Research progress in micro/nanobubbles for ultrasound diagnosis or treatment / 药学学报

In the past few decades, microbubbles were widely used as ultrasound contrast agents in the field of tumor imaging. With the development of research, ultrasound targeted microbubble destruction technology combined with drug-loaded microbubbles can achieve precise drug release and play a therapeutic role. As a micron-scale carrier, microbubbles are difficult to penetrate the endothelial cell space of tumors, and nano-scale drug delivery system—nanobubbles came into being. The structure of the two is similar, but the difference in size highlights the unique advantages of nanobubbles in drug delivery. Based on the classification principle of shell materials, this review summarized micro/nanobubbles used for ultrasound diagnosis or treatment and discussed the possible development directions, providing references for the subsequent development.

High-quality acceleration of the Chinese national schistosomiasis elimination programme to advance the building of Healthy China / 中国血吸虫病防治杂志

The goal of achieving elimination of schistosomiasis across all endemic counties in China by 2030 was proposed in the Outline of the Healthy China 2030 Plan. On June 16, 2023, the Action Plan to Accelerate the Elimination of Schistosomiasis in China (2023—2030) was jointly issued by National Disease Control and Prevention Administration and other 10 ministries, which deployed the targets and key tasks of the national schistosomiasis elimination programme in China. This article describes the progress of the national schistosomiasis control programme, analyzes the opportunities to eliminate schistosomiasis, and proposes targeted recommendations to tackle the challenges of schistosomiasis elimination, so as to accelerate the process towards schistosomiasis elimination and facilitate the building of a healthy China.

Study on the risk factors of cefoperazone/sulbactam-induced coagulation dysfunction in adult patients：a systematic review / 中国药房

OBJECTIVE To systematically evaluate the risk factors for cefoperazone/sulbactam-induced coagulation dysfunction in adult patients. METHODS Retrieved from CNKI， VIP， CBM， Wanfang data， PubMed， Embase and Cochrane Library， randomized controlled trial （RCT）， case-control study or cohort study about cefoperazone/sulbactam-induced coagulation dysfunction in adult patients were collected from the inception to Apr. 30th， 2023. After literature screening， data extraction and quality evaluation， meta-analysis was carried out by using RevMan 5.3 software. RESULTS A total of 13 studies were included， among which 11 studies were case-control studies， and 2 studies were cohort studies， involving 18 387 patients in total. Meta- analysis showed that the proportion of advanced age [OR＝2.04， 95%CI （1.14， 3.64）， P＝0.02]， liver insufficiency [OR＝5.95， 95%CI （4.21， 8.40）， P＜0.000 01]， renal insufficiency [OR＝3.51， 95%CI （3.04， 4.05）， P＜0.001]， hypoproteinemia [OR＝ 1.90， 95%CI（1.37， 2.62）， P＜0.001]， poor diet [OR＝7.25， 95%CI （5.13， 10.24）， P＜0.000 01]， daily dose of cefoperazone/ sulbactam ≥9 g [OR＝3.95， 95%CI （2.45，6.37）， P＜0.001]， medication duration of cefoperazone/sulbactam ≥10 d [OR＝2.43， 95%CI （1.81， 3.28）， P＜0.001]， combined use of anticoagulant drugs [OR＝2.84， 95%CI （2.03， 3.97）， P＜0.001]， combined with malignant tumor [OR＝1.60， 95%CI （1.20， 2.15），P＜0.001] in patients with abnormal coagulation function were significantly higher than those with normal coagulation function. CONCLUSIONS Advanced age， liver insufficiency， renal insufficiency， complicated with malignant tumors and hypoalbuminemia， combined use of anticoagulant drugs， poor diet， daily dose ≥9 g， and medication duration≥10 days are risk factors for coagulation dysfunction caused by cefoperazone/sulbactam.

Consistency between modified 12+ X prostate biopsy and systematic biopsy under transrectal interventional ultrasound and Gleason score after prostate cancer surgery / 中国医师杂志

Objective:To explore the consistency between modified 12+ X prostate biopsy under transrectal interventional ultrasound and postoperative Gleason score in prostate cancer patients.Methods:A retrospective study was conducted on 312 patients diagnosed with prostate cancer and underwent radical resection at Zhongshan People′s Hospital from January 2020 to December 2022. All patients underwent modified 12+ X prostate biopsy and prostate system biopsy under transrectal interventional ultrasound before surgery. Using the Gleason score of postoperative pathological specimens as the " gold standard", the detection rates of prostate cancer and clinically significant prostate cancer using modified 12+ X prostate biopsy and prostate system biopsy under transrectal interventional ultrasound were compared, and the consistency between the two methods alone or in combination and postoperative Gleason score was compared.Results:Among 312 patients, the positive detection rate of the improved 12+ X puncture biopsy combined with the system puncture biopsy was significantly higher than that of the individual detection (95.51% vs 80.77% vs 76.92%), with a statistically significant difference ( P<0.05). The improved 12+ X puncture biopsy combined with system puncture biopsy showed a clinically significant higher detection rate of prostate cancer in positive patients compared to the two tests alone (94.63% vs 77.78% vs 80.00%), with a statistically significant difference ( P<0.05). There was no statistically significant difference in the detection rate of clinically significant prostate cancer among patients who missed diagnosis, either alone or in combination with biopsy ( P>0.05). The upgrade rate of Gleason score after prostate improvement 12+ X puncture biopsy (25.00%) was significantly lower than that of prostate system puncture (44.17%), which was significantly higher than combined puncture biopsy (11.74%), with a statistically significant difference ( P<0.05). After 312 patients received combined puncture biopsy, urinary retention was found in 14 cases (4.49%), hematuria in 30 cases (9.62%), fever in 28 cases (8.97%), and blood in stool in 18 cases (5.77%). After symptomatic treatment, they basically improved within 3 days after puncture. Conclusions:The combination of modified 12+ X prostate biopsy with systematic biopsy under transrectal interventional ultrasound can improve the detection rate of prostate cancer, and has good consistency with the postoperative Gleason score of prostate cancer patients, which has good clinical application value.

