Chronic refractory pain is an excruciating pain caused by various reasons, which is easily recurrent and barely responded to multiple drugs. It affects more than 10% of the global population and thus causes a huge burden on the society and the economy. With the development of neuroscience, neuromodulation technologies have been well concerned, which guide a novel direction in the treatment of chronic refractory pain. This review summarizes the research progresses on repetitive transcranial magnetic stimulation, transcranial direct current stimulation, transcranial focused ultrasound stimulation, optogenetics and other non-invasive neuromodulations in the treatment of chronic refractory pain.

Objective To investigate the effects of ulinastatin on renal expression of endothelin￣1 and nitric oxide (NO) in rats with toxic acute kidney injury(AKI). Methods Twenty￣four male SD rats were randomly divided into the normal control group,model control group and treatment groups, with 8 rats in each group. Except normal control group, rats were subcutaneously injected with gentamicin (300 mg.kg-1 .d-1 ) for 3 days to establish a model of toxic AKI.Rats in the treatment group were intraperitoneally injected with a 7￣day course of ulinastatin (30 000 U.kg-1 .d-1 ) from the fourth day.While the other two groups were injected with 0.9% sodium chloride injection (3 mL.kg-1 .d-1 ). The serum level of creatinine and cystatin￣C,urinary concentration of kidney injury molecule￣1(Kim￣1) and neutrophil gelatinase￣associated lipocalin (NGAL), level of endothelin￣1 and NO,expression of endothelin￣1 mRNA,endothelial nitric oxide synthase (eNOS),induced nitric oxide synthase (iNOS),eNOS mRNA and iNOS mRNA in homogenate of renal tissues in each group were detected on the eleventh day. Results Compared with the normal control group,serum level of creatinine and Cystatin￣C,urinary concentration of Kim￣1 and NGAL,level of endothelin￣1 and NO,expression of endothelin￣1 mRNA,iNOS and iNOS mRNA in homogenate of renal tissues were higher in model control group (P<0.01, respectively), while which were lower in treatment group than those in model control group ( P < 0. 01, respectively). And no statistical significant difference of eNOS and eNOS mRNA expression in homogenate of renal tissues existed among the three groups. Conclusion Ulinastatin possesses curative role against rat with toxic AKI via down￣regulating renal expression of endothelin￣1,NO and iNOS.

Based on the analysis of the existing problems in outpatient nursing education, this study builds an organizational framework of outpatient nursing education based on the competency model, and proposes measures such as the construction of outpatient nursing education teachers, the optimization of the education mode and training facilities and so on. The results show that there are statistical differences in the teaching ability, teaching quality, student feedback and total scores before and after constructing the organizational framework of outpatient nursing education based on the competency model, indicating that the framework guarantees the basis of the dynamic selection mechanism of nursing education teachers, ensures the quality of outpatient nursing education, and can provide a reference for the development of outpatient nursing specialty and talent training.

Objective:To compare the differences of brain activation in patients with neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) under contact heat stimulation (CHS), and to explore the characteristics of pain-related brain networks in NMOSD and MS patients.Methods:Fourteen NMOSD patients (NMOSD group) and 12 MS patients (MS group) admitted to Affiliated Hospital of North Sichuan Medical College from September 2022 to December 2022 who met the diagnostic criteria were collected. Twelve healthy individuals (HC group) matched with gender and age were recruited during the same period. Visual Analogue Scale (VAS) score was used to evaluate the pain of the subjects, CHS painful stimuli were given, and task-state functional magnetic resonance imaging (fMRI) scans were performed at the same time, and the differences in brain activation among the 3 groups were analyzed and compared.Results:(1) Compared with the HC group, the NMOSD group had a stronger activation degree than the HC group in the brain regions including the cortex around the left distance fissure, bilateral medial superior frontal gyrus; the activation degree of the NMOSD group was weaker than that of the HC group in the brain areas including the left medial and paracingulate gyrus, right superior parietal gyrus, left postcentral gyrus, and right supplementary motor area (all P<0.05). (2) Compared with the HC group, the brain regions whose activation degree was weaker in the MS group included the left caudate nucleus, left medial and paracingulate gyrus, left paracentral lobule, right superior parietal gyrus, left postcentral gyrus, left precuneus, right supplementary motor area, right superior temporal gyrus and right thalamus, and there was no brain area in the MS group whose activation degree was stronger than that of the HC group (all P<0.05). (3) Compared with the MS group, the brain regions with stronger activation degree in the NMOSD group included the left perifissure cortex and right thalamus, but no brain regions with weaker activation degree were found in the NMOSD group (all P<0.05). (4) There was a correlation between somatic pain VAS scores and activation of the medial superior frontal gyrus in the NMOSD group ( r=0.66, P<0.05). Conclusions:The results of CHS-fMRI in the NMOSD group, MS group and HC group showed that multiple brain regions were activated, indicating that multiple brain regions were involved in the generation and processing of pain, and there was a pain-related brain network. Pain-related brain networks were altered in NMOSD patients and MS patients, and there were differences in pain-related brain networks between the two diseases.

