Abstract Backgroud Homocitrulline (Hcit), is involved in the pathological processes of some diseases. However, the role and function of Hcit (CBL) in human skin remains largely obscure. Objective To investigate the correlation of the level of Hcit in seborrheic keratosis, skin aging, and its clinical significance. Methods Immunohistochemistry was used to analyze the level of Hcit in skin lesions of seborrheic keratosis (SK), unaffected skin (distant 0.5 centimeters from SK lesion), and normal skin of healthy subjects in the control group. ELISA test was used to detect the serum level of CBL in SK patients and healthy subjects of different ages. Results Hcit was mainly localized in the nucleus of epidermal cells. In healthy control skin, the expression of Hcit increased with age and showed a positive correlation with age (the correlation coefficient was 0.806, p = 0.0002). The expressional level of Hcit in SK lesions was higher than that in healthy control skin (Z = −3.703, p = 0.0002). The serum level of CBL in healthy subjects and in SK patients increased with age (the correlation coefficient were 0.5763, p = 0.0032; 0.682, p = 0.004. respectively). The serum level of CBL in SK patients was higher than that in healthy subjects (Z = −2.19, p = 0.030). Study limitations The small serum sample size in the study. Conclusion The high expressional level of Hcit is correlated with seborrheic keratosis and skin aging. HCit may be one of the potential biomarkers of skin aging.

Abstract Aiming to provide a new way that preserves more active components in Eucommia ulmoides (EU) leaves, this paper utilizes 4 methods, i.e., microwave, steam, air heating, and frying, to process EU leaves before drying, and their respective effects on the leaves were evaluated. The antioxidant activity of EU leaves in vitro was measured by the DPPH free radical method; the contents of total flavonoids (TFC) and total phenols (TPC) were analyzed by spectrophotometry; and the contents of main active components were determined by high-performance liquid chromatography (HPLC). The results showed the pre-process improved the quality of the EU leaves. As a simple and fast process, the microwave process is the most effective technique in the retention of flavonoids and four active ingredients except aucubin. High power (800 W) and short time (2.5 min) are more conducive to the retention of active ingredients, with high antioxidant activity. Appropriate steam and frying processes also exhibited benefits for the active components. In particular, the samples treated with steam for 10 minutes showed great potential for industrial application with the highest antioxidant activity and polyphenol content. Therefore, proper pre-processing before drying should be conducted to effectively protect the active components of EU leaves.

Pulmonary fibrosis (PF) is a major public health issue with limited treatment options. As the active ingredient of the n-butanol extract of Amygdalus mongolica (BUT), amygdalin inhibits PF. However, its mechanisms of action are unclear and need further verification. Therefore, the purpose of the present studies was to investigate the anti-fibrotic effects of BUT on PF by serum metabolomics and the transforming growth factor β (TGF-β) pathway. Sixty male Sprague-Dawley rats were randomly divided into control, untreated PF, prednisone-treated (5 mg/kg), and BUT-treated (1.75, 1.25, 0.75 g/kg) groups, and the respective drugs were administered intragastrically for 21 days. The serum metabolomics profiles were determined by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) and metabolism network analysis. The expression of TGF-β1, Smad-3, Smad-7, and α-smooth muscle actin (α-SMA) was measured using a real-time polymerase chain reaction in the lung tissue. BUT significantly alleviated fibrosis by reducing the mRNA expressions of TGF-β1 (from 1.73 to 1.13), Smad-3 (from 2.01 to 1.19), and α-SMA (from 2.14 to 1.19) and increasing that of Smad7 (from 0.17 to 0.62). Twenty-eight potential biomarkers associated with PF were identified. In addition, four key biomarkers were restored to baseline levels following BUT treatment, with the lowest dose showing optimal effect. Furthermore, A. mongolica BUT was found to improve PF by the pentose phosphate pathway and by taurine, hypotaurine, and arachidonic acid metabolism. These findings revealed the mechanism of A. mongolica BUT antifibrotic effects and metabolic activity in PF rats and provided the experimental basis for its clinical application.