Comparison of long-term quality of life between Billroth-I and Roux-en-Y anastomosis after distal gastrectomy for gastric cancer: a randomized controlled trial / 中华医学杂志(英文版)

BACKGROUND@#The results of studies comparing Billroth-I (B-I) with Roux-en-Y (R-Y) reconstruction on the quality of life (QoL) are still inconsistent. The aim of this trial was to compare the long-term QoL of B-I with R-Y anastomosis after curative distal gastrectomy for gastric cancer.@*METHODS@#A total of 140 patients undergoing curative distal gastrectomy with D2 lymphadenectomy in West China Hospital, Sichuan University from May 2011 to May 2014 were randomly assigned to the B-I group ( N  = 70) and R-Y group ( N  = 70). The follow-up time points were 1, 3, 6, 9, 12, 24, 36, 48, and 60 months after the operation. The final follow-up time was May 2019. The clinicopathological features, operative safety, postoperative recovery, long-term survival as well as QoL were compared, among which QoL score was the primary outcome. An intention-to-treat analysis was applied.@*RESULTS@#The baseline characteristics were comparable between the two groups. There were no statistically significant differences in terms of postoperative morbidity and mortality rates, and postoperative recovery between the two groups. Less estimated blood loss and shorter surgical duration were found in the B-I group. There were no statistically significant differences in 5-year overall survival (79% [55/70] of the B-I group vs. 80% [56/70] of the R-Y group, P  = 0.966) and recurrence-free survival rates (79% [55/70] of the B-I group vs. 78% [55/70] of the R-Y group, P  = 0.979) between the two groups. The scores of the global health status of the R-Y group were higher than those of the B-I group with statistically significant differences (postoperative 1 year: 85.4 ± 13.1 vs . 88.8 ± 16.1, P  = 0.033; postoperative 3 year: 87.3 ± 15.2 vs . 92.8 ± 11.3, P  = 0.028; postoperative 5 year: 90.9 ± 13.7 vs . 96.4 ± 5.6, P  = 0.010), and the reflux (postoperative 3 year: 8.8 ± 12.9 vs . 2.8 ± 5.3, P  = 0.001; postoperative 5 year: 5.1 ± 9.8 vs . 1.8 ± 4.7, P  = 0.033) and epigastric pain (postoperative 1 year: 11.8 ± 12.7 vs. 6.1 ± 8.8, P  = 0.008; postoperative 3 year: 9.4 ± 10.6 vs. 4.6 ± 7.9, P  = 0.006; postoperative 5 year: 6.0 ± 8.9 vs . 2.7 ± 4.6, P  = 0.022) were milder in the R-Y group than those of the B-I group at the postoperative 1, 3, and 5-year time points.@*CONCLUSIONS@#Compared with B-I group, R-Y reconstruction was associated with better long-term QoL by reducing reflux and epigastric pain, without changing survival outcomes.@*TRIAL REGISTRATION@#ChiCTR.org.cn, ChiCTR-TRC-10001434.

Knockdown of IGF2BP2 inhibits colorectal cancer cell proliferation, migration and promotes tumor immunity by down-regulating MYC expression / 细胞与分子免疫学杂志

Objective To investigate the effect of insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) on the proliferation, migration and tumor immune microenvironment of colorectal cancer cells and its possible molecular mechanism. Methods The Cancer Genome Atlas (TCGA) database was used to analyze the expression levels of IGF2BP2 and MYC in colorectal cancer and adjacent tissues. The expression of IGF2BP2 in HCT-116 and SW480 human colorectal cancer cells was silenced by RNA interference (RNAi), and the silencing effect was detected by quantitative real-time PCR. After knocking down IGF2BP2, colony formation assay, CCK-8 assay and 5-ethynyl-2'-deoxyuridine (EdU) assay were employed to detect cell colony formation and proliferation ability. TranswellTM assay was used to detect cell migration ability. Quantitative real-time PCR was used to detect the mRNA expression of IGF2BP2, MYC, tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β) and interleukin-10 (IL-10). The protein expression of IGF2BP2 and MYC was detected by western blot. The binding ability of IGF2BP2 and MYC in HCT-116 cells was detected by quantitative real-time PCR after RNA immunoprecipitation. Results The results of TCGA database showed that the expression of IGF2BP2 and MYC in colorectal cancer tissues was significantly higher than that in adjacent tissues, and the survival time of colorectal cancer patients with high expression of IGF2BP2 was shorter. After silencing IGF2BP2, the viability, proliferation and migration of HCT-116 and SW480 cells were decreased. The mRNA expression of MYC, TGF-β and IL-10 in IGF2BP2 knockdown group was significantly decreased, while the expression of TNF-α mRNA was increased. The expression of MYC protein and the stability of MYC mRNA were significantly decreased. RIP-qPCR results showed that IGF2BP2 could bind to MYC mRNA. Conclusion Knockdown of IGF2BP2 inhibits colorectal cancer cell proliferation, migration and promotes tumor immunity by down-regulating MYC expression.

