Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

OBJECTIVE To investigate the effect of the medical intelligent dispensing machine in the dispensing of pharmacy intravenous admixture services（PIVAS） parenteral nutrition drugs. METHODS From December 1st to 31st， 2023， 14 PIVAS staff members in Shandong Provincial Hospital Affiliated to Shandong First Medical University were selected to participate in manual dispensing and dispensing with the medical intelligent dispensing machine in the form of rotation. Ten prescribed formulas are prepared daily by each of the two groups. The dispensing efficiency and quality of specified parenteral nutrition drugs were compared between 2 groups， and the effects of the introduction of medical intelligent dispensing machine on the cleanliness class were also compared. RESULTS The medical intelligent dispensing machine group prepared a total of 310 bags of parenteral nutrition solution， while the manual dispensing group prepared a total of 306 bags； the time for drug dispensing per bag， the residual amount of drug liquid， the number of dispensing punctures， the leakage rate of finished infusion inlet and desquamation rate of vial glue plug in the medical intelligent dispensing machine group were less or lower than manual dispensing group （P＜ 0.05）. Before and after the introduction of the medical intelligent dispensing machine， the qualified rate of sedimentation bacteria detection in mixing operation room and horizontal laminar flow clean workbench in both groups was 100%. CONCLUSIONS The application of medical intelligent dispensing machine in the dispensing of PIVAS parenteral nutrition drugs can improve the efficiency of drug dispensing and improve the quality of finished infusion without affecting the cleanliness level of operation room and horizontal laminar flow clean workbench.

italic>Psidium guajava Linn. is an evergreen shrub or small tree of Psidium Linnaeus in the Myrtaceae family. One new glycoside (1) together with 3 known meroterpenoids (2-4) and 9 known glycosides (5-13) were isolated from the fruits of Psidium guajava Linn.. The structure of the new compound was elucidated by the spectroscopic data analysis of HR-ESIMS, 1D- and 2D-NMR, and it was named psiguaoside A (1). The known compounds were identified as guajadial (2), 4,5-diepipsidial A (3), psidial A (4), chrysin-8-C-β-D-glucoside (5), 2,6-dihydroxy-3,5-dimethyl-4-O-β-D-glucopyranosyl-benzophenone (6), quercetin-3-O-β-D-glucopyranoside (7), quercetin-3-O-xyloside (8), guaijaverin (9), avicularin (10), guavinoside E (11), guavinoside B (12), guajaphenone A (13). In the bioactivity assay, compound 3 exhibited significant inhibitory activitiy of U87 with IC₅₀ values of 8.379 μmol·L^-1.

Differentiated cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by overexpressing defined transcription factors. The process of reprogramming requires the interaction of various transcription factors to regulate the transformation of cell fate. Hoxd12 (Homeobox D12) is one of the transcription factors regulating the embryonic development of vertebrates, and it plays an outstanding role in the development of the limb, body axis formation, and cell signal transduction. However, any roles of Hoxd12 may play in the somatic cell reprogramming and the pluripotency of embryonic stem cells (ESCs) have not been reported. In this study, we firstly used 7 factors (Sall4-Esrrb-Jdp2-Glis1-Mkk6-Nanog-Kdm2b) and Yamanaka factors (Oct4-Klf4-Sox2) as the research model, combined with RNA interference (shRNA) and gene overexpression, to explore the mechanism of Hoxd12 in somatic cell reprogramming. Moreover, we used CRISPR/Cas9 gene editing to construct Hoxd12 knockout embryonic stem cell lines, and combined embryoid body formation (EB) and RNA sequencing (RNA-seq) to explore the function of Hoxd12 in the pluripotency of ESCs. The conclusions are as follows: (1) Knocking down of Hoxd12 inhibits 7 factor-induced reprogramming (

