Objective:To investigate the expression of transforming growth factor ?1(TGF-?1) in dog mandibular distraction osteogenensis (DO). Methods: Mandibular DO model was established in 12 dogs and nonunion model in another 12 dogs, 4 dogs were used as the no-treatment control. Tissue samples were obtained 6 d,2 and 8 weeks after operation respectively.Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were used to determine the expressions of TGF-?1 in the samples.Results: TGF-?1 (ng/g) in control group was 1394.3?20.1,6 d after operation that in DO and nonunion groups was 1928.5?33.5(vs control,P

Objective To investigate whether increasing the concentration of serum potassium facilitates the cardioversion to sinus rhythm during cardiopulmonary resuscitation (CPR) in a rat ventricular fibrillation (VF) model. Methods Sprague-Dawley (SD) rats with sustained VF by electrical induction were randomized into two groups by random number table. Five minutes after onset of electrical induction, 2.5% potassium chloride solution at a dose of 0.8 mL/kg (KCl group, n = 9) or equivalent normal saline (NS group, n = 9) was given respectively via femoral vein followed by traditional CPR. The changes of electrocardiogram (ECG) and the effect of defibrillation were compared between the two groups. Results During the CPR, the number of animals with spontaneous cardioversion (2 vs. 1, P = 1.000) and successful defibrillation (7 vs. 3, P = 0.026) were both increasing in KCl group compare with those in the NS group, which required fewer defibrillation (1.60±0.79 vs. 2.70±0.58, P = 0.064), lower calculative defibrillation energy (J: 4.00±3.00 vs. 8.30±2.89, P = 0.068), more animals restore spontaneous circulation (ROSC, 9 vs. 4, P = 0.029) and shorter ROSC time (s: 265.10±134.58 vs. 421.30±162.06, P = 0.096). At the beginning of CPR, animals in two groups all presented the fine amplitude (amplitude < 0.5 mV). At CPR 3 minutes the KCl group presented significantly larger amplitude compared with NS group (mV: 0.92±0.16 vs. 0.67±0.23, P = 0.030); The amplitude decreased in the animals which did not attain cardioversion to sinus rhythm over time. The animal number of fine amplitude at CPR 7 minutes were 0 and 5, respectively, in the KCl group and the NS group. Conclusion Increasing serum potassium concentration facilitates the VF amplitude enlargement, promotes the spontaneous conversion, increases the successful rate of defibrillation and reduces the energy for defibrillation in a rat VF model.

Objective To study the effect of potassium chloride (KCl) before CPR on successful resuscitation of rats with ventricular fibrillation (VF).Methods Sprague-Dawley (SD) rats with VF induced by alternating electricity current were randomly (ramdam runmber) divided into KCl group and normal saline (NS) group.Rats of two groups were prepared with 0.8 mL/kg of 2.5％ KCl in KCI group and equivalent volume of NS in NS group instead before CPR.The resuscitation was considered to be failure if ROSC was absent for 10 min.The comparisons of time required for ROSC,the average attempt of defibrillation,the average joule used for defibrillation,ROSC rate and 72 h survival rate were carried out between the two groups.Results The length of time required for ROSC in the KCl group (n =10) was shorter than that in NS group (n=10) [(283.89±152.44) svs.(404.38±164.27) s] (t=1.369,P =0.196).The average attempt of defibrillation in KCl group were fewer compared to the NS group [(1.50 ± 0.75) times vs.(2.66 ± 0.57) times,(t =2.701,P =0.022)],the average joule used for defibrillation in KCl group were less compared to NS group [(3.75 ± 2.86) J vs.(8.33 ± 2.88) J,(t =2.78,P =0.019)].The ROSC rate in the KCl group was higher than that in NS group (P =0.011).The 72 h survival rate in KCl group was higher than that in NS group (P =0.001).Conclusions Increasing plasma potassium level before CPR could increase the ROSC rate and survival rate in rats with VF.

OBJECTIVETo observe the effects of ryanodine on rapamycin treated endothelial outgrowth cells (EOCs).