Application of PDX model in the evaluation of nano-delivery systems / 药学学报

Malignant tumor is a major disease affecting human health. The nano-delivery system itself has a unique size effect and it can achieve tumor-targeted distribution of drug molecules, improve the therapeutic effect, and reduce the toxic and side effects on normal tissues and cells after functional modification. Patient-derived xenografts (PDX) models can be established by transplanting patient-derived cancer cells or small tumor tissue into immunodeficient mice directly. Compared with the tumor cell line model, this model can preserve the key features of the primary tumor such as histomorphology, heterogeneity, and genetic abnormalities, and keep them stable between generations. PDX models are widely used in drug evaluation, target discovery and biomarker development, especially providing a reliable research platform for the diagnosis and treatment evaluation of nano-delivery systems. This review summarizes the application of several common cancer PDX models in the evaluation of nano-delivery systems, in order to provide references for researchers to perform related research.

Research progress of intelligent reversible drug delivery system / 药学学报

In the research on cancer theranostics, most environment-sensitive drug delivery systems can only achieve unidirectional and irreversible responsive changes under pathological conditions, thereby improving the targeting effect and drug release performance of the delivery system. However, such irreversible changes pose potential safety hazards when the dynamically distributed delivery system returns to the blood circulation or transports to the normal physiological environment. Intelligent reversible drug delivery systems can respond to normal physiological and pathological microenvironments to achieve bidirectional and reversible structural changes. This feature will help to precisely control the drug release of the delivery system, prolong the blood circulation time, improve the targeting efficiency, and avoid the potential safety hazards of the irreversible drug delivery system. In this review, we describe the research progress of intelligent reversible drug delivery system from two main aspects: controlled drug release and prolonged blood circulation time/enhanced cellular internalization of drug.

Publication and citation analyses of Chinese Journal of Schistosomiasis Control from 2011 to 2020 / 中国血吸虫病防治杂志

Objective To investigate the publications and citations of Chinese Journal of Schistosomiasis Control from 2011 to 2020, so as to provide insights into improving the journal quality and impact.. Methods All publications were retrieved from 60 issues of 10 volumes of Chinese Journal of Schistosomiasis Control from 2011 to 2020, and publication and citation analyses were performed using a bibliometric method. Results A total of 1 867 articles were published in Chinese Journal of Schistosomiasis Control from 2011 to 2020, with the largest number in 2012 (220 publications) and the lowest in 2020 (135 publications), and original article (36.48%), control experience (17.14%) and control study (10.34%) were the three most common article type. The overall proportion of grant-supported articles was 59.08% (1 103/1 867), and the number of grant per article was (2.34±1.58) grants. The mean duration from submission to publication was (173.48±105.84) days per article, and there was a significant difference in the mean duration from submission to publication among years (F = 30.883, P < 0.01). Jiangsu Province (492 publications, 26.35%), Shanghai Municipality (264 publications, 14.14%) and Hubei Province (230 publications, 12.32%) were the three most productive provinces where the first author lived, and disease control and prevention institutions were the predominant affiliations of the first author (67.22%), with Jiangsu Institute of Schistosomiasis Control, National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, and Wannan Medical College as the three most productive affiliations. The number of authors was 5.94 authors per publication, and the proportion of co-authored publications was 95.45% in Chinese Journal of Schistosomiasis Control from 2011 to 2020. Journal article was the predominant type of cited (89.97%), and the mean number of citations was (15.70±11.56) citations per publication, with a significant difference in the mean number of citations per publication among years (F = 2.205, P < 0.05). The impact factors of Chinese Journal of Schistosomiasis Control ranged from 0.877 to 1.676 during the period from 2011 to 2020, and the overall Price index was 47.59%. Conclusions Both the academic impact and national transmissibility of Chinese Journal of Schistosomiasis Control appeared a tendency towards a rise from 2011 to 2020. Seeking high-quality contributions, increasing interdisciplinary integration, shortening the duration from submission to publication, expanding the coverage of publication services and enhancing impact are the future priorities of the journal.

