Objective To explore the effects of bilirubin on myeloid differentiation factor 88 (MyD88)and interleukin-1 receptor associated kinase-4(IRAK-4).Methods Seven-day-old Sprague Daw-ley rats (clean grade),male or female,weighing 12.0 to 15.0 g,were randomly assigned to 6 groups.There were normal saline group(Ⅰ),lipopolysaccharide(LPS)control group (LPS,Ⅱ),15 mg /kg bilirubin con-trol (free-LPS)group (Ⅲ),15 mg /kg group (Ⅳa),30 mg /kg group (Ⅳb)and 50 mg /kg group (Ⅳc), and then subsequently divided into 2 h,5 h and 24 h subgroups in each groups.Some of the 200 newborn rats died amid the experiment.Finally a total of 144 were involved in the analysis of results,and 8 rats in each subgroups.Newborn Sprague Dawley rats were administered at various doses of bilirubin (15 mg /kg, 30 mg /kg and 50 mg /kg respectively)intravenously;1 h after injection,the rats were administered LPS intrap-eritoneally at a dose of 1 mg /kg;MyD88 and IRAK-4 were detected by immunohistochemistry at 2 h,5 h and 24 h after the injection of bilirubin.Results (1 )LPS could stimulate the expression of MyD88 and IRAK-4 in spleen cells (qMyD88 2 h =49.89,qMyD88 5 h =139.54,qIRAK-4 2 h =7.93,qIRAK-4 5 h =24.30,qIRAK-4 24 h =6.97 ,P <0.01 ).(2)Low concentration of bilirubin could promote the expression of MyD88 and inhibit the ex-pression of IRAK-4 (qMyD88 2 h =0.76,qMyD88 5 h =5.05,qIRAK-4 2 h =6.43,qIRAK-4 5 h =22.37,qIRAK-4 24 h =1.50, P <0.01 ).(3)LPS stimulation MyD88 affected by low concentration of bilirubin was not obvious (q2 h =1.48,q5 h =1.45,q24 h =0.10,P >0.05).Effects of medium and high concentration of bilirubin on LPS stim-ulation MyD88 were inhibitory(qⅣb 2 h =42.87,qⅣc 2 h =51.38,qⅣb 5 h =103.61 ,qⅣc 5 h =1 15.44,qⅣb 24 h =1.18,qⅣc 24 h =1 1.66,P <0.01 ).(4)Effects of low,medium and high concentration of bilirubin on LPS stimulation IRAK-4 were inhibitory(qⅣa 2 h =9.52,qⅣb 2 h =14.39,qⅣc 2 h =25.55,qⅣa 5 h =38.83,qⅣb 5 h =54.62,qⅣc 5 h =60.51 ,qⅣa 24 h =2.41 ,qⅣb 24 h =1.47,qⅣc 24 h =7.61 ,P <0.01 ).(5)The inhibition of biliru-bin to MyD88 and IRAK-4 was observed at 2 h,strengthened at 5 h,disappeared at 24 h in low-mid concen-trations of bilirubin(P <0.01 )while still visible at 24 h in high concentration of bilirubin.(6)There was neg-atively correlation between the expression level of MyD88,IRAK-4 and bilirubin concentration(rsMyD88 2 h =-0.86, rsMyD88 5 h =-0.92,rsMyD88 24 h =-0.53,rsIRAK-4 2 h =-0.82,rsIRAK-4 5 h =-0.86,rsIRAK-4 24 h =-0.57,P <0.01).(7) Under the effect of bilirubin and LPS,there were positively correlation between the expression levels of MyD88 and IRAK-4 of spleen cells(r2 h =0.77,r5 h =0.9,r24 h =0.67,P <0.01).Conclusion Bilirubin could inhibit the expression of MyD88 and IRAK-4.As the concentration of bilirubin increasing,its inhibition is more obvious and prolonged.The mechanism that bilirubin affects immune function of newborn rat may be related to regulation of expression of MyD88 and IRAK-4 at toll-like receptor 4 signal pathway.

Objective To investigate a feasibility of using dose constraint template (DCT) to increase conformity index (CI) of planning target volume (PTV) and improve intensity modulated radiation therapy (IMRT) planning efficiency for early stage nasopharyngeal carcinoma. Methods Ten patients with pathological diagnosed and treated by IMRT were selected for this study. Target volumes were delineated with Corvus 6.3 of treatment planning system, two dose limiting regions(DLR) around PIN were added by extending from PIN,each DLR was 1 cm thick. We created three plans:Plan0,Planl and Plan2. PianO was without DLR and DCT, Planl without DLR but with DCT, Plan2 with both condition;but to compare dose distribution in PLTV and normal tissue using three plans. Results Three plans could fill equal request of dose distribution in PLTV and normal tissue, and their difference was not statistical significant. CI of Plan2 was increased and planning time was decreased significantly compared with Piano and Planl. Conclusloa Usage of DCT together with DLR can increase CI of PTV and improve IMRT planning efficiency for early stage nasopharyngeal carcinoma, planning time is shortened significantly.

