Establishment of Reference Range for Leucine Arylamidase in Pregnant Women in China.

BACKGROUND: Leucine arylamidase (LAP) is a type of proteinase. During pregnancy, the LAP value of women will continue to rise, but there is currently no established normal range for this value. METHODS: A total of 26,208 records of LAP information from pregnant women who visited Qingdao Municipal Hospital between 2016 and 2022 were selected, including 25,582 records of healthy pregnant women. The study used the AU5800 Series Clinical Chemistry Analyzer as the detection equipment. The Wilcoxon method was appropriate for calculating confidence intervals in this study since LAP values in pregnant women have a skewed distribution. RESULTS: The reference ranges obtained were 64.00 - 70.50 U/L, 161.00 - 166.00 U/L, and 174.50 - 182.50 U/L for the first trimester, second trimester, and third trimester, respectively. CONCLUSIONS: LAP can rise significantly during pregnancy, so it is essential to establish an appropriate reference range for pregnant women. Abnormal values of LAP carry a risk of developing various pregnancy disorders.

Current progress of immune checkpoint inhibitors for advanced colorectal cancer: concentrating on the efficacy improvement.

Immune checkpoint inhibitors (ICIs) have paved a new pathway and revolutionized cancer treatment. Currently, ICIs have been extensively used for patients with advanced colorectal cancer (CRC), especially those harboring microsatellite instability (MSI). However, the efficacy of ICIs varies tremendously in different individuals, and some patients may not benefit from ICIs, which limits their clinical application. How to improve the efficacy of ICIs is an important issue to be solved. On the one hand, it is urgent to discover the predictive biomarkers to accurately screen the patients who gain benefit from ICIs, like microsatellite stability, tumor mutation burden (TMB), DNA polymerase ε/DNA polymerase δ1 mutations, and the expression of programmed death-ligand 1 (PD-L1). The rational use of these biomarkers will help clinicians identify suitable candidates who will benefit from ICI treatment, thereby improving therapeutic efficiency. Additionally, it is vital to design combination therapeutic strategies for optimizing the therapeutic effectiveness of ICIs. Nowadays, treatment strategies like chemotherapy, radiotherapy, targeted therapy along with ICIs, have helped improve the therapeutic effectiveness of ICIs. In this review, we have focused on the recent advancements in the predictive biomarkers and combination therapeutic strategies with ICIs for colorectal cancer.

Identification of novel α-glucosidase and ACE inhibitory peptides from Douchi using peptidomics approach and molecular docking.

In this study, the effect of Douchi extract (DWE) on α-glucosidase and angiotensin-converting enzymes (ACE) were investigated, and several novel peptides with inhibitory activity against α-glucosidase and ACE were identified using peptidomics approach based on UPLC-MS/MS. The average inhibition rates of DWE on α-glucosidase and ACE were 73.75-78.10% and 4.56-27.07%, respectively. In the DWE, a total of 710 peptides were detected. Two novel peptides with potential inhibitory activity against α-glucosidase were identified using the correlation analysis, database alignment and molecular docking methods. They were DVFRAIPSEVL and DRPSINGLAGAN, with the IC50 values of 0.121 and 0.128 mg/mL, respectively. Also, four novel peptides with potential inhibitory activity against ACE were identified: PSSPFTDLWD, EEQDERQFPF, PVPVPVQQAFPF and PSSPFTDL, with IC50 values of 1.388, 0.041, 0.761 and 0.097 mg/mL, respectively. These results indicated that combining peptidomics and molecular docking is an effective alternative strategy for rapidly screening numbers of novel bioactive peptides from foods.

Calculation of active earth pressure on external corners with equal length on both sides in excavation engineering.

Taking the external corner with equal lengths as the research object, two failure modes of the equilateral external corner are established, and the active earth pressure calculation formula of the equilateral external corner in the limit state is further deduced when the external angle is 90°. The comparison between the theoretical calculation results and Midas/GTS simulation results shows that when the ratio of the side length B to the depth H is large, the sliding wedge failure will occur at the external corner, and the active earth pressure of the external corner in the range of wedge-shaped slider will not change with the change of size B. When the ratio of the side length B to the depth H is small, the displaced soil is composed of two parts, and the earth pressure varies with the change of size B. In this paper, the magnitude and distribution law of the active earth pressure obtained by the horizontal micro-layered limit equilibrium analysis method is similar to the three-dimensional simulation value of the Midas/GTS software, which can prove the feasibility and rationality of the theoretical calculation.

Study on the taste active compounds in Douchi using metabolomics method.