Establishment and evaluation of a method for extracting exogenous short DNA fragments of Schistosoma japonicum from urine samples / 中国血吸虫病防治杂志

Objective To establish the method for extracting exogenous short DNA fragments of Schistosoma japonicum from urine samples, and to evaluate the efficiency of this method for extraction from urine samples treated with various methods. Methods The S. japonicum SjG28 gene fragment was selected as a target sequence, and the 81 bp short DNA fragment was amplified on the target sequence using PCR assay. Following characterization using sequencing, the short DNA fragment was added into the urine samples as an exogenous short DNA fragment. Primers and probes were designed with SjG28 as a target gene, to establish the real-time fluorescent quantitative PCR (qPCR) assay. The sensitivity of this qPCR assay was evaluated with exogenous short DNA fragments that were diluted at a 1:10 dilution ratio as the DNA template, and the specificity of the qPCR assay was evaluated with the genomic DNA of S. mansoni, S. haematobium, Babesia, Ancyiostoma duodenaie, Cionorchis sinensis, and Paragonimus westermani as DNA templates. Exogenous short DNA fragments were added into artificial and healthy volunteers’ urine samples, followed by pH adjustment, centrifugation and concentration, and the efficiency of extracting exogenous short DNA fragments from urine samples was compared with the QIAmp Viral RNA Mini Kit (Qiagen kit) and BIOG cfDNA easy kit (BIOG kit). Results An 81 bp small DNA fragment of S. japonicum was successfully prepared, and the lowest detection limit of the established qPCR assay was 100 copies/μL of the 81 bp small DNA fragment of S. japonicum. If the genomic DNA of S. japonicum, S. mansoni, S. haematobium, Babesia, A. duodenaie, C. sinensis, and P. westermani served as DNA templates, the qPCR assay only detected fluorescent signals with S. japonicum genomic DNA as the DNA template. If the pH values of artificial urine samples were adjusted to 5, 6, 7 and 8, the recovery rates were (49.12 ± 2.09)%, (84.52 ± 4.96)%, (89.38 ± 3.32)% and (87.82 ± 3.90)% for extracting the exogenous short DNA fragment of S. japonicum with the Qiagen kit, and were (2.30 ± 0.07)%, (8.11% ± 0.26)%, (13.35 ± 0.61)% and (20.82 ± 0.68)% with the BIOG kit, respectively (t = 38.702, 26.955, 39.042 and 29.571; all P values < 0.01). If the Qiagen kit was used for extracting the exogenous short DNA fragment from artificial urine samples, the lowest recovery rate was seen from urine samples with a pH value of 5 (all P values < 0.05), and there were no significant differences in the recovery rate from urine samples with pH values of 6, 7 and 8 (all P values > 0.05). Following centrifugation of artificial [(64.30 ± 1.00)% vs. (58.87 ± 0.26)%; t = 12.033, P < 0.05] and healthy volunteers’ urine samples [(31 165 ± 1 017) copies/μL vs. (28 471 ± 818) copies/μL; t = 23.164, P < 0.05]. In addition, concentration of artificial urine samples with the 10 kDa Centrifugal Filter and concentration of healthy volunteers’ urine samples with the 100 kDa Centrifugal Filter were both effective to increase the recovery of the Qiagen kit for extracting the exogenous short DNA fragment of S. japonicum (both P values < 0.01). Conclusions A method for extracting exogenous short DNA fragments of S. japonicum from urine samples has been successfully established, and the Qiagen kit has a high extraction efficiency. Adjustment of urine pH to 6 to 8 and concentration of healthy volunteers’ urine samples with the 100 kDa Centrifugal Filter are both effective to increase the efficiency of extracting exogenous short DNA fragments of S. japonicum.

Construction of a human health literacy indicator system for prevention of parasitic diseases based on Delphi method / 中国血吸虫病防治杂志

Objective To construct a human health literacy indicator system for prevention of parasitic diseases based on Delphi method. Methods Based on literature reviews and expert interviews, a questionnaire was designed and a two-round Delphi consultation was performed. A human health literacy indicator system for prevention of parasitic diseases was constructed according to the deletion criteria and experts’ advice. Results A total of 14 experts completed the two-round consultation. The second-round authority coefficients were 0.91 to 0.96 for the first-level indicators, 0.87 to 0.97 for the second-level indicators and 0.86 to 0.97 for the third-level indicators. A human health literacy indicator system for prevention of parasitic diseases was constructed with the main framework of basic knowledge and awareness, healthy behaviors, and healthy skills, which contained 3 first-level indicators, 12 second-level indicators and 48 third-level indicators. Among the three first-level indicators, basic knowledge and awareness had the highest weighting coefficient (0.336 5), followed by healthy behaviors (0.334 9), and healthy skills had the lowest weighting coefficient (0.328 6). The three secondary-level indicators with the highest combined weights included awareness of the epidemic status (0.088 2), awareness of the resource of infection (0.085 8) and basic awareness of parasitic diseases (0.085 5). Conclusion A human health literacy indicator system for prevention of parasitic diseases is preliminarily constructed, which provides insights into the development of health literacy evaluation tools for prevention of parasitic diseases in the new era.

