Objective To explore the effect of Sangxing Zhike Formula in rats with cough vari-ant asthma(CVA)and its possible mechanism based on the cyclic adenosine monophosphate(cAMP)/cystic fibrosis transmembrane conductance regulator(CFTR)pathway.Methods SD rats were randomly divided into control group,model group,dexamethasone group(0.5 mg/kg)and low-,medium-,high-dose Sangxing Zhike Formula groups(9.6,19.2 and 38.4 g/kg)using a ran-dom number table method,with 9 rats in each group.Except for the control group,CVA rat models were established in the other groups.Rats in each group were administered the drug by gavage once a day for 14 consecutive days.The general conditions of rats in each group were observed.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of interleukin-1β(IL-1β)and interleukin-18(IL-18)in rat serum.Hematoxylin-eosin(HE)staining and periodic acid-Schiff(PAS)staining were used to observe the pathological changes in rat lung and bronchial tissues,and the acid-base balance of airway surface liquid(ASL)was measured.Western blot and real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)were used to detect the expression levels of pro-tein kinase A(PKA),CFTR protein and their mRNA in lung tissues of rats.Results Compared with the control group,rats in the model group showed listlessness,dull fur,slow weight gain,a significantly expanded area of alveolar septal consolidation,and a large number of inflammatory cell infiltrations around the bronchi.Compared with the model group,rats in each intervention group had better general conditions and reduced inflammatory infiltrations in lung tissues and bronchial lu-mens.Compared with the control group,the serum levels of IL-1 β and IL-18 in the model group were increased,and the pH values of ASL in the model group,low-dose Sangxing Zhike Formula group,medium-dose Sangxing Zhike Formula group,and high-dose Sangxing Zhike Formula group were all decreased,with statistically significant differences(P＜0.05).Compared with the model group,the serum levels of IL-1β and IL-18 in each intervention group were decreased,and the pH values of ASL in the dexamethasone group,medium-dose Sangxing Zhike Formula group,and high-dose Sangxing Zhike Formula group were increased,with statistically significant differences(P＜0.05).Compared with the control group,the expressions of PKA protein and PKA mRNA in the model group,low-dose Sangxing Zhike Formula group,and medium-dose Sangxing Zhike Formula group were all decreased,and the expressions of CFTR protein and CFTR mRNA in the model group and each intervention group were all decreased,with statistically significant differences(P＜0.05).Compared with the model group,the expressions of PKA protein and PKA mRNA in the dexametha-sone group and high-dose Sangxing Zhike Formula group were increased,and the expressions of CFTR protein and CFTR mRNA in the high-dose Sangxing Zhike Formula group were increased,with statistically significant differences(P＜0.05).Conclusion Sangxing Zhike Formula can im-prove the general conditions of CVA rats,regulate the acid-base balance of ASL,reduce airway in-flammatory cell infiltration andairway remodeling,and decrease the levels of inflammatory factors IL-1β and IL-18.Its mechanism may be related to the cAMP/CFTR pathway.

