AAV-mediated base-editing therapy ameliorates the disease phenotypes in a mouse model of retinitis pigmentosa.

Base editing technology is an ideal solution for treating pathogenic single-nucleotide variations (SNVs). No gene editing therapy has yet been approved for eye diseases, such as retinitis pigmentosa (RP). Here, we show, in the rd10 mouse model, which carries an SNV identified as an RP-causing mutation in human patients, that subretinal delivery of an optimized dual adeno-associated virus system containing the adenine base editor corrects the pathogenic SNV in the neuroretina with up to 49% efficiency. Light microscopy showed that a thick and robust outer nuclear layer (photoreceptors) was preserved in the treated area compared with the thin, degenerated outer nuclear layer without treatment. Substantial electroretinogram signals were detected in treated rd10 eyes, whereas control treated eyes showed minimal signals. The water maze experiment showed that the treatment substantially improved vision-guided behavior. Together, we construct and validate a translational therapeutic solution for the treatment of RP in humans. Our findings might accelerate the development of base-editing based gene therapies.

Synergistic Incorporation of Two ssDNA Activators Enhances the Trans-Cleavage of CRISPR/Cas12a.

CRISPR/Cas12a has been believed to be powerful in molecular detection and diagnostics due to its amplified trans-cleavage feature. However, the activating specificity and multiple activation mechanisms of the Cas12a system are yet to be elucidated fully. Herein, a "synergistic activator effect" is discovered, which supports an activation mechanism that a synergistic incorporation of two short ssDNA activators can promote the trans-cleavage of CRISPR/Cas12a, while either of them is too short to work independently. As a proof-of-concept example, the synergistic activator-triggered CRISPR/Cas12a system has been successfully harnessed in the AND logic operation and the discrimination of single-nucleotide variants, requiring no signal conversion elements or other amplified enzymes. Moreover, a single-nucleotide specificity has been achieved for the detection of single-nucleotide variants by pre-introducing a synthetic mismatch between crRNA and the "helper" activator. The finding of "synergistic activator effect" not only provides deeper insight into CRISPR/Cas12a but also may facilitate its expanded application and power the exploration of the undiscovered properties of other CRISPR/Cas systems.

Compute-and-Release Logic-Gated DNA Cascade Circuit for Accurate Cancer Cell Imaging.

Accurate identification of cancer cells is an essential prerequisite for cancer diagnosis and subsequent effective curative interventions. The logic-gate-assisted cancer imaging system that allows a comparison of expression levels between biomarkers, rather than just reading biomarkers as inputs, returns a more comprehensive logical output, improving its accuracy for cell identification. To fulfill this key criterion, we develop a compute-and-release logic-gated double-amplified DNA cascade circuit. This novel system, CAR-CHA-HCR, consists of a compute-and-release (CAR) logic gate, a double-amplified DNA cascade circuit (termed CHA-HCR), and a MnO2 nanocarrier. CAR-CHA-HCR, a novel adaptive logic system, is designed to logically output the fluorescence signals after computing the expression levels of intracellular miR-21 and miR-892b. Only when miR-21 is present and its expression level is above the threshold CmiR-21 > CmiR-892b, the CAR-CHA-HCR circuit performs a compute-and-release operation on free miR-21, thereby outputting enhanced fluorescence signals to accurately image positive cells. It is capable of comparing the relative concentrations of two biomarkers while sensing them, thus allowing accurate identification of positive cancer cells, even in mixed cell populations. Such an intelligent system provides an avenue for highly accurate cancer imaging and is potentially envisioned to perform more complex tasks in biomedical studies.

Circular Guide RNA for Improved Stability and CRISPR-Cas9 Editing Efficiency in Vitro and in Bacteria.

Due to its intrinsic RNA properties, guide RNA (gRNA) is the least stable component of the CRISPR-Cas9 complex and is a major target for modification and engineering to increase the stability of the system. While most strategies involve chemical modification and special processes, we created a more stable gRNA with an easy-to-use biological technique. Since circular RNAs are theoretically immune to all RNA exonucleases, we attempted to construct a circular gRNA (cgRNA) employing the autocatalytic splicing mechanism of the RNA cyclase ribozyme. First, the formation of the cgRNA, which has a length requirement, was optimized in vivo in E. coli cells. It was found that a cgRNA with an insert length of 251 bp, designated 251cgRNA, was functional. More importantly, cgRNA increased the editing efficiency of the tested base editors relative to normal linear gRNA. The cgRNAs were more stable in vitro under all tested temperature conditions and maintained their function for 24 h at 37 °C, while linear gRNAs completely lost their activity within 8 h. Enzymatically purified 251cgRNA demonstrated even higher stability, which was obviously presented on gels after 48 h at 37 °C, and maintained partial function. By inserting a homologous arm into the 251cgRNA to 251HAcgRNA cassette, the circularization efficiency reached 88.2%, and the half-life of 251HAcgRNA was 30 h, very similar to that of purified 251cgRNA. This work provides a simple innovative strategy to greatly increase the stability of gRNA both in vivo in E. coli and in vitro, with no additional cost or labor. We think this work is very interesting and might revolutionize the form of gRNAs people are using in research and therapeutic applications.