Objective:To observe the changes in brain functional magnetic resonance imaging (fMRI) in migraine patients under olfactory stimuli and analyze the characteristics of olfactory-related brain networks.Methods:Twenty-seven migraine patients (migraine group) enrolled in the Department of Neurology, Affiliated Hospital of North Sichuan Medical College from January 2021 to January 2022 were included, and 20 healthy adults were recruited as control group during the same period. All subjects underwent synchronous fMRI scanning under olfactory task stimulation, and magnetic resonance imaging data processing was performed using SPM12 and Matlab2019b softwares, and statistical analysis was performed with SPSS 23.0 software.Results:The activated brain regions in the control group included the left cerebellum, left inferior temporal gyrus, left fusiform gyrus, right middle frontal gyrus, right anterior central gyrus, insula, right central sulcus, superior marginal gyrus, right lenticular putamen, middle cingulate gyrus, paracentral lobule, and superior parietal gyrus ( P<0.05). The activated brain regions in the migraine group included the left cerebellum, right fusiform gyrus, right inferior temporal gyrus, right anterior central gyrus, and right posterior central gyrus ( P<0.05). Compared with the control group, the activation intensity of the migraine group was weaker in the right insula, right middle frontal gyrus orbit, left inferior frontal gyrus orbit, right dorsolateral superior frontal gyrus, right superior temporal gyrus, right superior occipital gyrus, medial and paracingulate gyrus, and right superior parietal gyrus ( P<0.05). Conclusion:Migraine patients have multiple brain regions involved in olfactory processing and have specific olfactory-related brain networks.

Fatty acid binding protein 7 (FABP7) is a small molecular cytoplasmic protein. As a cellular fatty acid chaperone, it binds specifically to ligands such as DHA and is widely involved in physiological and pathological processes. During brain development, FABP7 is heavily expressed in neural stem cells, astrocytes and oligodendrocyte precursor cells, which plays a key role in regulating the pathology process of the central nervous system diseases. This article reviews the structure, expression and function of FABP7 and its related research progress in central nervous system disease.