Douchi is a traditional famous seasoning in China. This study adopted electronic tongue and metabolomics to analyze the taste characteristics and taste active compounds of 12 samples from three most famous types of Douchi (Liuyang Douchi, Yangjiang Douchi, Yongchuan Douchi). Thirty-six differential metabolites mainly enriched from the arginine biosynthesis were identified among these Douchis. Umami and bitterness are considered as two taste that bring positive and negative perceptions for Douchi. The succinic acid was found to be responsible for the umami in LY, YJ and YC Douchi, with the TAVs of 2054, 643, 174, respectively, rather than the glutamic acid and aspartic acid. The leucine was identified as the main metabolite for bitterness, with the TAVs of 9, 9, 7 respectively. KEGG enrichment analysis found that the umami, sourness and saltiness might be related to alanine, aspartate and glutamate metabolism and the bitterness might be related to aminoacyl-tRNA biosynthesis pathway.

Risks of applying mobilising agents for remediation of arsenic-contaminated soils: Effects of dithionite-EDTA and citric acid on arsenic fractionation, leachability, oral bioavailability/bioaccessibility and speciation.

Arsenic (As) mobilisation assists in remediating As-contaminated soils but might increase ecological and health risks. In this study, risks of applying two mobilising agents were assessed, i.e. an emerging reducing-chelating composite agent [dithionite (Na2S2O4)-EDTA] and a classical low-molecular-weight organic acid (LMWOA) [citric acid (C6H8O7)]. Results showed that both agents induced sharp increase in leachability-based ecological risk of As. Interestingly, the two agents had opposite performances regarding health risks. Na2S2O4-EDTA significantly increased As relative bioavailability (RBA) to 1.83 times that in controls based on in vivo mouse model, and As bioaccessibility to 1.96, 1.65 and 1.20 times in gastric, small intestinal and colon phases based on in vitro PBET-SHIME model. Besides, it caused significant increase of highly toxic As(Ⅲ) in colon fluid. In contrast, C6H8O7 significantly reduced RBA and bioaccessibility of soil As in colon by 44.44% and 14.65%, respectively. Importantly, C6H8O7 restrained bioaccessible As(V) reduction and promoted bioaccessible As(Ⅲ) methylation, further reducing health risk. The phenomena could mainly be attributed to excessive metal components release from soil by C6H8O7 and gut microbiota metabolism of C6H8O7. In summary, C6H8O7 and similar LMWOAs are recommended. The study contributes to mobilising agent selection and development and provides a reference for managing remediation sites.

Comparison of 68Ga-FAPI and 18F-FDG PET/CT for the diagnosis of primary and metastatic gastric signet-ring cell carcinoma / 中华核医学与分子影像杂志

Objective:To investigate the clinical utility of 68Ga-labeled fibroblast activation protein inhibitor (FAPI) PET/CT in the detection of primary and metastatic gastric signet-ring cell carcinoma (GSRCC) and compared the results with those of 18F-FDG PET/CT. Methods:A total of 21 patients (10 males, 11 females, average age 52 years) with primary and metastatic GSRCC who underwent 68Ga-FAPI and 18F-FDG PET/CT at the First Affiliated Hospital of Xiamen University from June 2020 to May 2022 were retrospectively analyzed. Pathological results of surgery and (or) biopsy were used as the " gold standard" for final diagnosis. In cases whose surgery or tissue biopsies were not available, clinical and radiographic follow-up results were used as the reference standards. Wilcoxon signed-rank test was used to compare the SUV max of 18F-FDG and 68Ga-FAPI. McNemar χ2 test was used to compare the detection rate between 18F-FDG and 68Ga-FAPI PET/CT. Results:68Ga-FAPI PET/CT showed higher SUV max than 18F-FDG in primary tumors (5.3(2.4, 15.7) vs 2.4(1.8, 2.5); z=2.31, P=0.021), local recurrences (7.8(6.0, 8.9) vs 2.4(1.9, 3.4); z=2.20, P=0.028), lymph nodes metastases (7.7(4.5, 12.2) vs 2.4(1.9, 3.6); z=6.01, P<0.001) and bone/visceral metastases (6.7(5.3, 11.1) vs 2.4(2.0, 3.4); z=11.36, P<0.001). Regarding diagnostic accuracy, 68Ga-FAPI PET/CT showed higher sensitivities than 18F-FDG for primary tumors (7/9 vs 2/9; χ2=3.20, P=0.063) and local recurrences (7/7 vs 2/7; χ2=3.20, P=0.063). It also demonstrated higher lesion detection rates than 18F-FDG for suspicious lymph node metastases (86%(65/76) vs 32%(24/76); χ2=31.37, P<0.001) and bone/visceral metastases (99%(184/185) vs 39%(73/185); χ2=107.08, P<0.001). Conclusions:68Ga-FAPI PET/CT showed higher tumor uptake and lesion detection rate than 18F-FDG in the primary and metastatic GSRCC. 68Ga-FAPI PET/CT demonstrates good diagnostic performance for tumor detection, staging, and restaging of GSRCC, which is helpful to further guide clinical treatment strategy.

