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: To observe the characteristics of changes in non-invasive hemodynamic parameters in neonates with septic shock so as to provide clinical reference for diagnosis and treatment. METHODS: A observational study was conducted. The neonates with sepsis complicated with septic shock or not admitted to neonatal intensive care unit (NICU) of the First Affiliated Hospital of Shantou University Medical College were enrolled as the study subjects, who were divided into preterm infant (< 37 weeks) and full-term infant (≥ 37 weeks) according to the gestational age. Healthy full-term infants and hemodynamically stable preterm infants transferring to NICU after birth were enrolled as controls. Electronic cardiometry (EC) was used to measure hemodynamic parameters, including heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), stroke volume index (SVI), cardiac output (CO), cardiac index (CI), systemic vascular resistance (SVR) and systemic vascular resistance index (SVRI), before treatment in the septic shock group, at the time of diagnosis of sepsis in the sepsis without shock group, and before the discharge from the obstetric department or on the day of transferring to NICU in the control group. RESULTS: Finally, 113 neonates with complete data and parental consent for non-invasive hemodynamic monitoring were enrolled, including 32 cases in the septic shock group, 25 cases in the sepsis without shock group and 56 cases in the control group. In the septic shock group, there were 17 cases at the compensated stage and 15 cases at the decompensated stage. There were 21 full-term infants (20 cured or improved and 1 died) and 11 premature infants (7 cured or improved and 4 died), with the mortality of 15.62% (5/32). There were 18 full-term infants and 7 premature infants in the sepsis without shock group and all cured or improved without death. The control group included 28 full-term infants and 28 premature infants transferring to NICU after birth. Non-invasive hemodynamic parameter analysis showed that SV, SVI, CO and CI of full-term infants in the septic shock group were significantly lower than those in the sepsis without shock group and control group [SV (mL): 3.52±0.99 vs. 5.79±1.32, 5.22±1.02, SVI (mL/m²): 16.80 (15.05, 19.65) vs. 27.00 (22.00, 32.00), 27.00 (23.00, 29.75), CO (L/min): 0.52±0.17 vs. 0.80±0.14, 0.72±0.12, CI (mL×s^-1×m^-2): 40.00 (36.67, 49.18) vs. 62.51 (56.34, 70.85), 60.01 (53.34, 69.68), all P < 0.05], while SVR and SVRI were significantly higher than those in the sepsis without shock group and control group [SVR (kPa×s×L^-1): 773.46±291.96 vs. 524.17±84.76, 549.38±72.36, SVRI (kPa×s×L^-1×m^-2): 149.27±51.76 vs. 108.12±12.66, 107.81±11.87, all P < 0.05]. MAP, SV, SVI, CO and CI of preterm infants in the septic shock group were significantly lower than those in the control group [MAP (mmHg, 1 mmHg ≈ 0.133 kPa): 38.55±10.48 vs. 47.46±2.85, SV (mL): 2.45 (1.36, 3.58) vs. 3.96 (3.56, 4.49), SVI (mL/m²): 17.60 (14.20, 25.00) vs. 25.50 (24.00, 29.00), CO (L/min): 0.32 (0.24, 0.63) vs. 0.56 (0.49, 0.63), CI (mL×s^-1×m^-2): 40.01 (33.34, 53.34) vs. 61.68 (56.68, 63.35), all P < 0.05], while SVR and SVRI were similar to the control group [SVR (kPa×s×L^-1): 1 082.88±689.39 vs. 656.63±118.83, SVRI (kPa×s×L^-1×m^-2): 126.00±61.50 vs. 102.37±11.68, both P > 0.05]. Further analysis showed that SV, SVI and CI of neonates at the compensation stage in the septic shock group were significantly lower than those in the control group [SV (mL): 3.60±1.29 vs. 4.73±1.15, SVI (mL/m²): 19.20±8.33 vs. 26.34±3.91, CI (mL×s^-1×m^-2): 46.51±20.34 vs. 61.01±7.67, all P < 0.05], while MAP, SVR and SVRI were significantly higher than those in the control group [MAP (mmHg): 52.06±8.61 vs. 48.54±3.21, SVR (kPa×s×L^-1): 874.95±318.70 vs. 603.01±111.49, SVRI (kPa×s×L^-1×m^-2): 165.07±54.90 vs. 105.09±11.99, all P < 0.05]; MAP, SV, SVI, CO and CI of neonates at the decompensated stage in the septic