Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

Objective To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine(MDMA)and its metabolite 4,5-methylene dioxy amphetamine(MDA)in rats af-ter single and continuous administration of MDMA,providing reference data for the forensic identifica-tion of MDMA.Methods A total of 24 rats in the single administration group were randomly divided into 5,10 and 20 mg/kg experimental groups and the control group,with 6 rats in each group.The ex-perimental group was given intraperitoneal injection of MDMA,and the control group was given intraperi-toneal injection of the same volume of normal saline as the experimental group.The amount of 0.5 mL blood was collected from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.In the continuous administration group,24 rats were randomly divided into the experi-mental group(18 rats)and the control group(6 rats).The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5,7,9,11,13,15,17 mg/kg per day,respectively,while the control group was given the same volume of normal saline as the experimental group by in-traperitoneal injection.On the eighth day,the experimental rats were randomly divided into 5,10 and 20 mg/kg dose groups,with 6 rats in each group.MDMA was injected intraperitoneally,and the con-trol group was injected intraperitoneally with the same volume of normal saline as the experimental group.On the eighth day,0.5 mL of blood was taken from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels,and statistical software was employed for data analysis.Results In the single-administration group,peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration,respectively,with the largest detection time limit of 12 h.In the continuous administration group,peak concentrations were reached at 30 min and 1.5 h af-ter administration,respectively,with the largest detection time limit of 10 h.Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows:T=10.362C-1.183,R2=0.974 6;T=7.397 3C-0.694,R2=0.961 5(T:injection time;C:concentration ratio of MDMA to MDA in plasma).Conclusions The toxicokinetic data of MDMA and its metabolite MDA in rats,obtained through single and continuous administration,including peak concentration,peak time,detection time limit,and the relationship between concentration ratio and administration time,provide a theoretical and data foundation for relevant forensic identification.

BACKGROUND:The gluteus medius not only abducts the hip joint,but also plays an important role in limiting the external movement of the femoral head.At present,there is a lack of research on the correlation between gluteus medius status and non-traumatic femoral head necrosis. OBJECTIVE:To investigate the relationship between the gluteus medius width ratio and the medial space ratio of the hip joint and the progression of non-traumatic femoral head necrosis,and to explore the effect of gluteus medius atrophy on the surface and necrotic zone stress of the femoral head necrosis through finite element analysis. METHODS:Retrospective analysis of unilateral non-traumatic femoral head necrosis patients admitted to Third Affiliated Hospital of Guangzhou University of Chinese Medicine was performed.All patients were followed up for an average of more than 2 years.They were divided into a collapsed group and a non-collapsed group based on whether there was collapse of the femoral head during the follow-up.Medial space ratio,gluteus medius width ratio,Sharp angle,gluteus medius length ratio,and gluteus medius activation angle were measured and calculated.The differences in these indicators were compared between the two groups.At the first visit and follow-up at 3,6,12,and 24 months,the medial space ratio and gluteus medius width ratio were measured and calculated to explore the changes of these two indicators in the course of non-traumatic femoral head necrosis.In addition,using three-dimensional finite element analysis,a Japanese Investigation Committee classification C1 type femoral head necrosis model was constructed based on CT data.At the same time,based on MRI data,a model of the gluteus medius muscle was constructed and divided into a gluteus medius muscle atrophy group(gluteus medius width ratio:74%-76%)and a gluteus medius muscle normal group(gluteus medius width ratio:94%-96%).Each group constructed 10 models,with 6 degrees of freedom of the distal femur constrained to zero.600 N pressures were applied along the Z-axis to the upper surface of the sacrum.The stress distribution,maximum stress values on the surface and necrotic area of the femoral head,and the maximum displacement of the necrotic area were compared between two groups of models. RESULTS AND CONCLUSION:(1)A total of 153 patients(67 males and 86 females)with 153 hips were included in this study.(2)At the 24-hour follow-up,the medial space ratio of the collapsed group was significantly higher than that of the non-collapsed group(P<0.05).The gluteus medius width ratio of the collapsed group was significantly lower than that of the non-collapsed group(P<0.05).There was no statistically significant difference in Sharp angle,gluteus medius activation angle,and gluteus medius length ratio between the two groups(P>0.05).(3)Since the follow-up time exceeded 3 months,the gluteus medius width ratio of the collapsed group was lower than that of the non-collapsed group(P<0.05).Since the follow-up time exceeded 12 months,the medial space ratio of the collapsed group was higher than that of the non-collapsed group(P<0.05).(4)Pearson correlation analysis showed a significant positive correlation between follow-up time and medial space ratio in the collapsed group(P<0.05),and a significant negative correlation between follow-up time and gluteus medius width ratio(P<0.05).The regression coefficient of gluteus medius width ratio was larger than that of medial space ratio.(5)The group with middle gluteal muscle atrophy showed significant stress concentration on the surface of the femoral head,and the stress zone was significantly located on the outside.The maximum stress on the surface of the femoral head in the group with middle gluteal muscle atrophy was significantly greater than that in the group with normal middle gluteal muscle(P<0.05).There was significant stress concentration in the necrotic area of the middle gluteal muscle atrophy group,and the maximum stress was located at the edge of the necrotic area.The maximum stress and maximum displacement in the necrotic area of the middle gluteal muscle atrophy group were significantly greater than those of the normal group(P<0.05).(6)It is indicated that gluteus medius width ratio is an effective indicator for evaluating changes in gluteal muscle atrophy.In the progression of non-traumatic femoral head necrosis,atrophy of the gluteus medius muscle first occurs,followed by widening of the medial hip joint space.The mechanical mechanism may be that the atrophy of the gluteus medius muscle affects the stability of the hip joint,leading to external displacement of the femoral head,and increasing stress and displacement on the surface and necrotic area of the femoral head.

OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of vericiguat in the treatment of heart failure （HF） by rapid health technology evaluation method， and provide reference for the selection and decision-making of clinical treatment plans. METHODS Chinese and foreign databases such as CNKI， PubMed and related health technology evaluation websites were searched by computer. Relevant researchers independently screened literature， extracted data， and comprehensively analyzed the results of the included literature based on literature quality evaluation. RESULTS A total of 17 pieces of literature were included， involving 12 systematic reviews/meta-analyses and 5 pharmacoeconomic studies. The effectiveness analysis showed： for HF patients， compared with placebo， vericiguat （10 mg/d） significantly improved the EuroQol five dimensions questionnaire （EQ-5D） index and decreased the rate of hospitalization due to HF （P＜0.05）. For heart failure with reduced ejection fraction （HFrEF） patients， vericiguat reduced the incidence of hospitalization due to HF compared with sodium-glucose cotransporter 2 inhibitor （SGLT2i）（P＜0.05）； compared with angiotensin-converting enzyme inhibitor， vericiguat significantly reduced the occurrence risk of composite endpoints of cardiovascular death or hospitalization due to HF（P＜0.05）. For HFrEF patients with chronic kidney disease， vericiguat had a tendency to reduce the occurrence risk of composite endpoints of cardiovascular death or hospitalization due to HF compared with neurohormone inhibitors. Safety analysis showed： vericiguat did not increase drug-related adverse reactions compared to placebo （P＞0.05）. Economic analysis showed： domestic studies indicated that vericiguat had a higher incremental cost-effectiveness ratio. CONCLUSIONS Vericiguat has good safety and efficacy in the treatment of HF but does not possess an economic advantage in the Chinese population.

Platycodonis Radix is the dry root of Platycodon grandiflorum of Campanulaceae, which has a variety of pharmacological effects and is a commonly used bulk Chinese medicine. In this study, the chloroplast genome sequences of six P. grandiflorum from different producing areas has been sequenced with Illumina HiSeq X Ten platform. The specific DNA barcodes were screened, and the germplasm resources and genetic diversity were analyzed according to the specific barcodes. The total length of the chloroplast genome of 6 P. grandiflorum samples was 172 260-172 275 bp, and all chloroplast genomes showed a typical circular tetrad structure and encoded 141 genes. The comparative genomics analysis and results of amplification efficiency demonstrated that trnG-UCC and ndhG_ndhF were the potential specific DNA barcodes for identification the germplasm resources of P. grandiflorum. A total of 305 P. grandiflorum samples were collected from 15 production areas in 9 provinces, for which the fragments of trnG-UCC and ndhG_ndhF were amplificated and the sequences were analyzed. The results showed that trnG-UCC and ndhG_ndhF have 5 and 11 mutation sites, respectively, and 5 and 7 haplotypes were identified, respectively. The combined analysis of the two sequences formed 13 haplotypes (named Hap1-Hap13), and Hap4 is the main genotype, followed by Hap1. The unique haplotypes possessed by the three producing areas can be used as DNA molecular tags in this area to distinguish from the germplasm resources of P. grandiflorum from other areas. The haplotype diversity, nucleotide diversity and genetic distance were 0.94, 4.79×10^-3 and 0.000 0-0.020 3, respectively, suggesting that the genetic diversity was abundant and intraspecific kinship was relatively close. This study laid a foundation for the identification of P. grandiflorum, the protection and utilization of germplasm resources, and molecular breeding.