Small molecule inhibitors of RORγt for Th17 regulation in inflammatory and autoimmune diseases / 药物分析学报

As a ligand-dependent transcription factor,retinoid-associated orphan receptor γt(RORyt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the pro-gression of several inflammatory and autoimmune conditions.An emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORyt to decrease Th17 cell development and IL-17 production.Several RORyt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORyt by binding to orthosteric-or allosteric-binding sites in the ligand-binding domain.Some of small-molecule inhibitors have entered clinical evaluations.Therefore,in current review,the role of RORyt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was highlighted.Notably,the recently developed RORyt inhibitors were summarized,with an emphasis on their optimization from lead compounds,ef-ficacy,toxicity,mechanisms of action,and clinical trials.The limitations of current development in this area were also discussed to facilitate future research.

Clinical characteristics and prognosis of 12 cases of lupus nephritis complicated with thrombotic microangiopathy / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical characteristics, pathological features, treatment regimen, and prognosis of children with lupus nephritis (LN) and thrombotic microangiopathy (TMA), as well as the treatment outcome of these children and the clinical and pathological differences between LN children with TMA and those without TMA.@*METHODS@#A retrospective analysis was conducted on 12 children with LN and TMA (TMA group) who were admitted to the Department of Nephrology, Children's Hospital of Nanjing Medical University, from December 2010 to December 2021. Twenty-four LN children without TMA who underwent renal biopsy during the same period were included as the non-TMA group. The two groups were compared in terms of clinical manifestations, laboratory examination results, and pathological results.@*RESULTS@#Among the 12 children with TMA, 8 (67%) had hypertension and 3 (25%) progressed to stage 5 chronic kidney disease. Compared with the non-TMA group, the TMA group had more severe tubulointerstitial damage, a higher Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score at onset, and higher cholesterol levels (P<0.05). There were no significant differences between the two groups in the percentage of crescent bodies and the levels of hemoglobin and platelets (P>0.05).@*CONCLUSIONS@#There is a higher proportion of individuals with hypertension among the children with LN and TMA, as well as more severe tubulointerstitial damage. These children have a higher SLEDAI score and a higher cholesterol level.

Xixin Decoction improves learning and memory ability of SAMP8 by enhancing neuroprotective effect and inhibiting neuroinflammation / 中国中药杂志

This study aimed to explore the possible effect of Xixin Decoction(XXD) on the learning and memory ability of Alzheimer's disease(AD) model senescence-accelerated mouse-prone 8(SAMP8) and the related mechanism in enhancing neuroprotective effect and reducing neuroinflammation. Forty SAMP8 were randomly divided into a model group(10 mL·kg~(-1)·d~(-1)), a probiotics group(0.39 g·kg~(-1)·d~(-1)), a high-dose group of XXD granules(H-XXD, 5.07 g·kg~(-1)·d~(-1)), a medium-dose group of XXD granules(M-XXD, 2.535 g·kg~(-1)·d~(-1)), and a low-dose group of XXD granules(L-XXD, 1.267 5 g·kg~(-1)·d~(-1)). Eight senescence-accelerated mouse-resistant 1(SAMR1) of the same age and strain were assigned to the control group(10 mL·kg~(-1)·d~(-1)). After ten weeks of intragastric administration, the Morris water maze was used to test the changes in spatial learning and memory ability of mice after treatment. Meanwhile, immunofluorescence staining was used to detect the positive expression of receptor for advanced glycation end products(AGER), Toll-like receptor 1(TLR1), and Toll-like receptor 2(TLR2) in the hippocampal CA1 region of mice. Western blot was employed to test the protein expression levels of silencing information regulator 2 related enzyme 1(SIRT1), AGER, TLR1, and TLR2 in the hippocampus of mice. Enzyme linked immunosorbent assay(ELISA) was applied to assess the levels of Aβ_(1-42) in the hippocampus of mice and the levels of nuclear factor κB p65(NF-κB p65), NOD-like receptor protein 3(NLRP3), tumor necrosis factor-α(TNF-α), and interleukin-1β(IL-1β) in the serum and hippocampus of mice. Compared with the model group, XXD significantly improved the spatial learning and memory ability of SAMP8, increased the expression of neuroprotective factors in the hippocampus, decreased the levels of neuroinflammatory factors, and inhibited the expression of Aβ_(1-42). In particular, H-XXD significantly increased the expression of SIRT1 in the hippocampus of mice, reduced the expression levels of NF-κB p65, NLRP3, TNF-α, and IL-1β in the serum and hippocampus of mice, and decreased the expression of AGER, TLR1, and TLR2 in the hippocampus of mice(P<0.05 or P<0.01). XXD may improve the spatial learning and memory ability of AD model SAMP8 by enhancing the neuroprotective effect and inhibiting neuroinflammation.