Objective:To observe the efficacy and safety of combined lienal polypeptide injection therapy in the treatment of Mycoplasma pneumoniae pneumonia（MPP）in children aged 3 to 14 years old in multiple clinical centers.Methods:A randomized，controlled，multi-center clinical study design was adopted.A total of 240 hospitalized children aged 3 to 14 years old with MPP from 7 hospitals from September 1，2023 to January 31，2024 were included.According to the severity of pneumonia，they were divided into the mild MPP group with 80 cases and the severe MPP/refractory MPP（SMPP/RMPP）group with 160 cases，and then randomly divided into the control group and the experimental group at a ratio of 1 ∶1，using the random number table method.After screening，subjects entered a treatment period of 5 to 7 days.The control group was treated with azithromycin，while the experimental group was treated with azithromycin plus lienal polypeptide injection .The recovery of lung CT，length of hospital stay，duration of fever，cough score，whether mild cases developed into severe or refractory cases，duration of hormone use，use of intravenous immunoglobulin（IVIG），bronchoscopy treatment，and immune function were observed between the two groups to evaluate the efficacy of lienal polypeptide injection.Adverse events after medication，vital signs，blood routine，urine routine，liver function，myocardial enzymes，renal function，and electrocardiogram were observed to evaluate the safety. Results:A total of 231 subjects have completed the trial in the 7 hospitals，including 118 cases in the experimental group and 113 cases in the control group.Main observation index：the rate of lung CT aggravation in the experimental group was lower than that in the control group（2.6% vs 15.3%， P<0.01），and the difference was statistically significant.Secondary indexes：there were no statistically significant differences in the length of hospital stay，duration of fever，cough score，duration of hormone use，whether IVIG treatment was used，the number of bronchoscopy treatment cases，and immunoglobulin between the two groups（all P>0.05）.However，the rate of cases of plastic bronchitis（PB）found under bronchoscopy in the experimental group was lower than that in the control group（0 vs 18.8%， P=0.03），and the difference was statistically significant.Among the mild MPP（72 cases），there were no statistically significant differences in the length of hospital stay，duration of fever，cough score，duration of hormone use，whether IVIG treatment was used，the number of bronchoscopy treatment cases，and the improvement rate of lung CT between the two groups（all P>0.05）.However，compared with the control group，the rate of cases developing into SMPP/RMPP in the experimental group was less（24.3% vs 48.6%， P=0.03），and the difference in IgG before and after treatment was small［0.53（-0.04，1.18）g/L vs 1.33（0.48，2.25）g/L， P=0.01］.Among the SMPP/RMPP cases（159 cases），the rate of cases of PB found under bronchoscopy in the experimental group was less than that in the control group（0 vs 20%， P=0.04），and the rate of cases with aggravated lung CT in the experimental group was less than that in the control group（1.3% vs 19.5%， P<0.01），and the improvement rate of lung CT in the experimental group was higher than that in the control group（88.8% vs 75.3%， P=0.03），with statistically significant differences.There were no statistically significant differences in the length of hospital stay，duration of fever，cough score，duration of hormone use，whether IVIG treatment was used，the number of bronchoscopy treatment cases，and immunoglobulin between the two groups（all P>0.05）.Two cases in the experimental group developed rashes，which improved after the drug was discontinued.There were no serious adverse reactions such as abnormal vital signs like dyspnea and cyanosis due to the use of lienal polypeptide injection.There were no obvious changes in blood routine，liver function，myocardial enzymes，renal function，electrocardiogram，and urine routine values before and after medication compared with the baseline. Conclusion:The combined use of lienal polypeptide injection in the treatment of MPP in children can reduce the probability of the transformation from mild cases to SMPP/RMPP，reduce the rate of aggravation of the image findings，promote the absorption of lung inflammation，reduce the rate of PB found under bronchoscopy，and has good safety.

Ribosome is an intracellular ribonucleoprotein particle that serves as the site of protein biosynthesis. Ribosomal dysfunction caused by mutations in genes encoding ribosomal proteins (RPs) and ribosome biogenesis factors (RBFs) can lead to a spectrum of diseases, collectively known as ribosomopathy. Phase separation is a thermodynamic process that produces multiple phases from a homogeneous mixture. The formation of membraneless organelles and intracellular structures, including ribosomes and nucleoli, cannot occur without the involvement of phase separation. Here, ribosome structure, biogenesis, and their relationship with ribosomopathy are systematically reviewed. The tissue specificity of ribosomopathy and the role of phase separation in ribosomopathy are particularly discussed, which may offer some clues for understanding the mechanisms of ribosomopathy. Then, some new ideas for the prevention, diagnosis, and treatment of ribosomopathy are provided.
Humans ; Ribosomes/physiology* ; Ribosomal Proteins/metabolism* ; Mutation ; Animals ; Cell Nucleolus/metabolism* ; Protein Biosynthesis ; Phase Separation

The pharmaceutical industry faces challenges in quality digitization for complex multi-stage processes, especially in small-sample systems. Here, an intelligent quality prediction and diagnostic (IQPD) framework was developed and applied to Tong Ren Tang's Niuhuang Qingxin Pills, utilizing four years of data collected from four production units, covering the entire process from raw materials to finished products. In this framework, a novel path-enhanced double ensemble quality prediction model (PeDGAT) is proposed, which combines a graph attention network and path information to encode inter-unit long-range and sequential dependencies. Additionally, the double ensemble strategy enhances model stability in small samples. Compared to global traditional models, PeDGAT achieves state-of-the-art results, with an average improvement of 13.18% and 87.67% in prediction accuracy and stability on three indicators. Additionally, a more in-depth diagnostic model leveraging grey correlation analysis and expert knowledge reduces reliance on large samples, offering a panoramic view of attribute relationships across units and improving process transparency. Finally, the IQPD framework integrates into a Human-Cyber-Physical system, enabling faster decision-making and real-time quality adjustments for Tong Ren Tang's Niuhuang Qingxin Pills, a product with annual sales exceeding 100 million CNY. This facilitates the transition from experience-driven to data-driven manufacturing.

