Reference values for carotid artery intima-media thickness among community adult dwellers in Shenzhen City / 中华预防医学杂志

Objective: To establish reference values for carotid intima-media thickness (CIMT) of adult dwellers in Shenzhen City. Methods: The study was conducted based on the Shenzhen heart failure epidemiological survey from 2021 to 2022. In this survey, residents aged 18 years and above in Shenzhen were selected by using a multi-stage stratified random sampling method. General information, cardiovascular disease (CVD) related behavior and carotid ultrasound examination and etc. were collected from the participants. People with CVD factors, a history of atherosclerotic cardiovascular disease, carotid plaque or having no carotid ultrasound examination results were excluded. The parameter regression model based on fractional polynomial was used to establish the reference values of CIMT by age and sex. Results: A total of 2 163 healthy individuals were enrolled in the final analysis, including 576 males (26.6%) and 1 587 females (73.4%). The fractional polynomial regression of the CIMT mean and standard deviation was obtained. For men, the regression was meanCIMT=0.324 7+0.006 9×age and SDCIMT=0.076 9+0.001 2×age. For women, the regression was meanCIMT=0.354 9+0.005 4×age and SDCIMT=0.041 6+0.002 0×age. Conclusion: The age and sex reference values for CIMT of adult people in Shenzhen established in this study could provide the latest reference standards for early screening of subclinical CVD.

Tajectories of the self-efficacy of HIV testing among MSM based on latent class growth model / 中华预防医学杂志

Objective: To analyze the trajectories of HIV testing self-efficacy among men who have sex with men (MSM) based on latent class growth model. Methods: From August 2019 to May 2021, 404 MSM were recruited in Shandong Province and subjected to a 1-year follow-up study with individual intervention (pushing intervention pictures and videos in WeChat and follow-up questionnaires) and community intervention (forwarding to friends and sharing and discussing HIV testing-related information in WeChat groups). The level of HIV testing self-efficacy among MSM was measured. The long-term trend of HIV testing self-efficacy was analyzed using the latent class growth model (LCGM), and the influencing factors of the trend were analyzed. Results: A total of 404 MSM were (28.25±8.95) years old, with the oldest being 58 and the youngest being 18. The scores of HIV testing self-efficacy M(Q1, Q3) at baseline and 4 follow-ups were 18.00 (17.00, 21.00), 19.00 (18.00, 22.00), 19.00 (18.00, 22.00), 19.00 (18.00, 22.00) and 19.00 (18.00, 22.00). The results of the freely estimated two-category LCGM model showed that the trend of HIV testing self-efficacy among MSM could be divided into two classes, "intervention response group" [255(63.1%)] and "intervention non-response group" [149(36.9%)]. The former had a higher level of HIV testing self-efficacy which tended to increase at first and then decrease over time, while the latter had a lower and more stable level. The results of the multifactorial logistic regression analysis showed that the OR values of MSM in business or service and jobless or unemployed were 0.261 (95%CI: 0.108-0.633) and 0.186 (95%CI: 0.057-0.610), respectively, using the students as the reference group. Conclusion: There is a group heterogeneity in the trend of HIV testing self-efficacy in the intervention conditions among MSM, and occupation may be an influencing factor.

Associations of genetic variations in pyroptosis related genes with acute adverse events in postoperative rectal cancer patients receiving concurrent chemoradiotherapy / 中华肿瘤杂志

