (using haematoxylin and eosin staining).Results Compared with C group,the W/D ratio and MDA content were significantly increased,and the SOD activity was decreased in I/R,D and DY groups (P＜0.05).Compared with I/R group,the W/D ratio and MDA content were significantly decreased,and the SOD activity was increased in D group (P＜0.05).Compared with DY group,the W/D ratio and MDA content were significantly decreased,and the SOD activity was increased in group D (P＜0.05).The pathological changes of lung tissues were significantly attenuated in D group as compared with I/R and DY groups.Conclusion The mechanism by which dexmedetomidine inhibits lipid peroxidation is related to activating α2 adrenergic receptors during lung I/R injury in rats.

Objective To evaluate the effect of emulsified isoflurane post-conditioning on the mitochondrial function during lung ischemia-reperfusion (I/R) in rats in an in vitro experiment.Methods Twenty-four SPF healthy male Sprague-Dawley rats,weighing 250-300 g,were used in the study.After the animals were anesthetized,the lungs were removed,connected to the perfusion system and then divided into 4 groups (n=6 each) using a random number table:control group (group C),group I/R,emulsified isoflurane post-conditioning group (group EI) and intralipid post-conditioning group (group IL).After 20 min of equilibration,the lungs were continuously perfused for 105 min in group C,and the lungs were subjected to 45 min ischemia followed by 60 min reperfusion to establish the model of lung I/R injury in the other three groups.During the reperfusion period,the common perfusate was used in group I/R,the perfusate containing 1.68 mmol/L emulsified isoflurane was used in group EI,and the equal volume of perfusate containing 30％ intralipid was used in group IL.At the end of the equilibration (T0),immediately after beginning of reperfusion (T1) and at 30 and 60 min of reperfusion (T2.3),the arterial oxygen partial pressure (PaO2),airway resistance,pulmonary compliance and tidal volume (VT) were recorded.The right upper lobe of the lung was removed at T3 for determination of wet to dry weight ratio (W/D ratio).The right middle lobe of the lung was removed at T3 for pathologic examination with light microscope.The contents of reactive oxygen species (ROS),NAD+ and ATP in lung tissues were detected.Results Compared with group C,the PaO2,pulmonary compliance and Vr were significantly decreased,and the airway resistance was increased at T1-3,and the W/D ratio and ROS content were increased,and NAD+ and ATP contents were decreased at T3 in I/R,EI and IL groups (P＜0.05).Compared with I/R and IL groups,the PaO2,pulmonary compliance and VT were significantly increased,and the airway resistance was decreased at T2.3,and the W/D ratio and ROS content were decreased,and NAD+ and ATP contents were increased at T3 in group EI (P＜0.05).The pathologic changes of lungs were significantly attenuated in group EI as compared with group I/R.Conclusion The mechanism by which emulsified isoflurane post-conditioning attenuates lung I/R injury is related to decrease in mitochondrial dysfunction in rats in an in vitro experiment.