shock group were significantly lower than those in the control group [MAP (mmHg): 35.13±6.08 vs. 48.54±3.21, SV (mL): 2.89±1.17 vs. 4.73±1.15, SVI (mL/m²): 18.50±4.99 vs. 26.34±3.91, CO (L/min): 0.41±0.19 vs. 0.65±0.15, CI (mL×s^-1×m^-2): 43.34±14.17 vs. 61.01±7.67, all P < 0.05], while SVR and SVRI were similar to the control group [SVR (kPa×s×L^-1): 885.49±628.04 vs. 603.01±111.49, SVRI (kPa×s×L^-1×m^-2): 114.29±43.54 vs. 105.09±11.99, both P > 0.05]. CONCLUSIONS Full-term infant with septic shock exhibit a low cardiac output, high vascular resistance hemodynamic pattern, while preterm infant with septic shock show low cardiac output and normal vascular resistance. At the compensated stage the hemodynamic change is low output and high resistance type, while at the decompensated stage it is low output and normal resistance type. Non-invasive hemodynamic monitoring can assist in the identification of neonatal septic shock and provide basis for clinical diagnosis and treatment.
Humans ; Shock, Septic/physiopathology* ; Infant, Newborn ; Hemodynamics ; Female ; Male ; Case-Control Studies ; Infant, Premature

Small molecule drug screening technology is continuously evolving and expanding along with drug discovery,and the innovation in drug screening technology can improve the research and development efficiency and success rate,shorten the cycle time,and reduce the cost.From traditional screening technologies based on known active compounds and high-throughput screening(HTS)to new technologies such as structure-based drug discovery(SBDD),fragment-based drug discovery(FBDD),DNA encoded compound library(DEL)and proteolysis targeting chimeras(PROTAC),small molecule drug screening technologies are continuously broadening the market potential for small molecule drugs.This article will provide an overview of the current status of small molecule drug screening technology,systematically review each technique along with their advantages and disadvantages,and offer essential insights for the development of new small molecule drug screening technologies.

【Objective】 To investigate the frequency of platelet antibodies in voluntary blood donors and patients in Zhongshan, Guangdong Province, and to study the specificity and cross-matching of platelet antibodies. 【Methods】 Platelet antibodies of blood donors and patients were screened by solid-phase immunoadsorption (SPIA), rechecked by flow cytometry (FCM), and antibody specificity was identified by PakPlus enzyme immunoassay, and platelet cross-matching was simulated by SPIA. 【Results】 A total of 1 049 blood donor samples and 598 patient samples were tested, with 6 (0.57%) and 49 (8.19%) samples positive for SPIA,respectively(P<0.05); In SPIA positive samples, the positive concordance rate of FCM in blood donors and patients was 100% vs 95%, and that of enzyme immunoassay was 100% vs 88%. Among the initial screening positive samples of blood donors, 5 were anti-HLA Ⅰ antibodies, accounting for 83%, and 1 was anti CD36 antibody, accounting for 17%, with an incidence rate of 0.10%. Among the 14 samples of enzyme immunoassay positive patients, 2 were anti-GP Ⅱb/Ⅲa, 1 was anti-GP Ⅱa/Ⅱa, 8 were anti HLA Ⅰ, and 3 were mixed antibodies (HLA Ⅰ, GP Ⅱb/Ⅲa, GP Ⅰa/Ⅱa). According to the types of antibodies, HLA Ⅰ antibodies were the most common, accounting for 65% (11/17), followed by HPA related anti GP, accounting for 35% (6/17). The majority of patients had a platelet antibody positive typing rate below 30%, accounting for 71.4% (10/14). 【Conclusions】 The positive rate of platelet antibody of patients in Zhongshan area is significantly higher than that of voluntary blood donors, and most of them are anti-HLA Ⅰ and anti-GP, and the incidence of anti-CD36 is extremely low. Therefore, it is necessary to establish a known platelet antigen donor bank, and at the same time, carry out platelet antibody testing and matching of patients, which is helpful to solve the issue of platelet transfusion refractoriness.