Objective: This study aims to investigate the associations between genetic variations of pyroptosis pathway related key genes and adverse events (AEs) of postoperative chemoradiotherapy (CRT) in patients with rectal cancer. Methods: DNA was extracted from the peripheral blood which was collected from 347 patients before CRT. Sequenom MassARRAY was used to detect the genotypes of 43 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight pyroptosis genes, including absent in melanoma 2 (AIM2), caspase-1 (CASP1), caspase-4(CASP4), caspase-5 (CASP5), caspase-11 (CASP11), gasdermin D (GSDMD), gasdermin E (GSDME) and NLR family pyrin domain containing 3 (NLRP3). The associations between 43 htSNPs and AEs were evaluated by the odd ratios (ORs) and 95% confidence intervals (CIs) by unconditional logistic regression models, adjusted for sex, age, clinical stage, tumor grade, Karnofsky performance status (KPS), surgical procedure, and tumor location. Results: Among the 347 patients with rectal cancer underwent concurrent CRT with capecitabine after surgery, a total of 101(29.1%) occurred grade ≥ 2 leukopenia. rs11226565 (OR=0.41, 95% CI: 0.21-0.79, P=0.008), rs579408(OR=1.54, 95% CI: 1.03-2.29, P=0.034) and rs543923 (OR=0.63, 95% CI: 0.41-0.98, P=0.040) were significantly associated with the occurrence of grade ≥ 2 leukopenia. One hundred and fifty-six (45.0%) had grade ≥ 2 diarrhea, two SNPs were significantly associated with the occurrence of grade ≥ diarrhea, including CASP11 rs10880868 (OR=0.55, 95% CI: 0.33-0.91, P=0.020) and GSDME rs2954558 (OR=1.52, 95% CI: 1.01-2.31, P=0.050). In addition, sixty-six cases (19.0%) developed grade ≥2 dermatitis, three SNPs that significantly associated with the risk of grade ≥2 dermatitis included GSDME rs2237314 (OR=0.36, 95% CI: 0.16-0.83, P=0.017), GSDME rs12540919 (OR=0.52, 95% CI: 0.27-0.99, P=0.045) and NLRP3 rs3806268 (OR=1.51, 95% CI: 1.03-2.22, P=0.037). There was no significant difference in the association between other genetic variations and AEs of rectal cancer patients (all P>0.05). Surgical procedure and tumor location had great impacts on the occurrence of grade ≥2 diarrhea and dermatitis (all P<0.01). Conclusion: The genetic variants of CASP4, CASP11, GSDME and NLRP3 are associated with the occurrence of AEs in patients with rectal cancer who received postoperative CRT, suggesting they may be potential genetic markers in predicting the grade of AEs to achieve individualized treatment of rectal cancer.

Effect of meridian sinew releasing technique on moxibustion sensation of heat-sensitive moxibustion in patients with knee osteoarthritis / 中国针灸

OBJECTIVE@#To observe the effect of meridian sinew releasing technique on moxibustion sensation of heat-sensitive moxibustion in patients with knee osteoarthritis (KOA).@*METHODS@#A total of 60 patients with KOA were randomly divided into an observation group and a control group, 30 cases each group. In the observation group, on the basis of the meridian sinew releasing technique, moxibustion sensation exploration method was applied at Dubi (ST 35) area on the affected side. In the control group, moxibustion sensation exploration method was applied at Dubi (ST 35) area on the affected side. The meridian sinew releasing technique was performed for 20 min each time, the moxibustion sensation exploration method was performed for 60 min each time, once a day for 3 days. The excitation rate, latency, duration time and intensity value of moxibustion sensation of heat-sensitive moxibustion were recorded on the 1st, 2nd and 3rd days of exploration in the two groups.@*RESULTS@#The excitation rate on the 3rd day of exploration and total excitation rate in the observation group were higher than the control group (P<0.05). On the 1st, 2nd and 3rd days of exploration, the latency of moxibustion sensation of heat-sensitive moxibustion in the observation group was shorter than the control group (P<0.05), the duration time was longer than the control group (P<0.05), and the intensity value was higher than the control group (P<0.05).@*CONCLUSION@#Meridian sinew releasing technique could improve the excitation rate of moxibustion sensation of heat-sensitive moxibustion in patients with KOA, shorten the latency, prolong the duration time, and improve the intensity value.

Determination of 9 halogenated alkanes in toothpaste by GC⁃MS / 上海预防医学

ObjectiveTo establish a GC-MS method for the detection of 9 halogenated alkanes in toothpastes. MethodsVarious brands of toothpastes on the market were collected as the samples. Methanol was used as the extraction solution. After shaking， vortex and centrifugation， the supernatant was filtered by 0.45 μm microporous filter membrane. The content of 9 halogenated alkanes including chloromethane， dichloromethane， chloroform， 1，1，1-trichloroethane， carbon tetrachloride， 1，2-dichloroethane， 1，1，2-trichloroethane， 1，2-dibromoethane， 1，2，3-trichloropropane in the filtrate were determined by GC-MS. ResultsThe 9 halogenated alkanes showed a good linear relationship in the concentration range of 0.03‒1.00 μg·mL-1. The correlation coefficient was ≥0.998 7 with the detection limits of 0.015‒0.056 mg·kg-1. The spiked recoveries were 83.2%‒108.9% with the RSD of 2.0%‒9.8%. In the actual sample analysis， 1，1，2-trichloroethane and 1，2，3-trichloropropane were respectively detected in 6 toothpaste samples from 5 brands. ConclusionThe method is simple， sensitive， accurate， and has good spiked recoveries. It can be used for the determination of halogenated alkanes in toothpastes.