Chinese herbal medicines for treating ulcerative colitis via regulating gut microbiota-intestinal immunity axis / 中草药·英文版

Ulcerative colitis (UC) is one of types of inflammatory bowel disease with high recurrence. Recent studies have highlighted that microbial dysbiosis as well as abnormal gut immunity are crucial factors that initiate a series of inflammatory responses in the UC. Modulating the gut microbiota-intestinal immunity loop has been suggested as one of key strategies for relieving UC. Many Chinese herbal medicines including some of single herb, herbal formulas and the derived constituents have been reported with protective effect against UC through modulating gut microbiome and intestinal immunity. Some clinical trials have shown promising results. This review thus focused on the current knowledge on using Chinese herbal medicines for treating UC from the mechanism aspects of regulating intestinal homeostasis involving microbiota and gut immunity. The existing clinical trials are also summarized.

Efficacy and Safety of Allogeneic Hematopoietic Stem Cell Transplantation with Decitabine-containing Regimen in Myelodysplastic Syndromes and Myelodysplastic Syndromes Transformed Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with decitabine (Dec)-conditioning regimen in the treatment of myelodysplastic syndrome (MDS) and MDS transformed acute myeloid leukemia (MDS-AML).@*METHODS@#The characteristics and efficacy data of 93 patients with MDS and MDS-AML who received allo-HSCT in our center from April 2013 to November 2021 were retrospectively analyzed. All patients were administered by myeloablative conditioning regimen containing Dec (25 mg/m2 /d×3 d).@*RESULTS@#Among the 93 patients, 63 males and 30 females, were diagnosed as MDS（n ＝77）, MDS-AML（n ＝16）. The incidence of I/II grade regimen-related toxicity (RRT) was 39.8%, and III grade RRT was only found in 1 patient (1%). Neutrophil engraftment was successful in 91 (97.8%) patients after a median neutrophil engraftment time of 14 (9-27) days; Successful platelet engraftment was achieved in 87 (93.5%) patients, with a median engraftment time of 18 (9-290) days. The incidence of acute graft versus host disease（aGVHD） and grade III-IV aGVHD was 44.2% and 16.2%, respectively. The incidence of chronic graft versus host disease（cGVHD） and moderate-to-severe cGVHD was 59.5% and 37.1%, respectively. Of the 93 patients, 54 (58%) developed posttransplant infections, among which lung infection (32.3%) and bloodstream infection (12.9%) were the most common. The median follow-up after transplantation was 45 (0.1-108) months. The 5-year overall survival (OS) rate, disease-free survival (DFS) rate, treatment-related mortality, and cumulative incidence of relapse were 72.7%, 68.4%, 25.1%, and 6.5%, respectively. And the 1-year graft-versus-host disease/relapse-free survival rate was 49.3%. The patients in different group of relative high-risk prognostic scoring or low-risk prognostic scoring, with or without poor-risk mutation(s), with mutations number ≥3 or <3 had similar 5-year OS rate (more than 70%). Multivariate analysis showed that the incidence of grade III-IV aGVHD was the independent risk factor affecting OS（P =0.008）and DFS (P =0.019).@*CONCLUSION@#Allo-HSCT with Dec-conditioning regimen is feasible and effective in the treatment of patients with MDS and MDS-AML, especially those in high prognostic risk and with poor-risk mutations.

A case study on the bearing characteristics of a bottom uplift pile in a layered foundation.

The bottom uplift pile, which has been applied in practical projects, has the following advantages: the pile body is not easy to crack, good bearing characteristics, and small displacement of the pile top. Based on the bearing capacity test of foundation piles in the third stage expansion project of Lanzhou Zhongchuan International Airport, the upper part pile of the self-balancing test method was used to simulate the bottom uplift pile, and the anchor piles in the anchor pile method were regarded as normal uplift piles. The bearing characteristics of the bottom uplift pile in a layered foundation were studied by comparing these two kinds of piles. The results show that under the same displacement of the pile top, the ultimate uplift bearing capacity of the bottom uplift pile can be more than twice that of the normal uplift pile because of the fully exerted frictional resistance of the soil at the bottom of the pile, the Poisson effect of the pile body and the avoidance of the influence of pile body deformation on the pile top displacement. The maximum axial force of the bottom uplift pile appears at the bottom of the pile and gradually decreases from the bottom to the top, which is opposite to that of the normal uplift pile. The properties and thickness of the soil layers around the pile have a great influence on the distribution curves of the frictional resistance along the pile length of the two kinds of uplift piles. With changing soil layer conditions, the distribution curve may be a "parabola", a "straight line" or a "double line". The soil property plays a decisive role in the frictional resistance, which may cause softening. The influence of the pile diameter on the ultimate uplift bearing capacity is greater than that of the pile length, while the elastic modulus of the pile has little influence.