Objective:To investigate the clinical effect of open reduction and internal fixation for the treatment of double-column acetabular fractures by lateral rectus abdominis approach.Methods:A retrospective case series study was conducted to analyze the data of 44 patients with double-column acetabular fractures admitted to Shandong Provincial Hospital Affiliated to Shandong First Medical University from June 2015 to June 2019. There were 29 males and 15 females, with the age of 21-72 years [(41.3±8.4)years]. All patients were treated by open reduction and internal fixation through a single lateral rectus abdominis approach. Operation time, intraoperative blood loss and fracture healing time were recorded. The quality of fracture reduction was assessed according to the Matta reduction criteria, and hip function by the modified Merle D'Aubigne and Postel score at last follow-up. Postoperative complications were observed.Results:A total of 40 patients were followed up and 4 patients were lost to follow-up. The follow-up time was 12-46 months [(30.5±6.4)months]. The operation time ranged from 45 to 150 minutes[(111.2±20.6)minutes], and the intraoperative blood loss was 200-1 200 ml [(398.5±78.5)ml]. The fractures were healed, with the healing time of 10 to 16 weeks [(11.8±3.3)weeks]. At last follow-up, according to the Matta criteria, the results were excellent in 29 patients, good in 7, fair in 3, poor in 1, with the excellent and good rate of 90%. At last follow-up, according to the Merle D'Aubigne and Postel score, the results were excellent in 27 patients, good in 6, fair in 6, poor in 1, with the excellent and good rate of 83%. One patient had heterotopic ossification with no impact on hip function, and no special treatment was given. One patient with the reaction of foreign body was finally controlled by anti-infection treatment, and the internal fixation was removed again one year after operation. Three patients with mild osteoarthritis were relieved by oral anti-inflammatory and analgesic drugs. Two patients with deep venous thrombosis of lower extremities were cured by anti-coagulation therapy such as low molecular weight heparin.Conclusions:The single rectus abdominis approach for open reduction and internal fixation of double-column acetabular fractures can take into account the anterior column, quadrilateral body and posterior column. Meanwhile, this approach has advantages of satisfactory acetabular reduction and functional recovery, and less postoperative complications, suggesting an alternative procedure for treatment of double-column acetabular fractures.

Objective:To investigate the application value of magnetic resonance neurography (MRN) in pelvic fractures with lumbosacral plexus injury.Methods:From January 2014 to June 2020, data of 9 patients with pelvic fractures combined with lumbosacral plexus injury who were diagnosed with MRN and were performed surgical treatment were analyzed retrospectively. Among them, there were 8 males and 1 female, aged from 18 to 54 years, with an average age of 40.6±11.0 years. There were 2 fresh fractures within 3 weeks and 7 old pelvic fractures in 9 patients. According to AO classification, there were 6 cases of C1.3 type, 3 cases of C3 type. According to Denis classification of sacral fracture, there were 8 cases of Denis II type, 1 case of Denis III. Gibbons classification of nerve injury: 2 cases of grade II, 4 cases of grade III, 3 cases of grade IV; According to the criteria by the Nervous Injury Committee of British Medical Research Council (BMRC): 2 cases of M1, 3 cases of M2, 2 cases of M3, 2 cases of M4. Before the operation, the MRN technology was used to accurately locate the location and extent of the lumbosacral nerve injury, and nerve exploration release or internal fixation combined with nerve exploration release was employed for treatment.Results:All 9 patients underwent surgery successfully. The operation time ranged from 150 to 360 min, with an average of 217.8±63.8 min; intraoperative blood loss ranged from 200 to 1 100 ml, with an average of 388.9±293.4 ml. All patients were followed up for 21.6±19.3 months. All the fractures were healed, and the healing time was 12.7±2.2 months (range, 10-18 months). At the last follow-up, Gibbons classification of nerve injury: 3 cases of grade I, 5 cases of grade II, and 1 case of grade III. According to the criteria of BMRC: the muscle strength achieved M5 in 6 cases, M4 in 2 cases, M3 in 1 case. One patient developed a urinary system infection 2 months after discharge and recovered after treatment.Conclusion:MRN technique can assist the surgeon to fully understand the compression and traction damage of the lumbosacral nerve by the fracture before the operation, and make clear qualitative and localized diagnosis of the nerve damage, making the operation more precise and minimally invasive, which is a supplement to the traditional diagnosis method of lumbosacral plexus injury.