The use of melittin to enhance transgene expression mediated by recombinant adeno-associated virus serotype 2 vectors both in vitro and in vivo / 中西医结合学报

OBJECTIVE@#Melittin, a cell-penetrating peptide, improves the efficiency of many non-viral gene delivery vectors, yet its application in viral vectors has not been well studied. The non-pathogenic recombinant adeno-associated virus (rAAV) vector is an ideal in vivo gene delivery vector. However, its full potential will only be achieved after improvement of its transduction efficiency. To improve the transduction efficiency of rAAV2 vectors, we attempted to develop a melittin-based rAAV2 vector delivery strategy.@*METHODS@#The melittin peptide was inserted into the rAAV2 capsid either in the loop VIII of all viral proteins (VPs) or at the N terminus of VP2. Various rAAV2-gfp or -fluc vectors were subjected to quantitative real-time polymerase chain reaction and Western blot assays to determine their titers and integrity of capsid proteins, respectively. Alternatively, the vectors based on wild-type capsid were pre-incubated with melittin, followed by transduction of cultured cells or tail vein administration of the mixture to C57BL/6 and BALB/c nude mice. In vivo bioluminescence imaging was performed to evaluate the transgene expression.@*RESULTS@#rAAV2 vectors with melittin peptide inserted in the loop VIII of VPs had low transduction efficiency, probably due to dramatically reduced ability to bind to the target cells. Fusing the melittin peptide at the N-terminus of VP2 produced vectors without the VP2 subunit. Interestingly, among the commonly used rAAV vectors, pre-incubation of rAAV2 and rAAV6 vectors with melittin significantly enhanced their transduction efficiency in HEK293 and Huh7 cells in vitro. Melittin also had the ability to increase the rAAV2-mediated transgene expression in mouse liver in vivo. Mechanistically, melittin did not change the vector-receptor interaction. Moreover, cell counting kit-8 assays of cultured cells and serum transaminase levels indicated melittin had little cytotoxicity.@*CONCLUSION@#Pre-incubation with melittin, but not insertion of melittin into the rAAV2 capsid, significantly enhanced rAAV2-mediated transgene expression. Although further in vivo evaluations are required, this research not only expands the pharmacological potential of melittin, but also provides a new strategy to improve gene therapy mediated by rAAV vectors.

The effects of naringenin on pancreatic fibrosis in chronic pancreatitis mouse model and activation, proliferation and apoptosis of pancreatic stellate cells / 中华胰腺病杂志

Objective:To study the effects of naringenin on pancreatic fibrosis in the mouse model of chronic pancreatitis (CP) and its effects on the activation, proliferation and apoptosis of pancreatic stellate cells (PSCs).Methods:Eighteen C57BL/6 mice were randomly divided into control group, CP group and naringenin group, with 6 mice in each group. The CP mouse model was established by intraperitoneal injections of caerulein. Naringenin group was given naringenin (200 mg/kg/day) by gavage once a day from the first day of the fourth week of modeling process to the day before the killing; the control group and CP group were treated by gavage with an equivalent amount of drug solvent containing 0.5% sodium carboxymethyl cellulose (CMC-Na). Mice were killed 5 days after the last caerulein injection, and their pancreatic tissues were collected for hematoxylin-eosin staining and Sirius Red staining, pathological scoring and collagen sedimentation detection. Naringenin with different concentrations (0, 5, 10, 20, 50, 100, 150, 200 μmol/L) were used to intervene HPSC for 24 hours, and CCK-8 method was used to detect the cell activity. TGF-β1 recombinant protein (2 ng/ml) was used to induce PSCs for 1 hour (TGF-β1 stimulation group), and naringenin with low (50 μmol/L), middle (100 μmol/L) and high (150 μmol/L) concentration was used to intervene for 36 hours after TGF-β1 stimulation, respectively. Western Blotting was used to detect the expression of PSC activation related proteins FN and COL1A1, cell proliferation marker p21, anti-apoptotic protein Bcl-xL, pro-apoptotic protein Bax and Bid.Results:The pathological scores of pancreatic tissue [(7.33±1.15), (4.67±1.15)] and the percentage of collagen positive areas [(46±4), (28±2)%] in CP group and naringenin group were higher than those in the control group [0, (4±2)%]. However, these indexes in the naringenin group were lower than those in CP group, and the differences were all statistically significant (all P value <0.05). The relative expression of FN in control group, TGF-β1 stimulation group and low, medium and high naringenin group was 0.02, 0.76, 0.67, 0.34 and 0.07, respectively; the expression of COL1A1 in these groups was 0.51, 1.71, 1.34, 0.84 and 0.11. The expression of FN and COL1A1 in TGF-β1 stimulation group was significantly higher than that in control group, and the expression of FN and COL1A1 in low, medium and high naringenin group was significantly lower than that in TGF-β1 stimulation group, and the differences were all statistically significant (all P value <0.05). The expression of p21 in the above five groups was 0.87, 1.18, 1.27, 1.22 and 1.00. The expression of p21 in TGF-β1 stimulation group was higher than that in control group, and the expression of p21 in high naringenin group was obviously lower than that in TGF-β1 stimulation group, and the differences were all statistically significant (all P value <0.05). In addition, the expression of Bcl-xL in these groups was 2.09, 2.21, 2.38, 2.50 and 2.12; the expression of Bax was 0.98, 0.88, 0.98, 1.00 and 0.88; the expression of Bid was 1.15, 1.09, 1.14, 1.18 and 1.18. There was no statistically significant difference among these groups (all P value >0.05). Conclusions:Naringenin could significantly alleviate the inflammation, atrophy and fibrosis in the CP mouse model, and inhibit the activation and proliferation of PSCs. However, naringenin had no significant effect on the apoptosis of PSCs, indicating that naringenin may be potentially used to treat pancreatic fibrosis in CP.