Abstract The AMC-HN-8 cell line and the primary human laryngeal epithelial cell lines were utilized in this work to explore the molecular mechanism of miR-548-3p regulating the gene DAG1 to induce the occurrence and malignant transformation of laryngeal carcinoma. Non-coding RNA miR-548- 3p overexpression plasmid, interference plasmid and blank plasmid were constructed, and the plasmids were transfected into AMC-HN-8 cells, respectively. Meanwhile, a non-transfected plasmid group and a human laryngeal epithelial primary cell group were set up. Five groups of cells were named as NC (Normal control), Model, Ov-miR-548-3p, Sh-miR-548-3p and Blank-plasmid group. The luciferase reporter experiment was used to analyze the regulation characteristics of hsa-miR-548-3p on dystrophin-associated glycoprotein 1 (DAG1). Immunofluorescence was used to analyze the relative expression characteristics of the protein DAG1. The cell cloning experiment was used to analyze the proliferation characteristics of AMC-HN-8. The scratch healing test was used to analyze the migration ability of AMC-HN-8. The transwell test was used to analyze the invasion ability of AMC-HN-8. The RT-PCR was used to analyze the expression level of miR-548-3p. Western blot experiments were used to analyze the expression of protein DAG1, laminin α2 (LAMA2) and utrophin (UTRN). The luciferase report experiment and immunofluorescence test found that the expression of DAG1 and miR-548-3p are positively correlated. Cell cloning, scratching and migration experiments identified that the activity of laryngeal cancer cells was positively correlated with the expression of DAG1. The results of Western blot analysis further strengthened the above conclusions. Through carrying out research on the cellular levels, our work has demonstrated that miR-548-3p regulated the content of protein DAG1, and then further induced malignant transformation of laryngeal carcinoma.

Resumen En este trabajo se utilizaron la línea celular AMC-HN-8 y la línea celular epitelial laríngea humana primaria, para explorar el mecanismo molecular regulador del miR-548-3p sobre el gen DAG1 para inducir la aparición y la transformación maligna del carcinoma laríngeo. Se construyeron el plásmido de sobreexpresión de miR-548-3p de ARN no codificante, el plásmido de interferencia y el plásmido en blanco, y los plásmidos se transfectaron en células AMCHN-8 respectivamente. Mientras tanto, se establecieron un grupo de plásmidos no transfectados y un grupo de células primarias epiteliales laríngeas humanas. Se nombraron cinco grupos de células como NC (control normal), modelo, OvmiR-548-3p, Sh-miR-548-3p y grupo de plásmido en blanco. El experimento indicador de luciferasa se utilizó para analizar las características de regulación de hsa-miR-548-3p en la glicoproteína 1 asociada a distrofina (DAG1). Se utilizó inmunofluorescencia para analizar las características de expresión relativa de la proteína DAG1. El experimento de clonación celular se utilizó para analizar las características de proliferación de AMC-HN-8. Se utilizó la prueba de cicatrización por rascado para analizar la capacidad de migración de AMC-HN-8. La prueba de transwell se utilizó para analizar la capacidad de invasión de AMCHN-8. Se utilizó RT-PCR para analizar el nivel de expresión de miR-548-3p. Se usó un experimento de transferencia Western (Western blot) para analizar las expresiones de la proteína DAG1, laminina α2 (LAMA2) y utrofina (UTRN). El experimento de reporte de luciferasa y la prueba de inmunofluorescencia encontraron que la expresión de DAG1 y miR-548-3p están positivamente correlacionadas. Los experimentos de clonación celular, rascado y migración, identificaron que la actividad de las células cancerosas de laringe se correlacionó positivamente con la expresión de DAG1. Los resultados del análisis de transferencia Western fortalecieron aún más las conclusiones anteriores. A través de la investigación a nivel celular, nuestro proyecto ha demostrado que miR-548-3p regula el contenido de la proteína DAG1 y luego induce la transformación maligna del carcinoma de laringe.