Predicting the Risk of Diabetic Foot Ulcers From Diabetics With Dysmetabolism: A Retrospective Clinical Trial.

Background: Diabetic foot ulcer (DFU) in patients with type 2 diabetes mellitus (T2D) often leads to amputation. Early intervention to prevent DFU is urgently necessary. So far, there have been no studies on predictive models associated with DFU risk factors. Our study aimed to quantify the predictive risk value of DFU, promote health education, and further develop behavioral interventions to reduce the incidence of DFU. Methods: Data from 973 consecutive patients with T2D was collected from two hospitals. Patients from the Guangxi Medical University First Affiliated Hospital formed the training cohort (n = 853), and those from the Wuming Hospital of Guangxi Medical University formed the validation cohort (n = 120). Independent variable grouping analysis and multivariate logistic regression analysis were used to determine the risk factors of DFUs. The prediction model was established according to the related risk factors. In addition, the accuracy of the model was evaluated by specificity, sensitivity, predictive value, and predictive likelihood ratio. Results: In total, 369 of the 853 patients (43.3%) and 60 of the 120 (50.0%) were diagnosed with DFUs in the two hospitals. The factors associated with DFU were old age, male gender, lower body mass index (BMI), longer duration of diabetes, history of foot disease, cardiac insufficiency, no use of oral hypoglycemic agent (OHA), high white blood cell count, high platelet count, low hemoglobin level, low lymphocyte absolute value, and high postprandial blood glucose. After incorporating these 12 factors, the nomogram drawn achieved good concordance indexes of 0.89 [95% confidence interval (CI): 0.87 to 0.91] in the training cohort and 0.84 (95% CI: 0.77 to 0.91) in the validation cohort in predicting DFUs and had well-fitted calibration curves. Patients who had a nomogram score of ≥180 were considered to have a low risk of DFU, whereas those having ≥180 were at high risk. Conclusions: A nomogram was constructed by combining 12 identified risk factors of DFU. These 12 risk factors are easily available in hospitalized patients, so the prediction of DFU in hospitalized patients with T2D has potential clinical significance. The model provides a reliable prediction of the risk of DFU in patients with T2D.

Imperfect guide-RNA (igRNA) enables CRISPR single-base editing with ABE and CBE.

CRISPR base editing techniques tend to edit multiple bases in the targeted region, which is a limitation for precisely reverting disease-associated single-nucleotide polymorphisms (SNPs). We designed an imperfect gRNA (igRNA) editing methodology, which utilized a gRNA with one or more bases that were not complementary to the target locus to direct base editing toward the generation of a single-base edited product. Base editing experiments illustrated that igRNA editing with CBEs greatly increased the single-base editing fraction relative to normal gRNA editing with increased editing efficiencies. Similar results were obtained with an adenine base editor (ABE). At loci such as DNMT3B, NSD1, PSMB2, VIATA hs267 and ANO5, near-perfect single-base editing was achieved. Normally an igRNA with good single-base editing efficiency could be selected from a set of a few igRNAs, with a simple protocol. As a proof-of-concept, igRNAs were used in the research to construct cell lines of disease-associated SNP causing primary hyperoxaluria construction research. This work provides a simple strategy to achieve single-base base editing with both ABEs and CBEs and overcomes a key obstacle that limits the use of base editors in treating SNP-associated diseases or creating disease-associated SNP-harboring cell lines and animal models.

Molecular Mechanism of the Cytosine CRISPR Base Editing Process and the Roles of Translesion DNA Polymerases.