SWATH-MS-based proteomics reveals functional biomarkers of Th1/Th2 responses of tropomyosin allergy in mouse models.

Type-I food allergies are hypersensitive reactions compromising the immune organs and epithelial barriers. To investigate the organ-specific proteomic alterations of the allergy responses, the spleen and intestine of mice sensitized with high (shrimp and clam) and weak (fish) allergenic tropomyosins were analyzed using sequential windowed acquisition of all theoretical fragment ion mass spectra (SWATH-MS)-based proteomics. The results showed that Th1 and Th2 tropomyosin-induced responses in the spleen are characterized by the unique upregulation of innate (cochlin) and adaptive (Ig κ chain V-III region PC 7175) immune regulators, respectively. In the intestine, tropomyosin allergy concurred with the downregulation of 35 differentiating proteins featuring the overall impairment of metabolic pathways, absorption processes and ammonium ion responses. These data provide new functional biomarkers of tropomyosin-induced immune responses as well as candidate targets for intervention.

High flow nasal cannula therapy for obstructive sleep apnea in adults.

PURPOSE: Obstructive sleep apnea hypopnea syndrome (OSAHS) is characterized by the aggravation of upper airway constriction or obstruction, and it is associated with high incidence of various metabolic diseases and high mortality. Continuous positive airway pressure (CPAP) is now recommended as the first-line therapy for OSAHS, but its application is limited by its unsatisfactory patient tolerance. Previous studies have showed that high flow nasal cannula (HFNC) may improve symptoms in some patients with OSAHS. Therefore, the aim of the present study was to evaluate the effect of HFNC on OSAHS in a larger cohort than in previous research and to study the details of its therapeutic characteristics. METHODS: Polysomnography recording with and without HFNC was performed in 56 OSAHS patients with a wide spectrum of disease severity. Subgroups were divided by different treatment response criteria to identify the effect of this device. RESULTS: Of 56 patients enrolled, 9 were of mild severity (AHI, 5 to <15 events/h), 30 were of moderate severity (AHI, 15 to <30 events/h), and 17 patients were severe (AHI ≥ 30 events/h); 34 patients were younger than 50 years old and 22 patients were older than 50 years old. AHI decreased significantly (from 26.9 ± 14.7 to 21.5 ± 17.0 events/h, p < 0.001) after HFNC treatment in general. The subjects of responder group accounted for 21%. There was a negative correlation between the difference of AI and the difference of HI in nonresponder group before and after HFNC treatment, and the negative correlation was strong (Pearson's test, r = - 0.804, p = 0.000). Of the patients with mild to moderate severity, 76% achieved any AHI reduction and 24% of patients achieved at least 50% reduction in AHI. Older patients (the age of responder group 52.6 ± 11.7 vs. nonresponder group 43.7 ± 12.1 years old, p < 0.05), especially patients older than 50 years, had a better response rate (≤ 50 years 9% vs. > 50 years 41%, p = 0.007). CONCLUSION: HFNC may be useful in treating patients with OSAHS, especially older patients and those with mild to moderate severity. HFNC may be an alternative treatment when patients are intolerant of CPAP.

Clinicopathological characteristics and prognostic factor analysis of Siewert Ⅱ and Ⅲ adeno-carcinoma of esophagogastric junction / 中华消化外科杂志