Objective:To explore the neuroprotective effects and mechanisms of memantine on sepsis-associated encephalopathy (SAE) model mice.Methods:Totally 90 male C57BL/6J mice aged 8-12 weeks were randomly divided into 3 groups (with 30 mice in each group) : sham group, model group and memantine group. The SAE mouse model was established by cecum ligation and puncture while mouse in sham group received open and closed abdomen only. The mice in the memantine group were irrigation with memantine (15 mg · kg -1· d -1) 3 hours before surgery and 7 consecutive days after modeling. The mice in the model group and sham group were irrigation with an equal volume of 0.9% sodium chloride solution. The 7-day survival rate was observed, neurobehavioral and cognitive function scores of each group of mice after modeling were assessed.Blood-brain barrier permeability was measured by detecting the content of Evans blue. Immunofluorescence staining was used to detect the expression of astrocytes. Enzyme linked immunosorbent assay was conducted to detect cellular inflammatory factors and the glutamic acid content detection kit was used to detect the expression of glutamic acid. All data were analyzed by Graphpad Prism 8.3.0 software, survival rate was analyzed using Kaplan-Meier survival curve.Multigroup comparisons were conducted by one-way ANOVA or Kruskal-Wallis test. Results:(1) There was a statistically significant difference in the 7-day survival rate among the three groups of mice after modeling ( F=24.11, P<0.01), and the 7-day survival rate of the memantine group was higher than that of the model group (57% (17/30), 27% (8/30), P<0.01). (2)The behavioral results showed that after 7 days of modeling, there were statistically significant differences in the total distance of the open field test, central area stay time, four corner area stay time, neurobehavioral scores, pole climbing test, and preference index for new object recognition test among the three groups of mice ( F/ χ2=17.67, 17.30, 9.39, 14.06, 10.36, 14.81, all P<0.05).The neurobehavioral score, pole climbing test score, preference index for new object recognition test, total distance of open field test, and central area stay time of the model group were all lower than those of the sham group (all P<0.05), while four corner area stay time of the model group was higher than that of the sham group ( P<0.05).The total distance of open field test (1 564.07(1 363.24, 1 988.19) cm, 913.91 (574.32, 1 096.23) cm), central area stay time (5.21 (4.91, 8.76) s, 1.09 (0.25, 1.64) s), neurobehavioral scores (9.75±0.50, 8.25±0.50), pole climbing test scores (5.67±0.52, 4.56±0.53), and preference index for new object recognition test (56.50±10.59, 26.84±2.91) of the memantine group were all higher than those of the model group (all P<0.05). The four corner area stay time was lower than that of the model group ((480.30±50.64) s, (529.80±36.20) s, P<0.05).(3)The comparison of molecular indicators showed that there were statistically significant differences in the content of Evans blue in the brain, the number of astrocytes in the hippocampus and cerebral cortex, pro-inflammatory cytokines (TNF-α、IL-1β、IL-6), anti-inflammatory cytokines (IL-10), and glutamic acid among the three groups of mice ( F/ χ2=8.84, 6.43, 28.46, 23.63, 12.23, 16.04, 69.22, 6.65, all P<0.05).The content of Evans blue, the number of astrocytes in the hippocampus and cerebral cortex, the expression of TNF-α、IL-1β、IL-6, and glutamate in the model group were all lower than those in the sham group(all P<0.05). The levels of IL-10 in the model group was lower than that in the sham group ( P<0.05).The content of Evans blue ((5.67±1.38)μg/g, (11.08±2.79)μg/g), the number of astrocytes in the hippocampus (16.50 (13.75, 22.25)/μm 2), 80.00 (73.50, 83.50)/μm 2) and the cerebral cortex (40.00 (29.00, 48.00)/μm 2, 81.50 (72.25, 89.00)/μm 2) in the memantine group were lower than those in the model group (all P<0.05).The pro-inflammatory factor TNF-α, IL-1β, IL-6 and glutamic acid expression in the memantine group were lower than those in the model group (all P<0.05), and the anti-inflammatory cytokine IL-10 was higher than that in the model group ( P<0.05). Conclusions:Memantine can improve the neurobehaviors and cognitive functions of SAE mice through improving the integrity of the damaged blood-brain barrier, alleviating inflammation in the brain, as well as reducing glutamate levels in the brain.

