Protein-protein interaction (PPI) plays an important role in the regulation of life. Most of the PPI interfaces are large and discontinuous, and it is difficult for small molecules to specifically bind to them. Peptides are critical in PPI surface interactions due to their higher affinity and specificity. However, peptides have some defects such as easy hydrolysis by protease and poor membrane permeability. Due to good biocompatibility and chemical diversity, cyclic peptides play an important role in drug discovery. Therefore, the development of efficient cyclic peptide construction methods has become a frontier issue in peptide drug research. In recent years, a series of new progresses have been made in the synthesis strategy and the application of cyclic peptides, providing powerful technical tools for the research and development of cyclic peptide drugs. In this review, the synthesis strategies of cyclic peptides and their application will be reviewed from four aspects: synthesis strategies, property improvement, biological activity and prospect.

Paeonia veitchii and P. lactiflora are both original plants of the famous Chinese medicinal drug Paeoniae Radix Rubra in the Chinese Pharmacopoeia. They have important medicinal value and great potential in the flower market. The selection of stable and reliable reference genes is a necessary prerequisite for molecular research on P. veitchii. In this study, two reference genes, Actin and GAPDH, were selected as candidate genes from the transcriptome data of P. veitchii. The expression levels of the two candidate genes in different tissues(phloem, xylem, stem, leaf, petiole, and ovary) and different growth stages(bud stage, flowering stage, and dormant stage) of P. veitchii were detected using real-time fluorescence quantitative technology(qRT-PCR). Then, the stability of the expression of the two reference genes was comprehensively analyzed using geNorm, NormFinder, BestKeeper, ΔCT, and RefFinder. The results showed that the expression patterns of Actin and GAPDH were stable in different tissues and growth stages of P. veitchii. Furthermore, the expression levels of eight genes(Pv-TPS01, Pv-TPS02, Pv-CYP01, Pv-CYP02, Pv-CYP03, Pv-BAHD01, Pv-UGT01, and Pv-UGT02) in different tissues were further detected based on the transcriptome data of P. veitchii. The results showed that when Actin and GAPDH were used as reference genes, the expression trends of the eight genes in different tissues of P. veitchii were consistent, validating the reliability of Actin and GAPDH as reference genes for P. veitchii. In conclusion, this study finds that Actin and GAPDH can be used as reference genes for studying gene expression levels in different tissues and growth stages of P. veitchii.
Real-Time Polymerase Chain Reaction/methods* ; Paeonia/genetics* ; Actins/genetics* ; Reproducibility of Results ; Transcriptome ; Glyceraldehyde-3-Phosphate Dehydrogenases/genetics* ; Reference Standards ; Gene Expression Profiling/methods*