Effect of lipopolysaccharide-stimulated exosomes from human dental pulp stem cells combined with stromal cell-derived factor-1 on dental pulp regeneration / 中华口腔医学杂志

Objective: To investigate the effect of exosomes from mild-inflammation- stimulated human dental pulp stem cells (hDPSC) combined with stromal cell-derived factor-1 (SDF-1) on dental pulp regeneration in rats. Methods: Primary hDPSCs were isolated, cultured and then stimulated by using lipopolysaccharide (LPS). The exosomes from the hDPSCs with (L-EXO) or without (N-EXO) LPS were extracted by overspeed differential centrifugation and were identified by transmission electron microscopy and Western blotting. Forty SD rats, aged 6-8 weeks, were equally divided into S group (SDF-1 alone), L+S group (L-EXO combined with SDF-1), N+S group (N-EXO combined with SDF-1) and blank control group (no substance implanted into the root canal) by random number table method. Bilateral mandibular first molars were used as the experimental teeth to establish pulpless root canal models and different contents were implanted into the root canals according to the groups. All rats were over-anesthetized and sacrificed at the 30th day after content implantation. Bilateral mandibular tissues were taken for histological evaluation by means of HE, Masson and immunohistochemical stainings. Results: The HE staining showed new pulp-like tissue in the root canals of all three experimental groups. The amount of new tissues and the number of cells in the tissues were greatest in L+S group and least in S group. Masson staining showed that the mineralized tissue in L+S group was arranged longitudinally along the root canal wall and the collagen fibers were arranged in an orderly fashion, while those in N+S group showed an irregular and disordered distribution. Quantitative analysis of the area of neovascularization in each group showed that the density of vessels in the L+S group [(2.03±0.65)%] was significantly higher than that in the S group [(0.65±0.05)%] and the N+S group [(1.06±0.38)%] respectively (F=5.879, P<0.05). Immunohistochemical staining showed that the expression of CXC chemokine receptor 4 (CXCR4) was significantly lower in S and L+S groups than in N+S group, with a statistically significant difference (F=8.633, P<0.01). Conclusions: Exosomes secreted by hDPSCs combined with SDF-1 might increase the amount of new tissue in the root canal and the density of blood vessels in the tissue. L-EXO showed a stronger effect than N-EXO did. The combination of L-EXO with SDF-1 might result in more regular arrangement of mineralized tissue and collagen fibers in the regenerative tissues.