Objective To explore the effects of bilirubin on myeloid differentiation factor phospho-p38 mitogen-activated protein kinase (p-p38MAPK) and apoptosis in splenocytes of neonatal rats.Methods Seven-day-old Sprague Dawley rats (clean grade),male or female,weighting 12.0-15.0 g,were randomly assigned to 6 groups.There were blank control group (Ⅰ),lipopolysaccharide (LPS) control group (Ⅱ),15 mg/kg bilirubin control (free-LPS) group (Ⅲ),15 mg/kg group (Ⅳa),30 mg/kg group (Ⅳb) and 50 mg/kg group (Ⅳc),and then subsequently divided into 2 h,5 h and 24 h subgroups in each groups.Some of the 200 newborn rats died amid the experiment,tinally,a total of 144 cases were involved in the analysis of results,and 8 rats in each subgroups.Newborn Sprague Dawley rats were administered at various doses of bilirubin (15 mg/kg,30 mg/kg and 50 mg/kg,respectively) intravenously; 1 h after injection,the rats were administered LPS intraperitoneally at a dose of 1 mg/kg;p-p38MAPK were detected by immunohistochemistry;Apoptosis in splenocytes was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling methods at 2 h 5 h and 24 h after the injection of bilirubin.Results 1.Expression of p-p38MAPK in each group:bilirubin in low-mid concentrations of range inhibited LPS-induced p38MAPK activation (qⅣa =20.93,10.37,respectively at 2 h,and 5 h,all P ＜ 0.01 ;qⅣ b =79.97,14.79,all P ＜ 0.01).The inhibition strengthened with increasing concentration of bilirubin.The effect was observed at 2 h,strengthened at 5 h,disappeared at 24 h.Bilirubin in the high concentrations of range stimulated the expression of p-p38MAPK (qⅣc =32.55,19.23,27.72,respectively at 2 h,5 h and 24 h,all P ＜0.01),observed at 5 h,reduced at 24 h.2.Effects of bilirubin on apoptosis in splenocytes:LPS could increased the apoptosis index (AI) of splenocytes(q =54.62,P ＜ 0.01);The AI of splenocytes had no significant change in low concentrations of range of bilirubin (q =43.92,P ＞ 0.05).Low-mid concentration of bilirubin with LPS reduced the AI of splenocytes (q Ⅳ a =4.48,P ＜ 0.01 ;q Ⅳ b =2.07,P ＜ 0.05),while high concentration of bilirubin with LPS increased the AI of splenocytes (q =5.08,P ＜ 0.01).Conclusions Bilirubin in low-mid concentrations of range could inhibit the expression of LPS-induced p38MAPK,while bilirubin in high concentrations of range stimulated the expression.As the concentration of bilirubin elevated,its inhibition was prolonged.Bilirubin in high concentrations of range bilirubin could induce apoptosis in splenocytes.The immune dysfunction in neonatal hyperbilirubinemia may have something to do with the regulation of phosphorylation of p38MAPK and activation of apoptotic pathways.

