Glucagon-like peptide-1 receptor agonists (GLP-1RA) have been widely used in the treatment of type 2 diabetes mellitus (T2DM). However, the acceleration of heart rate caused by GLP-1RA should not be ignored. In the general population and patients with diabetes, increased heart rate has an independent correlation with the incidence and mortality of cardiovascular diseases. In general, the long-acting GLP-1RA seem to exert a greater effect in increasing heart rate, and the effect is dose-dependent and negatively correlated with baseline heart rate. The increase in heart rate caused by GLP-1RA may be related to enhanced sympathetic nervous activity, reflex tachycardia as a response to vasodilation, etc. It is advisable to closely monitor the increased heart rate induced by GLP-1RA in clinical practice, especially in patients with high-risk factors for cardiovascular disease. In case of elevated heart rate, the management begins with immediate discontinuation of the GLP-1RA and symptomatic intervention should be given if necessary.

Objective:To explore the clinical features of nivolumab-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).Methods:Relevant databases at home and abroad (as of December 31, 2023) were searched to collect case reports of nivolumab-induced SJS/TEN, and the demographic characteristics, nivolumab application, combination drugs, clinical manifestations, intervention measures, and outcomes were extracted and analyzed descriptively and statistically.Results:A total of 27 case reports were included and 29 patients were enrolled in the study, including 18 males and 11 females. The age ranged from 45 to 86 years, with an average age of 67 years. The primary diseases were mainly melanoma, stomach cancer, and lung cancer. Twelve patients had records of nivolumab administration, and the dosage was within the recommended range in the labels; 13 patients had records of combination drugs, mainly other antineoplastic drugs, hypoglycemic drugs, antihypertensive drugs, lipid-regulating drugs, etc. The time from using nivolumab to the diagnosis of SJS/TEN was 7 d to 3 years, and 20 patients were <8 weeks. The clinical manifestations were mainly diffuse erythema, flaky skin peeling and erosion, mucosal involvement, etc. Sixteen patients had skin biopsy records, all of which met the histopathological characteristics of SJS/TEN. After the diagnosis of SJS/TEN, 17 patients discontinued nivolumab and received symptomatic treatments, of which 15 patients had improved skin symptoms, one patient had worsened skin symptoms, and one patient had no record of skin outcome; 12 patients had no record of whether or not discontinuing nivolumab, of which 8 patients had improved skin symptoms, 2 patients had worsened skin symptoms, one patient had no record of skin outcome, and one had no record of prognosis. One patient rechallenged nivolumab, severe SJS/TEN recurred. Thirteen of 29 patients died. Of them, 1 died due to cardiac arrest, 4 due to worsened skin rash, and 8 due to primary disease progression.Conclusions:SJS/TEN caused by nivolumab mostly occurs within 8 weeks of treatment, and the clinical manifestations were similar to those caused by other drugs. The mortality rate of nivolumab-induced SJS/TEN is high, and skin rash could be improved after withdrawal of nivolumab and symptomatic treatments.

Glucagon-like peptide-1 receptor agonists (GLP-1RA) have been widely used in the treatment of type 2 diabetes mellitus (T2DM). However, the acceleration of heart rate caused by GLP-1RA should not be ignored. In the general population and patients with diabetes, increased heart rate has an independent correlation with the incidence and mortality of cardiovascular diseases. In general, the long-acting GLP-1RA seem to exert a greater effect in increasing heart rate, and the effect is dose-dependent and negatively correlated with baseline heart rate. The increase in heart rate caused by GLP-1RA may be related to enhanced sympathetic nervous activity, reflex tachycardia as a response to vasodilation, etc. It is advisable to closely monitor the increased heart rate induced by GLP-1RA in clinical practice, especially in patients with high-risk factors for cardiovascular disease. In case of elevated heart rate, the management begins with immediate discontinuation of the GLP-1RA and symptomatic intervention should be given if necessary.