Objective:To explore the clinical diagnosis and treatment experience of pelvic fracture complicated with anterior sacroiliac joint dislocation.Methods:The data of 19 patients with pelvic fracture and anterior sacroiliac joint dislocation admitted from June 2013 to September 2019 were retrospectively analyzed. There were 12 males and 7 females; aged 9-67 years, with an average of 28.0 years. There were 11 cases of traffic accident injury, 6 of falling injury and 2 of crashing injury caused by machine extrusion. According to the Tile classification, there were 8 cases of type C1, 2 of type C2, and 9 of type C3; 6 cases of modified mangled extremity severity score (MESS) were greater than or equal to 7, of which 2 cases underwent hip amputation, 4 cases underwent king-steelquis semipelvectomy. 13 cases underwent limb-salvage surgery, of which 3 cases underwent external fixation surgery, and the remaining 10 cases underwent open reduction and internal fixation with steel plate. The reduction quality was evaluated according to the Matta imaging criteria of pelvis, the pain was evaluated according to the visual analogue scale (VAS), and the pelvic function was evaluated according to the Majeed score.Results:The operation time was 2 to 4 hours, with an average of 3.2 hours; the intraoperative blood loss was 400 to 1 200 ml, with an average of 768.4 ml. The 18 surviving patients were followed up for 6 to 24 months, with an average of 11.6 months. One of the 6 amputation patients died one week after the operation due to septic shock and multiple organ failure. The overall survival rate of the patients was 94.7% (18/19), and the amputation rate was 31.6% (6/19). The pelvic fractures of the 18 surviving patients were all healed, and the fracture healing time was 3 to 6 months, with an average of 4.2 months. No delayed union or nonunion occurred. At the last follow-up of the 18 surviving patients, the VAS was 2.4±1.9 points (range, 0-6 points). Among them, there were no pain in 3 cases, mild pain in 9 cases and moderate pain in 6 cases. At the last follow-up, 13 patients undergoing limb salvage treatment evaluated the quality of reduction according to Matta imaging criteria. Among them, 6 cases were excellent, 4 were good, 2 were fair, and 1 was poor. The excellent and good rate was 76.9% (10/13). The Majeed functional score was 81.8±11.9 points (range, 53-95 points). Among them, 6 cases were excellent, 5 were good, 1 was fair, and 1 was poor. The excellent and good rate was 84.6% (11/13). In the limb salvage treatment group, 4 patients with lumbosacral nerve injury caused limited hip joint movement function, and unilateral lower limb sensation and movement were weakened. After neurolysis and nutritional support treatment, the patient's sensorimotor function was significantly improved.Conclusion:The mortality and disability rate of pelvic fractures combined with anterior sacroiliac joint dislocation is high. In order to save the patient's life, early diagnosis of limb injury and early surgical intervention should be performed. If necessary, hip disarticulation or king-steelquis should be selected.