CRISPR-mediated base editing causes damage to DNA, mainly uracil, apurinic/apyrimidinic (AP) sites, and nicks, which require various DNA repair mechanisms to complete the base conversion process. Currently, there are only hypotheses explaining the base editing process, but the molecular mechanism and roles of the repair systems in the process are relatively unknown. To explore the mechanism of base editing repair, a base editor, nCas9-PmCDA1, was applied in the model eukaryote, Saccharomyces cerevisiae, either with the wild type or its derivatives with genes encoding translesion DNA synthesis (TLS) polymerases knocked out. We found that C-to-G and C-to-A conversions resulted mainly from the repair of AP sites created by Ung and required Polζ as an extender. Rev1 is the main TLS polymerase for specifically incorporating Cs on the opposite position of AP sites to cause the dominant C-to-G conversion, while Polδ incorporates Ts or As on the opposite of AP sites, resulting in C-to-A and C-to-T conversions. Polη is not involved in the repair of AP sites caused by the base editor. Furthermore, our data suggested that the indels of base editing are mainly caused by the breakage of AP sites. Different from the current hypothesis model of the base editing mechanism, this work first elucidates the key roles of TLS polymerases in the cytosine base editing process. This work also suggests a new direction for the development of genomic and base editing techniques by employing, manipulating, and engineering TLS polymerases.

The efficacy and safety of selective COX-2 inhibitors for postoperative pain management in patients after total knee/hip arthroplasty: a meta-analysis.

BACKGROUND: Many selective cyclooxygenase (COX-2) inhibitors are currently used in clinical practice. COX-2 inhibitors have good anti-inflammatory, analgesic, antipyretic effects, and gastrointestinal safety. However, the analgesic effects and adverse reactions of COX-2 after total knee/hip arthroplasty (TKA/THA) are not fully known. OBJECTIVE: To evaluate the efficacy and safety of selective COX-2 inhibitors in postoperative pain management in patients receiving TKA/THA. METHODS: Randomized controlled trials (RCTs) were retrieved from medical literature databases. Risk ratios (RR) Std mean difference (SMD) and 95% confidence intervals (CI) were calculated to analyze the primary and safety endpoints. RESULTS: In total, 18 articles (23 trial comparisons) were retrieved comprising 3104 patients. Among them, 1910 patients (61.5%) were randomized to the experimental group whereas 1194 patients (38.5%) were randomized to the control group. The primary endpoints were the patients' VAS score at rest or on ambulation (within 3 days). We found that VAS score in patients that received selective COX-2 inhibitor was significantly lower compared to those of the control group. CONCLUSION: This meta-analysis shows that selective COX-2 inhibitor therapy is effective, safe, and reliable in relieving postoperative pain of THA/TKA.

Molecular identification and phylogenetic analysis of the mitogenome of Solenaia oleivora MG.

Solenaia oleivora, belongs to Bivalvia, Unionidae, and Gonideinae, is a burrowing bivalve uniquely distributed in China. In this study, the complete mitochondrial genome of S. oleivora MG was sequenced and determined. The complete mitogenome of S. oleivora MG is 16,392 bp in total length, consist of 22 tRNA genes, 13 protein-coding genes (PCGs), and 2 rRNA genes. The overall base composition of the S. oleivora MG mitogenome is 36.90% A, 23.85% T, 27.09% C, and 12.16% G, respectively, exhibits a similar AT bias (60.75%) feature to other invertebrate bivalve mitogenomes. The phylogenetic analysis that S. oleivora MG clustered in genus Solenaia. This result provides useful data to the conservation and sustainable utilization of S. oleivora MG and other invertebrate mussels.

SIRT4 inhibits the proliferation, migration, and invasion abilities of thyroid cancer cells by inhibiting glutamine metabolism.

BACKGROUND: SIRT4, a protein localized in the mitochondria, is one of the least characteristic members of the sirtuin family. It is known that SIRT4 has deacetylase activity and plays a role in energy metabolism, but little is known about its possible role in carcinogenesis. Recently, several studies have suggested that SIRT4 may function as either a tumor oncogene or a tumor suppressor gene. However, its relationship with thyroid cancer remains unclear. METHODS: We stably overexpressed SIRT4 or silenced its expression in the human thyroid cancer cell line BCPAP by means of lentiviral vectors. We conducted a variety of tests, such as CCK-8, wound healing, migration, and invasion assays, to investigate the role of SIRT4 in the proliferation, migration, and invasion abilities of thyroid cancer cells. We also investigated the effects of SIRT4 overexpression on cell cycle progression and apoptosis of BCPAP cells and studied the role of glutamine metabolism in the effects of SIRT4 on BCPAP cell migration and invasion. Finally, we analyzed SIRT4 expression levels in thyroid cancer specimens by immunohistochemistry and investigated their association with clinicopathological features. RESULTS: Overexpression of SIRT4 inhibited the proliferation, migration, and invasion abilities of BCPAP thyroid cancer cells, blocked the cell cycle in the G0/G1 phase, and induced apoptosis. Mechanistically, SIRT4 inhibited BCPAP migration and invasion by inhibiting glutamine metabolism. Moreover, we found that SIRT4 protein levels in thyroid cancer tissues were markedly lower than in their non-neoplastic tissue counterparts (P<0.001). CONCLUSION: SIRT4 plays a pivotal role in the growth and metastasis of thyroid cancer cells and could be a potential therapeutic target in thyroid cancer.