Objective:To investigate the effect of lappaconitine (LA) on neuropathic pain (NPP) mediated by retrograde transport of purinergic P2X3 receptor (P2X3R) in dorsal root ganglion (DRG) neurons of rats with chronic constriction injury (CCI) of the sciatic nerve.Methods:Seventy-two male healthy SD rats were selected to construct the NPP model following CCI of the sciatic nerve by ligating the right sciatic nerve. according to the random number table method. The rats were divided into CCI group, CCI+LA group and normal control group according to the random number table method, with 24 rats in each group. In normal control group, the right sciatic nerve was exposed without ligation. In CCI+LA group, the rats were given 2 g/L LA (ie, 4 mg/kg intravenously for once a day for one day only) after the same treatment as CCI group. Other two groups were injected with the identical amount of normal saline in the same way. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were evaluated before injury and at 2, 6, 12 and 24 hours after injury to evaluate the symptoms of neuralgia caused by nerve injury. The proximal and distal nerve fragments were collected in the three groups at 2, 6, 12 and 24 hours after injury. Western blotting was applied to analyze the expression of P2X3R at 2, 6, 12 and 24 hours after injury and the expression of neurotrophic factor (NGF) and tyrosine kinase receptor A (TrkA) at 24 hours after injury to evaluate the effect of LA on P2X3R, NGF and TrkA.Results:There were insignificant differences in MWT and TWL among all groups before injury (all P>0.05). Compared with normal control group, MWT and TWL were significantly decreased in CCI group and CCI+LA group at 2, 6, 12 and 24 hours after injury (all P<0.05 or 0.01). There were insignificant differences in MWT and TWL between CCI group and CCI+LA group at 2 and 6 hours after injury (all P>0.05), while MWT and TWL were significantly higher in CCI+LA group than those in CCI group at 12 and 24 hours after injury (all P<0.05 or 0.01). In the proximal sciatic nerve segment, Western blotting showed similar levels of P2X3R among all groups at 2, 6, 12 and 24 hours after injury (all P>0.05). In the distal sciatic nerve segment, Western blotting showed higher expression of P2X3R in CCI group than that in normal control group at 2, 6, 12, 24 hours after injury (all P<0.01), higher expression of P2X3R in CCI+LA group than that in normal control group at 2, 6 and 12 hours after injury (all P<0.05), similar expression of P2X3R expression between CCI+LA group and normal control group at 24 hours after injury ( P>0.05), similar expression of P2X3R between CCI group and CCI+LA group at 2 and 6 hours after injury (all P>0.05), and lower expression of P2X3R in CCI+LA group than that in CCI group at 12 and 24 hours after injury ( P<0.05 or 0.01). In the proximal and distal nerve fragments, the expression of NGF was lower in normal control group than that in CCI group and CCI+LA group ( P<0.05 or 0.01), but was similar between CCI group and CCI+LA group at 24 hours after injury ( P>0.05). In the proximal and distal nerve fragments, there were insignificant differences in the expression of TrkA among all groups at 24 hours after injury (all P>0.05). Conclusion:Early LA treatment after injury can alleviate mechanical and thermal hyperalgesia in NPP rats, which may be related to the reduction of P2X3R retrograde transport in DRG neuron axonal.

Objective:To explore the effect of perioperative whole-course closed-loop temperature management system for prevention of hypothermia in elderly patients with femoral neck fracture.Methods:A retrospective case-control study was conducted to analyze the clinical data of 120 elderly patients with femoral neck fracture admitted to Chengdu First People's Hospital from January 2020 to December 2020. There were 48 males and 72 females, aged 60-79 years［（68.3±5.0）years］. All patients underwent total hip arthroplasty. Heat warming with the whole-course closed-loop temperature management system was applied in 40 patients（closed-loop group）, with the medical heating mattress in 40 patients（heat preservation group）, and with the quilt in 40 patients（control group）. The core body temperature of the three groups was recorded 8 minutes after wearing the temperature sensor（T0）, immediately after induction of anesthesia（T1）, 30 minutes after induction of anesthesia（T2）, 60 minutes after induction of anesthesia（T3）, at the end of surgery（T4）, and 20 minutes after entering the postanesthesia care unit（PACU）（T5）. The thrombin time（TT）, prothrombin time（PT）and activated partial thromboplastin time（APTT）were compared among groups before operation and at T4. The incidence of intraoperative hypothermia, incidence of shivering during PACU, incidence of surgical site infection, extubation time（from the day of drug withdrawal to the time of tracheal tube removal）, length of hospital stay（from the day of operation to the time of discharge）and adverse reactions related to the devices were compared among groups.Results:There was no statistically significant difference in core body temperature among three groups at T0（ P>0.05）. The core body temperature in closed-loop group［（36.61±0.28）℃］was higher than that in heat preservation group［（36.45±0.28）℃］and control group［（36.44±0.27）℃］at T1（ P<0.05）, but no statistically significant difference