ObjectiveTo explore the effect and possible mechanism of Shenqi Pills （肾气丸） on cognitive impairment and hippocampal glucose energy metabolism in type 2 diabetes mellitus （T2DM）. MethodsSixty C57BL/6 mice were randomly divided into control group， model group， rosiglitazone group and Shenqi Pills low-， medium- and high-dose groups， with 10 mice in each group. T2DM model was induced by a high-fat diet combined with intraperitoneal injection of streptozotocin in all the groups except for the control group. After successful modeling， the high-， medium-， and low-dose Shenqi Pills groups were given 2.08， 1.04， and 0.52 g/（kg·d） of Shenqi Pills granules by gavage respectively， while the rosiglitazone group was given 3 mg/（kg·d） of rosiglitazone tablets by gavage， and the control group and model group were gavaged with 10 ml/（kg·d） of distilled water， all for 8 consecutive weeks. The body weight and fasting blood glucose （FBG） level were recorded every two weeks. The Morris water maze test was performed on the 8th week of medication. After 8-week medication， oral glucose tolerance test （OGTT） and fasting insulin level were measured， hippocampal glucose energy metabolism-related products were quantitatively detected by liquid chromatography tandem mass spectrometry， and KEGG annotation analysis was performed. ResultsCompared to those measured at the same timepoints in the control group， the body mass on week 6 and 8， as well as the FBG level on week 2， 4， 6 and 8 in the model group increased； the blood glucose level at 0， 30， 60 and 120 minutes of the OGTT test increased， while fasting insulin level after 8-week medication decreased. The escape latency of the model group was significantly prolonged on the 3rd and 4th days， and the escape latency time increased， while the total swimming distance， platform quadrant residence time and the number of platform crossings decreased （P＜0.05 or P＜0.01）. Compared to those measured at the same timepoints in the model group， the body mass on week 6 in the low-dose Shenqi Pills group， on week 6 and 8 in the medium- and high-dose groups， and on week 8 in the rosiglitazone group were significantly reduced； the FBG levels in all the Shenqi Pills groups and rosiglitazone group on week 6 and 8 decreased， while fasting insulin levels increased. In the OGTT test， blood glucose in the medium-dose group of Shenqi Pills at all timepoints decreased； in the Morris water maze test， the escape latency period of the medium- and high-dose Shenqi Pills groups was shortened on the 3rd and 4th days， while the escape latency time was reduced， and the total swimming distance， platform quadrant residence time， and number of platform crossings increased in the medium-dose Shenqi Pills group （P＜0.05 or P＜0.01）.The medium-dose Shenqi Pills showed best effect， therefore it was selected for the targeted quantitative detection of metabolites. The medium-dose Shenqi Pills group could regulate the disorder of glucose metabolism in the hippocampus of T2DM mice， and 13 differential metabolites were found，up-regulating α-ketoglutarate and 3-phosphoglyceric acid， and down-regulating fumaric acid， glutamatic acid， lactatic acid， inosine， malic acid， adenine， fructose 1,6-diphosphate and others. KEGG annotation of differential metabolites suggested that Shenqi Pills was closely related to the regulation of glucose metabolism disorder and insulin resistance in the hippocampus region of T2DM model mice， as well as neurodegenerative diseases and ABC transport， hypoxia-inducible factor 1 （HIF）， forkhead transcription factor （FoXO） and cyclic adenosine monophosphate （cAMP） signaling pathways. ConclusionShenqi Pills can improve learning and memory abilities and cognitive impairment in T2DM mice， and may act its role by regulating glucose energy metabolism in the hippocampus of T2DM.

Objective To establish a method for evaluating the disinfecting effect of positive-pressure protective hoods by testing the disinfecting effect of canine influenza virus(CIV)on the positive-pressure protective hood with 1％Virkon S disinfectant.Methods The neutralizer was selected considering the characteristics of 1％Virkon S disinfectant in accordance with"Disinfection technical specifications"(2002 edition),and the effectiveness of the neutralizer was verified by determining median tissue culture infectious dose(TTCID50)of different samples inoculated with canine renal cells;in the same environment the effects of viral vectors and environment on viral activity were detected by measuring the TCID50 at different time points when CIV acted on the positive pressure protective hood;the optimal disinfection time was determined by establishing a viral vector model and a viral infiltration and sampling method,combining the results of viral recovery rates by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay and viral titer measurements by TCID50 and 50％egg infectious dose(EID50).Results The phosphate buffer solution of 0.1％lecithin,2％Tween 80 and 0.5％sodium thiosulfate could be used as a neutralizer for 1％Virkon S disinfectant;the viral vectors and environment had no effects on CIV activity at different time points;the average recover rate was 96.12％for the samples inoculated with canine renal cells and 95.98％for the chicken eggs,and 1％Virkon S disinfectant behaved the best 4 min after its action on CIV on the positive-pressure protective hood.Conclusion The method proposed for evaluating the disinfection effect of the positive-pressure protective hood is effective in establishing optimal disinfection conditions for the positive-pressure protective hood.[Chinese Medical Equipment Journal,2023,44(9):33-37]

