The central amygdala (CeA) is a crucial modulator of emotional, behavioral, and autonomic functions, including cardiovascular responses. Despite its importance, the specific circuit by which the CeA modulates blood pressure remains insufficiently explored. Our investigations demonstrate that photostimulation of GABAergic neurons in the centromedial amygdala (CeM^GABA), as opposed to those in the centrolateral amygdala (CeL), produces a depressor response in both anesthetized and freely-moving mice. In addition, activation of CeM^GABA axonal terminals projecting to the nucleus tractus solitarius (NTS) significantly reduces blood pressure. These CeM^GABA neurons form synaptic connections with NTS neurons, allowing for the modulation of cardiovascular responses by influencing the caudal or rostral ventrolateral medulla. Furthermore, CeM^GABA neurons targeting the NTS receive dense inputs from the CeL. Consequently, stimulation of CeM^GABA neurons elicits hypotension through the CeM-NTS circuit, offering deeper insights into the cardiovascular responses associated with emotions and behaviors.
Animals ; GABAergic Neurons/physiology* ; Male ; Central Amygdaloid Nucleus/physiopathology* ; Hypotension/physiopathology* ; Mice ; Blood Pressure/physiology* ; Mice, Inbred C57BL ; Solitary Nucleus/physiology* ; Photic Stimulation ; Neural Pathways/physiology*

Objective Based on the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,data mining was conducted on hematological adverse events related to antibody drug conjugates(ADC),providing reference for the safe use of ADC drugs in clinical practice.Methods The report data from the third quarter of 2011 to the fourth quarter of 2022 were retrieved from the FAERS database.After data cleaning such as deduplication and name standardization,extract hematological adverse events related to ADC,and use report odds ratio method and the information component method for signal detection.Results A total of 101 610 adverse event reports were extracted,with 8 ADC drugs as the primary suspected drugs,and 5 768 ADC related hematological adverse event reports.Among them,3 423 cases of agranulocytosis were involved,and the signal intensity from strong to weak were sacituzumab govitecan(SG),gemtuzumab ozogamicin(GO),brentuximab vedotin(BV),polatuzumab vedotin(PV),enfortumab vedotin(EV),trastuzumab deruxtecan(TD),inotuzumab ozogamicin(IO)and ado-trastuzumab emtansine(TDM-1).There were 2 327 cases hematopoietic cell deficiency,with signals ranging from strong to weak were IO,SG,BV,EV,PV,TD,TDM-1,and GO.Report with clinical outcome of death of ADC drug related hematological adverse events included BV 179(16.84％),TDM-1 102(13.01％),TD 88(27.08％),GO 12(16.90％),IO 8(11.59％),EV 54(24.32％),PV 22(27.16％),and SG 84(21.05％).Adverse event time analysis showed that the number of events on the first day of TD,IO,and SG medication accounts for ≥ 40％of the total number of cases.The median time of hematological adverse events in TD,GO,IO,EV,PV,and SG was within one treatment course(21 days).Conclusion Attention should be paid to the risk of ADC drug-related hematological adverse event,during the clinical medication process,blood cell count changes should be closely monitored,and any abnormalities should be promptly diagnosed and treated.

Chronic Guillain-Barre syndrome, also known as chronic inflammatory demyelinating polyradiculoneuropathy(CIDP), is an immune-mediated demyelinating peripheral neuropathy. This article analyzes the clinical data of a CIDP patient presenting primarily with limb numbness, pain, and weakness. Along with literature review, this study explores the differential diagnosis between CIDP and diabetic peripheral neuropathy in terms of the pathogenesis, clinical manifestations, laboratory tests, and treatment.

Recently, small nucleolar RNAs (snoRNAs) have transcended the genomic "noise" to emerge as pivotal molecular markers due to their essential roles in tumor progression. Substantial evidence indicates a strong association between snoRNAs and critical clinical features such as tumor pathology and drug resistance. Historically, snoRNA research has concentrated on two classical mechanisms: 2'-O-ribose methylation and pseudouridylation. This review specifically summarizes the novel regulatory mechanisms and functional patterns of snoRNAs in tumors, encompassing transcriptional, post-transcriptional, and post-translational regulation. We further discuss the synergistic effect between snoRNA host genes (SNHGs) and snoRNAs in tumor progression. More importantly, snoRNAs extensively contribute to the development of tumor cell resistance as oncogenes or tumor suppressor genes. Accordingly, we provide a comprehensive review of the clinical diagnosis and treatment associated with snoRNAs and explore their significant potential as novel drug targets.