Recombinant Schistosoma japonicum egg ribonuclease SjCP1412 inhibits the activation of LX-2 hepatic stellate cells in vitro / 中国血吸虫病防治杂志

Objective To investigate the effect of recombinant Schistosoma japonicum egg ribonuclease SjCP1412 (rSjCP1412) on proliferation, cell cycle, apoptosis and activation of human hepatic stellate cells LX-2 in vitro, and explore the underlying mechanisms. Methods The rSjCP1412 protein was expressed in Escherichia coli BL21 by prokaryotic expression, and the highly purified soluble rSjCP1412 protein was prepared by Ni NTA affinity chromatography and urea gradient refolding dialysis. Yeast RNA was digested using 12.5, 25.0, 50.0 µg rSjCP1412 proteins at 37 °C for 2, 3, 4 h, and the enzymatic products were electrophoresed on 1.5% agarose gel to observe the RNAase activity of rSjCP1412 protein. The proliferation of LX-2 cells stimulated by different doses of rSjCP1412 protein for 48 hours was measured using CCK-8 assay, and the apoptosis of LX-2 cells stimulated by different doses of rSjCP1412 protein for 48 hours was detected using the Annexin V-FITC/PI double staining, while the percentage of LX-2 cells at G0/G1, S and G2/M phases of cell cycle following stimulation with different doses of rSjCP1412 protein for 48 h was detected by DAPI staining. The type I collagen, type III collagen and α-smooth muscle actin (α-SMA) mRNA expression was quantified using quantitative florescent real-time PCR (qPCR) assay and Western blotting at transcriptional and translational levels in LX-2 cells following stimulation with different doses of rSjCP1412 protein for 48 h, while soluble egg antigen (SEA) served a positive control and PBS without rSjCP1412 protein as a normal control in the above experiments. The expression of collagen I, α-SMA and Smad4 protein was determined using Western blotting in LX-2 cells following stimulation with rSjCP1412 protein, transforming growth factor-β1 (TGF-β1) alone or in combination, to examine the signaling for the effect of rSjCP1412 protein on LX-2 cells. Results The rSjCP1412 protein was successfully expressed and the highly purified soluble rSjCP1412 protein was prepared, which had a RNase activity. Compared with the normal group, the survival rates of LX-2 cells significantly decreased post-treatment with 12.5, 25.0, 50.0 µg/mL rSjCP1412 protein and SEA for 48 h (F = 22.417 and 20.448, both P values < 0.05). The apoptotic rates of LX-2 cells significantly increased post-treatment with 12.5, 25.0, 50.0 µg/mL rSjCP1412 protein for 48 h (F = 11.350, P < 0.05), and treatment with 12.5, 25.0, 50.0 µg/mL rSjCP1412 protein for 48 h resulted in arrest of LX-2 cells in G0/G1 phase (F = 20.710, P < 0.05). Treatment with 12.5, 25.0, 50.0 µg/mL rSjCP1412 protein for 48 h caused a significant reduction in relative expression levels of collagen I (F = 11.340, P < 0.05), collagen III (F = 456.600, P < 0.05) and α-SMA mRNA (F = 23.100, P < 0.05) in LX-2 cells, and both rSjCP1412 protein and SEA treatment caused a significant reduction in collagen I (F = 1 302.000, P < 0.05), α-SMA (F = 49.750, P < 0.05) and Smad4 protein expression (F = 52.420, P < 0.05) in LX-2 cells. In addition, rSjCP1412 protein treatment inhibited collagen I (F = 66.290, P < 0.05), α-SMA (F = 31.300, P < 0.05) and Smad4 protein expression (F = 27.010, P < 0.05) in LX-2 cells activated by TGF-β1. Conclusion rSjCP1412 protein may induce apoptosis of LX-2 cells and inhibit proliferation, cell cycle and activation of LX-2 cells through down-regulating Smad4 signaling molecules.

Study on the effect of natural compound XCQ-9 of Cynanchum paniculatum on the proliferation and apoptosis of Jurkat cell and its mechanism / 中国药房

OBJECTIVE To investigate the inhibitory effect of natural compound XCQ-9 of Cynanchum paniculatum on the proliferation and apoptosis of Jurkat cell line of human T-cell acute lymphoblastic leukemia and its possible mechanism. METHODS Jurkat cell was used as the leukemia cell model， and MTT assay was adopted to detect the inhibitory effects of 0 （blank control）， 2.5， 5， 10， 20 and 40 μmol/L XCQ-9 on the proliferation of Jurkat cell after treated for 24， 48， 72 h. After treated with 0 （blank control）， 2.5， 5， 10 μmol/L XCQ-9 for 24 h and 48 h， the cell cycle and apoptosis were analyzed by flow cytometry. The expressions of Caspase-9， Cleaved Caspase-9， Caspase-3， Cleaved Caspase-3， poly ADP-ribose poly-merase （PARP）， Cleaved-PARP， cyclin-dependent kinase 1 （CDK1） and Cyclin B1 were detected by Western blot after treated for 24 h. RESULTS Compared with blank control group， XCQ-9 at different concentrations could significantly decrease the survival rate of Jurkat cells （P＜0.01）， and showed a dose and time-dependent manner. After 48 h treatment of 5， 10 μmol/L XCQ-9， Jurkat cell apoptosis was induced significantly （P＜0.05 or P＜0.01）， and the cell was arrested in G2 phase （P＜0.01）. After 24 h treatment of 10 μmol/L XCQ-9， the protein expressions of CDK1 and Caspase-9 were remarkably down-regulated （P＜0.01）， while the protein expressions of Cyclin B1， Cleaved Caspase-9， Cleaved Caspase-3 and Cleaved PARP were significantly up-regulated （P＜0.05 or P＜0.01）. CONCLUSIONS XCQ-9 plays anti-tumor effect through inducing G2 phase arrest to inhibit proliferation and 5008） activating Caspase pathway to increase apoptosis.