Objective To explore the role of miR-20a on pulmonary surfactant synthesis of alveolar epithelial cells A549 and its potential mechanism.Methods Lentivirus miR-20a overexpression vector(miR-20a group) or lentivirus no-load vector(no-load group) was transfected into A549 cells,and the expression of green fluorescent protein(GFP) was observed to determinate the transfection effficiency;cell proliferation was detected by using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT);the bioinformatics software and database were applied to predict and analyze the target genes of miR-20a about lung development;expressions of miR-20a,pulmonary surfactant-associated protein A(SP-A),pulmonary surfactant-associated protein B(SP-B),pulmonary surfactant-associated protein C(SP-C) and pulmonary surfactant-associated protein D(SP-D) mRNA were detected by using quantitative real-time PCR(qPCR);the expressions of SP-A protein,SP-B protein,SP-C protein,SP-D protein and protein signal transducers and activators of transcription 3 (STAT3) were detected by using Western blot.Results Observation of GFP expression under a fluorescent microscope indicated similar transfection efficiency,and real time-PCR showed that the expression of miR-20a increased after being transfected with lentivirus miR-20a overexpression vector(3.85 ± 0.18)compared with the normal group (0.99 ± 0.04)and the no-load group (1.21 ± 0.12),and the differences were significant(t =10.85,9.64,all P ＜0.001).As a result,lentivirus miR-20a overexpression vector was constructed successfully.Online software predicted that STAT3 gene was likely to be the target gene of miR-20a.Compared with the normal group (24 h,48 h,72 h:0.23 ± 0.01,0.39 ± 0.01,0.56 ± 0.03) and the no-load group (24 h,48 h,72 h:0.25 ± 0.01,0.44 ± 0.05,0.59 ± 0.01),miR-20a did not change the cell proliferation at different time points(24 h,48 h,72 h:0.26 ± 0.01,0.41 ± 0.02,0.58 ± 0.02) (all P ＞ 0.05).Compared with the normal group (1.00 ± 0.05,1.24 ± 0.20,1.31 ± 0.09,0.89 ± 0.12) and the no-load group (0.76 ± 0.10,1.31 ± 0.13,1.50 ± 0.11,1.01 ± 0.11),miR-20a up-regulated the mRNA expressions of SP-A,SP-B,SP-C and SP-D (2.05 ± 0.17,2.14 ± 0.10,2.84 ± 0.09,1.66 ± 0.08),and the differences were significant (all P ＜ 0.05).Compared with the normal group (0.46 ± 0.01,0.27 ± 0.03,0.69 ± 0.01,0.43 ± 0.01) and no-load group (0.43 ± 0.01,0.21 ± 0.01,0.79 ± 0.02,0.44 ± 0.02),miR-20a also increased the protein expressions of SP-A,SP-B,SP-C and SP-D (0.55 ±0.01,0.47 ±0.05,0.96 ±0.02,0.59 ±0.03),the diffe-rences were statistically significant (all P ＜0.05).The expression of STAT3 in miR-20a group(0.37 ±0.05) was significantly lower than that in the normal group(0.60 ±0.04) and the no-load group (0.68 ±0.06),and the differences were statstically significant (all P ＜ 0.05) in A549.Conclusions STAT3 is a downstream target gene of miR-20a.miR-20a can promote pulmonary surfactant synthesis of alveolar epithelial cells A549 by inhibiting STAT3.

Post-transplant diabetes mellitus (PTDM) often occurs after solid organ transplantation, and treatment of PTDM is different from that of type 2 diabetes mellitus, the current research in this field is increasing gradually. The present paper summarizes the characteristics of blood glucose change in PTDM, risk assessment, the safety of hypoglycemic drugs, and the effect of immunosuppressive drugs on blood glucose in PTDM patients, and focuses on the efficacy and safety of new hypoglycemic drugs in PTDM patients, as well as the clinical research evidence such as the type of immunosuppressant used and the formula of administration has been summarized, so as to select a more optimized PTDM treatment options.

Objective To investigate the effects of the Wnt antagonist Dickkopf-1(Dkk-1) on epithelial mesenchymal transdifferentiation in human proximal tubular epithelial cells induced by transforming growth factor-β1 (TGF-β1). Methods Human proximal tubular epithelial cells (HKC) were cultured in vitro and divided into three groups as follows: control group, TGF-β1 group, and TGF-β1+Dkk-1 group. The cells in the control group underwent routine culture with medium containing 10% fetal calf serum. For the TGF-β1 group, TGF-β1 (final concentration 20ng/ml) was added into the routine culture medium. For TGF- β1+Dkk-1 group, TGF-β1 (final concentration 20ng/ml) and Dkk-1(final concentration 100ng/ml) were added at the same time. After cultured for 48h, we performed morphologic observation using an inverted contrast microscope. RT-PCR and Western blotting were adopted to detect the expressions of Wnt4, β-catenin, E-cadherin, and α-SMA mRNA. E-cadherin and α-SMA expressions were detected by cell immunofluorescence. Results Compared with control group, the mRNA expression of Wnt4 and the protein expression of Wnt4 were significantly increased in TGF-β1 and TGF-β1+Dkk-1 groups (P<0.05). There was no significant difference between two groups (P>0.05). There was no obvious difference between each group in mRNA expression of β-catenin (P>0.05). The β-catenin protein exhibited low expression in control group, whereas the expression significantly increased in TGF-β1 group. The expression of β-catenin in TGF-β1+Dkk-1 group was lower than that in TGF-β1 group (P<0.05), but there was no significant difference between TGF-β1+Dkk-1 group and control group (P>0.05). The mRNA and protein expression of E-cadherin were high in control group, but were significantly decreased in TGF-β1 group. Their expressions in the TGF-β1+Dkk-1 group were increased compared with that in TGF-β1 group (P<0.05), however, there was no significant difference compared with control group (P>0.05). The mRNA and protein expression of α-SMA were decreased in control and TGF-β1+Dkk-1 groups, compared with TGF-β1 group (P<0.05). Immune fluorescent staining showed that the expression of E-cadherin and α-SMA were consistent with the results of RT-PCR and Western blotting. Conclusion Wnt antagonist Dickkopf-1(Dkk-1) can inhibit epithelial mesenchymal transdifferentiation induced by TGF-β1.