Objective To study the medication law of Professor Qian Ying in the treatment of primary liver cancer based on data mining technology;To provide ideas for the clinical treatment of primary liver cancer.Methods Outpatient TCM prescriptions of Professor Qian Ying for the treatment of liver cancer from November 2008 to August 2020 were collected,and a data table was established after sorting.The drug frequency,property and taste and tropism were analyzed using Excel 2019.The medical case analysis module of the Great Physician Inheritance Platform was used to analyze the core drugs,the symbiosis analysis between drug pairs,the drug association analysis,and the drug clustering analysis of the screened TCM prescriptions.Results Totally 108 prescriptions were included,involving 188 kinds of Chinese materia medica,with a total frequency of 1 322 times.High-frequency drugs included Hedyotis Sinensis,Angelicae Sinensis Radix,Visci Herba,Curcumae Radix,Salviae Miltiorrhizae Radix et Rhizoma,etc.The medicinal properties were mainly cold,mild and warm,and the tastes were mainly bitter,sweet and pungent,and the main meridians were liver meridians,spleen meridians,kidney meridians and stomach meridians.There were 9 pairs of high frequency drug combinations in drug association,such as Curcumae Radix-Polygoni Orientalis Fructus,Visci Herba-Curcumae Rhizoma.In the correlation analysis of drug disease,the ones with higher correlations include"stomachache-Salviae Miltiorrhizae Radix et Rhizoma""abdominal mass-Paeoniae Radix Rubra and Citri Reticulatae Pericarpium""tinnitus-Adenophorae Radix,Lycii Fructus,Visci Herba""prolonged sublingual collaterals-Curcumae Rhizoma,Polygoni Orientalis Fructus,Salviae Miltiorrhizae Radix et Rhizoma"and so on.Drug clustering could be divided into three potential drug clusters.Conclusion Professor Qian Ying often uses heat-clearing drugs,tonifying drugs,and promoting qi and blood circulation drugs to treat liver cancer,with Huqi Powder as the main formula and modified according to the syndromes.Clearing heat and detoxifying,soothing liver and relieving depression,removing blood stasis and regulating collatrals are used to treat its symptoms,and tonifying qi and invigorating spleen,regulating liver and nourishing liver and kidney are used to treat its essence.

Objective:To understand the negative experiences of male master of nursing students during their studies.Methods:In this qualitative study, totally 11 male master of nursing students from China Medical University and Wuhan University were selected by purposive sampling in March 2023 for semi-structured interviews, and the data were analyzed using the KJ method.Results:Four themes were extracted: research pressure, pressure of time and finances, confusion about the future and development, and lack of identification with the nursing profession.Conclusions:Male master of nursing students experience negative emotions during their studies. Nursing educators and administrators should pay attention to the emotional management of male master of nursing students and gradually improve the training methods for nursing graduate students.

The most common neurological clinical manifestations of refeeding syndrome(RFS)are seizures and altered consciousness. This article presents a case in which central pontine myelinolysis(CPM) is a complication of RFS and describes its diagnosis and treatment process. This case highlights the importance of early cranial MRI examination to exclude CPM in patients with persistent hypoghosphatemia and altered consciousness during the course of RFS treatment.