OBJECTIVE: To investigate the viral etiology and allergen distribution in infants and young children at high risk of asthma during a wheezing episode. METHODS: A total of 135 infants and young children at high risk of asthma were enrolled who were admitted due to asthmatic bronchitis or asthmatic bronchopneumonia between April 2016 and August 2017. Fluorescent probe PCR was used to measure influenza A (Flu A), respiratory syncytium virus (RSV), adenovirus (ADV), parainfluenza virus (PinF), human rhinovirus (HRV), human partial lung virus (hMPV) and human bocavirus (HBoV) in nasopharyngeal aspirates. ImmunoCAP was used to measure inhaled allergens, food allergens, and total IgE concentration. RESULTS: Among the 135 patients, the overall virus detection rate of nasopharyngeal aspirates was 49.6%, and HRV had the highest detection rate of 25.2%, followed by HBoV (9.6%), RSV (8.1%), PinF (5.9%), Flu-A (3.7%), ADV (1.5%) and hMPV (0.7%). The 1-3 years group had a significantly higher detection rate of HRV than the <1 year group (P<0.05). The positive rate of allergen screening was 59.3%, with 44% for inhaled allergens and 89% for food allergens. Among the inhaled allergens, dust mites had the highest positive rate of 77%, followed by mould (37%), pollen (26%) and animal dander (9%). Among the food allergens, egg white had a positive rate of 73% and milk had a positive rate of 68%. The <1 year group had a significantly higher positive rate of inhaled allergens than the 1-3 years group (P<0.05). The 1-3 years age group had a significantly higher level of T-IgE than the <1 year group (P<0.05). The positive virus group had a significantly higher positive rate of inhaled allergens than the non-virus group (P<0.05). The children with the second wheezing episode had significantly higher positive rates of inhaled allergens and food allergens and level of T-IgE than those with the first wheezing episode (P<0.05). The children with the second wheezing episode also had significantly higher positive rates of dust mites and mould than those with the first wheezing episode (P<0.05). CONCLUSIONS Early HRV infection and inhaled allergen sensitization are closely associated with the development of wheezing in infants and young children at high risk of asthma.
Allergens ; Animals ; Asthma ; Child ; Child, Preschool ; Egg Hypersensitivity ; Humans ; Infant ; Pyroglyphidae ; Respiratory Sounds

Managing the dysregulated host response to infection remains a major challenge in sepsis care. Chinese treatment guideline recommends adding XueBiJing, a five-herb medicine, to antibiotic-based sepsis care. Although adding XueBiJing further reduced 28-day mortality modulating the host response, pharmacokinetic herb-drug interaction is a widely recognized issue that needs to be studied. Building on our earlier systematic chemical and human pharmacokinetic investigations of XueBiJing, we evaluated the degree of pharmacokinetic compatibility for XueBiJing/antibiotic combination based on mechanistic evidence of interaction risk. Considering both XueBiJing‒antibiotic and antibiotic‒XueBiJing interaction potential, we integrated informatics-based approach with experimental approach and developed a compound pair-based method for data processing. To reflect clinical reality, we selected for study XueBiJing compounds bioavailable for drug interactions and 45 antibiotics commonly used in sepsis care in China. Based on the data of interacting with drug metabolizing enzymes and transporters, no XueBiJing compound could pair, as perpetrator, with the antibiotics. Although some antibiotics could, due to their inhibition of uridine 5'-diphosphoglucuronosyltransferase 2B15, organic anion transporters 1/2 and/or organic anion-transporting polypeptide 1B3, pair with senkyunolide I, tanshinol and salvianolic acid B, the potential interactions (resulting in increased exposure) are likely desirable due to these XueBiJing compounds' low baseline exposure levels. Inhibition of aldehyde dehydrogenase by 7 antibiotics probably results in undesirable reduction of exposure to protocatechuic acid from XueBiJing. Collectively, XueBiJing/antibiotic combination exhibited a high degree of pharmacokinetic compatibility at clinically relevant doses. The methodology developed can be applied to investigate other drug combinations.

One undescribed and two known furocoumarins were isolated from the stems of the Clausenalansium through a series of isolation and purification approaches including HPD-100 macroporous resin column, silica gel, reverse phase C₁₈ and so on. Their structures were determined to be 8-[(2S,3S,6E)-2,3-epoxy-3,7-dimethyl-oct-6-enyloxy] psoralen (1), 8-(7',8'-epoxygeranyloxy) psoralen (2) and 8-[(2E)-6-oxo-3,7-dimethyloct-2-enyloxy] psoralen (3) by spectroscopic methods. Compound 1 is a new furocoumarin. Compound 2 showed cytotoxicity to H460 (IC₅₀ = 43.94 μmol·L^-1) and compound 3 showed cytotoxicity to HeLa (33.76 μmol·L^-1) through the cytotoxic tests against five human cancer cell lines (H460, H7402, HCT-8, HeLa and MCF-7) for all compounds.