Objective:To investigate the clinicopathological characteristics and prognostic factors of Siewert Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG).Methods:The retrospetcive cohort study was conducted. The clinicopathological data of 399 patients with AEG who were admitted to Peking University People′s Hospital from January 1998 to December 2015 were collected. There were 318 males and 81 females, aged 66(range, 19-87)years. Observation indicators: (1) clinicopathological characteristics of Siewert Ⅱ and Ⅲ AEG; (2) follow-up and survival; (3) prognostic factors analysis. Patients were followed up by telephone interview and outpatient examination to detect postoperative survival up to December 2018. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Kaplan-Meier method was used to draw survival curves and calculate survival rates. Log-rank test was used for survival analysis. Univariate and multivariate analyses were done using the COX proportional hazard model. Results:(1) Clinicopathological characteristics of Siewert Ⅱ and Ⅲ AEG. Of 399 patients, 198 cases were Siewert Ⅱ AEG and 201 cases were Siewert Ⅲ AEG. There were 130 cases undergoing transthoracic radical AEG surgery, 172 cases undergoing trans-abdominal proximal gastrectomy and 97 cases undergoing transabdominal total gastrectomy. The age, tumor diameter, cases with surgical method as transthoracic radical AEG surgery, transabdo-minal proximal gastrectomy and transabdominal total gastrectomy, the number of positive lymph nodes, cases in tumor TNM stage Ⅰ, Ⅱ, Ⅲ, Ⅳ were (65±10)years, (5.1±2.4)cm, 102, 68, 28, 17(range, 12?22), 20, 57, 117, 4 for patients with Siewert Ⅱ AEG, versus (62±12)years, (6.3±3.2)cm, 28, 104, 69,18(range, 14?27), 16, 41, 134, 10 for patients with Siewert Ⅲ AEG, showing significant differ-ences betweeen them ( t=2.83, ?3.82, χ2=66.97, U=17 407.05, 17 532.00, P<0.05). (2) Follow-up and survival. All 399 patients were followed up for 34(range, 2?160)months. The 5-year overall survival rate was 29.3% for patients with Siewert Ⅱ AEG, versus 37.0% for patients with Siewert Ⅲ AEG, showing no significant difference betweeen them ( χ2=1.46, P>0.05). The median survival time and 5-year overall survival rate were 29.0 months [95% confidence interval ( CI) as 23.4?34.6 months] and 22.9% for patients undergoing transthoracic radical AEG surgery, 43.0 months(95% CI as 33.9?52.1 months) and 34.7% for patients undergoing transabdominal proximal gastrectomy, 54.0 months (95% CI as 37.6?70.4 months)and 44.3% for patients undergoing transabdominal total gastrectomy, showing a significant difference in the survival among the 3 groups ( χ2=13.81, P<0.05). Of the 198 Siewert Ⅱ AEG patients, the 5-year overall survival rate was 24.6% for the 96 patients undergoing transabdominal surgery, versus 35.4% for the 102 patients undergoing transthoracic surgery, showing no significant difference in the survival between them ( χ2=3.10, P>0.05). Of the 201 Siewert Ⅲ AEG patients, the 5-year overall survival rate was 40.0% for the 173 patients undergoing transabdominal surgery, versus 16.1% for the 28 patients undergoing transthoracic surgery, showing a significant difference between them ( χ2=11.32, P<0.05). (3) Prognostic factors analysis. Results of univariate analysis showed that surgical method, pathological N staging, patholgical M staging were related factors for prognosis of Siewert Ⅱ and Ⅲ AEG ( hazard ratio=0.68, 1.25, 2.18, 95% CI as 0.54?0.86, 1.15?1.36, 1.28?3.73, P<0.05). Results of multivariate analysis showed that transthoracic approach, pathological stage N2?N3 and pathological stage M1 were independent risk factors for prognosis of Siewert Ⅱ and Ⅲ AEG ( hazard ratio=0.64, 1.25, 2.18, 95% CI as 0.51?0.80, 1.16?1.35, 1.28?3.70, P<0.05). Conclusions:Compared with Siewert Ⅲ AEG, Siewert Ⅱ AEG has a smaller tumor diameter, less positive lymph nodes, poorer prognosis. Transthoracic approach is preffered for the Siewert Ⅱ AEG. Transthoracic approach, pathological stage N2?N3 and pathological stage M1 are independent risk factors for prognosis of Siewert Ⅱ and Ⅲ AEG.

Molecular epidemiological investigation on Theileria in yellow cattle from Xiangxi Autonomous Prefecture of Hunan Province / 中国血吸虫病防治杂志

Objective To investigate the prevalence and genetic variation of Theileria in yellow cattle in Xiangxi Autonomous Prefecture of Hunan Province. Methods A total of 184 blood specimens were collected from Fenghuang, Huanyuan and Baojing counties of Xiangxi Autonomous Prefecture during the period from August 2018 through August 2019, and were detect using PCR assay with the specific 18S ribosomal rRNA (18S rRNA) gene targeting Theileria. The gene sequences of positive specimens were aligned with the sequences recorded in GenBank, and a phylogenetic tree was created with Plasmodium ovale 18S rRNA as an outgroup. Results A total of 143 blood samples were positive for Theileria, with a mean detection rate of 77.7%. Theileria was prevalent in the blood samples from yellow cattle in all three counties, with detection rates of 85.0% in Fenghuang County, 88.3% in Huayuan County and 61.0% in Baojing County, respectively. There was no significant difference in the detection rate of Theileria between Xiangxi yellow cattle and normal yellow cattle (77.2% vs. 79.5%; χ2 = 0.08, P > 0.05), while the detection of Theileria was significantly lower in the housed yellow cattle than in free-range cattle (68.9% vs. 89.7%; χ2 = 22.36, P < 0.01). A total of 18 PCR positive samples were randomly selected for sequencing and analysis, and all samples showed more than 99.0% homology with T. luwenshuni isolates. Phylogenetic analysis showed that the 18 positive samples were clustered into the same branch with T. luwenshuni, but were far away from other isolates. Conclusions The prevalence of Theileria is high in yellow cattle from Xiangxi Autonomous Prefecture of Hunan Province, and T. luwenshuni may be the dominant parasite species.