Lead poisoning severely threatens human health with its cumulation and durability in the body. The analysis of lead in blood is vital for screening, diagnosis, treatment, and prognostication of lead poisoning and for indirectly monitoring the level of lead in the environment. Although the detection programs are available throughout our country, the accuracy and comparability of the results cannot meet the expectation. A variety of factors can affect the accuracy of blood lead testing. To promote the application of blood lead analysis in clinical trials and reduce the bias of results, a better reference system for blood lead analysis should be established to evaluate the accuracy of traditional methods, promote the standardization of blood lead analysis and achieve accurate blood lead testing.

Objective:To explore the clinical effects of free anterolateral thigh perforator flap pedicled with descending genicular artery in repairing wounds after lower leg limb-sparing surgery.Methods:A retrospective observational study was conducted. From January 2019 to June 2021, 12 patients with wounds after lower leg limb-sparing surgery who met the inclusion criteria were admitted to Suzhou Ruihua Orthopedic Hospital, including 6 males and 6 females, aged 17 to 74 years, with original wound area ranging from 17 cm×9 cm to 40 cm×15 cm. Five patients had infection in wounds. The wounds were all repaired by free anterolateral thigh perforator flap from contralateral thigh, with area of 18 cm×10 cm to 37 cm×9 cm. The artery of flap was anastomosed with the descending genicular artery, and the wounds in donor areas were sutured directly. Seven patients were transplanted with split-thickness skin grafts from the contralateral thigh to cover the remaining wounds that can not be covered by flap and the wounds in donor areas were covered with gauze. During the operation, the types of perforating branch carried by flap and the types of arteries and veins in recipient areas were recorded. The survival and occurrence of vascular crisis of flap, the survival of skin graft, the wound healing in donor and recipient areas, and the length of hospital stay after flap transplant surgery were recorded. During follow-up, the color and texture of flap, reinfection in lower leg, and fracture healing were recorded. At the last follow-up, the limb salvage function of patients was evaluated according to the functional evaluation criteria of Chen Zhongwei's amputated limb replantation.Results:The types of perforating branches carried by flaps were as follows: 6 cases of only carrying the descending branch of the lateral circumflex femoral artery, 3 cases of only carrying the oblique branch of the lateral circumflex femoral artery, and 3 cases of carrying the descending branch of the lateral circumflex femoral artery and oblique branch of the lateral circumflex femoral artery after internal pressurization anastomosis. The types of arteries in the recipient area of flap were as follows: one case of main trunk of the descending genicular artery, 8 cases of the saphenous branch of the descending genicular artery, and 3 cases of the articular branch of the descending genicular artery. The types of veins in the recipient area of flap were as follows: 8 cases of one accompanying vein of the descending genicular artery and one branch of the great saphenous vein, and 4 cases of two branches of the great saphenous vein. All the flaps survived without vascular crisis, and all the skin grafts also survived. The wounds in the donor and recipient areas were all healed. The length of hospital stay of patient after flap transplant surgery ranged from 13 to 79 days. During the follow-up of 6 to 23 months, the color and texture of flap were both good, with no infection in lower leg wound. Internal or external fixation were removed after fracture healing in 5 patients, and bone graft internal fixation was performed in 7 patients whose fractures were not healed after surgery and all the incisions healed without infection. At the last follow-up, the limb salvage effect of patients was evaluated as followings: excellent in 7 patients, good in 4 patients, and fair in one patient.Conclusions:Free anterolateral thigh flap pedicled with descending genicular artery can effectively repair the wounds after lower leg limb-sparing surgery and control infection with short length of hospital stay, while not increasing the risk of secondary injury of distal limb vessels. Thus, it can obtain satisfactory limb salvage effect which is worthy of clinical promotion.