Objective To observe the adverse reactions of different anesthesia methods used in bronchoscopic diagnosis and treatment,and provide ideas for clinical selection of the best anesthesia methods.Methods 150 patients from June 2022 to June 2023 for bronchoscope were randomly divided into group W(atomization with lidocaine combined with intravenous sedation),group Q(laryngeal mask general anesthesia)and group H(lidocaine sprayed by laryngeal anesthetic tube combined with general anesthesia),with 50 cases in each group.Heart rate(HR),mean arterial pressure(MAP)and percutaneous arterial oxygen saturation(SpO2)values were recorded at different time points,adverse reactions during recovery,recovery time and dosage of anesthetic drugs were recorded.Results At T1 and T2,SpO2 in group W(89.4±0.7)%and(91.8±0.3)%were lower than that(99.6±0.8)%in T0,and lower than those(98.6±1.3)%and(98.5±1.6)%in group Q and(99.7±0.3)%and(98.4±1.6)%in group H,the difference were statistically significant(P<0.05).At T1 and T2,the MAP of group W were(108.5±7.8)and(105.6±7.3)mmHg,which were significantly higher than those of T0(87.5±8.6)mmHg,and higher than those of group Q(92.6±8.5)and(85.8±11.3)mmHg,respectively,higher than those(85.7±9.2)and(85.2±10.8)mmHg in group H,the differences were statistically significant(P<0.05).The MAP of group Q at T1 and T3 was(92.6±8.5)and(91.4±8.6)mmHg,respectively,higher than that of T0(87.8±7.5)mmHg,and higher than those of group H(85.7±9.2)and(86.5±7.2)mmHg,with statistical significance(P<0.05).At T1 and T2,the HR of group W was(92.7±9.6)and(91.3±9.2)times/min,higher than that of T0(72.3±8.4)times/min,and higher than those of group Q(75.3±11.6)and(78.5±12.8)times/min,respectively,and higher than those of group H(76.6±10.7)and(77.2±8.5)times/min,and the differences were statistically significant(P<0.05).The hypoxemia,arrhythmia and cough rates in group Q were higher than those in group W and group H,and the differences were statistically significant(P<0.05).The recovery time of group H was(11.5±7.2)min,which was significantly lower than that of group W(16.8±8.5)min and group Q(17.6±6.4)min,and the differences were statistically significant(P<0.05).The dosage of propofol in group H was(314.3±12.7)mg and remifentanil was(211.6±12.5)μg,both lower than those in group W(390.5±12.4)mg and(268.4±13.6)μg,and lower than those in group Q(387.6±15.2)mg and(372.5±15.3)μg.The differences were statistically significant(P<0.05).The dosage of micuronium chloride was(23.7±3.8)mg in group H,lower than(32.5±4.3)mg in group Q,and the difference was statistically significant(P<0.05).Conclusion Lidocaine sprayed by laryngeal anesthetic tube combined with general anesthesia is the best anesthesia method for bronchoscopic diagnosis and treatment,which is beneficial to respiratory management and less adverse reactions in perioperative period.

Atherosclerotic cardiovascular disease(ASCVD)frequently results in sudden death and poses a serious threat to public health worldwide.The drugs approved for the prevention and treatment of ASCVD are usually used in combination but are inefficient owing to their side effects and single therapeutic targets.Therefore,the use of natural products in developing drugs for the prevention and treatment of ASCVD has received great scholarly attention.Andrographolide(AG)is a diterpenoid lactone compound extracted from Andrographis paniculata.In addition to its use in conditions such as sore throat,AG can be used to prevent and treat ASCVD.It is different from drugs that are commonly used in the prevention and treatment of ASCVD and can not only treat obesity,diabetes,hyperlipidaemia and ASCVD but also inhibit the pathological process of atherosclerosis(AS)including lipid accumulation,inflammation,oxidative stress and cellular abnormalities by regulating various targets and pathways.However,the pharmaco-logical mechanisms of AG underlying the prevention and treatment of ASCVD have not been corrobo-rated,which may hinder its clinical development and application.Therefore,this review summarizes the physiological and pathological mechanisms underlying the development of ASCVD and the in vivo and in vitro pharmacological effects of AG on the relative risk factors of AS and ASCVD.The findings support the use of the old pharmacological compound('old bottle')as a novel drug('novel wine')for the pre-vention and treatment of ASCVD.Additionally,this review summarizes studies on the availability as well as pharmaceutical and pharmacokinetic properties of AG,aiming to provide more information regarding the clinical application and further research and development of AG.