METHODSThe mononuclear cells were harvested from umbilical cord blood by Ficoll density gradient centrifugation, then induced into EOCs and expanded in vitro. The endothelial characteristics of EOCs were identified by immunostaining and fluorescent staining. The EOCs were pretreated with or without ryanodine (10 µmol/L) for 1 h, and then treated with or without rapamycin (10 nmol/L) for 24 h. Proliferation was evaluated by CCK8 and migration was measured by Transwell. The protein expression of EOCs was evaluated by immunobloting technique with total eNOS antibody and phospho-eNOS (Thr495) antibody.

RESULTSCompared with control group, the proliferation and migration capacities of EOCs were significantly reduced while the phosphorylation of eNOS (Thr495) protein was significantly upregulated in rapamycin group (P < 0.05), expression of total eNOS was not affected by rapamycin (P > 0.05). Compared with rapamycin group, the proliferation and migration capacities of EOCs were significantly increased and the phosphorylation of eNOS (Thr495) protein was significantly downregulated in ryanodine + rapamycin group (P < 0.05). The proliferation and migration capacities, the phosphorylation of eNOS (Thr495) protein and the expression of total eNOS were not affected by ryanodine alone (P > 0.05).

CONCLUSIONSRapamycin reduced proliferation and migration capacities while upregulated the phosphorylation of eNOS (Thr495) protein of EOCs and these effects could be partly reversed by cotreatment with ryanodine.

Cells, Cultured ; Down-Regulation ; Drug Synergism ; Endothelial Cells ; cytology ; drug effects ; metabolism ; Humans ; Nitric Oxide Synthase Type III ; metabolism ; Phosphorylation ; Ryanodine ; pharmacology ; Sirolimus ; pharmacology

Objective:To explore the clinical therapeutic effect and follow-up prognosis of preterm infants with neonatal respiratory distress syndrome (NRDS) managed by less invasive surfactant administration (LISA) and traditional intubation-surfactant-extubation (INSURE) of pulmonary surfactant (PS).Methods:Data during hospitalization and follow-up period of 187 NRDS preterm infants (gestational age 24 weeks to 31 + 6 weeks, and birth weight <1 500 g) admitted to the Department of Neonatology, the Women and Children′s Hospital of Chongqing Medical University from March 2019 to February 2021 were retrospectively analyzed.NRDS preterm infants who were injected with PS by LISA were included in the LISA group (144 cases), and those who were injected with PS by INSURE were included in the INSURE group (43 cases). The propensity score matching method was used to correct the confounding factors between groups, and the covariate equilibrium samples between groups were obtained (39 cases in each group). Clinical treatment effect and prognosis of physical development, hearing and vision development, nervous system development, respiratory system diseases and other conditions of the two groups of children were compared using the t test, Chi- square test and other statistical analysis methods as appropriate. Results:(1)Compared with that of the INSURE group, the incidence of BPD [12 cases (33.3%) vs.23 cases (63.9%), χ2=6.727, P=0.009] and ROP [13 cases (36.1%) vs.26 cases (72.2%), χ2=9.455, P=0.002] in the LISA group were significantly lower.The incidence of mild BPD [8 cases (22.2%) vs.16 cases (44.4%), χ2=4.000, P=0.046] and stage Ⅰ-Ⅱ ROP [11 cases (30.6%) vs.22 cases (61.1%), χ2=6.769, P=0.009] in the LISA group was significantly lower than that of the INSURE group.There was no significant difference in the incidence of moderate and severe BPD and stageⅢ ROP and above between groups (all P>0.05). (2)There were no statistical differences in the repeated use of PS, mechanical ventilation rate within 72 h, pneumothorax/pulmonary hemorrhage, grade Ⅲ-Ⅳ periventricula-rintraventricular hemorrhage, stage Ⅱ-Ⅲ neonatal necrotizing enterocolitis, sepsis, abnormal amplitude integrated electroencephalogram, mortality in 36 weeks of corrected gestational age, total oxygen inhalation duration and hospitalization duration between the two groups (all P>0.05). (3)Follow-up within 1 year of corrected age after discharge.There were no significant differences in extrauterine body mass, body length and head circumference development, visual development, hearing development, Neonatal Behavioral Neurological Assessment score at corrected gestational age of 40 weeks, Bayley Scales of Infants Development score at corrected gestational age of 6 months and age of 1 year, pneumonia and re-hospitalization due to respiratory diseases between groups (all P>0.05). Conclusions:PS administration with LISA technology can reduce the incidence of mild BPD and stage Ⅰ-Ⅱ ROP in premature infants with NRDS who had the gestational age of 24-31 + 6 weeks and birth weight<1 500 g, without increasing the risk of other complications.The long-term prognosis of them treated with PS administration with LISA and INSURE is similar.