Overexpression of SIRT4 inhibits the proliferation of gastric cancer cells through cell cycle arrest.

The sirtuins (SIRTs) are a family of nicotinamide-adenine dinucleotide (NAD)+-dependent protein deacetylases. SIRT4 is a mitochondrial NAD+-dependent adenosine diphsophate-ribosyltransferase. Recent studies demonstrated that SIRT4 can regulate glutamine metabolism and thus act as a tumor suppressor. However, the association of SIRT4 with gastric cancer remains unknown. The present study investigated the potential role of SIRT4 in the proliferation of human gastric cancer cells. Gastric cancer cell lines (SGC-7901 and MNK45) overexpressing SIRT4 were established by lentiviral infection. The effect of overexpression of SIRT4 in gastric cancer was evaluated by determining the cell viability, proliferation activity and colony-forming ability of gastric cancer cells in vitro. Furthermore, the cell cycle profiles of SGC-7901 and MNK45 cells overexpressing SIRT4 were evaluated to provide insights into potential underlying molecular mechanisms. Overexpression of SIRT4 significantly inhibited the proliferation and colony-forming ability of the gastric cancer cells in vitro. Furthermore, overexpression of SIRT4 induced G1 cell cycle arrest via suppression of phosphorylated extracellular signal-regulated kinase, cyclin D and cyclin E. In conclusion, the results of the present study indicated that SIRT4 may function as a tumor suppressor in gastric cancer by regulating cell proliferation, therefore SIRT4 may be a potential therapeutic target against this disease.

Profile and Management of Musculoskeletal Injuries Associated With the Lushan Earthquake in 2013.

On April 20, 2013, a 7.0-magnitude earthquake hit Lushan County, Ya'an City, Sichuan Province in southwest China. West China Hospital of Sichuan University, the largest and best hospital in Sichuan Province, is located in the city of Chengdu-about 100 km from the epicenter-and provided medical treatment to a total of 400 seismic patients. In this article, we retrospectively investigated 199 patients with musculoskeletal injuries who were treated in the Department of Orthopedics. Based on the seismic intensity distribution map, injury-occurring locations were divided into 5 grade-related areas: IX, VIII, VII, VI, and ≤V grade-area. The characteristics of seismic injuries were analyzed according to the geographic distribution of victims. We found that the constituent ratio of injury causes significantly differed in different earthquake areas according to the seismic intensity. (Disaster Med Public Health Preparedness. 2018; 12: 408-410).

Fixation versus Excision of Osteochondral Fractures after Patellar Dislocations in Adolescent Patients: A Retrospective Cohort Study.

BACKGROUND: Patellar dislocation is one of the most common knee injuries in the adolescent population. It is often combined with osteochondral fracture. The purpose of this study was to compare the outcomes between fixation and excision of osteochondral fractures not involving the bearing surface in adolescent patients with patellar dislocations. METHODS: Patients who underwent surgery for osteochondral fracture following patellar dislocation in our institution from 2007 to 2014 were retrospectively evaluated. Visual analog scale (VAS) of pain and the International Knee Documentation Committee (IKDC) form were used to assess knee pain and function at follow-up. Patient satisfaction was evaluated. Differences in the values of variables among groups were assessed using t-test if equal variance or Mann-Whitney U-test if not equal variance. The Pearson's Chi-square test was applied for dichotomous variables if expected frequency was >5 or Fisher's exact test was applied if not. A value of P < 0.05 was considered statistically significant. RESULTS: Forty-three patients were included, with the average age of 14.1 ± 2.3 (range, 9.0-17.0) years. Nineteen underwent fixation of osteochondral fractures and 24 did not. The average follow-up time was 28 ± 10 months. There was no significant difference in age, gender, follow-up time, causes of injury, times of dislocation, and location of osteochondral fracture between fixation and excision groups. The fixation group had a significantly longer surgery time (82 ± 14 min) and larger size of osteochondral fracture (2.30 ± 0.70 cm2) than the excision group (43 ± 10 min, 1.88 ± 0.62 cm2, respectively, t = 10.77, P < 0.01 and t = 0.84, P < 0.05). At the last follow-up, the average IKDC score in the fixation group (82.52 ± 8.71) was significantly lower than that in the excision group (89.51 ± 7.19, t = 2.65, P < 0.01). There was no significant difference in VAS of pain and patients' satisfaction. There were 7 (16%) patients with recurrent dislocation. CONCLUSION: Excision of osteochondral fractures has equivalent or better outcomes compared to fixation in adolescent patients with patellar dislocations when these fractures do not involve the bearing surface.