Optimized arterial perfusion strategy in total arch replacement for acute type A aortic dissection with malperfusion syndrome / 中国胸心血管外科临床杂志

@#Objective    To investigate the effect of optimized arterial perfusion strategy on total arch replacement for acute type A aortic dissection (AAAD) with malperfusion syndrome (MPS). Methods    From 2017 to 2019, 51 patients with AAAD and MPS who had received total arch replacement with optimized arterial perfusion strategy in our hospital were included in the optimized perfusion group, including 40 males and 11 females, with an average age of 47.43±13.39 years. A total of 40 patients with AAAD and MPS who had been treated with traditional Sun's surgery were taken as the traditional control group, including 31 males and 9 females, with an average age of 50.66±12.05 years. The perioperative clinical data of the two groups were compared. Results    The preoperative baseline data of the two groups were basically consistent (P>0.05). The comparison of operative data between the optimized perfusion group and the traditional control group showed that in the optimized perfusion group, the extracorporeal circulation time, aortic occlusion time, and circulation-out cerebral perfusion time were significantly less than those in the traditional control group (223.64±65.13 min  vs. 266.77±87.04 min, 114.48±27.28 min vs. 138.20±39.89 min, 8.28±3.81 min vs. 50.53±23.60 min, all P≤0.05). The lowest intraoperative nasopharyngeal temperature in the optimized perfusion group was significantly higher than that in the traditional control group (27.10±1.18℃ vs. 23.6±3.30℃, P=0.000). Postoperative wakefulness time of the optimized perfusion group was earlier than that of the traditional control group (4.50±1.35 h vs. 5.27±1.15 h, P=0.019). The volume of blood transfusions in the optimized perfusion group was significantly less than that in the traditional control group (13.25±9.06 U vs. 16.95±7.53 U, P=0.046). There was no significant difference in ICU time and invasive ventilation time between the two groups (P>0.05). Postoperative complications of the two groups showed that the incidence of postoperative continuous renal replacement therapy in the optimized perfusion group was significantly lower than that in the traditional control group, with a statistically significant difference (21.6% vs. 42.5% P=0.003). The incidence of postoperative delirium, coma, low cardiac row syndrome and limb ischemia in the optimized perfusion group was lower than that in the traditional control group, but the difference was not statistically significant (P>0.05). The incidence of postoperative hemiplegia, sepsis, and secondary thoracotomy in the optimized perfusion group was higher than that in the traditional control group, and the difference was not statistically significant (P>0.05). Postoperative mortality in the optimized perfusion group was significantly lower than that in the traditional control group (13.7% vs. 27.5%), but the difference was not statistically significant (P=0.102). Conclusion    Optimized arterial perfusion strategy and its related comprehensive surgical technique reduce surgical trauma, shorten the operation time, reduce perioperative consumption of blood products. Postoperative wakefulness is rapid and the incidence of complications of nervous system, kidney and limb ischemia is low. Optimized arterial perfusion strategy is suitable for operation of AAAD with MPS by inhibiting the related potential death risk factors to reduce operation mortality.

Cloning of transcription factor PcFBA-1 in Pogostemon cabin and its interaction with FPPS promoter / 中国中药杂志

Farnesyl diphosphate synthase(FPPS) is a key enzyme at the branch point of the sesquiterpene biosynthetic pathway, but there are no reports on the transcriptional regulation of FPPS promoter in Pogostemon cabin. In the early stage of this study, we obtained the binding protein PcFBA-1 of FPPS gene promoter in P. cabin. In order to explore the possible mechanism of PcFBA-1 involved in the regulation of patchouli alcohol biosynthesis, this study performed PCR-based cloning and sequencing analysis of PcFBA-1, analyzed the expression patterns of PcFBA-1 in different tissues by fluorescence quantitative PCR and its subcellular localization using the protoplast transformation system, detected the binding of PcFBA-1 protein to the FPPS promoter in vitro with the yeast one-hybrid system, and verified its transcriptional regulatory function by dual-luciferase reporter gene assay. The findings demonstrated that the cloned PcFBA-1 had an open reading frame(ORF) of 1 131 bp, encoding a protein of 376 amino acids, containing two conserved domains named F-box-like superfamily and FBA-1 superfamily, and belonging to the F-box family. Moreover, neither signal peptide nor transmembrane domain was contained, implying that it was an unstable hydrophilic protein. In addition, as revealed by fluorescence quantitative PCR results, PcFBA-1 had the highest expression in leaves, and there was no significant difference in expression in roots or stems. PcFBA-1 protein was proved mainly located in the cytoplasm. Furthermore, yeast one-hybrid screening and dual-luciferase reporter gene assay showed that PcFBA-1 was able to bind to FPPS promoter both in vitro and in vivo to enhance the activity of FPPS promoter. In summary, this study identifies a new transcription factor PcFBA-1 in P. cabin, which directly binds to the FPPS gene promoter to enhance the promoter activity. This had laid a foundation for the biosynthesis of patchouli alcohol and other active ingre-dients and provided a basis for metabolic engineering and genetic improvement of P. cabin.