Objective:To explore the clinical features of nivolumab-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).Methods:Relevant databases at home and abroad (as of December 31, 2023) were searched to collect case reports of nivolumab-induced SJS/TEN, and the demographic characteristics, nivolumab application, combination drugs, clinical manifestations, intervention measures, and outcomes were extracted and analyzed descriptively and statistically.Results:A total of 27 case reports were included and 29 patients were enrolled in the study, including 18 males and 11 females. The age ranged from 45 to 86 years, with an average age of 67 years. The primary diseases were mainly melanoma, stomach cancer, and lung cancer. Twelve patients had records of nivolumab administration, and the dosage was within the recommended range in the labels; 13 patients had records of combination drugs, mainly other antineoplastic drugs, hypoglycemic drugs, antihypertensive drugs, lipid-regulating drugs, etc. The time from using nivolumab to the diagnosis of SJS/TEN was 7 d to 3 years, and 20 patients were <8 weeks. The clinical manifestations were mainly diffuse erythema, flaky skin peeling and erosion, mucosal involvement, etc. Sixteen patients had skin biopsy records, all of which met the histopathological characteristics of SJS/TEN. After the diagnosis of SJS/TEN, 17 patients discontinued nivolumab and received symptomatic treatments, of which 15 patients had improved skin symptoms, one patient had worsened skin symptoms, and one patient had no record of skin outcome; 12 patients had no record of whether or not discontinuing nivolumab, of which 8 patients had improved skin symptoms, 2 patients had worsened skin symptoms, one patient had no record of skin outcome, and one had no record of prognosis. One patient rechallenged nivolumab, severe SJS/TEN recurred. Thirteen of 29 patients died. Of them, 1 died due to cardiac arrest, 4 due to worsened skin rash, and 8 due to primary disease progression.Conclusions:SJS/TEN caused by nivolumab mostly occurs within 8 weeks of treatment, and the clinical manifestations were similar to those caused by other drugs. The mortality rate of nivolumab-induced SJS/TEN is high, and skin rash could be improved after withdrawal of nivolumab and symptomatic treatments.

Objective To investigate the effects of abdominal massage combined with electroacupuncture point-through-point method on the expressions of circadian clock genes of Clock,BMAL1,PER1 and neurotransmitters contents of ACh and Glu in insomnia rats and its possible mechanism.Methods Totally 50 SD male rats were randomly divided into normal group,model group,abdominal massage group,electroacupuncture point-through-point group and combination group,with 10 rats in each group.Except for the normal group,an insomnia rat model was established by intraperitoneal injection of p-chlorophenylalanine.Abdominal massage group received abdominal massage;electroacupuncture point-through-point group was treated with flat acupuncture,"Baihui"through"Shenting","Sanyinjiao"through"Yinlingquan"(bilateral),"Shenmen"through"Neiguan"(bilateral),the electroacupuncture instrument dilatational wave,frequency of 1 Hz/20 Hz was connected;the combination group was treated with electroacupuncture through acupoints after abdominal massage;1 time/d for each treatment group,a total of 7 days.The normal group and model group were not intervened.HE staining was used to observe the pathological changes of neurons in hypothalamic tissue,the expression of Clock,BMAL1 and PER1 mRNA were detected by RT-qPCR,the expressions of Clock,BMAL1 and PER1 in hypothalamic tissue were detected by immunohistochemical staining,the expression of Clock,BMAL1 and PER1 protein in hypothalamic tissue were detected by Western blot,the contents of ACh and Glu in serum were detected by ELISA.Results Compared with the normal group,the model group rats had a longer sleep latency,shorter sleep duration,severe damage to the cellular structure of the hypothalamic tissue,and a vacuolar like change,with a decrease in the number of neuronal cells,the expressions of Clock and BMAL1 mRNA and protein in hypothalamic tissue increased,while the expressions of PER1 mRNA and protein decreased;the contents of serum ACh and Glu increased,with statistical significance(P<0.05).Compared with the model group,the abdominal massage group,electroacupuncture point-through-point group,and combination group could all shorten the sleep latency,prolong sleep duration,and improve the morphology of hypothalamic neurons,reduce the expressions of Clock and BMAL1 mRNA and protein in hypothalamic tissue,up-regulate the expressions of PER1 mRNA and protein,and reduce the contents of serum ACh and Glu,with statistical significance(P<0.05),the combination group showed the most obvious effects(P<0.05).Conclusion Abdominal massage combined with electroacupuncture point-through-point method can improve insomnia.Its mechanism may be related to the regulation of circadian clock genes Clock,BMAL1,PER1 mRNA and protein expression,as well as neurotransmitter content.

