BACKGROUND:Croton cream can activate ERK pathways and have anti-apoptotic effects on neuronal cells.It is not clear whether it synergistically exerts anti-apoptotic effects by inhibiting the activation of JNK and p38 pathways. OBJECTIVE:To explore the effects and mechanisms of croton cream on neuronal damage and apoptosis in the ischemic cortex of rats with cerebral ischemia-reperfusion injury. METHODS:(1)Ninety Sprague-Dawley rats were randomly divided into sham operation group,model group,croton cream low-dose group,croton cream medium-dose group,croton cream high-dose group and nimodipine group,with 15 rats in each group.Except for the sham operation group,animal models of middle cerebral artery occlusion were prepared in rats by the thread method.Rats in the three croton cream groups were given 20,40,and 60 mg/kg croton cream,respectively.Rats in the sham operation and model groups were given the same amount of normal saline,once a day,for 7 consecutive days.The optimal concentration of croton cream,namely the high dose of croton cream,was selected based on neurological deficit score,TTC staining,brain tissue water content,hematoxylin-eosin staining and Nissl staining.(2)Another 120 Sprague-Dawley rats were randomly divided into sham operation group,model group,croton cream group,JNK inhibitor group,croton cream+JNK inhibitor group,p38 MAPK inhibitor group,croton cream+p38 MAPK inhibitor group,and nimodipine group,with 15 rats in each group.Animal models of middle cerebral artery occlusion were prepared using the thread method in all the groups except in the sham operation group.Thirty minutes before modeling,10 μL of SP600125(JNK inhibitor)and 10 μL of SB203580(p38 MAPK inhibitor)were injected into the lateral ventricle of the rats,respectively.Rats in croton cream groups were intragastrically given 60 mg/kg croton cream.Seven days later,the JNK/p38 MAPK signaling pathway,apoptosis-related proteins and cell apoptosis were detected by western blot,TUNEL staining and flow cytometry,respectively. RESULTS AND CONCLUSION:(1)Compared with the sham operation group,neurological deficit score,cerebral water content,cerebral infarction volume and apoptosis rate were significantly increased in the model group(P<0.05),where nerve cells showed scattered distribution.Compared with the model group,neurological deficit score,water content of brain tissue and cerebral infarction volume were significantly decreased in the croton cream medium-dose group,high-dose group and nimodipine group(P<0.05),and the pathological morphology of nerve cells was significantly improved.(2)Compared with the JNK inhibitor group,p-JNK/JNK,p-p38/p38 and Bax expressions in rat brain tissue and the apoptotic rate were significantly decreased in the croton cream+inhibitor groups(P<0.05),while the expression of and Bcl-2 was significantly increased(P<0.05).To conclude,croton cream may inhibit the activation of JNK/p38 MAPK signaling pathway and reduce neuronal apoptosis to achieve neuroprotective effects in rats with cerebral ischemia-reperfusion injury.