OBJECTIVETo observe the effect of curcumin on nitric oxide (NO) in plasma of atherosclerotic rabbits, activity of constitutive nitric oxide synthase (cNOS) and asymmetric dimethylarginine (ADMA), and discuss curcumin's effect against AS and its correlation with ADMA.

METHODThirty-eight male Japanese white rabbits were randomly divided into four groups: the control group (eight rabbits fed with standard diets), the model group (ten rabbits fed with high-fat diets), the low dose curcumin group (ten rabbits fed with high-fat diets and 100 mg . kg-1 d -1 ) and the high dose curcumin group (ten rabbits fed with high-fat diets and 200 mg kg-1 d-1 curcumin). At the end of the 12th week, their plasmas were tested for TC, LDL-C, NO, endothelin (ET) , ADMA and activity of aortic cNOS. Aortic tissues were collected for histological examinations.

RESULTThe three groups fed with high-fat diets showed higher plasma ADMA and ET than the control group (P <0. 01) , but with decrease in plasma NO concentration and arterial cNOS activity (P <0. 01). Compared with the model group (P <0. 05) , the curcumin groups showed lower plasma ADMA and ET (P <0. 05), but higher plasma NO concentration and arterial cNOS activity than the model group (P <0. 01). There was no significant difference between the two curcumin groups.

CONCLUSIONCurcumin may play an important protective role in AS process by reducing plasma ADMA level. [Key words] atherosclerosis; asymmetric dimethylarginine; crucumin; nitric oxide; nitric oxide synthase

Animals ; Arginine ; analogs & derivatives ; blood ; Atherosclerosis ; blood ; drug therapy ; metabolism ; Curcumin ; therapeutic use ; Endothelium, Vascular ; drug effects ; Male ; Nitric Oxide Synthase ; metabolism ; Rabbits

Sulfur-fumigation processing technology is an ancient maintenance method, which plays a certain role in storage and preservation for Chinese herbal medicine. But in recent years, with the further explanation of sulfur-fumigation processing mechanism and more attention to the safety of drugs, such traditional maintenance method of Chinese herbal medicine is now being questioned by more and more people. The authors think we should have selective inheritance rather than abslute discard to this ancient processing technology after reviewing the literatures published in recent 20 years, and some suggestions are also put forward, which can supply some references for related drug supervision departments.
Drugs, Chinese Herbal ; Fumigation ; methods ; Humans ; Medicine, Chinese Traditional ; methods ; Sulfur ; therapeutic use