Abstract This article performed a model of osteoporosis rats using the method of ovariectomy and observed efficacy of Tianchang Capsule on treatment of osteoporosis rats. Comparing the effect with positive drug to explore the mechanism of Tianchang Capsule in postmenopausal osteoporosis. Female SD rats were randomly assigned to 6 groups (10 in each group): control (sham-treated), OVX (by ovariectomy), OVX+AL (by ovariectomy, received alendronate sodium), OVX+LTC (by ovariectomy, received low dosage Tianchang Capsule), OVX+MTC (by ovariectomy, received middle dosage Tianchang Capsule), OVX+HTC (by ovariectomy, received high dosage Tianchang Capsule). After ovariectomy operation, alendronate or Tian Chang capsule were given for 12 weeks. Bone metabolism was measured by bone mineral density (BMD). With 12-week treatment, BMD reduced in OVX group, in bone formation and resorption parameters increased however, pathological sections indicated destruction of trabecular bone structure in the meanwhile (P < 0.05 or P < 0.01). In alendronate sodium and Tianchang Capsule treatments groups, comparing with control, both treatments significantly increased BMD level and improved the trabecular bone tissue damage, also inhibit excessive actively bone resorption and bone formation (P < 0.05 or P < 0.01). Tianchang Capsule were used as good natural drugs for the treatment of ovariectomy induced osteoporosis rats, by increasing bone mineral density, bone formation and bone resorption.

Abstract This study aimed to prepare the total saponins from Panax japonicus (TSPJ), and investigate their protective effects on learning and memory ability of aging mice induced by D-galactose. The TSPJ product with content of 81.03% was obtained. Fifty mice were randomly divided into control, model, and low-, middle- and high-dose TSPJ groups. The D-galactose-induced aging model was established in model, and low-, middle- and high-dose TSPJ groups. Then, the low-, middle- and high-dose TSPJ groups were treated with 20, 40 and 80 mg/kg TSPJ by gavage, respectively, for 8 weeks. At the end of treatment, compared with model group, in 40 and 80 mg/kg TSPJ groups the brain aging symptoms were obviously moderated, the step-down latency was increased, the frequency of mistake was decreased, the brain index was increased, the brain tissue SOD and GSH-Px levels were increased, the brain tissue MDA level was decreased, and the brain tissue Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities were increased. In conclusion, TSPJ can reduce the brain tissue oxidative stress injury and protect the cell membrane transport capacity, thus improving the learning and memory ability in aging mice.

ABSTRACT The aim of this study was to detect the volatile components in co-fermented fruit wines made by Lycium ruthenicum Murray (LRM) and wine grapes using gas chromatography–mass spectrometry (GC-MS). A total of 52 kinds of volatile components were detected in the co-fermented fruit wines, more than those detected in commercially available Changyu dry red wine (30 kinds) and 0# wine (26 kinds) made by wine grapes in the laboratory. Esters (22 kinds) and alcohols (17 kinds) constituted a major proportion of co-fermented fruit wines, then followed by volatile acids, phenols, aldehydes and ketones. The relative intensity of aroma in the co-fermented fruit wines was greater than that of the Changyu wine and 0# wine, exhibiting a comprehensive fruit and floral aroma profile. Additionally, grape wines (containing Changyu wine and 0# wine) were distinguished from the co-fermented fruit wines (1#–9#), 1# wines distinguished from the other co-fermented fruit wines (2#–8#) in second layer of clustering, indicating that the composition of raw material and fermentation conditions were the main influencing factor in the attributes of volatile components. Overall, co-fermented fruit wines possess more advantages in composition of volatile components and aromas, which showed a richer volatile and aroma structures.

Abstract Background: Unsubstantiated concerns have been raised on the potential correlation between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and infertility, leading to vaccine hesitancy in reproductive-aged population. Herein, we aim to evaluate the impact of inactivated SARS-CoV-2 vaccination on embryo ploidy, which is a critical indicator for embryo quality and pregnancy chance. Methods: This was a retrospective cohort study of 133 patients who underwent preimplantation genetic testing for aneuploidy (PGT-A) cycles with next-generation sequencing technology from June 1st 2021 to March 17th 2022 at a tertiary-care medical center in China. Women fully vaccinated with two doses of Sinopharm or Sinovac inactivated vaccines (n = 66) were compared with unvaccinated women (n = 67). The primary outcome was the euploidy rate per cycle. Multivariate linear and logistic regression analyses were performed to adjust for potential confounders. Results: The euploidy rate was similar between vaccinated and unvaccinated groups (23.2 ± 24.6% vs. 22.6 ± 25.9%, P = 0.768), with an adjusted β of 0.01 (95% confidence interval [CI]: -0.08–0.10). After frozen-thawed single euploid blastocyst transfer, the two groups were also comparable in clinical pregnancy rate (75.0% vs. 60.0%, P = 0.289), with an adjusted odds ratio of 6.21 (95% CI: 0.76–50.88). No significant associations were observed between vaccination and cycle characteristics or other laboratory and pregnancy outcomes. Conclusions: Inactivated SARS-CoV-2 vaccination had no detrimental impact on embryo ploidy during in vitro fertilization treatment. Our finding provides further reassurance for vaccinated women who are planning to conceive. Future prospective cohort studies with larger datasets and longer follow-up are needed to confirm the conclusion.