Objective To assess the improvements of left ventricular systolic function by three‐dimensional speckle tracking imaging ( 3D‐STI) in type 2 diabetes mellitus ( T2DM ) patients after short‐term insulin pump intensive therapy . Methods Thirty‐five T2DM patients complicated with microangiopathy and thirty‐two healthy volunteers were studied ,underwent the dynamic image of the four‐chamber view ,three‐dimensional images of left ventricle were obtained for all the individuals . The left ventricular global longitudinal strain ( LVGLS) ,left ventricular global circumferential strain ( LVGCS) ,left ventricular ejection fraction (LVEF) ,peak basal and apical rotation (LV‐ProtB ,LV‐ProtA) ,peak LV twist ( LV‐tw ) were calculated using TomTec software .After insulin pump intensive therapy for two weeks ,all the indexes were reexamined in T2DM patients . Results Compared with control group ,the LVGLS , LVGCS ,LV‐tw and LV‐ProtA were significantly decreased in diabetes mellitus group before and after treatment ( P < 0 .01 or P < 0 .05) . Compared with diabetes mellitus patients before treatment ,the LVGLS ,LVGCS had significant higher level after treatment( P <0 .05) . The LVGLS ,LVGCS ,LV‐tw and LV‐ProtA were significantly correlated with LVEF in type 2 diabetes mellitus patients and normal controls . Conclusions Insulin pump intensive treatment could improve left ventricular systolic function in type 2 diabetes patients complicated with microangiopathy . 3D‐STI can be sensitive to accurately assess the therapeutic effect and has the important clinical value .

In the last twenty years， the progress in minimally invasive spine surgery has been remarkable. An increasing number of spine surgeons have adopted and performed minimally invasive spine surgery， which is beneficial to patients with spinal diseases. Furthermore， the exploration and development of the surgery continues to flourish. In China minimally invasive spine surgery has been leaping from traditional minimally invasive spine surgery （T-MISS） to digital minimally invasive spine surgery （D-MISS）. This paper reviews the development history of minimally invasive spine surgery in China in the last two decades and looks forward to its development prospect in future.