Aim To investigate the targeting mechanism of miR-23b on PINKl/Parkin pathway in transdifferentiation of NRK-52E cellsinduced by TGF-β1, and to elucidate the intervention mechanism of Qingshen granules drug-containing serum on NRK-52E cell transdifferentiation. Methods Ultra-high performance liquid chromatography ( UPLC ) fingerprinting method was used to analyze Qingshen granules. The NRK-52E transdifferentiation model induced by TGF-β1 was constructed. The NRK-52E cells were divided into simulated no-load control group, miR-23b-5p simulated group, inhibitor no-load control group, and miR-23b-5p inhibitor group, after transfection with siRNA, and the effect of miR-23b-5p on PINK1 expression was ob-served. The NRK-52E cells were then divided into normal group, TGF-(31 group, Qingshen granule group, miR-23 b-mimic group, miR-23 b-mimic group, and miR-23b-mimic + Qingshen granule group. Western blot was used to detect the expression of Pinkl, Parkin, LC3 n, Beclin-1, P62 and a-SMA proteins, and RT- PCR was used to detect the expression of miR-23 b-5p, Pinkl, Parkin, Beclin-1 and a-SMA mRNA in NRK- 52E cells. Dual-Luciferase Reporter gene experiment was used to detect the targeting relationship between miR-23b-5p and PINKL Results UPLC fingerprinting method found 11 active components in Qingshen granules. After overexpression of miR-23b-5p, the expression of PINkl mRNA significantly increased (P < 0. 05). And after silencing of miR-23 b-5 p expression, the expression of PINkl mRNA also significantly decreased (P < 0. 05 ). Dual-Luciferase Reporter Assay showed that Rno-miR-23b-5p could significantly down- regulate the luciferase activity of Rno-PINKl-WT (P < 0. 05 ), but could not down-regulate the luciferase activity of mutant Rno-PINKl -mut ( P > 0. 05 ). The experimental results showed that the expressions of miR- 23b-5p, Pinkl, Parkin, Beclin-1, LC3 II and LC3 II/ I ratio in TGF-β1 group were significantly lower than those in normal group, but the expressions of P62 and a-SMA were significantly higher than those in normal group ( P <0.05). The expressions of miR-23 b-5 p, Pinkl, Parkin, Beclin-1, LC3 II and LC3 11/ I ratio in Qingshen granule group and miR-23 b-mimic group were significantly higher than those in TGF-β1 group, and the expressions of P62 and a-SMA were significantly lower than those in TGF-β1 group (P < 0. 05 ). The performance of miR-23 b-mimic + Qingshen granule group was better than that of miR-23 b-mimic group (P < 0. 05 ). Conclusions Qingshen granules can up- regulate the expression of miR-23b-5p in NRK-52E cellsand inhibit the transdifferentiation process of NRK- 52E cells by enhancing the mitochondrial autophagy activity mediated by PINKl/Parkin pathway.

The aim of this study was to investigate the renal toxicity of rhubarb and its mechanism. The SD rats were randomly divided into three groups: normal group and two rhubarb extract groups (16, 2 g·kg⁻¹). According to the dose conversion method between human and animal, rhubarb 16 g·kg⁻¹ and 2 g·kg⁻¹ were equivalent to 10 times and 1.25 times of human clinical dose respectively. Rhubarb extract was administered by a gastric gavage to rats once daily for 30 days. Serum urea nitrogen （BUN）, creatinine （CRE） and urine KIM-1, NGAL and renal morphology were analyzed. The expressions of OAT1, OAT3 and clusterin mRNA in kidney were measured. The results showed that the low dose of rhubarb had no obvious renal toxicity. The high dose group showed mild and moderate renal injury and a down-regulation of clusterin mRNA expression in the kidney tissue. The renal toxicity in male animals was heavier than that in female animals. There was no significant change in blood BUN and CRE in the high dose group. But urine NGAL level of the high dose group increased by 51.53% compared with normal group, of which male animals increased more significantly (<0.05, compared with the normal group). The expressions of renal OAT1 and OAT3 mRNA in the low dose group were obviously higher than that in the normal group. The results indicated that the high dose of rhubarb could cause the renal toxicity. The dosage should be controlled reasonably in the clinical use. OAT1 and OAT3 mRNA related to anionic transport in kidney tissue played a compensatory protective role in rhubarb-induced renal injury. But the compensatory effect is relatively weak at the high dose level. In addition, routine renal function indicators BUN and CRE had limitation for monitoring the kidney toxicity of rhubarb. It is suggested that urine NGAL detection might be helpful for monitoring the renal toxicity of rhubarb.