Objective:To analyze the factors influencing the difference in location of cricothyroid membrane between traditional surface palpation and ultrasonic biplane.Methods:One hundred and seven subjects of both sexes, aged 18 yr, underwent neck ultrasound examination in our hospital from August 2021 to December 2021, were selected.The structure of cervical airway was observed by ultrasound.The subjects in whom the structure of cricothyroid membrane was clearly shown were selected.The middle point of cricothyroid membrane was located by otorhinolaryngologist using surface palpation method and by ultrasonic doctor using ultrasonic biplane method.The distance between two positioning points was measured by a ruler.The subjects were divided into accurate group (distance between two points≤3 mm) and difference group (distance between two points>3 mm). The distance between cricoid cartilage and thyroid cartilage (spacing of cricoid cartilage and thyroid cartilage) and distance between the midpoint of cricothyroid membrane and skin (spacing of cricothyroid membrane and skin) were measured by ultrasound.The neck length and the maximum submaxillary distance in head up were measured by a ruler.The factors influencing the difference in location between the two methods were analyzed by multivariate logistic regression.Results:One hundred and four subjects with clear cricoid cartilage and cricothyroid membrane under ultrasound were selected.There were significant differences in the ratio of gender, body mass index (BMI), cricothyroid membrane-skin distance, neck length, and maximum submandibular distance between the two groups ( P<0.05). Multivariate logistic analysis showed that female ( OR=9.091, P<0.001), BMI ( OR=11.214, P=0.001) and increased cricothyroid membrane-skin distance ( OR=5.649, P=0.015) were the factors influencing the difference in location between the two cricothyroid membrane localization methods. Conclusions:Female, obesity (BMI>28.0 kg/m 2) and increased distance between cricothyroid membrane and skin are the factors affecting the difference in location of cricothyroid membrane between ultrasonic biplane method and surface palpation method, and bedside ultrasound is recommended for location in those with the factors mentioned above.

Objective:To explore the safety and efficacy of 20% glucose solution in the treatment of adult diabetic patients with hypoglycemia.Methods:A non-randomized controlled paired design trial was conducted. The diabetes patients with hypoglycemia (blood glucose < 3.9 mmol/L) who were admitted to the department of endocrinology and metabolism of Affiliated Hospital of Jiangsu University from December 2020 to May 2021 were enrolled. When the patients developed hypoglycemia for the first time, 75 mL of 20% glucose solution was pumped intravenously at a constant speed within 15 minutes, which was named the 20% glucose solution group. When the patients had hypoglycemia again, 30 mL of 50% glucose solution was pumped intravenously at a constant speed within 3 minutes, which was named the 50% glucose solution group. If the blood glucose was still ≤ 3.9 mmol/L at 15 minutes of hypoglycemia treatment, or the patients were uncomfortable due to too fast drip speed, it should be terminated immediately. The hypoglycemia treatment should be handled according to the Chinese guidelines for the prevention and treatment of type 2 diabetes (2020 edition). The peripheral blood glucose level and the range of increase at 15 minutes of treatment, the success rate of one treatment, the peripheral blood glucose values at 60 minutes after successful hypoglycemia treatment, the incidence of phlebitis and exudation after hypoglycemia treatment, and the pain of local blood vessels in patients with hypoglycemia treatment were analyzed and compared between the two groups. Results:A total of 65 patients completed the treatment of hypoglycemia with 20% glucose solution and the success rate of one treatment was 100%. The peripheral blood glucose value at 15 minutes of hypoglycemia treatment was (8.30±1.37) mmol/L, and the increased range was (4.86±1.30) mmol/L. The peripheral blood glucose value at 60 minutes after successful hypoglycemia treatment was (6.96±1.48) mmol/L, which indicated that 20% glucose solution could effectively increase blood glucose. Among 65 patients, 32 patients had hypoglycemia again, who were treated with 50% glucose solution, and the success rate of one treatment was 100%. When patients who received 50% glucose solution for hypoglycemia formed a paired design with the first 20% glucose solution treatment, the results showed that there was no significant difference in the peripheral blood glucose value and the increased range in blood glucose at 15 minutes of hypoglycemia treatment between the 20% glucose solution and the 50% glucose solution groups [peripheral blood glucose (mmol/L): 8.20 (7.70, 9.70) vs. 8.30 (7.80, 8.80), increase in blood glucose (mmol/L): 4.96±1.39 vs. 4.70±1.32, both P > 0.05], indicating that the glucose changing at 15 minutes of hypoglycemia treatment with 20% glucose solution was similar to that with 50% glucose solution. The peripheral blood glucose value at 60 minutes after successful hypoglycemia treatment of 20% glucose solution group was significantly lower than that of 50% glucose solution group (mmol/L: 6.37±1.04 vs. 7.20±1.36, P < 0.01), which meant that the blood glucose tended to be more stable. There was no phlebitis and exudation after hypoglycemia treatment in both groups. The pain score of 20% glucose solution group was 0, however, 3 patients in 50% glucose solution group complained of local vascular pain, and the pain score was 1. Conclusions:20% glucose solution can effectively treat hypoglycemia in diabetic patients, which has the same curative effect as 50% glucose solution and much safer. It can be used in patients with severe hypoglycemia.