Objective To explore the funding situation and hot research directions of NSFC(National Natural Science Foundation of China)projects in the discipline of acupoints and meridians from 1991 to 2022;To provide reference for this discipline to apply for the NSFC.Methods National Natural Science Foundation of China was login in to query website.The acupoints and meridians discipline project from 1991 to 2022 were retrieved.The project leader,project name,supporting unit,province,funding category,funding amount,keywords and other information were extracted.The data were input to Excel 2023 to establish a database,and descriptive analysis of project funding situation was performed.Target keywords were extracted,and the word table was classified and uploaded to the micro-word cloud online to draw the word cloud map to analyze the research hotspots.Results From 1991 to 2022,the number of projects funded by the NSFC for acupoints and meridians was 173.The funding category was mainly general projects,and the supporting units were mainly TCM colleges and universities and scientific research institutions.The main research directions were meridian essence,acupoint-viscera/body related effects and mechanism of action,and the signal molecules and related pathways were the entry points.Conclusion From 1991 to 2022,the NSFC-funded acupoints and meridians disciplines are mainly based on general projects,mainly concentrated in scientific research institutions and TCM colleges and universities,with uneven regional distribution.The essence of meridians and collaterals,acupoints-viscera/body-related effects and mechanisms(mechanisms)are the key research directions.

Objective To investigate the effects of acute sleep deprivation on the behavior and synaptic protein expression of rats.Methods Seventy healthy male Wistar rats were randomly divided into seven groups,a Control group and sleep deprivation groups(24,48,72,96,120 and 144 hours).The sleep deprivation rat model was established by the modified multiplatform water environment sleep deprivation method.Spatial learning and memory were assessed by the Morris water maze.Anxiety was assessed by the open field test.The morphology and quantity of hippocampal neurons were observed by Nissl staining.Western blot and Real-time PCR were used to determine the expression of synaptophysin(SYN),post-synaptic density protein-95(PSD-95),and brain-derived neurotrophic factor(BDNF)in rats.Results Compared with the Control group,the numbers of standing and modification were significantly increased by prolongation of the sleep deprivation time(P＜0.05).The escape latency and path length were significantly increased in 120 and 144 h groups(P＜0.05),whereas the number of platform crossings and the percentage of the target quadrant time were significantly decreased(P＜0.01)and negatively correlated to the sleep deprivation time.The expression levels of BDNF,SYN,and PSD-95 were significantly decreased with the prolongation of sleep deprivation time(P＜0.01).Conclusions With the increase in sleep deprivation time,cognitive dysfunction and anxiety gradually deteriorated,which may be related to decreases in the expression of synaptic biomarkers.

Lectins are proteins responsible for recognizing the signals of sugar molecules in the body. Sialic acid-binding immunoglobulin-like lectins (Siglecs) regulate the innate and adaptive immune responses in the tumor microenvironment by recognizing the glycan structure containing sialic acid and mediating downstream signals through immune receptor tyrosine inhibitory motifs. In recent years, a variety of tumor treatment strategies targeting the sialic acid-Siglecs axis have been introduced, including sialoglycoprotein-mediated drug delivery and antibody mediated inhibition of Siglecs from recognizing tumor surface ligands. In the future, by combining with glycoprotein nanotherapy, antibody therapy and gene therapy, Siglecs can be used to accurately locate tumor targets and release the anti-tumor immunity, so as to achieve the purpose of effective cure of tumors.
Sialic Acid Binding Immunoglobulin-like Lectins/metabolism* ; N-Acetylneuraminic Acid ; Immunoglobulins/metabolism* ; Receptors, Immunologic ; Ligands