Scutellarin alleviates lipopolysaccharide-induced renal injury via mediating cysteine-rich protein 61-connective tissue growth factor-nephroblastoma overexpressed gene 1 expression to inhibit nuclear factor-κB signaling pathway / 中华危重病急救医学

Objective:To explore the protective effect and mechanism of scutellarin (Scu) on sepsis associated-acute kidney injury (SA-AKI).Methods:① In vivo experiment: 36 male C57BL/6 mice were divided into normal saline (NS) control group, lipopolysaccharide (LPS) induced SA-AKI model group (LPS group), 20 mg/kg Scu control group (Scu 20 control group), and 5, 10, 20 mg/kg Scu pretreatment groups by random number table with 6 mice in each group. The SA-AKI model was reproduced by intraperitoneal injection of 10 mg/kg LPS. The NS control group was injected with NS intraperitoneally. The Scu pretreatment groups were intraperitoneally injected with different doses of Scu every day before LPS injection for 1 week. Scu 20 control group was injected with 20 mg/kg Scu for 1 week. After 24 hours of LPS treatment, mice in each group were sacrificed, kidney tissues were collected, and kidney injury was detected by hematoxylin-eosin (HE) staining. Western blotting was used to detect the protein expression levels of nuclear factor-κB (NF-κB) signaling pathway related molecules, apoptosis-related proteins and cysteine-rich protein 61-connective tissue growth factor-nephroblastoma overexpressed gene 1 (CCN1). ② In vitro experiment: human renal tubular epithelial cell line HK-2 was cultured in vitro and used for experiment when the cells fused to 80%. In the cells without LPS treatment and after 100 g/L LPS treatment, pcDNA3.1-CCN1 and small interfering RNA (siRNA) CCN1 sequence were transfected to overexpress and inhibit CCN1 expression, respectively, to observe whether CCN1 was involved in NF-κB signaling pathway activation and apoptosis. In addition, 100g/L LPS and 20 μmol/L Scu were added into HK-2 cells transfected with and without CCN1 siRNA to investigate the mechanism of protective effect of Scu on LPS-induced HK-2 cells injury. Results:① The results of in vivo experiment: the renal function of SA-AKI mice induced by LPS was significantly decreased, and had kidney histological damage and severely damaged renal tubules. Scu could alleviate renal function and histological damage in a dose-dependent manner. Western blotting results showed Scu could reduce the protein expression of NF-κB signaling pathway related molecules and CCN1 in the renal tissue, and had a significant alleviating effect on apoptosis, indicating that CCN1 was involved in NF-κB signaling pathway activation and apoptosis. ② The results of in vitro experiment: in HK-2 cells not treated with LPS, CCN1 overexpression had no effect on apoptosis related protein and pro-inflammatory factors of NF-κB signaling pathway. In HK-2 cells treated with LPS, overexpression of CCN1 significantly inhibited the mRNA expressions of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1), with significant differences as compared with cells stimulated only by LPS [IL-1β mRNA (2 -ΔΔCT): 3.20±0.57 vs. 4.88±0.69, TNF-α mRNA (2 -ΔΔCT): 2.99±0.44 vs. 5.00±0.81, MCP-1 mRNA (2 -ΔΔCT): 2.81±0.50 vs. 5.41±0.75, all P < 0.05], and the apoptosis-related protein was significantly down-regulated. However, when siRNA was used to inhibit the expression of CCN1, the mRNA expressions of pro-inflammatory factors were significantly increased as compared with cells stimulated only by LPS [IL-1β mRNA (2 -ΔΔCT): 6.01±1.13 vs. 4.88±0.69, TNF-α mRNA (2 -ΔΔCT): 5.15±0.86 vs. 5.00±0.81, all P < 0.05], and apoptosis-related protein was significantly up-regulated. In the LPS-induced HK-2 cells, the mRNA expressions of pro-inflammatory factors were significantly down-regulated after Scu treatment as compared with cells stimulated only by LPS [IL-1β mRNA (2 -ΔΔCT) : 2.55±0.50 vs. 6.15±1.04, TNF-α mRNA (2 -ΔΔCT): 2.58±0.40 vs. 3.95±0.52, MCP-1 mRNA (2 -ΔΔCT): 2.64±0.44 vs. 6.21±0.96, all P < 0.05], and apoptosis-related protein was also significantly reduced. When the expression of CCN1 was inhibited by siRNA, the protective effect of Scu on cells was weakened, which showed that the mRNA expressions of pro-inflammatory factors in cells was significantly up-regulated compared with the cells without inhibition of CCN1 expression [IL-1β mRNA (2 -ΔΔCT): 5.34±0.76 vs. 2.55±0.50, TNF-α mRNA (2 -ΔΔCT): 3.66±0.54 vs. 2.58±0.40, MCP-1 mRNA (2 -ΔΔCT): 5.15±0.79 vs. 2.64±0.44, all P < 0.05], and the expression of apoptosis related protein was also significantly up-regulated. Conclusions:Scu could protect the renal function in SA-AKI mice, and the protective effect is associated with NF-κB signaling pathway and CCN1. Thus, Scu could alleviate LPS-induced kidney injury by regulating the NF-κB signaling pathway.