Clinicopathological characteristics and prognosis of patients with small bowel tumors: A single center analysis of 220 cases / 中华胃肠外科杂志

Objective: To analyze the clinicopathological characteristics and prognosis of patients with small bowel tumors. Methods: This was a retrospective, observational study. We collected clinicopathological data of patients with primary jejunal or ileal tumors who had undergone small bowel resection in the Department of Gastrointestinal Surgery, West China Hospital, Sichuan University between January 2012 and September 2017. The inclusion criteria included: (1) older than 18 years; (2) had undergone small bowel resection; (3) primary location at jejunum or ileum; (4) postoperative pathological examination confirmed malignancy or malignant potential; and (5) complete clinicopathological and follow-up data. Patients with a history of previous or other concomitant malignancies and those who had undergone exploratory laparotomy with biopsy but no resection were excluded. The clinicopathological characteristics and prognoses of included patients were analyzed. Results: The study cohort comprised 220 patients with small bowel tumors, 136 of which were classified as gastrointestinal stromal tumors (GISTs), 47 as adenocarcinomas, and 35 as lymphomas. The median follow-up for all patient was 81.0 months (75.9-86.1). GISTs frequently manifested as gastrointestinal bleeding (61.0%, 83/136) and abdominal pain (38.2%, 52/136). In the patients with GISTs, the rates of lymph node and distant metastasis were 0.7% (1/136) and 11.8% (16/136), respectively. The median follow-up time was 81.0 (75.9-86.1) months. The 3-year overall survival (OS) rate was 96.3%. Multivariate Cox regression-analysis results showed that distant metastasis was the only factor associated with OS of patients with GISTs (HR=23.639, 95% CI: 4.564-122.430, P<0.001). The main clinical manifestations of small bowel adenocarcinoma were abdominal pain (85.1%, 40/47), constipation/diarrhea (61.7%, 29/47), and weight loss (61.7%, 29/47). Rates of lymph node and distant metastasis in patients with small bowel adenocarcinoma were 53.2% (25/47) and 23.4% (11/47), respectively. The 3-year OS rate of patients with small bowel adenocarcinoma was 44.7%. Multivariate Cox regression-analysis results showed that distant metastasis (HR=4.018, 95%CI: 2.108-10.331, P<0.001) and adjuvant chemotherapy (HR=0.291, 95% CI: 0.140-0.609, P=0.001) were independently associated with OS of patients with small bowel adenocarcinoma. Small bowel lymphoma frequently manifested as abdominal pain (68.6%, 24/35) and constipation/diarrhea (31.4%, 11/35); 77.1% (27/35) of small bowel lymphomas were of B-cell origin. The 3-year OS rate of patients with small bowel lymphomas was 60.0%. T/NK cell lymphomas (HR= 6.598, 95% CI: 2.172-20.041, P<0.001) and adjuvant chemotherapy (HR=0.119, 95% CI: 0.015-0.925, P=0.042) were independently associated with OS of patients with small bowel lymphoma. Small bowel GISTs have a better prognosis than small intestinal adenocarcinomas (P<0.001) or lymphomas (P<0.001), and small bowel lymphomas have a better prognosis than small bowel adenocarcinomas (P=0.035). Conclusions: The clinical manifestations of small intestinal tumor are non-specific. Small bowel GISTs are relatively indolent and have a good prognosis, whereas adenocarcinomas and lymphomas (especially T/NK-cell lymphomas) are highly malignant and have a poor prognosis. Adjuvant chemotherapy would likely improve the prognosis of patients with small bowel adenocarcinomas or lymphomas.