Retinopathy is a major cause of morbidity in diabetes and remains the primary cause of new blindness. Therefore, it is necessary to find new drug to treat diabetic retinopathy. Type 2 diabetes mellitus (T2DM) rats were induced by injection (ip) with streptozotocin (STZ) 35 mg x kg(-1) and fed with a high-carbohydrate/high-fat diet 2 weeks later. From week 17 to 32, diabetic rats were given different doses of berberine 75, 150, and 300 mg x kg(-1), fenofibrate 100 mg x kg(-1) and rosiglitazone 4 mg x kg(-1), separately. Retinal structure was observed with hematoxylin-eosin staining and peroxisome proliferator-activated receptors (PPARs) alpha/delta/gamma protein expressions were detected by immunohistochemistry. The retina of control rats was thicker than that of other groups, 16 weeks treatment with berberine (150 and 300 mg x kg(-1)) and rosiglitazone 4 mg x kg(-1) thickened the diabetic retina, but no difference existed in retinal structure among groups. Both berberine (150 and 300 mg x kg(-1)) and rosiglitazone 4 mg x kg(-1) significantly decreased PPARy expression in diabetic retina; while berberine (150 and 300 mg x kg(-1)) and fenofibrate 100 mg x kg(-1) obviously increased both PPARalpha and PPARdelta expressions in diabetic retina. Berberine modulates PPARalpha/delta/gamma protein levels in diabetic retina which may contribute to ameliorate retinopathy complication induced by STZ and a high-carbohydrate/high-fat diet. It is expected that berberine might be a more beneficial drug to treat diabetic retinal complication comparing with fenofibrate and rosiglitazone.
Animals ; Berberine ; pharmacology ; Diabetes Mellitus, Experimental ; metabolism ; Diabetes Mellitus, Type 2 ; metabolism ; Diabetic Retinopathy ; metabolism ; Fenofibrate ; pharmacology ; Hypoglycemic Agents ; pharmacology ; Male ; PPAR alpha ; metabolism ; PPAR delta ; metabolism ; PPAR gamma ; metabolism ; Rats ; Rats, Wistar ; Retina ; metabolism ; pathology ; Thiazolidinediones ; pharmacology

The tumor immune microenvironment (TIME) is broadly composed of various immune cells, and its heterogeneity is characterized by both immune cells and stromal cells. During the course of tumor formation and progression and anti-tumor treatment, the composition of the TIME becomes heterogeneous. Such immunological heterogeneity is not only present between populations but also exists on temporal and spatial scales. Owing to the existence of TIME, clinical outcomes can differ when a similar treatment strategy is provided to patients. Therefore, a comprehensive assessment of TIME heterogeneity is essential for developing precise and effective therapies. Facilitated by advanced technologies, it is possible to understand the complexity and diversity of the TIME and its influence on therapy responses. In this review, we discuss the potential reasons for TIME heterogeneity and the current approaches used to explore it. We also summarize clinical intervention strategies based on associated mechanisms or targets to control immunological heterogeneity.

BACKGROUNDTo evaluate the relationship between estrogen receptor (ER) expression and level of serum sexual hormones in male patients with lung cancer.

METHODSThe levels of serum estradiol (E 2), testosterone (T), follicle stimulating hormone (FSH) and lutenising hormone (LH) were measured in 25 patients with lung cancer and 30 healthy men by enzyme immunoassay magnetic solid phase (IEMA), the ER expression was detected in 25 cancer tissues, 25 paracancerous tissues, and 11 benign pulmonary tissues by immunocytochemistry (ICC).

RESULTSThe level of plasma E₂ in male patients with lung cancer was significantly higher than that in normal controls [(22.4±15.7) ng/L [WTBX]vs ( 12.6±4.8) ng/L, P=0.001 9] while the level of T was significantly lower while the level of T was significantly lower [(2.9±1.3) μg/L [WTBX]vs (4.1±1.5) μg/L, P= 0.003 0]. The ratio of E₂/T of male patients with lung cancer was also remarkably higher than that of control . The ratio of E₂/T of male patients with lung cancer was also remarkably higher than that of control [(9.7±10.0) ×10⁻³[WTBX]vs ( 3.4±1.6)×10⁻³, P=0.004 6]. The expression rate of ER in lung cancer tissue samples was 60.0% (15/25), but no ER expression was found in the paracancerous tissues and benign pulmonary tissues. The level of E₂ had positive correlation with the expression of ER in male patients with lung cancer (. The expression rate of ER in lung cancer tissue samples was 60.0% (15/25), but no ER expression was found in the paracancerous tissues and benign pulmonary tissues. The level of E₂ had positive correlation with the expression of ER in male patients with lung cancer (r=0.916 7, P < 0.001).

CONCLUSIONSThere are disorders and imbalances of sexual hormone metabolism in male patients with lung cancer, and these imbalances relate to the expression of ER. The elevation of E₂ level in peripheral blood might be related to the overexpression of ER.