Objective To explore the predictive value of lung ultrasound score on the severity of neonatal respiratory distress syndrome(NRDS).Methods The clinical data of 65 children with NRDS in our NICU from July 2021 to July 2022 were retrospectively analyzed,and 65 children were included in the NRDS group,while 40 children with other common pulmonary diseases(neonatal wet lung and infectious pneumonia)were selected as the other pulmonary disease group during the same period,and all children were examined by pulmonary ultrasound and X-ray to observe the children in both groups.The lung conditions of the two groups of children were observed:abnormal pleural line,disappearance of A line,isolated B line,fused B line,diffuse B line,lung consolidation,with or without bronchial inflation sign,and other lung ultrasound manifestations.The lung ultrasound scores of the two groups of children were compared,and the X-ray grading distribution of children in the NRDS group was analyzed,correlation between lung ultrasound scoring and X-ray grading was used by Pearson correlation analysis.The clinical value of lung ultrasound score in the differential diagnosis of NRDS and the severity of the disease was analyzed by receiver operator characteristic(ROC)curve.Results The proportion of solid lung,abnormal pleural line,disappearance of A-line,white lung detection,fused B-line,and bronchial inflation sign was significantly higher in the NRDS group than in the other lung disease groups,and the proportion of isolated B-line and double lung point detection was significantly lower than in the other lung disease groups,with statistically significant differences(P<0.05).The lung ultrasound scores of both lungs,left lung,right lung,bilateral lung,and base of both lungs were significantly higher in the NRDS group than in the other lung disease groups(P<0.05).With the increase of X-ray grading,the lung ultrasound score gradually increased,and there was a statistically significant difference between groups at each grade(P<0.05).Pearson correlation analysis showed that there was a significant positive correlation between lung ultrasound score and X-ray grade(r=0.704,P<0.05).The area under curve(AUC)of lung ultrasound score in differentiating NRDS from common lung diseases was 0.907,with sensitivity and specificity of 89.0%and 92.5%,respectively;the AUC of mild and moderate,moderate and severe NRDS in the differential diagnosis by lung ultrasound score was 0.914 and 0.933,respectively,which had high clinical value.Conclusion The lung ultrasound score has certain value in identifying NRDS.The lung ultrasound score can quantitatively assess the changes in the condition of NRDS,and the lung ultrasound and X-ray grading have good consistency,it has the advantages of radiation free,fast,and intuitive,and can be used as an effective method for early diagnosis of NRDS and evaluation of the severity of the disease.

ObjectiveTo investigate the intervention effect of heat shock protein 60 (HSP60) on learning and memory impairment induced by combined exposure to lead and hypertension in mice, and the relative mechanism of triggering receptor expressed on myeloid cells 2 (TREM2). Methods Specific pathogen-free C57BL/6J male mice were randomly divided into control group, hypertension group, lead-exposed group and lead-exposed + hypertension group, or into control group, heat shock protein 60 (HSP60) control group, lead-exposed + hypertension group and HSP60 intervention group, with 10 mice in each group. Mice of hypertension group and lead-exposed + hypertension group were intraperitoneally injected with angiotensin Ⅱ at a dose of 0.5 mg/(kg·d) for seven consecutive days to induce hypertension model. Mice of the lead-exposed group, lead-exposed + hypertension group, and HSP60 intervention group were given lead acetate drinking water with a mass concentration of 250.0 mg/L, while mice in the control group, hypertension group, and HSP60 control group were given purified water for 12 weeks. Mice of the HSP60 control group and HSP60 intervention group were intraperitoneally injected with a solution of HSP60 at a dose of 4 mg/kg body weight, every other day for a total of three times at the 12th week. The learning and memory ability of mice was detected using the Morris water maze test. The enzyme-linked immunosorbent assay was used to detect the levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in the hippocampal tissues of the mice. The relative expression of ionized calcium binding adaptor molecule-1 (IBA1) and TREM2 protein in the hippocampus of mice was detected using Western blot. Results i) The number of platform crossings of the mice in the hypertension group and the lead-exposed group was lower than that in the control group (both P<0.05). The escape latency of the mice on the third day was longer and the number of platform crossings was lower in the lead-exposed + hypertension group compared with the control group, hypertension group and lead-exposed group (all P<0.05). The levels of IL-1β, IL-6, and TNF-α in the hippocampus of the other three groups increased compared with the control group (all P<0.05). The relative expression of IBA1 protein in the hippocampus of lead-exposed group and lead-exposed + hypertension group increased (all P<0.05), while the relative protein expression of TREM2 decreased compared with the control group (all P<0.05). The levels of IL-1β, IL-6, TNF-α, and the relative protein expression of IBA1 protein in the hippocampus of the lead-exposed+hypertension group were higher (all P<0.05), and relative expression of TREM2 protein was lower (P<0.05) than those in the hypertension group. The level of TNF-α and the relative expression of IBA1 protein in the hippocampus of lead-exposed+hypertension group were higher than those in lead-exposed group (all P<0.05). ii) The escape latency of mice in the lead-exposed + hypertension group was longer than that in the control group (P<0.05), and the number of platform crossings was fewer than that in the control group (P<0.05). The escape latency of mice in the HSP60 intervention group was shortened (P<0.05), the number of platform crossings increased (P<0.05), and the levels of IL-1β, IL-6, TNF-α and relative expression of IBA1 protein decreased in the hippocampus (all P<0.05), while the relative expression of TREM2 protein increased (P<0.05) compared with the lead-exposed+hypertension group. Conclusion Combined exposure of lead and hypertension has a synergistic effect on learning and memory impairment in mice. The mechanism may be related to the inhibition of TREM2 expression by lead in the hippocampus of hypertensive mice and aggravating the neuroinflammatory response. Intervention with TREM2 receptor agonist HSP60 can alleviate learning and memory impairment in mice exposed to lead and hypertension by up-regulating TREM2 expression in the hippocampus.