Protective mechanism of tetramethylpyrazine on cardiovascular system / 中国中药杂志

Tetramethylpyrazine is the main component of Ligusticum chuanxiong. Studies have found that tetramethylpyrazine has a good protective effect against cardiovascular diseases. In the heart, tetramethylpyrazine can reduce myocardial ischemia/reperfusion injury by inhibiting oxidative stress, regulating autophagy, and inhibiting cardiomyocyte apoptosis. Tetramethylpyrazine can also reduce the damage of cardiomyocytes caused by inflammation, relieve the fibrosis and hypertrophy of cardiomyocytes in infarcted myocardium, and inhibit the expansion of the cardiac cavity after myocardial infarction. In addition, tetramethylpyrazine also has a protective effect on the improvement of familial dilated cardiomyopathy. Besides, the mechanisms of tetramethylpyrazine on blood vessels are more abundant. It can inhibit endothelial cell apoptosis by reducing oxidative stress, maintain vascular endothelial function and homeostasis by inhibiting inflammation and glycocalyx degradation, and protect vascular endothelial cells by reducing iron overload. Tetramethylpyrazine also has a certain inhibitory effect on thrombosis. It can play an anti-thrombotic effect by reducing inflammatory factors and adhesion molecules, inhibiting platelet aggregation, and suppressing the expression of fibrinogen and von Willebrand factor. In addition, tetramethylpyrazine can also reduce the level of blood lipid in apolipoprotein E-deficient mice, inhibit the subcutaneous deposition of lipids, inhibit the transformation of macrophages into foam cells, and inhibit the proliferation and migration of vascular smooth muscle cells, thereby reducing the formation of atherosclerotic plaque. In combination with network pharmacology, the protective mechanism of tetramethylpyrazine on the cardiovascular system may be mainly achieved through the regulation of phosphatidylinositol 3 kinase/protein kinase B(PI3K/Akt), hypoxia-inducible factor 1(HIF-1), and mitogen-activated protein kinase(MAPK) pathways. Tetramethylpyrazine hydrochloride and sodium chloride injection has been approved for clinical application, but some adverse reactions have been found in clinical application, which need to be paid attention to.

Protective mechanism of salvianolic acid B on blood vessels / 中国中药杂志

Salvianolic acid B(Sal B) is the main water-soluble component of Salvia miltiorrhiza Bunge. Studies have found that Sal B has a good protective effect on blood vessels. Sal B can protect endothelial cells by anti-oxidative stress, inducing autophagy, inhibiting endoplasmic reticulum stress(ERS), inhibiting endothelial inflammation and adhesion molecule expression, inhibiting endothelial cell permeability, anti-thrombosis, and other ways. In addition, Sal B can alleviate endothelial cell damage caused by high glucose(HG). For vascular smooth muscle cell(VSMC), Sal B can reduce the synthesis and secretion of inflammatory factors by inhibiting cyclooxygenase. It can also play a vasodilatory role by inhibiting Ca~(2+) influx. In addition, Sal B can inhibit VSMC proliferation and migration, thereby alleviating vascular stenosis. Sal B also inhibits lipid deposition in the subendothelium, inhibits macrophage conversion to foam cells, and reduces macrophage apoptosis, thereby reducing the volume of subendothelial lipid plaques. For some atherosclerosis(AS) complications, such as peripheral artery disease(PAD), Sal B can promote angiogenesis, thereby improving ischemia. It should be pointed out that the conclusions obtained from different experiments are not completely consistent, which needs further research. In addition, previous pharmacokinetics showed that Sal B was poorly absorbed by oral administration, and it was unstable in the stomach, with a large first-pass effect in the liver. Sal B had fast distribution and metabolism in vivo and short drug action time. These affect the bioavailability and biological effects of Sal B, and the development of clinically valuable Sal B non-injectable delivery systems remains a great challenge.

Ideal cardiovascular health and mortality: pooled results of three prospective cohorts in Chinese adults / 中华医学杂志(英文版)

BACKGROUND@#Evidence on the relations of the American Heart Association's ideal cardiovascular health (ICH) with mortality in Asians is sparse, and the interaction between behavioral and medical metrics remained unclear. We aimed to fill the gaps.@*METHODS@#A total of 198,164 participants without cancer and cardiovascular disease (CVD) were included from the China Kadoorie Biobank study (2004-2018), Dongfeng-Tongji cohort (2008-2018), and Kailuan study (2006-2019). Four behaviors (i.e., smoking, physical activity, diet, body mass index) and three medical factors (i.e., blood pressure, blood glucose, and blood lipid) were classified into poor, intermediate, and ideal levels (0, 1, and 2 points), which constituted 8-point behavioral, 6-point medical, and 14-point ICH scores. Results of Cox regression from three cohorts were pooled using random-effects models of meta-analysis.@*RESULTS@#During about 2 million person-years, 20,176 deaths were recorded. After controlling for demographic characteristics and alcohol drinking, hazard ratios (95% confidence intervals) comparing ICH scores of 10-14 vs. 0-6 were 0.52 (0.41-0.67), 0.44 (0.37-0.53), 0.54 (0.45-0.66), and 0.86 (0.64-1.14) for all-cause, CVD, respiratory, and cancer mortality. A higher behavioral or medical score was independently associated with lower all-cause and CVD mortality among the total population and populations with different levels of behavioral or medical health equally, and no interaction was observed.@*CONCLUSIONS@#ICH was associated with lower all-cause, CVD, and respiratory mortality among Chinese adults. Both behavioral and medical health should be improved to prevent premature deaths.

Progress in research of influenza vaccination in pregnant women / 中华流行病学杂志

Influenza is an acute respiratory infectious disease caused by influenza virus. Pregnancy is associated with physiologic and immunological changes that may increase the risk for influenza virus infection and influenza-related complications. Influenza vaccination is the most effective way to prevent influenza virus infection. WHO and many countries have classified pregnant women as a priority population for influenza vaccination, however, there are still many challenges for promoting influenza vaccination in pregnant women in China, influenza vaccination coverage in pregnant women remains low and some influenza vaccine package inserts list pregnancy as an absolute contraindication. In this paper, we summarize the research progress in the effects of influenza infection and influenza vaccination during pregnancy both at home and abroad, then discuss the strategies to promote influenza vaccination in pregnancy for the purpose of providing reference for the related research and policy development in China.