Anatomical Knee Variants in Discoid Lateral Meniscal Tears.

BACKGROUND: Discoid lateral meniscus was a common meniscal dysplasia and was predisposed to tear. There were some anatomical knee variants in patients with discoid lateral meniscus. The aim of this study was to analyze the relationship between anatomical knee variants and discoid lateral meniscal tears. METHODS: There were totally 125 cases of discoid lateral meniscus enrolled in this study from February 2008 to December 2013. Eighty-seven patients who underwent arthroscopic surgery for right torn discoid lateral meniscus were enrolled in the torn group. An additional 38 patients who were incidentally identified as having intact discoid lateral menisci on magnetic resonance imaging (MRI) findings were included in the control group. All patients were evaluated for anatomical knee variants on plain radiographs, including lateral joint space distance, height of the lateral tibial spine, height of the fibular head, obliquity of the lateral tibial plateau, squaring of the lateral femoral condyle, cupping of the lateral tibial plateau, lateral femoral condylar notch, and condylar cutoff sign. The relationship between anatomical variants and meniscal tear was evaluated. These anatomical variants in cases with complete discoid meniscus were also compared with those in cases with incomplete discoid meniscus. RESULTS: There were no significant differences between the two groups in lateral joint space distance (P = 0.528), height of the lateral tibial spine (P = 0.927), height of the fibular head (P = 0.684), obliquity of the lateral tibial plateau (P = 0.672), and the positive rates of squaring of the lateral femoral condyle (P = 0.665), cupping of the lateral tibial plateau (P = 0.239), and lateral femoral condylar notch (P = 0.624). The condylar cutoff sign was significantly different between the two groups, with the prominence ratio in the torn group being smaller than that in the control group (0.74 ± 0.11 vs. 0.81 ± 0.04, P = 0.049). With the decision value of the prominence ratio (0.78) in predicting discoid lateral meniscal tear, the sensitivity and specificity of the cutoff sign were 66% and 71%, respectively. There were no significant differences in radiographic variants between the complete and incomplete discoid lateral meniscal groups. CONCLUSIONS: The condylar cutoff sign observed on the tunnel view of the radiograph is helpful in predicting meniscal tear in adult patients with discoid lateral meniscus. As for these patients, further MRI test is recommended.

Relationship between Inflammatory Response and Estimated Complication Rate after Total Hip Arthroplasty.

BACKGROUND: After total hip arthroplasty (THA), there is a noteworthy inflammatory response. The inflammatory response is associated with postoperative recovery and complications. However, there had been few reports on the relationship between inflammatory response and postoperative complication rate. The aim of the present study was to investigate early inflammatory response in the first 3 days after THA, and to identify the relationship between inflammatory response and estimated complication rate after surgery. METHODS: It was a prospective, nonrandomized cohort study. There were 148 patients who underwent unilateral THA in our hospital enrolled. Blood samples were collected preoperatively in the morning of the surgery and at 24, 48, and 72 h after surgery. C-reactive protein (CRP) and interleukin-6 (IL-6) in peripheral blood were measured. The modified physiological and operative severity score for the enumeration of the morbidity (POSSUM) was recorded pre- and intra-operatively. Based on the score, estimated complication rate was calculated. Harris score was used to assess hip function before and after surgery. RESULTS: IL-6 levels reached the peak at 24 h after surgery and CRP at 48 h. After that, both of the levels decreased. The mean Harris scores significantly increased from 41.62 ± 23.47 before surgery to 72.75 ± 9.13 at 3 days after surgery. The Harris scores after surgery did not have a significant relation with either IL-6 or CRP peak levels (P = 0.165, P = 0.341, respectively). Both CRP and IL-6 peak levels significantly and positively correlated with estimated complication rate after surgery. The estimated complication rate calculated using the POSSUM system was 43 cases of 148 patients. Actually, there were only 28 cases that were observed to get postoperative complications during hospitalization. However, there was no significant difference between estimated and observed complication rates (P = 0.078). In the group with complications, the CRP and IL-6 peak levels were significantly higher than those in the group without complications (both P< 0.001). CONCLUSIONS: There were significantly positive relationships between both peak levels of CRP and IL-6 and estimated complication rate after THA. Inflammatory response could predict the incidence of complications after THA.