OBJECTIVE To analyze the clinical characteristics of liraglutide-induced pancreatitis， and to provide reference for clinical rational drug use. METHODS Retrieved from CNKI， VIP， Wanfang database， PubMed， Web of Science and Medline， case reports about liraglutide-induced pancreatitis were collected from the inception to December 31st， 2022. Demographic characteristics， drug use， clinical manifestations， intervention and outcome were analyzed using descriptive statistical method. RESULTS A total of 17 pieces of literature were collected and 17 patients were involved， including 7 males and 10 females. The patients aged from 25 to 75 years. All 17 patients had drug indications， including 14 cases of type 2 diabetes mellitus， 3 cases of obesity or overweight. Among 17 patients， liraglutide was used alone in 5 cases， and combined with other drugs in 12 cases. Time from liraglutide administration to pancreatitis occurrence ranged from 1 day to 11 months after medication in 17 patients， with 14 cases less than 6 months. The clinical manifestations mainly included abdominal pain， nausea and vomiting， etc. After the diagnosis of pancreatitis， liraglutide discontinuation occurred in 16 patients； 1 case did not receive any other interventions and the other 15 cases were managed with symptomatic supportive treatment； the symptoms of all 16 patients resolved； however， 2 patients suffered from second episode of severe pancreatitis several weeks after liraglutide discontinuation， pancreatitis recurred after liraglutide rechallenge in 1 case. The results of correlation evaluation showed that 1 case was “positive”， 4 cases were “possible”， and the remaining patients were “very likely”. CONCLUSIONS Liraglutide-induced pancreatitis mainly occurred within 6 months after drug administration. The majority of liraglutide-induced pancreatitis cases are mild to moderate， but there are also severe and even fatal cases. It is advisable to periodically monitor the level of pancreatic enzymes and closely observe patients’ clinical mani-festations. In case of suspected liraglutide-induced pancreatitis，drug withdrawal and symptomatic treatment should be taken immediately.

Objective:To prepare a fluorescent probe Cetuximab-IRDye800CW targeting epidermal growth factor receptor (EGFR) and investigate its application value in surgical navigation of glioblastoma (GBM).Methods:The fluorescence properties of Cetuximab-IRDye800CW were determined by fluorescence spectrophotometer. The specificity of Cetuximab-IRDye800CW bound to GBM cells was verified by Western blot. The competitive binding method of enzyme-linked immunosorbent assay (ELISA) was used to prove whether the probe could achieve tumor targeting by binding to EGFR. Subcutaneous models of 6 nude mice of GBM were divided into experimental group ( n=3; injected with Cetuximab-IRDye800CW) and control group ( n=3; injected with IRDye800CW), and images were obtained at 5 min, 24 h, 48 h and 72 h after injection. Differences of mean fluorescence intensity (MFI) and tumor to background ratio (TBR) between experimental group and control group were compared. In situ models of GBM nude mice were established ( n=6), and MRI and intraoperative navigation were conducted, which were compared with pathological distribution. Independent-sample t test was used to analyze the data. Results:The maximum emission wavelength of Cetuximab-IRDye800CW was 820 nm, which could be received by near infrared fluorescence imaging equipment. Western blot showed that Cetuximab-IRDye800CW was only bound to GBM cells. The competitive binding of ELISA showed that Cetuximab-IRdye800CW could achieve tumor targeting by binding with EGFR. At 5 min, 24 h, 48 h and 72 h after injection of fluorescent materials, the MFI values of experimental group were 109.00±3.81, 73.36±9.93, 55.24±8.82, 37.71±6.11, which were higher than those of control group (91.32±4.17, 42.91±5.39, 25.08±6.05, 8.33±1.00; t values: 4.36-9.40, P values: 0.011-0.049). The TBR of experimental group was higher than that of control group at 24 h and 48 h after injection (24 h: 2.40±0.28 vs 1.57±0.07, t=4.94, P=0.039; 48 h: 2.07±0.12 vs 1.22±0.08, t=9.85, P=0.010). GBM in situ model was successfully constructed and verified by MRI, and the tumor was visualized under the fluorescence device navigation. Pathological distribution of the tumor with HE staining was consistent with fluorescence imaging. Conclusion:Cetuximab-IRDye800CW has fluorescence imaging capability and can identify tumor boundaries in intraoperative navigation of GBM, which has potential clinical application value.