Circular RNA (circRNA), as a competitive endogenous RNA (ceRNA), plays an importantrole in the regulation of cell differentiation. The purpose of this study was to identify and analyze porcinecircular RNA insulin-like growth factor 1 receptor (circIGF1R), explore its expression patterns, construct a ceRNA regulatory network related to circIGF1R, and explore the regulation of its ectopicexpression on adipogenic differentiation of mouse mesenchymal stem cells (C3H10T1 / 2) effect. Forwardand reverse PCR, Sanger sequencing, RNase R enzyme digestion tests, and qRT-PCR were used toverify that circIGF1R is a circRNA formed by the second exon of insulin-like growth factor 1 receptor(IGF1R). It was expressed in all tissues of pigs, and its expression level increased with age in adiposetissues. miRDB, TargetScan and miRWalk online software were used to predict circIGF1R target genes. RNAhybrid software was used for binding site prediction. DAVID bioinformatics functional analysissoftware was used to perform GO and KEGG enrichment analysis on candidate target genes. Cytoscapesoftware was used to construct the ceRNA network diagram. Based on the gene expression correlation andpredicted target relationship, the GO and KEGG enrichment analysis was drawn and the ceRNA networkwas constructed; the dual luciferase reporter gene test was used, and we found that circIGF1R andFABP4 can bind to ssc (Sus scrofa chromosome) -miR-133a-5p. The circIGF1R overexpression vectorwas successfully constructed and expressed in C3H10T1/ 2 cells. It was found that after overexpression ofcircIGF1R, the expression of key adipogenic regulatory factors CEBPa, CEBPß, FABP4 and PPAR? increased significantly(P<0. 01), and the number of lipid droplets increased significantly. The results ofthis study show that circIGF1R exists in pig adipose tissues, and may positively regulate the adipogenicdifferentiation of C3H10T1/ 2 cells through the ceRNA mechanism, which lays a theoretical foundation forfurther research on circIGF1R regulating the adipogenic differentiation of pig precursor intramuscularadipocytes.

The protection of language function is one of the major challenges of brain surgery. Over the past century, neurosurgeons have attempted to seek the optimal strategy for the preoperative and intraoperative identification of language-related brain regions. Neurosurgeons have investigated the neural mechanism of language, developed neurolinguistics theory, and provided unique evidence to further understand the neural basis of language functions by using intraoperative cortical and subcortical electrical stimulation. With the emergence of modern neuroscience techniques and dramatic advances in language models over the last 25 years, novel language mapping methods have been applied in the neurosurgical practice to help neurosurgeons protect the brain and reduce morbidity. The rapid advancements in brain-computer interface have provided the perfect platform for the combination of neurosurgery and neurolinguistics. In this review, the history of neurolinguistics models, advancements in modern technology, role of neurosurgery in language mapping, and modern language mapping methods (including noninvasive neuroimaging techniques and invasive cortical electroencephalogram) are presented.
Brain Mapping ; Brain Neoplasms ; Humans ; Language ; Neurosurgery ; Neurosurgical Procedures