Background: Serum C-peptide results from various routine methods used in China are highly variable, warranting well-performing methods to serve as an accuracy base to improve the harmonization of C-peptide measurements in China. We developed an accurate isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC–MS/MS) method for serum C-peptide measurement and explored its use in harmonization. Methods: After protein precipitation with ZnSO4 solution, C-peptide was extracted from serum samples by anion-exchange solid-phase extraction and quantified by ID-LC–MS/MS in positive ion mode. The precision and analytical recovery of the ID-LC–MS/MS method were assessed. Seventy-six serum samples were analyzed using the ID-LC–MS/MS method and six routine immunoassays. Ordinary linear regression (OLR) and Bland-Altman (BA) analyses were conducted to evaluate the relationship between the ID-LC–MS/MS method and routine immunoassays. Five serum pool samples assigned using the ID-LC–MS/MS method were used to recalibrate the routine assays. OLR and BA analyses were re-conducted after recalibration. Results: The within-run, between-run, and total precision for the ID-LC–MS/MS method at four concentrations were 1.0%–2.1%, 0.6%–1.2%, and 1.3%–2.2%, respectively. The analytical recoveries for the ID-LC–MS/MS method at three concentrations were 100.3%–100.7%, 100.4%–101.0%, and 99.6%–100.7%. The developed method and the immunoassays were strongly correlated, with all R2 >0.98. The comparability among the immunoassays was substantially improved after recalibration. Conclusions The performance of the ID-LC–MS/MS method was carefully validated, and this method can be used to improve the harmonization of serum C-peptide measurements in China.

We herein describe AncPhore, a versatile tool for drug discovery, which is characterized by pharmacophore feature analysis and anchor pharmacophore (

Objective:Based on the technology-organization-environment model and the theory of planned behavior, to construct a theoretical model for exploring the influencing factors of the adoption intention of hepatic contrast-enhanced ultrasound by clinicians in a medical alliance.Methods:By agency of self-administered scales, a questionnaire survey was conducted among the clinicians in liver disease-related departments of four medical alliances from Fujian and Jiangxi provinces between February and August, 2019.Results:Behavioral attitudes, subjective norms, perceived behavioral control, organizational atmosphere, and industry technical environment all had positive impacts on the clinicians′ intention to adopt hepatic contrast-enhanced ultrasound technology in medical alliances. The total influence of the five types of factors on the adoption intention of hepatic contrast-enhanced ultrasound was as follows: perceived behavioral control(0.779), subjective norms(0.635), industry technical environment(0.578), behavioral attitudes(0.359), and organizational atmosphere(0.218).Conclusions:It is recommended to strengthen the intention to adopt corresponding health technologies by providing adequate technical education and training, giving play to the leading role of core members, and building an organizational atmosphere of advocating technological innovation and communication.

Objectives:To establish a candidate reference method of isotope dilution liquid chromatography tandem mass spectrometry (ID-LC/MS/MS) for the determination of human plasma normetanephrine, and to evaluate the performance of the method. The method was used to quantify the samples of the external quality assessment program, and to initially evaluate the detection status of plasma normetanephrine.Methods:The isotope standard solution of normetanephrine was selected as the internal standard, the gravimetric method was used for sampling, and the standard curve method was used for quantification. Protein precipitation combined with weak cation solid phase extraction was used for pretreatment, and ultra-high liquid chromatography-coupled triple quadrupole mass spectrometry was used for LC/MS analysis. According to the relevant EP documents, the specificity, matrix effect, detection limit, quantification limit, precision, accuracy, and uncertainty of the method were estimated. This method is used to quantify the samples of the 2020 National Center for Clinical Laboratories external quality assessment program of normetanephrine. Taking the average value of this method as the target value, the optimal allowable total error standard of biological variation as the evaluation limit, the quality of the laboratory testing was evaluated.Results:The method had good specificity, and the interferences and matrix effects did not affect the detection results. The detection limit and quantification limit of plasma normetanephrine were 1.08 pg/g and 3.54 pg/g, respectively. The intra-batch coefficient of variation ( CV) and total CV were 0.43%-1.10% and 0.61%-1.42%, respectively. The relative recovery rates were 98.5%～101.9%. The relative expansion uncertainty of the four plasma samples were 3.10%, 2.34%, 2.16%, and 1.73%, respectively. The results of the external quality assessment program showed that the pass rates of the 202013 and 202014 samples were 80% and 85%, respectively. Conclusions:The study established a candidate reference method of ID-LC/MS/MS for the measurement of plasma normetanephrine. The method is accurate, precise and simple, and is expected to be used as a reference method for the determination of plasma normetanephrine, and can be applied to quantify the samples of the external quality assessment program.