Objective:To compare the effects of different test meals on postprandial triglycerides and to optimize the standard meal composition and the blood sampling protocol for the oral fat tolerance test.Methods:This study is a prospective, open-label, randomized, cross-over trial. In March 2023, 36 volunteers were recruited in Hebei General Hospital. They underwent a health examination and oral glucose tolerance test. Twenty-six healthy volunteers(11 males and 15 females) were included in this study, with an average age of(39.08±4.56) years. Each volunteer received 75 g protein meal, 75 g fat meal, 700 kcal fixed-calorie high-fat mixed meal, and a high-fat mixed meal with energy adjusted based on 10 kcal/kg body weight. A one-week washout period of regular diet was applied before each trial. Blood was collected at fasting status and 1, 2, 3, 4, 5, and 6 hours after a meal to detect serum triglycerides, total cholesterol, low density lipoprotein-cholesterol(LDL-C), high density lipoprotein-cholesterol(HDL-C), glucose, and insulin. The variations of postprandial metabolic indicators over time following the consumption of different test meals were analyzed. The disparities in postprandial metabolic responses between the two types of mixed meals were compared.Results:The protein meal, fat meal, fixed-calorie high-fat mixed meal, and adjusted-calorie high-fat mixed meal resulted in postprandial triglyceride increases of 22.45%, 115.40%, 77.14%, and 63.63%, and insulin increase of 560.43%, 85.69%, 554.18%, and 598.97%, respectively, and with reductions in total cholesterol, LDL-C, and HDL-C ranging from 5.64%-21.81%, respectively. The blood glucose changed slightly. Changes in metabolic indicators mainly occured within 4 hours. The comparison of the characteristics of postprandial triglycerides between the two high-fat mixed meals showed no statistically significant differences( P>0.05). Conclusion:A standardize protocol with a 700 kcal fixed-calorie high-fat mixed meal as test meal, and blood lipid levels measured at fasting and at 1, 2, 3, and 4 hours after consumption, can serve as an optimized approach for oral fat tolerance test.

Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of～260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.

Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal chronic interstitial lung disease characterized by a progressive decline in lung function, and current treatment options are limited. cAMP is one of the most important second messengers and plays a key role in relaxing airway smooth muscle cells and reducing inflammation. Phosphodiesterase (PDE) is a superfamily of enzymes, and PDE4 enzymes dominate 11 PDE superfamily enzymes, available in four isoforms-PDE4A, PDE4B, PDE4C and PDE4D, which selectively decompose cAMP, while PDE4 inhibitors increase cAMP levels by preventing cAMP from breaking down, thereby exerting anti-inflammatory, anti-remodeling effects and providing an attractive drug target for the treatment of IPF. This review summarizes knowledge about the association of pulmonary fibrosis with PKE4, as well as emerging preclinical studies and clinical trials regarding PDE4 inhibitors.