A 29-year-old man visited Zhongshan Hospital, Fudan University in December 2021. The patient presented with recurrent coughing, sputum, and wheezing, high level of serum total IgE, positive aspergillus fumigatus-specific IgE and extremely severe mixed ventilatory dysfunction. These features and thoracic CT results scan showed bronchiectasis and allergic bronchopulmonary aspergillosis. In consideration of his clinical characteristics, including low levels of fractional exhaled nitric oxide (FeNO), and nasal nitric oxide (nNO), persistent cough after birth, consanguineous marriage of his parents, etc. we ratiocinated a possibility of hereditary diseases, especially primary ciliary dyskinesia (PCD). From this perspective, whole exome sequencing (WES) was performed and the diagnosis of PCD was ultimately confirmed.

ObjectiveThe purpose of this study was to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) on cognitive function of vascular dementia (VD) rats and its mechanism. MethodsVD rat model was established by modified two-vessel occlusion (2-VO). After modeling, TEAS and electroacupuncture (EA) were used to stimulate Baihui and Zusanli points of rats respectively for 14 d. After treatment, novel object recognition test, Morris water maze test, and Y maze test were used to evaluate the spatial memory and learning ability of rats. Hematoxylin and eosin staining was used to observe the morphology of hippocampal neurons. Transmission electron microscopy was used to observe the ultrastructure of hippocampal mitochondria. Enzyme-linked immunosorbent assay kits were used to detected the levels of SOD, CAT, GSH-Px, MDA and ROS in serum of rats. Western blot was used to detect the expression of PGC-1α, TFAM, HO-1, NQO1 proteins in the hippocampus, Keap1 protein in the cytoplasm and Nrf2, NRF1 proteins in the nucleus. ResultsAfter treatment for 14 d, compared to the model group, the escape latency of VD rats decreased, while the discrimination index, the times of rats crossing the original platform area, the residence time in the original platform quadrant, and the percentage of alternation increased. TEAS can improve the structure of hippocampal neurons and mitochondria of VD rats, showing that neurons were arranged more regularly and distributed more evenly, nuclear membrane and nucleoli were clearer, and mitochondrial swelling were reduced, mitochondrial matrix density were increased, and mitochondrial cristae were more obvious. The levels of SOD, GSH-Px and CAT in serum increased significantly, while the concentration of MDA and ROS decreased. TEAS also up-regulated the expression levels of PGC-1α TFAM, NQO1 and HO-1 proteins in the hippocampus and Nrf2, NRF1 proteins in the nucleus, but down-regulated the Keap1 protein in the cytoplasm. ConclusionTEAS can improve cognition, hippocampal neurons and mitochondrial structure of VD rats, and the effect is better than EA. The mechanism may be the activation of PGC-1α mediated mitochondrial biogenesis and antioxidant stress, which also provides a potential therapeutic technology and experimental basis for the treatment of VD.