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*

Neutralizing antibodies have been designed to specifically target and bind to the receptor binding domain (RBD) of spike (S) protein to block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus from attaching to angiotensin converting enzyme 2 (ACE2). This study reports a distinctive nanobody, designated as VHH21, that directly catalyzes the S-trimer into an irreversible transition state through postfusion conformational changes. Derived from camels immunized with multiple antigens, a set of nanobodies with high affinity for the S1 protein displays abilities to neutralize pseudovirion infections with a broad resistance to variants of concern of SARS-CoV-2, including SARS-CoV and BatRaTG13. Importantly, a super-resolution screening and analysis platform based on visual fluorescence probes was designed and applied to monitor single proteins and protein subunits. A spontaneously occurring dimeric form of VHH21 was obtained to rapidly destroy the S-trimer. Structural analysis via cryogenic electron microscopy revealed that VHH21 targets specific conserved epitopes on the S protein, distinct from the ACE2 binding site on the RBD, which destabilizes the fusion process. This research highlights the potential of VHH21 as an abzyme-like nanobody (nanoabzyme) possessing broad-spectrum binding capabilities and highly effective anti-viral properties and offers a promising strategy for combating coronavirus outbreaks.
Single-Domain Antibodies/immunology* ; Spike Glycoprotein, Coronavirus/metabolism* ; SARS-CoV-2/immunology* ; Animals ; Humans ; Antibodies, Neutralizing/immunology* ; Camelus ; COVID-19/immunology* ; Antibodies, Viral/immunology* ; Angiotensin-Converting Enzyme 2

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

OBJECTIVE: To design a portable respiratory device for transporting premature infants and explore its application effect in the in-hospital transportation of extremely premature infants in primary hospitals. METHODS: A prospective randomized controlled trial was conducted. The extremely premature infants born and transferred to neonatal intensive care unit (NICU) with oxygen therapy support from May to October in 2023 were selected and randomly divided into control group and observation group. The infants in the control group received respiratory support and in-hospital transportation using a traditional T-combination resuscitator connected to pure oxygen, and those in the observation group used a portable premature infant transport respiratory device designed and manufactured by medical staff to provide respiratory support and implement in-hospital transportation. The respiratory device for transporting premature infants is made of 304 stainless steel material, mainly consisting of a T-combination resuscitator, an air oxygen mixer, an air tank, a pure oxygen cylinder, a pressure reducing valve, a telescopic rod, a tray, a hook, a bottom plate, and four moving wheels, which can achieve precise control of the fraction of inspired oxygen (FiO₂) during transportation. The achievement rate of first-time target pulse oxygen saturation (SpO₂, achieving a target SpO₂ of 0.90-0.95 was considered as meeting the standard) and arterial partial pressure of oxygen (PaO₂) after being transferred to the NICU, as well as the manpower expenditure and time required for transportation of pediatric patients between the two groups were observed. RESULTS: A total of 73 extremely premature infants were enrolled, including 38 in the control group and 35 in the observation group. There was no significant difference in the gender, gestational age at birth, birth weight, mode of delivery, Apgar score at 1 minute and 5 minutes after birth, and oxygen therapy during the transportation between the two groups. The achievement rate of first-time target SpO₂ after NICU in the observation group was significantly higher than that in the control group [94.29% (33/35) vs. 26.32% (10/38), P < 0.05], the PaO₂ control range was better [mmHg (1 mmHg = 0.133 kPa): 85.50±6.36 vs. 103.00±2.83, P < 0.05], manpower expenditure and time required for transportation were significantly reduced [manpower expenditure (number): 2.14±0.35 vs. 3.17±0.34, time required for transportation (minutes): 10.42±0.76 vs. 15.54±0.34, both P < 0.05]. CONCLUSIONS The portable respiratory device for transporting premature infants is used for respiratory support during the transportation of extremely premature infants in primary hospitals. It can improve the achievement rate of target SpO₂, control PaO₂ within the target range, and avoid hypoxia or hyperoxia during transportation. The breathing apparatus is compact, easy to carry, can save labor resources and time during transport, is cost-effective, and is suitable for widespread application in primary hospitals.
Humans ; Infant, Newborn ; Transportation of Patients ; Prospective Studies ; Equipment Design ; Infant, Extremely Premature ; Intensive Care Units, Neonatal ; Infant, Premature

Objective To observe the ultrasonic manifestations of aggressive angiomyxoma(AAM).Methods Four patients with newly diagnosed AAM and 3 with recurrent AAM confirmed by pathology were retrospectively enrolled,and the ultrasonic manifestations were analyzed.Results Among 7 cases of AAM,the lesions located in subcutaneous regions of perineum in 3 cases,in both perineum and pelvic cavity in 2 cases,in pelvic cavity and in cervix each 1 case,with a median maximum diameter of 7.6 cm.The lesions mainly manifested as heterogeneous hypoechoic,scattered cord-like moderate/moderate-hyperechoic inside,regular or lobulated shape with finger-like protrusions,with clear boundary or unclear boundary with adjacent vagina/rectum.Layered structure could be observed with gray-scale ultrasound and CDFI.Conclusion AAM mainly affected pelvis and perineal region,often manifested as large lesion tended to infiltrate surrounding areas and form finger-like protrusions,most with clear boundaries and interior heterogeneous hypoechoic regions,also the characteristic stratified structures.