Performance of screening of contacts of COVID-19 cases in same flight / 中华流行病学杂志

Objective: To understand the performance of 2019-nCoV nucleic acid detection in screening of contacts of COVID-19 cases in same flights and provide evidence for the effective screening of persons at high risk for the infection in domestic flights. Methods: The information of passengers who took same domestic flights with COVID-19 cases in China from April 1, 2020 to April 30, 2022 were retrospectively collected,and χ2 test was used to analyze positive nucleic acid detection rates in the passengers in different times before the onsets of the index cases, in different seat rows and in epidemic periods of different 2019-nCoV variants. Results: During the study period, a total of 433 index cases were identified among 23 548 passengers in 370 flights. Subsequently, 72 positive cases of 2019-nCoV nucleic acid were detected in the passengers, in whom 57 were accompanying persons of the index cases. Further analysis of the another 15 passengers who tested positive for the nucleic acid showed that 86.67% of them had onsets or positive detections within 3 days after the diagnosis of the index cases, and the boarding times were all within 4 days before the onsets of the index cases. The positive detection rate in the passengers who seated in first three rows before and after the index cases was 0.15% (95%CI: 0.08%-0.27%), significantly higher than in the passengers in other rows (0.04%, 95%CI: 0.02%-0.10%, P=0.007),and there was no significant difference in the positive detection rate among the passengers in each of the 3 rows before and after the index cases (P=0.577). No significant differences were found in the positive detection rate in the passengers, except the accompanying persons, among the epidemics caused by different 2019-nCoV variants (P=0.565). During the Omicron epidemic period, all the positive detections in the passengers, except the accompanying persons, were within 3 days before the onset of the index cases. Conclusions: The screening test of 2019-nCoV nucleic acid can be conducted in the passengers took the same flights within 4 days before the onsets of the index cases on board. Passengers who seated within 3 rows from the index cases can considered as the close contacts at high risk for 2019-nCoV, for whom screening should be conducted first and special managements are needed. The passengers in other rows can be classified as general risk persons for screening and management.

The expression of adhesion molecules in Z310 cells induced by combined exposure to black carbon and lead / 中国职业医学

Objective: To investigate the effects of combined exposure to black carbon and lead on the expression of cell adhesion molecules and their regulating microRNAs (miRNAs) in the rat choroid plexus epithelial Z310 cells. Methods: i) Z310 cells were randomly divided into control group, black carbon exposure group, lead exposure group and combined exposure group. The lead exposure group and black carbon exposure group were treated with 10 μmol/L lead acetate and 10 mg/L black carbon, respectively, and the combined exposure group was treated with both in the above doses. After 12.0 hours, the expressions of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and mucosal vascular addressin cell adhesion molecule-1 (MAdCAM-1) in Z310 cells was detected by Western blotting. The expression of miR-326, miR-328-3p and miR-542-3p which regulated ICAM-1 was detected by real-time fluorescent quantitative polymerase chain reaction. ii) Z310 cells or Z310 cells transfected with miRNA-326 mimic were randomly divided into control group, miRNA-326 transfection control group, combined exposure group and miRNA-326 transfection combined exposure group. Cells in the two control groups were not treated. The two combined exposure groups were treated with 10 mg/L black carbon and 10 μmol/L lead acetate for 12.0 hours. The expression of ICAM-1 was detected by Western blotting. Results: i) The relative expression of ICAM-1, VCAM-1 and MAdCAM-1 in the cells of black carbon exposure group and ICAM-1 in the lead exposure group was higher than those in the control group (all P<0.05). The relative expression of ICAM-1 and MAdCAM-1 in the combined exposure group was higher than those in the other three groups (all P<0.05). The relative expression of VCAM-1 in cells of combined exposure group was higher than those in the control group and lead exposed group (all P<0.05). The relative expression of miR-326 in cells of the lead exposure group and black carbon exposure group was lower than those in the control group (all P<0.05). The relative expression of miR-326 in the combined exposure group was lower than that in the other three groups (all P<0.05). There was no significant difference between miR-328-3p and miR-542-3p in the four groups (all P>0.05). ii) The relative expression of ICAM-1 in cells of the miR-326 transfection control group cells was lower than that in the control group (P<0.05), while in the cells in the combined exposure and miRNA-326 transfection combined exposure group, it was higher than that in the control and miRNA-326 transfection control groups (all P<0.05), and lower in the miRNA-326 transfection combined exposure group than in the combined exposure group (P<0.05). Conclusion: Black carbon or lead exposure can upregulate the expression of ICAM-1, VCAM-1 and MAdCAM-1 in Z310 cells. Black carbon and lead combined exposure lead to a synergistic effect on upregulation of ICAM-1 and MAdCAM-1 expression, particularly ICAM-1. The combined exposure of black carbon and lead may upregulate the expression of ICAM-1 by downregulating the expression of miR-326.