Impact of bicuspid aortic valve or tricuspid aortic valve on hemodynamics and left ventricular reverse remodeling in patients after transcatheter aortic valve replacement / 中华心血管病杂志

Objective: To compare the impact of bicuspid aortic valve (BAV) or tricuspid aortic valve (TAV) on hemodynamics and left ventricular reverse remodeling after transcatheter aortic valve replacement (TAVR). Methods: We retrospectively analyzed the clinical data of patients who underwent TAVR in our hospital from January 2019 to March 2021. Patients were divided into BAV group and TAV group according to aortic contrast-enhanced CT. Each patient was followed up by N-terminal pro B-type natriuretic peptide (NT-proBNP) and echocardiography at four time points, namely before TAVR, 24 hours, 1 month and 6 months after TAVR. Echocardiographic data, including mean pressure gradient (MPG), aortic valve area (AVA), left ventricular ejection fraction (LVEF), left ventricle mass (LVM) and LV mass index (LVMi) were evaluated. Results: A total of 41 patients were included. The age was (75.0±8.6) years, and male patients accounted for 53.7%. There were 19 BAV patients and 22 TAV patients in this cohort. All patients undergoing TAVR using a self-expandable prosthesis Venus-A valve. MPG was (54.16±21.22) mmHg(1 mmHg=0.133 kPa) before TAVR, (21.11±9.04) mmHg at 24 hours after TAVR, (18.84±7.37) mmHg at 1 month after TAVR, (17.68±6.04) mmHg at 6 months after TAVR in BAV group. LVEF was (50.42±13.30)% before TAVR, (53.84±10.59)% at 24 hours after TAVR, (55.68±8.71)% at 1 month after TAVR and (57.42±7.78)% at 6 months after TAVR in BAV group. MPG and LVEF substantially improved at each time point after operation, and the difference was statistically significant (all P<0.05) in BAV group. MPG in TAV group improved at each time point after operation, and the difference was statistically significant (all P<0.05). LVMi was (164.13±49.53), (156.37±39.11), (146.65±38.84) and (134.13±39.83) g/m2 at the 4 time points and the value was significantly reduced at 1 and 6 months post TAVR compared to preoperative level(both P<0.05). LVEF in the TAV group remained unchanged at 24 hours after operation, but it was improved at 1 month and 6 months after operation, and the difference was statistically significant (all P<0.05). LVMi in TAV group substantially improved at each time point after operation, and the difference was statistically significant (all P<0.05). NT-proBNP in both two groups improved after operation, at 1 month and 6 months after operation, and the difference was statistically significant (all P<0.05). MPG in TAV group improved better than in BAV group during the postoperative follow-up (24 hours after TAVR: (11.68±5.09) mmHg vs. (21.11±9.04) mmHg, P<0.001, 1 month after TAVR: (10.82±3.71) mmHg vs. (18.84±7.37) mmHg, P<0.001, 6 months after TAVR: (12.36±4.42) mmHg vs. (17.68±6.04) mmHg, P=0.003). There was no significant difference in NT-proBNP between BAV group and TAV group at each time point after operation (all P>0.05). There was no significant difference in paravalvular regurgitation and second prosthesis implantation between the two groups (all P>0.05). Conclusions: AS patients with BAV or TAV experience hemodynamic improvement and obvious left ventricular reverse remodeling after TAVR, and the therapeutic effects of TAVR are similar between BAV and TAV AS patients in the short-term post TAVR.