Objective To observe the efficacy and safety of repetitive transcranial magnetic stimulation(rTMS)on refractory tinnitus and the differences of resting-state functional magnetic resonance imaging(rs-fMRI)imaging between before and after treatment,and to explore the possible central mechanism of rTMS regulation of tinnitus.Methods Thirty-seven patients with refractory tinnitus admitted in Affiliated Hospital of North Sichuan Medical College from September 2022 to February 2023 were selected and were divided into experimental group(n=20)and control group(n=1 7).The experimental group was given true rTMS treatment,and the control group was given sham stimulation with the same parameters.Tinnitus handicap inventory(THI)score,tinnitus loudness visual analogue scale(VAS)score and rs-fMRI scan were performed before and after treatment.Regional homogeneity(ReHo)was calculated after scanning,and the different brain regions were selected as the area of interest(ROI)and the whole brain functional connection(FC)was performed.Results There were no significant differences in age,gender,education level,tinnitus side,course of disease,hearing level,self-rating depression scale,self-rating anxiety scale the experimental group and control group.There were no significant differences in THI and VAS scores between the two groups before treatment;the THI and VAS scores in the experimental group decreased after 2 weeks of rTMS treatment(P＜0.001),while there was no significant difference in the two scores in the control group before and after treatment.Only 3 patients in the experimental group experienced left facial muscle tremor or transient mild scalp pain during treatment,without other serious side effects.The ReHo of the left cerebellar area 9 increased in the experimental group after rTMS(P＜0.005);the ReHo values in the right inferior temporal gyrus,left posterior central gyrus and left anterior central gyrus increased in the control group after intervention(P＜0.005).The FCs between the right inferior temporal gyrus and the left orbital inferior frontal gyrus,the left anterior cingulate gyrus increased in the experimental group(P＜0.005),and FC between the right inferior temporal gyrus and the left superior marginal gyrus decreased(P＜0.005).The FCs between the right cuneus and the left fusiform gyrus,right superior occipital gyrus decreased in the experimental group after rTMS(P＜0.005).The FC between the right cuneus and the left fusiform gyrus increased in the control group after intervention(P＜0.005),while other FCs remained unchanged.Conclusions rTMS has a certain therapeutic effect on refractory tinnitus with higher safety;regulation of auditory brain network and related non-auditory brain network may be one of the central mechanisms of rTMS treating refractory tinnitus.

OBJECTIVE To explore the application effects of the multi-disciplinary treatment （MDT）-based continuous pharmaceutical care system in patients undergoing anti-infection treatment. METHODS This research team innovatively developed an MDT continuous pharmaceutical care system， which was applied to cases of anti-infection treatment following MDT due to infection， aiming to innovate the continuous medication supervision model. A retrospective analysis method was used to collect data from 150 patients in the intensive care unit who underwent conventional anti-infection MDT consultations from January to October 2021 in Banan Hospital Affiliated to Chongqing Medical University， serving as the control group， and 130 patients in the intensive care unit who were under the MDT continuous pharmaceutical care system from January to October 2022 were selected as the intervention group. The general information of the patients， the information continuous tracking management， the outcomes of anti- infection treatment， adverse drug reactions， antibacterial drug management indicators， and the degree of satisfaction of relevant medical staff with the clinical pharmacists’ pharmaceutical services were compared between the two groups. RESULTS Comparison of general information between the two groups showed no statistically significant differences （P＞0.05）. The proportion of continuous tracking management in the intervention group was significantly higher than in the control group （P＜0.01）， and the differences in the initiators and reasons for continuous tracking management between the two groups were statistically significant （P＜0.05）. The intervention group had better outcomes in anti-infection treatment compared to the control group （P＜0.05）. The antibacterial drug management indicators （total length of hospital stay， duration of antibacterial drug use， total drug costs， and amount of antibacterial drugs used） in the intervention group were significantly lower than in the control group， while overall degree of satisfaction among medical staff was significantly higher in the intervention group than in the control group （P＜0.05）. No statistically significant differences were found in adverse reaction occurrence and antibacterial drug costs between the two groups （P＞0.05）. CONCLUSIONS The application of this system in patients who underwent anti-infection treatment after MDT can achieve continuous multi-disciplinary tracking management with clinical pharmacists at the core， which is beneficial for promoting the follow-up efficiency of the MDT team， raising the quality of clinical pharmacists’ pharmaceutical services， strengthening treatment outcomes， and promoting the rational use of antibacterial drugs in clinical practice.