was found in core body temperature between heat preservation group and control group（ P>0.05）. The core body temperature in closed-loop group［（36.46±0.28）℃,（36.40±0.30）℃,（36.45±0.37）℃,（36.50±0.27）℃］was higher than that in heat preservation group［（36.32±0.31）℃,（36.24±0.26）℃,（36.28±0.30）℃,（36.24±0.31）℃］and control group［（36.12±0.30）℃,（35.98±0.28）℃,（35.73±0.31）℃,（35.81±0.32）℃］at T2-T5（ P<0.05）, and a higher temperature was found in heat preservation group than control group（ P<0.05）. The core body temperature in closed-loop group was increased at T1 compared to that at T0（ P<0.05）, while there was no statistical difference at T0 and T1 in heat preservation group and control group（ P>0.05）. The core body temperature in closed-loop group showed no significant difference at T2-T5 and T0（ P>0.05）, while the core temperature in heat preservation group and control group was decreased at T2-T5 compared to that at T0（ P<0.05）. The core body temperature in closed-loop group was within the set target temperature range. There was no statistically significant difference in TT, PT and APTT among the three groups before operation（ P>0.05）. At T4, the levels of TT, PT and APTT in closed-loop group［（18.9±1.7）seconds,（11.9±0.7）seconds,（35.5±3.3）seconds］and heat preservation group［（18.8±1.7）seconds,（11.6±0.8）seconds,（32.8±2.7）seconds］were shorter than those in control group［（20.9±1.3）seconds,（13.0±0.8）seconds,（35.7±3.4）seconds］（ P<0.05）. At T4, the levels of APTT in closed-loop group and heat preservation group were longer than those before operation（ P<0.05）. At T4, the levels of TT, PT and APTT in control group were longer than those before operation（ P<0.05）. There was no significant difference in the incidence of intraoperative hypothermia or shivering during PACU between closed-loop group［18%（7/40）, 3%（1/40）］and heat preservation group［33%（13/40）, 8%（3/40）］（ P>0.05）, which were lower than those in control group［75%（30/40）, 33%（13/40）］（ P<0.05）. There was no significant difference in the extubation time between closed-loop group［（12.5±3.6）minutes］and heat preservation group［（13.2±3.9）minutes］（ P>0.05）, which was shorter than that in control group［（16.6±4.0）minutes］（ P<0.05）. The incidence of surgical site infection and length of hospital stay were statistically insignificant among the three groups（ P>0.05）. No adverse reactions such as allergic reaction or pressure ulcers occurred in the three groups. Conclusion:For the elderly patients with femoral neck fracture, the perioperative whole-course closed-loop temperature management system can effectively maintain the core body temperature, improve coagulation function, prevent hypothermia, reduce shivering and shorten the extubation time, without increasing the risk of other adverse events, so the system can be safely used in clinical practice.

Objective:To assess the feasibility of delayed-enhancement MRI in contouring the lumpectomy cavity (LC) for patients with invisible seroma or a low cavity visualization score (CVS≤2) in the excision cavity after breast-conserving surgery (BCS).Methods:Twenty-six patients with stage T 1-2N 0M 0 who underwent prone radiotherapy after BCS were recruited. The LC delineated on CT simulation images was denoted as LC CT. The LCs delineated on T 2WI, as well as on different delayed phases (2-, 5-and 10-minute) of delayed-enhancement T 1WI were defined as LC T2, LC 2T1, LC 5T1 and LC 10T1, respectively. Subsequently, the volumes and locations of the LCs were compared between CT simulation images and different sequences of MR simulation images using deformable image registration. Results:The volumes of LC T2, LC 2T1, LC 5T1 and LC 10T1 were all larger than that of LC CT. A statistical significance was found between the volume of LC CT and those of LC 2T1 or LC 5T1, respectively (both P<0.05). The conformal index (CI), degree of inclusion (DI), dice similarity coefficient (DSC) and the distance between the center of mass of the targets (COM) of LC CT-LC 10T1 were better than those of LC CT-LC T2, LC CT-LC 2T1 and LC CT-LC 5T1, however, there was no statistical difference among them (all P>0.05). Conclusions:It is feasible to delineate the LC based on prone delayed-enhancement MR simulation images in patients with low CVS after BCS. Meanwhile, the LCs derived from prone delayed-enhancement T 1WI of 10-minute are the most similar with those derived from prone CT simulation scans using titanium clips, regardless of the volumes and locations of LCs.

In order to improve the teaching quality of engineering courses, we introduced a multi-dimensional teaching method into the teaching reform of biology majors in colleges based on the portfolio assessment in the curriculum of Cell Engineering. We reformed the knowledge system, teaching form and implementation scheme of this course. By combining the reform of online teaching, interactive teaching, case teaching and other teaching modes, the students mastered the relevant professional knowledge and the scientific and technological frontier of Cell Engineering. Moreover, their learning interest and enthusiasm, ability of analyzing and solving professional problems related to Cell Engineering also improved. The implementation of teaching reform of this course provides a reference for other similar professional courses in colleges.
Humans ; Curriculum ; Students ; Learning ; Cell Engineering