Objective: To compare and correlate the findings of intravoxel incoherent motion (IVIM) magnetic resonance (MR) imaging and arterial spin labeling (ASL) imaging in characterizing parotid gland tumors. Materials and Methods: We retrospectively reviewed 56 patients with parotid gland tumors evaluated by MR imaging. The true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and fraction of perfusion (f) values of IVIM imaging and tumor-to-parotid gland signal intensity ratio (SIR) on ASL imaging were calculated. Spearman rank correlation coefficient, chi-squared, Mann-Whitney U, and Kruskal-Wallis tests with the post-hoc Dunn-Bonferroni method and receiver operating characteristic curve assessments were used for statistical analysis. Results: Malignant parotid gland tumors showed significantly lower D than benign tumors (p = 0.019). Within subgroup analyses, pleomorphic adenomas (PAs) showed significantly higher D than malignant tumors (MTs) and Warthin’s tumors (WTs) (p < 0.001). The D* of WTs was significantly higher than that of PAs (p = 0.031). The f and SIR on ASL imaging of WTs were significantly higher than those of MTs and PAs (p < 0.05). Significantly positive correlation was found between SIR on ASL imaging and f (r = 0.446, p = 0.001). In comparison with f, SIR on ASL imaging showed a higher area under curve (0.853 vs. 0.891) in discriminating MTs from WTs, although the difference was not significant (p = 0.720). Conclusion IVIM and ASL imaging could help differentiate parotid gland tumors. SIR on ASL imaging showed a significantly positive correlation with f. ASL imaging might hold potential to improve the ability to discriminate MTs from WTs.

Objective:To summarize the clinical manifestations, epidemiological features and progress of diagnosis and treatment of gout in the spinal canal.Methods:A 59-year-old male patient was admitted to the hospital due to back pain, weakness in both lower limbs, hypoaesthesia and feeling of walking and stepping on cotton for more than one month. The preoperative imaging examination showed there were space-occupying lesions in the spinal canal at the T 8, 9 level with severe canal stenosis. The patient underwent posterior T 8, 9 laminectomy decompression, debridement and T 7-T 10 pedicle screw internal fixation under general anesthesia. The thoracic spinal gout was diagnosed by postoperative pathology. Further, the following keywords, "gout", "gout of spinal canal", "gout of spine" and "intraspinal gout", were used to search in the Chinese and English databases. A total of 62 patients with intraspinal gout were retrieved. The age, gender, involved disease, history of gout or hyperuricemia, laboratory indicators and imaging data of 63 patients were collected. Results:A total of 63 patients with intraspinal gout were retrieved. The gender of one patient was unknown. The remaining patients included 54 males (87.1%, 54/62) and 8 females (12.9%, 8/62) with the ratio of male to female 6.75∶1. The average age was 52(35, 67) years (range 20-82 years) and the peak onset period was 60-79 years. Fifty-six cases (88.9%, 56/63) of all patients suffered the disease from one single site of the spine, including 26 cases in the lumbar-sacral (46.4%), 22 cases (39.3%) in the thoracic spine and 8 cases (14.3%) in the cervical spine. However, only 7 patients had the disease at more than two sites at the same time accounting for 11.1% of all patients (7/63). Fifty-three patients (91.4%, 53/58) had a history of hyperuricemia with an average duration of 8.6 years (range 3 months to 28 years). The clinical symptoms of intraspinal gout were not specific. There were 70.5% (43/61) patients had local pain and up to 98.4% (60/61) patients had varying degrees of neurological dysfunction. X-ray examinations often showed no positive results due to technical limitations. Among 41 patients with CT imaging data, 31 cases showed mid-to-high density elliptical or irregular calcifications in the spinal canal and the remaining 10 patients showed medium-low density soft tissue masses. There were 96.2% (51/53) of patients with intraspinal gout showed medium or low signal on T1WI MRI examination but without high signal or low signal on T2WI (40 cases of high signal, 13 cases of high signal or mixed signal). All 63 patients were finally diagnosed by pathological examination and 5 of them with histological features. The main pathological features included foreign body granuloma, red-stained crystal-like deposits in the cytoplasm of foreign body giant cells, birefringent spindle or needle-like crystals under polarized light microscope.Conclusion:Gout in the spinal canal is a rare condition. Dual-energy CT has high sensitivity and specificity in identifying gout and it can provide a more accurate method in diagnosis of spinal gout. However, the final diagnosis depends on postoperative pathology. If case of spinal instability or neurological dysfunction, surgery had to be performed. Hyperuricemia should be treated in order to reduce the risk of acute attacks.