Application of the Simodont dental trainer in preclinical manual dexterity training / 中华医学教育探索杂志

Objective:To explore the application of the Simodont dental trainer in preclinical manual dexterity training for dental students of different grades, and to discuss its effect by quantitatively evaluating their practice results.Methods:The evaluation was conducted among 118 students in the Department of Stomatology, Shantou University Medical College from Batch 2015 to Batch 2018. Each student had five different manual dexterity modules for training. Each module had three levels of difficulty and was required to be completed in 30 minutes. The assessment index included Target, Leeway Bottom and Sides, Container Bottom and Sides, which was provided by the Simodont dental trainer. The operating time (in seconds), the displacement of the dental hand pieces and the dental mirrors (in meters) were simultaneously recorded. SPSS 25.0 was used for statistical analysis.Results:For the index Target, Leeway Bottom and Sides, Container Bottom and Sides, the results showed that there was a statistical difference between students who passed pre-clinical training and who did not take the professional course ( P < 0.001). For the index Target, differences were showed among students from different grades in all modules ( P < 0.001). Conclusion:The circle module, channel module, hollow-circle module and cross-module in the Simodont dental trainer have sensitivity to discriminate the manual dexterity of different levels of dental students. The further assessment of the discrimination of the manual dexterity is required for assume-block module. The Simodont dental trainer can quantitatively measure the manual dexterity of dental students, which is important for the quantitative evaluation of dental preclinical education.

Unplanned readmission rate and risk factors during 30-days after cardiac surgery in children: A systematic review with Meta-analysis / 中国小儿急救医学

Objective:To systematically evaluate the rate of unplanned readmissions for children at 30 days after cardiac surgery, the causes and risk factors for unplanned readmissions for children at 30 days after cardiac surgery.Methods:We searched PubMed, Embase, Web of Science, CBM, CNKI, Wanfang Data, and VIP database to collect studies from inception to August 15, 2020 of unplanned readmission of children after cardiac surgery.RevMan5.3 software was used for Meta-analysis.Results:A total of 13 studies, involving 81 633 patients were included.Meta-analysis results showed that the unplanned readmission rate of children 30 days after cardiac surgery was 11.5%(95% CI 9.9%-13%). Cardiac complications[24%(95% CI 10.7%-45.7%)], infections[18.7%(95% CI 13.7%-25.3%)], respiratory complications[18.0%(95% CI 10.7%-27.5%)], pleural effusion[11.5%(95% CI 8.3%-16.7%)], and gastrointestinal complications[12.3%(95% CI 8.3%-17.4%)] were the main reasons for unplanned 30-day readmission, with statistically significant differences( P<0.001). Genetic syndrome( OR=1.25, 95% CI 1.18-1.33, P<0.05) and postoperative hospital stay >14 days( OR=1.62, 95% CI 1.05-2.50, P<0.05) were risk factors for unplanned 30-day readmission. Conclusion:The incidence rate of unplanned readmission among the children 30 days after cardiac surgery is relatively high.Cardiac complications, infection, respiratory complications, pleural effusion, and gastrointestinal complications are the main reasons for 30-day unplanned readmission.The genetic syndrome and postoperative hospital stay >14 days in children 30 days after cardiac surgery are the risk factors for unplanned readmission.

The use of miR122 and its target sequence in adeno-associated virus-mediated trichosanthin gene therapy / 中西医结合学报