Objective To investigate the value of tumor volume to uterine volume ratio(N/U)combined with tumor apparent diffusion coefficient(ADC)in predicting the pathological grade of endometrial carcinoma(EC).Methods Data of 107 patients with EC admitted from July 2020 to January 2023 were retrospectively ana-lyzed.All patients underwent preoperative magnetic resonance imaging(MRI),and pathological diagnosis was used as the gold standard.Patients with low differentiation were included in the high grade group,and patients with medium and high differentiation were included in the low grade group.The factors affecting the pathological grading of EC patients were analyzed,and the value of MRI index in predicting the pathological grading of EC patients was analyzed.Results The pathological examination showed that there were 24 high-grade patients and 83 low-grade patients..Logistic multivariate regression analysis showed that N/U,ADC,rADC internal obturator muscle were factors affecting the pathological grade of EC patients(P<0.05).ROC curve results showed that the sensitivity of N/U,ADC,rADC internus obturator muscle and their combination to predict the pathological grading of EC patients were 70.83%,75.00%,79.17%,83.33%,the specificity were 71.08%,79.52%,78.31%,85.54%,and the AUC were 0.734,0.756,0.741 and 0.891.Conclusion The combination of N/U,ADC,rADC and obturator internal muscle was effective in predicting the preoperative pathological grading of EC patients.

ObjectiveBy observing the effect of modified Zhenwutang on the expression of superoxide dismutase 1（SOD1）， malondialdehyde（MDA）， advanced oxidation protein product（AOPP）， nuclear factor kappa-B（NF-κB） p65，p-p65，IL-1β， TNF-α in serum and renal tissue of adenine-induced chronic renal failure rats and the pathology of heart and kidney tissue， the possible mechanism of modified Zhenwutang delaying the progression of chronic renal failure complicated with heart disease was discussed. MethodFifty SPF male SD rats were divided into normal group 10 and model group 40 according to the random number table method. After one week of adaptive feeding， the experimental chronic renal failure complicated with cardiovascular disease rat model was established by intragastric administration of adenine 150 mg·kg^-1·d^-1. After the model was completed， 3 rats in the normal group and the model group were randomly selected to detect whether the model was successful. After successful modeling， the rats in the model group were divided into model group ， modified Zhenwutang low-dose group ， modified Zhenwutang medium-dose group， modified Zhenwutang high-dose group and Benazepril hydrochloride group according to the random number table method， with 6 rats in each group. Drugs were administered once a day for 4 weeks. At the end of the 17^th week of the experiment， 24-hour urinary total protein（24 h-UTP） and urine creatinine（UCr）were detected. At the end of the 17^th week， the rats in each group were anesthetized and the abdominal aorta was taken. After centrifugation， the supernatant was taken to detect triglyceride（TG）， total cholesterol（TC）， serum calcium（Ca）， serum potassium， serum phosphate， serum creatinine（Scr）， blood urea nitrogen（BUN）； the expression levels of serum AOPP， IL-1β and TNF-α were detected by enzyme linked immunosorbent assay（ELISA）. The pathological changes of heart and kidney tissues were observed by hematoxylin-eosin（HE）/Masson method. The ultrastructural changes of proximal renal tubules were observed by transmission electron microscopy . The kidney tissue expressions of SOD1， MDA， AOPP， NF-κB p65，p-p65，IL-1β and TNF-α were observed by immunohistochemistry. The kidney tissue expression levels of SOD1， NF-κB p65， IL-1β and TNF-α mRNA were observed by real-time polymerase chain reaction（Real-time PCR）. The kidney tissue expression levels of SOD1， MDA， NF-κB p65 and p-p65 were detected by Western blot. Result①Compared with the normal group， the experimental rats in the model group showed an increase in 24-hour UTP （P<0.01）and a decrease in UCr（P<0.01）. The experimental rats in the model group showed an increase in Cr， BUN， TG， TC， serum phosphate， and serum potassium（P<0.01）.The levels of AOPP， IL-1β and TNF-α in serum of rats in the model group were significantly increased（P<0.01）. In the model group， the glomerular balloon space was significantly widened， the renal interstitium was significantly widened with a large number of inflammatory cell infiltration， a large number of renal tubular lumens were blocked by brown deposits， and there were a large number of collagen fiber deposition in the renal interstitium. The collagen fibers around the renal vessels， outside