[Inhibition of pulmonary nuclear factor -ΚB and tumor necrosis factor -α expression by diallyl sulfide in rats with paraquat poisoning].

OBJECTIVE: To investigate the mechanism of anti-inflammatory effect of diallyl sulfide (DAS) in protection against acute lung injury (ALI) in rats with paraquat poisoning. METHODS: Eighty male Wistar rats were randomly divided into four groups, namely: control group, model group, dexamethasone (DXM) treatment group, and DAS treatment group, with 20 rats in each group. The model of paraquat poisoning was reproduced by single does of 70 mg/kg given by gavage, while the same volume of normal saline (NS) was given in same manner in control group. 100 mg/kg of DAS, the same volume of NS, or 1 mg/kg DXM injection were given respectively in DAS treatment group, model group, or DXM treatment group intraperitoneally after exposure to paraquat, once a day for 14 days. Five rats in each group were sacrificed at 1, 3, 7, 14 days, respectively. The inferior lobe of right lung was harvested, and the degree of lung injury was observed with hematoxylin and eosin (HE) staining under optical microscope; the upper lobe of right lung was used to determine the lung wet/dry weight (W/D) ratio and for evaluation of the degree of pulmonary edema. The expression of nuclear factor -ΚB (NF-ΚB) in the middle lobe of right lung was assessed with immunohistochemistry. The expression of tumor necrosis factor -α ( TNF-α ) mRNA in the left lung was determined with the reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: (1) The pulmonary structure in control group was found to be intact. However, in the model group there were progressive pathological changes in lung, including marked edema and thickening of alveolar walls, collapse of alveoli, infiltration of inflammatory cells, alveolar wall, and obvious bleeding in the local lung tissue, and formation of transparent membrane in alveolar space. Less infiltration of inflammatory cells and no obvious destruction were found in alveolar structure in the DAS and DXM treatment groups. (2) Lung W/D ratio: lung W/D ratio of model group was apparently higher than that in control group at every time point, and peaking on the 3rd day ( 6.15 ± 0.54 vs. 4.15 ± 2.10, P < 0.05 ), and the ratio of lung W/D of DAS and DXM treatment groups was obviously lower than that in model group at every time point, especially on the 3rd day (3.99 ± 1.26, 4.30 ± 0.70 vs. 6.15 ± 0.54, both P < 0.05), but there was no significant difference between DAS and DXM treatment groups in this regard. (3) The immunocytochemistry analysis revealed minimal NF-ΚBp65 expression in the cell nuclei of the control group, while extensive NF-ΚBp65 expression was found in model group. Minimal NF-ΚBp65 positive expression in the cytoplasm and even less positive expression in the nucleus was found in the DAS and DXM treatment groups, and integral A value was significantly lower in the DAS and DXM treatment groups than that of the model group, especially on the 3rd day [(17.98 ± 0.06 )× 107, (18.53 ± 0.04) × 107 vs. (28.85 ± 0.61) × 107, both P < 0.01], but there was no significant difference between DAS and DXM treatment groups. (4) It was shown by RT-PCR that the expression of TNF-α mRNA in lung tissue of the model group was significantly higher than that in the control group on the 3rd day (gray value: 3.63 ± 0.62 vs. 0.51 ± 0.13, P < 0.05 ). The expression of TNF-α mRNA in lung tissue was significantly decreased in DAS and DXM treatment groups compared with model group ( gray value: 2.49 ± 0.57, 2.02 ± 0.26 vs. 3.63 ± 0.62, both P < 0.05 ), but there was no significant difference between DAS and DXM treated groups. CONCLUSIONS: Treatment with an intraperitoneally injection of DAS is capable of attenuate the extent of PQ-induced ALI in rats by alleviating pulmonary edema, inhibiting the expression of NF-ΚB and TNF-α in lung tissue, and ameliorating pathological changes in lung tissue.