OBJECTIVES: Geriatric nutritional risk index (GNRI) might predict the all-cause mortality in patients with heart failure (HF). We performed a meta-analysis to evaluate the correlation between GNRI and all-cause mortality in patients with HF. METHODS: We searched the PubMed, Medline, Cochrane Library, and Embase databases for clinical trials investigating the association between GNRI and all-cause mortality in patients with HF, having the primary endpoint as all-cause mortality. RESULTS: In total, nine studies involving 7,659 subjects were included in the systematic review and meta-analysis. The results indicated that major risk and moderate risk GNRI (GNRI<92) was associated with an increased risk of all-cause mortality in elderly patients with HF (hazard ratios [HR] 1.59, 95% confidence intervals [CI] 1.37-1.85). Low risk GNRI (GNRI<98) group predicted all-cause mortality in elderly HF patients (HR 1.56, 95%CI 1.12-2.18) when compared with the high GNRI value group. A subgroup analysis indicated that the relationship between GNRI and HF might differ based on the subtype of heart failure. CONCLUSIONS: GNRI is a simple and well-established nutritional assessment tool to predict all-cause mortality in patients with HF.

The etiology of subacute combined degeneration (SCD) of the spinal cord is closely associated with vitamin B12 (VitB12) deficiency. The clinical manifestations of SCD are complex and vary substantially. Due to some SCD patients with atypical manifestations and concomitant autoimmune disorders, the probability of misdiagnosis and missed diagnosis is still relatively high in the early stage. We report the cases of two patients who were missed or misdiagnosed at another hospital because of the normal initial VitB12 level and partial overlap of clinical manifestations, finally diagnosed as SCD with atypical manifestations and concomitant autoimmune disorders, pharyngeal-cervical-brachial Guillain-Barre syndrome in Case 1 and SCD with autoimmune thyroiditis in Case 2. After undergoing corresponding treatment, death was reported in Case 1 and improvement in Case 2. Analysis of the clinical manifestations and investigation of the underlying pathogenesis in such patients could help improve the rate of early diagnosis and allow timely treatment of SCD, thereby preventing disease progression and poor clinical outcomes.

RESUMO Introdução: A acupuntura tem sido amplamente utilizada para alívio de dor. No entanto, seus mecanismos são muito pouco conhecidos. Objetivo: Investigar a relação entre o efeito analgésico da eletroacupuntura e a regulação da expressão de adenosina e de substância P. Métodos: Utilizou-se um modelo de dor inflamatória crônica em ratos por injeção única do Adjuvante Completo de Freund e, em seguida, os animais foram tratados com eletroacupuntura diariamente. Foram aplicadas sete sessões bilaterais de eletroacupuntura (ST36 e BL60, 0,5 a 1,5 mA, força inicial de 0,5 mA, aumentada em 0,5 mA a cada 10 minutos, 30 minutos por sessão, uma sessão por dia) em ratos com Adjuvante Completo de Freund, por sete dias. O efeito analgésico da eletroacupuntura foi avaliado pela medida do limiar de retirada da pata em ratos que receberam estimulações mecânica e térmica. Resultados: A estimulação diária com eletroacupuntura aumentou efetivamente o limiar de retirada da pata em ratos com Adjuvante Completo de Freund. A eletroacupuntura aumentou o nível de adenosina na região zusanli. Estudos posteriores mostraram que a eletroacupuntura poderia diminuir os níveis de substância P, receptor de neurocinina-1, fator de necrose tumoral-alpha, interleucina-1β, interleucina-6 e CD68 nos gânglios da raiz dorsal. Curiosamente, a injeção direta de antagonistas do receptor de adenosina A1 ou de substância P, ou a transecção da raiz do nervo dorsal, podem prejudicar significativamente as ações analgésicas induzidas pela eletroacupuntura em ratos com Adjuvante Completo de Freund e reduzir os níveis de substância P, receptor de neurocinina-1, fator de necrose tumoral-alfa, interleucina-1β, interleucina-6 e CD68. Por fim, confirmamos que a injeção direta de um agonista do receptor da adenosina A1 reproduziu os efeitos analgésicos da eletroacupuntura. Conclusão: Nossos resultados indicam a regulação da secreção da substância P mediada pela adenosina. A via mediada pela substância P pode estar envolvida no processo de analgesia por eletroacupuntura em ratos.