the capsule wall of the renal capsule wall， glomerular basement membrane and renal tubular basement membrane were significantly increased， and the cardiac muscle fibers were significantly thickened. There was a small amount of inflammatory cell infiltration around the blood vessels， and a large number of collagen fibers around the cardiac vessels and between the myocardial cells. In the model group， high-density diamond-shaped needle-like crystals were observed in the proximal renal tubular epithelial cells of rats， with increased lysosomes， mitochondrial proliferation， mitochondrial cristae and dense mitochondrial outer membrane. The left ventricular diastolic wall thickness and systolic wall thickness of the experimental rats in the model group was increased in proximal renal tubular epithelial cells and their nuclei.In the model group， the expression of MDA， AOPP， NF-κB p65，p-p65 IL-1β and TNF-α in proximal renal tubular epithelial cells was significantly increased（P<0.01）， the expression of p-p65 in the nucleus of proximal renal tubular epithelial cells was significantly increased（P<0.01）， and the expression of SOD1 in proximal renal tubular epithelial cells was significantly decreased（P<0.01）. The kidney tissue expression of NF-κB p65， IL-1β and TNF-α mRNA in the model group was increased（P<0.01）， and the expression of SOD1 mRNA was decreased（P<0.01）. The kidney tissue expression of SOD1 protein in the model group was significantly decreased（P<0.01）. The kidney tissue expression of MDA， NF-κB p65 and p-p65 protein was increased （P<0.01）. ② Compared with the model group， after the intervention of modified Zhenwutang， 24 h-UTP was decreased （P<0.01）and UCr was increased（P<0.01）. Cr， BUN， TG， TC， serum phosphate， serum potassium was decreased （P<0.01）. Serum AOPP， IL-1β and TNF-α levels were decreased（P<0.01）. Cardiac and Renal pathological damage was reduced； mitochondrial damage in proximal renal tubules was reduced； the expression of MDA， AOPP， NF-κB p65， IL-1β， TNF-α in proximal renal tubular epithelial cells was decreased （P<0.01）， the expression of p-p65 in the nucleus of proximal renal tubular epithelial cells was significantly decreased （P<0.01）， and the expression of SOD1 in proximal renal tubular epithelial cells was significantly increased （P<0.01）. The kidney tissue expression of NF-κB p65， IL-1β， TNF-α mRNA was decreased （P<0.01）， and the expression of SOD1 mRNA was increased（P<0.01）. The kidney tissue expression of SOD1 protein was significantly increased （P<0.01）， and the expression of MDA， NF-κB p65 and p-p65 protein was decreased （P<0.01）. The Chinese medicine group showed a significant dose-effect trend. ConclusionModified Zhenwutang may reduce the production of oxidative stress and mitochondrial damage in proximal renal tubular epithelial cells， thereby reducing oxidative stress products and inhibiting the release of inflammatory factors caused by the activation of NF-κB signaling pathway， reducing the damage to heart and kidney tissues and functions， and delaying the progression of chronic renal failure complicated with heart disease， and the traditional Chinese medicine group has a dose-effect trend.

IPF is a chronic progressive interstitial lung disease of unknown etiology and poor prognosis, and despite receive treatment, most patients consideration are likely to progress or worsen. Integrins are heterodimer cell surface proteins that are promising therapeutic targets for intervention in pulmonary fibrosis. Alphav integrins are central to the development of fibrosis because they activate latent TGF-β, a known pro-fibrosis cytokine. The alphav subunit may form heterodimers with the β1, β3, β5, β6, or β8 subunits, one or more of which are essential for the development of pulmonary fibrosis, but their relative importance is unclear. This review summarizes the knowledge of the association of pulmonary fibrosis with alpha-val-integrins, as well as emerging preclinical studies and clinical trials of alpha-fibrosis inhibitors.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with unknown etiology, which is characterized by scarring of lung parenchyma, leading to reduced quality of life and premature death. At present, some studies have confirmed that hypothyroidism (HT) may play a role in the development of fibrosis. Many animal experiments have proved that thyroid hormone (TH) can inhibit pulmonary fibrosis by regulating glucose metabolism, improving mitochondrial function and inhibiting inflammation. This paper summarizes the correlation between TH and IPF, and deeply understands the relationship between TH and IPF, in order to have new treatment strategies for IPF in the future.