OBJECTIVE@#Plant-derived cytotoxic transgene expression, such as trichosanthin (tcs), regulated by recombinant adeno-associated virus (rAAV) vector is a promising cancer gene therapy. However, the cytotoxic transgene can hamper the vector production in the rAAV producer cell line, human embryonic kidney (HEK293) cells. Here, we explored microRNA-122 (miR122) and its target sequence to limit the expression of the cytotoxic gene in the rAAV producer cells.@*METHODS@#A miR122 target (122T) sequence was incorporated into the 3' untranslated region of the tcs cDNA sequence. The firefly luciferase (fluc) transgene was used as an appropriate control. Cell line HEK293-mir122 was generated by the lentiviral vector-mediated genome integration of the mir122 gene in parental HEK293 cells. The effects of miR122 overexpression on cell growth, transgene expression, and rAAV production were determined.@*RESULTS@#The presence of 122T sequence significantly reduced transgene expression in the miR122-enriched Huh7 cell line (in vitro), fresh human hepatocytes (ex vivo), and mouse liver (in vivo). Also, the normal liver physiology was unaffected by delivery of 122T sequence by rAAV vectors. Compared with the parental cells, the miR122-overexpressing HEK293-mir122 cell line showed similar cell growth rate and expression of transgene without 122T, as well as the ability to produce liver-targeting rAAV vectors. Fascinatingly, the yield of rAAV vectors carrying the tcs-122T gene was increased by 77.7-fold in HEK293-mir122 cells. Moreover, the tcs-122T-containing rAAV vectors significantly reduced the proliferation of hepatocellular carcinoma cells without affecting the normal liver cells.@*CONCLUSION@#HEK293-mir122 cells along with the 122T sequence provide a potential tool to attenuate the cytotoxic transgene expression, such as tcs, during rAAV vector production.

Research progress on the exposure pathway and toxic effect of microplastics / 中国职业医学

Global plastics production has been increasing year by year. Due to the large quantity of plastics and the difficulty of their degradation, plastics are continuously accumulated in the environment. Therefore, plastic waste has become one of the most serious threats to the global environment. Microplastics can be absorbed into organisms through the mouth, respiratory tract and skin, causing organ(intestine, liver) toxicity, reproductive and developmental toxicity, and neurotoxicity. Moreover, microplastics can also take up other pollutants distributed in the surrounding environment, such as heavy metals and organic pollutants, jointly exerting combined toxic effects. The extracts of microplastics, including microplastics unstable polymers and additives, also have toxic effects. The molecular mechanisms involved in the toxic effects induced by microplastics include oxidative stress, inflammation, disturbance of intestinal flora, disturbance of gene expression, and others.

Automated Breast Ultrasound: Interobserver Agreement,Diagnostic Value, and Associated Clinical Factors ofCoronal-Plane Image Features

Objective@#To evaluate the interobserver agreement, diagnostic value, and associated clinical factors of automated breastultrasound (ABUS) coronal features in differentiating breast lesions. @*Materials and Methods@#This study enrolled 457 pathologically confirmed lesions in 387 female (age, 46.4 ± 10.3 years),including 377 masses and 80 non-mass lesions (NMLs). The unique coronal features, including retraction phenomenon,hyper- or hypoechoic rim (continuous or discontinuous), skipping sign, and white wall sign, were defined and recorded. Theinterobserver agreement on image type and coronal features was evaluated. Furthermore, clinical factors, including the lesionsize, distance to the nipple or skin, palpability, and the histological grade were analyzed. @*Results@#Among the 457 lesions, 296 were malignant and 161 were benign. The overall interobserver agreement for imagetype and all coronal features was moderate to good. For masses, the retraction phenomenon was significantly associated withmalignancies (p < 0.001) and more frequently presented in small and superficial invasive carcinomas with a low histologicalgrade (p = 0.027, 0.002, and < 0.001, respectively). Furthermore, continuous hyper- or hypoechoic rims were predictive ofbenign masses (p < 0.001), whereas discontinuous rims were predictive of malignancies (p < 0.001). A hyperechoic rim wasmore commonly detected in masses more distant from the nipple (p = 0.027), and a hypoechoic rim was more frequently foundin large superficial masses (p < 0.001 for both). For NMLs, the skipping sign was a predictor of malignancies (p = 0.040). @*Conclusion@#The coronal plane of ABUS may provide useful diagnostic value for breast lesions.

Fruitflow，a Water-soluble Tomato Concentrate，Inhibits Platelet Activation，Aggregation and Thrombosis by Regulating the Signaling Pathway of PI3K/Akt and MAPKs / 中山大学学报(医学科学版)