Objective:To investigate the relationship between spread through air spaces(STAS) of peripheral stage ⅠA small adenocarcinoma of the lung(≤2 cm) and related factors such as clinical and CT morphological features, and to construct a nomogram model.Methods:Relevant clinical, pathological and imaging data of patients who underwent lung surgery and were diagnosed as peripheral stage ⅠA small lung adenocarcinoma by postoperative pathology in the Affiliated Hospital of Nantong University from 2017 to 2022 were collected, of which cases that met the inclusion criteria from 2017 to 2021 served as the training group, and those that met the inclusion criteria in 2022 served as the validation group. The independent risk factors for the occurrence of STAS in peripheral stage ⅠA lung small adenocarcinoma were investigated by using univariate analysis and multifactorial logistic regression analysis, based on which a nomogram prediction model was constructed, and the subjects were analyzed by using the receiver operating characteristic curve( ROC), correction model, etc. were used to evaluate the model. Results:A total of 430 patients who met the criteria were included, including 351 patients in the training group(109 STAS-positive and 242 STAS-negative) and 79 patients in the validation group(23 STAS-positive and 56 STAS-negative). Univariate analysis showed that the patients in the two groups showed a significant difference in age(>58 years old), gender, smoking history, tumor location(subpleural, non-subpleural), pleural pull, nodule type, nodule maximal diameter, solid component maximal diameter, consolidation tumor ratio(CTR), lobulation sign, burr sign, bronchial truncation sign, vascular sign(includes thickening and distortion of blood vessels in/around the nodes), satellite lesions, and ground-glass band sign were statistically significant( P<0.05). The results of multifactorial logistic regression analysis showed that CTR( OR=4.98, P<0.001), lobulation sign( OR=4.07, P=0.013), burr sign( OR=3.66, P<0.001), and satellite lesions( OR=3.56, P=0.009) were the independent risk factors for the occurrence of STAS. Applying the above factors to construct the nomogram model and validate the model, the results showed that the ROC curve was plotted by the nomogram prediction model, and the area under the ROC curve( AUC) of the training set was 0.840(sensitivity 0.835, specificity 0.734), and the validation set had an AUC value of 0.852(sensitivity 0.786, specificity 0.783), and the training set and validation set calibration curves have good overlap with the ideal curve. Conclusion:CTR, lobular sign, burr sign, and satellite lesions are independent risk factors for STAS, and the nomogram model constructed in this study has good predictive value.

Non-bifurcating cervical carotid artery(NBCCA)is a very rare anatomical variation of the cervical carotid artery,which may be related to the abnormal development of internal carotid artery(ICA)and external carotid artery in embryonic period.Neither carotid bulb nor a true carotid bifurcation can be observed on the ultrasound of carotid artery while a"stump-like"change was showed at the expected bifurcation level of carotid artery on DSA.Few cases has been reported in China and abroad so far.This article reported a middle-aged male with a history of hypertension and type 2 diabetes and was admitted to the hospital due to dizziness for one month.The left NBCCA accompanied with severe stenosis of the right ICA was confirmed by cerebral angiography.The patient received the right ICA stent implantation surgery as well as antihypertensive and glucose-control treatment and was discharged as his symptoms improved.Clinical data of this case and related literatures were reviewed,in order to improve clinicians'especially imaging diagnostic physicians'understanding on NBCCA to avoid misdiagnosis and related complications.

Exploring the risk "time interval window" of sequential medication of Reduning injection (RDN) and penicillin G injection (PG) by detecting the correlation between serum biochemical indexes and plasma metabonomic characteristics, in order to reduce the risk of adverse reactions caused by the combination of RDN and PG. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). The changes of biochemical indexes in serum of rats were detected by enzyme-linked immunosorbent assay. It was determined that RDN combined with PG could cause pseudo-allergic reactions (PARs) activated by complement pathway. Further investigation was carried out at different time intervals (1.5, 2, 3.5, 4, 6, and 8 h PG+RDN). It was found that sequential administration within 3.5 h could cause significant PARs. However, PARs were significantly reduced after administration interval of more than 4 h. LC-MS was used for plasma metabolomics analysis, and the levels of serum biochemical indicators and plasma metabolic profile characteristics were compared in parallel. 22 differential metabolites showed similar or opposite trends to biochemical indicators before and after 3.5 h. And enriched to 10 PARs-related pathways such as arachidonic acid metabolism, steroid hormone biosynthesis, linoleic acid metabolism, glycerophospholipid metabolism, and tryptophan metabolism. In conclusion, there is a risk "time interval window" phenomenon in the adverse drug reactions caused by the sequential use of RDN and PG, and the interval medication after the "time interval window" can significantly reduce the risk of adverse reactions.