ABSTRACT Background: Acupuncture has been widely used for alleviating pain. However, its mechanisms remain largely enigmatic. Objective: In the present study, we focused on whether the analgesic effect of electroacupuncture is related to its regulation on adenosine and substance P expression. Methods: We established chronic inflammatory pain model in rats through a single injection of Complete Freund’s Adjuvant, and then we treated animals using daily electroacupuncture. We applied seven bilateral sessions of electroacupuncture (ST36 and BL60, 0.5 to 1.5 mA, initial strength of 0.5 mA, increased by 0.5 mA every 10 minutes, for 30 minutes per session, one section per day) to Complete Freund’s Adjuvant rats for seven days. The analgesic effect of electroacupuncture was evaluated by measuring paw withdrawal threshold in rats that received mechanical and thermal stimulation. Results: Daily electroacupuncture stimulation effectively increased paw withdrawal threshold in Complete Freund’s Adjuvant rats. Electroacupuncture increased the adenosine level in zusanli. A further study showed that electroacupuncture could decrease substance P, neurokinin-1 receptor, tumor necrosis factor-alpha, interleukin-1β, interleukin-6 and CD68 levels in dorsal root ganglion. Interestingly, direct injection of adenosine A1 or substance P receptor antagonists, or dorsal nerve root transection could significantly impair electroacupuncture induced analgesic actions in Complete Freund’s Adjuvant rats could and reduce the levels of substance P, neurokinin-1 receptor, tumor necrosis factor-alpha, interleukin-1β, interleukin-6 and CD68. Finally, we confirmed that direct injection of adenosine A1 receptor agonist replicated the analgesic effect of electroacupuncture. Conclusion: Our results indicate regulation of adenosine-mediated substance P secretion. Substance P-mediated pathway may be involved in the analgesia process by electroacupuncture in rats.

RESUMO OBJETIVO Neste estudo, investigamos a função do COL6A3 na mobilidade celular e na via PI3K/AKT em osteossarcomas. METODOLOGIA A expressão relativa do COL6A3 foi obtida a partir de dados GEO em tecidos de osteossarcoma. O RNA de interferência (siRNA) foi utilizado para reduzir a expressão do COL6A3 nas células, e o teste de contagem de células kit-8 (CCK-8) e a análise de formação de colônias foram realizados para examinar o potencial de proliferação celular. Além disso, o Transwell comprovou os efeitos do si-COL6A3 na invasão celular e migração em células de osteossarcoma. Para medir os níveis de expressão das proteínas e mRNAs, utilizamos transcriptase reversa quantitativa (qRT-PCR) e western blot. RESULTADOS O COL6A3 foi regulado nos tecidos e células do osteossarcoma quando comparado com o controle normal. A redução de COL6A3 reduziu a proliferação e a capacidades de formação de colônias em relação ao COL6A3 sem interferência. Do Mesmo modo, ao contrário do observado no grupo si-con, a invasão e migração celular foram inibidas no grupo si-COL6A3. Além disso, o resultado do western blot sugere que a via PI3K/AKT foi manipulada, medindo a expressão proteica dos marcadores relacionados à PI3K/AKT, devido à inibição do COL6A3. CONCLUSÃO O COL6A3 desempenha um papel crucial na modulação de vários aspectos da progressão do osteossarcoma, o que pode representar um possível tratamento eficaz para a doença.