Vitiligo， a skin pigmentation disorder caused by the loss of melanocytes in the basal layer of the skin， is manifested as creamy white or ivory white pigmented islands on the head， face， hair， areola， genitals， mucous membranes and traumatic areas with distinct borders， seriously affecting the patient’s social， physical， and mental health. The disease has attracted wide attention in the medical circle as a difficult aesthetic dermatosis with an increasing prevalence year by year. There are still blind spots in the hypotheses that autoimmunity， melanocyte autophagy， oxidative stress， autocytotoxicity， neurohumors， and genetic and environmental factors are associated with the pathogenesis of this disease. The commonly used Western medical therapies， including glucocorticoids， small-molecule antagonists， calcium-regulated neurophosphatase inhibitors， biologics， vitamin D derivatives， phototherapy， and surgery are flawed with side effects and prone to recurrence. Traditional Chinese Medicine （TCM） can treat vitiligo via a wide range of pathways and targets， with definite effects and low adverse reactions. Studies have demonstrated that TCM can promote autophagy of melanocytes and protect them from oxidative stress. However， there are few systematic summaries of the signaling pathways in the TCM treatment of vitiligo. Therefore， this paper introduces the main signaling pathways involved in the TCM treatment of vitiligo by reviewing the relevant articles published at home and abroad in recent years. Specifically， the signaling pathways include the molecular hydrogen-activated nuclear factor erythroid-related factor 2 （Nrf2）， tyrosine kinase receptor （c-Kit）， nuclear transcription factor-κB （NF-κB）， Janus tyrosine protein kinase （JAK）， mitogen-activated protein kinase （MAPK）， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）， and adenosine monophosphate-activated protein kinase （AMPK） signaling pathways.

Objective:To explore whether barium chloride (BaCl 2) preconditioning has the protective effect on lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) model in mice and the possible mechanism. Methods:Sixty 8-12 week old healthy C57BL/6 male mice were randomly divided into control group, ARDS model group and BaCl 2 pretreatment group, with 20 mice in each group. The BaCl 2 pretreatment group was continuously injected with BaCl 2 (4 mg/kg through the tail vein) for 3 days before ARDS model establishment. ARDS model was established by intratracheally injecting (3 mg/kg) LPS. The control group was intratracheally given the same volume of 0.9% normal saline. On 24th hour after ARDS model establishment, some mice were sacrificed for obtaining fresh lung tissue. And the right lower lobe of the lung was separated for observing the pathological changes of lung tissue while the left lung tissue was used to measure the wet/dry weight ratio (W/D) of the lung. Some mice were sacrificed for observing pulmonary microvascular permeability at 2nd hours after injecting Evans blue (EB) through tail vein. The left mice were killed for alveolar lavage to measure the levels of tumor necrosis factor-α (TNF-α) via enzyme linked immunosorbent assay (ELISA). Results:Comparing with the control group, ARDS model group showed typical ARDS pathological changes, which included the increased W/D ratio (4.951±0.161 vs. 3.449±0.299, P < 0.01) and the content of EB in the lung tissue (μg/g: 0.130±0.027 vs. 0.085±0.011, P < 0.01), the damaged alveolar wall structure, lung congestion and exudates in the alveoli, as well as amounts of inflammatory cells. The pathological score of lung injury (10.33±1.15 vs. 1.67±0.58) and the level of TNF-α in BALF (ng/L: 900.85±247.80 vs. 68.21±5.79) were significantly increased in the ARDS model group (both P < 0.01). Comparing with the ARDS model group, the lung W/D ratio (4.620±0.125 vs. 4.951±0.161) and the EB content in the lung tissue (μg/g: 0.108±0.011 vs. 0.130±0.027) of BaCl 2 pretreatment group were significantly reduced (both P < 0.01). And the damaged pulmonary structural BaCl 2 pretreatment group were significantly alleviated. In addition, the pulmonary pathological score (5.00±1.00 vs. 10.33±1.15) and the level of TNF-α in BALF (ng/L: 169.16±73.33 vs. 900.85±247.80) were significantly decreased (both P < 0.01). Conclusion:Barium chloride pretreatment can improve the lung histopathological changes of ARDS model mice induced by LPS by reducing the permeability of pulmonary capillaries and local inflammatory reaction.Barium chloride has the protective effect against LPS attack in mice model of ARDS.