SUMMARY OBJECTIVE In this study, we aimed to investigate the role of COL6A3 on cell motility and the PI3K/AKT signaling pathway in osteosarcoma. METHODS The relative expression of COL6A3 was achieved from a GEO dataset in osteosarcoma tissue. siRNA technology was applied to decrease the COL6A3 expression in cells, and cell counting kit-8 (CCK-8) assay and colony formation analysis were used to examine the cell proliferation potential. Knockdown COL6A3 made the proliferation and colony formation abilities worse than the COL6A3 without interference. Likewise, in contrast to the si-con group, cell invasion and migration were inhibited in the si-COL6A3 group. Moreover, the western blot results suggested that the PI3K/AKT signaling pathway was manipulated by measuring the protein expression of the PI3K/AKT pathway-related markers, due to the COL6A3 inhibition. CONCLUSION COL6A3 plays a crucial role in modulating various aspects of the progression of osteosarcoma, which would provide a potentially effective treatment for osteosarcoma.

This is a retrospective, single-center observational study to explore the predictors of chest drainage for neonatal pneumothorax. A total of 183 neonates (age ≤28 days) who presented to the Children's Hospital of Soochow University between January 1, 2015 and December 31, 2018 for pneumothorax or developed pneumothorax during a hospital stay were included. Demographic data, clinical presentation, and imaging characteristics of neonatal pneumothorax were collected and analyzed. We used univariate and multivariate logistic regression analyses to determine significant predictors of chest drainage of pneumothorax in neonates. Pneumothorax occurred within 24 h after birth in 131 (71.6%) cases, between 24 and 48 h after birth in 41 (22.4%) cases, and 48 h after birth in 11 (6.0%) cases. Univariate and multivariate logistic regression analyses revealed that lung collapse ≥1/3 on initial chest X-ray (OR 4.99, 95%CI 2.25-11.07), chest retractions (OR 8.12, 95%CI 2.88-22.89), cyanosis (OR 2.25, 95%CI 1.08-4.66), and frothing from mouth (OR 2.49, 95%CI 1.12-5.49) (P<0.05 for all) were significant predictors of the need for chest drainage due to pneumothorax. In conclusion, the thorough evaluation of the above predictive factors can guide treatment and improve patient outcome.

Abstract The aqueous enzymatic extraction (AEE) of oil from shrimp processing by-products was investigated. Four kinds of proteases, including alkaline protease, neutral protease, flavor protease and compound protease, were applied to hydrolysis shrimp processing by-products. The results showed that flavor protease was the best hydrolysis enzyme for shrimp processing by-products to obtain high oil recovery. The influences of four factors, including enzyme amount, liquid/solid ratio, hydrolysis time and hydrolysis temperature, on shrimp oil extraction yield were also studied. The flavor enzyme hydrolysis condition was optimized as following: enzyme amount of 2.0% (w/w), liquid/solid ratio of 9.0ml/g, hydrolysis time of 2.6 h and hydrolysis temperature of 50 °C. Under these optimum hydrolysis conditions, the experimental oil extraction yield was 88.9%.

Abstract Purpose The research is intended for clarification of the efficacy as well as the underlying mechanism of GSK-3β inhibitors on the advancement of acute lung injuries in acute necrotizing pancreatitis (ANP) in rats. Methods Seventy-two rats were randomly divided into 6 groups: (1)ANP-vehicle; (2)ANP-TDZD-8;(3)ANP-SB216763;(4)Sham-vehicle;(5)Sham-TDZD-8;(6)Sham-SB216763; Blood biochemical test, histopathological examination and immunohistochemical analysis of rats pancreas and lung tissues were performed. The protein expression of GSK-3β, phospho-GSK-3β (Ser9), iNOS, ICAM-1, TNF-α, and IL-10 were detected in lung tissues by Western-blot. Results The outcomes revealed that the intervention of GSK-3β inhibitors alleviated the pathological damage of pancreas and lung (P<0.01), reduced serum amylase, lipase, hydrothorax and lung Wet-to-Dry Ratio, attenuated serum concentrations of IL-1β and IL-6 (P<0.01), inhibited the activation of NF-κB, and abated expression of iNOS, ICAM-1 and TNF-α protein, but up-regulated IL-10 expression in lung of ANP rats (P<0.01). The inflammatory response and various indicators in ANP-TDZD-8 groups were lower than those in ANP-SB216763 groups. Conclusions Inhibition of GSK-3β weakens acute lung injury related to ANP via the inhibitory function of NF-κB signaling pathway. Different kinds of GSK-3β inhibitors have different effects to ANP acute lung injury.