@#【Objective】Platelet hyper- reactivity plays an important role in thrombosis and cardiovascular diseases. As a dietary supplement，Fruitflow，a water-soluble tomato concentrate，plays an important role in preventing cardiovascular diseases，but the mechanisms have been poorly understood，and there is no direct evidence about the effect of Fruitflow on thrombosis. This study intends to explore the effects of Fruitflow on platelet aggregation，activation and thrombosis in healthy people，and explore its possible mechanism.【Methods】Platelets from healthy men and women were incubated with different concentrations（0，20，40，80 mg/L）of Fruitflow，and the platelet aggregation was measured by platelet aggregometer. Platelet αIIbβ3 activation and fibrinogen binding to the activated platelets was measured by flow cytometry. The thrombosis in FeCl3- induced mesenteric artery thrombosis model in mice was observed by stereoscopic fluorescence microscope. The bleeding time was measured by tail clipping in mice. The total and phosphorylation levels of platelet Akt， Erk1/2 and JNK were determined by Western blotting.【Results】After the stimulation of ADP，Fruitflow could significantly attenuate platelet aggregation in the dose of 20，40，80 mg/L. Compared with that in the control group（43.75±5.91）%， platelet aggregation in the 80 mg/L group decreased to（8.25 ± 4.57）%（P < 0.000 1）. Fruitflow also inhibited the activation of platelet αIIbβ3. Compared with that in the control group（79.36±6.26），the platelet αIIbβ3 in the 80 mg/L group decreased to（65.79±5.73，P < 0.01）. Fruitflow reduced the platelet fibrinogen binding to the activated platelets. Compared with that in the control group（69.34 ± 6.63），platelet fibrinogen binding to the activated platelets in the 80 mg/L group decreased to（56.70±8.86，P < 0.05）. Fruitflow attenuated the thrombosis in FeCl3-induced mesenteric artery thrombosis model. Compared with that in the control group（22.50±4.86），the vessel occlusion in the 80 mg/L group was extended to（39.20 ± 4.61，P < 0.01）. There was no statistical difference between the control group （5.95 ± 0.69） and the 80 mg/L group（5.74 ± 0.76）in bleeding time（P > 0.05）. Fruitflow down- regulated the phosphorylation levels of platelet Akt， Erk1/2 and JNK proteins. Compared with the control group，P- Akt/Akt decreased from 0.97 ± 0.07 to 0.33 ± 0.13（P <0.001），P-Erk1/2/Erk1/2 decreased from 0.89±0.09 to 0.24±0.02（P < 0.01），and P-JNK/JNK decreased from 0.97±0.12 to 0.45±0.04（P < 0.01）in the 80 mg/L group.【Conclusion】Inhibition of platelet PI3K/Akt and MAPKs signaling pathway may be one of the mechanisms that Fruitflow inhibits platelet aggregation ，activation and thrombosis.

Efficacy of high-flow nasal cannula versus nasal continuous positive airway pressure in the treatment of respiratory distress syndrome in neonates: a Meta analysis / 中国当代儿科杂志

OBJECTIVE@#To systematically evaluate the efficacy and safety of high-flow nasal cannula (HFNC) therapy versus nasal continuous positive airway pressure (nCPAP) in the treatment of respiratory distress syndrome (RDS) in neonates.@*METHODS@#PubMed, Embase, Cochrane Library, Web of Science, China Biology Medicine disc, Wanfang Database, CNKI, and Weipu Database were searched for the randomized controlled trials (RCTs) of HFNC versus nCPAP in the treatment of neonatal RDS published up to April 1, 2020. RevMan5.3 software was used to perform a Meta analysis of the eligible RCTs.@*RESULTS@#A total of 12 RCTs were included, with 2 861 neonates in total, among whom 2 698 neonates (94.30%) had a gestational age of ≥28 weeks and 163 (5.70%) had a gestational age of 0.05). For primary respiratory support and post-extubation respiratory support, the HFNC group had a significantly lower incidence rate of nasal injury than the nCPAP group (P0.05).@*CONCLUSIONS@#Based on the current clinical evidence, HFNC has a higher failure rate than nCPAP when used as primary respiratory support for neonates with RDS, and therefore it is not recommended to use HFNC as the primary respiratory support for neonates with RDS. In RDS neonates with a gestational age of ≥28 weeks, HFNC can be used as post-extubation respiratory support in the weaning phase.

Mechanism of aquaporin 4 in regulating 1,2-dichloroethane-induced blood-brain barrier permeability in mice / 中国职业医学

OBJECTIVE: To study the effect of aquaporin 4(AQP4) in regulating the permeability of blood-brain barrier(BBB) induced by subacute 1,2-dichloroethane(1,2-DCE) inhalation. METHODS: Specific pathogen free healthy CD-1 male Aqp4 genetically engineered mice(Aqp4~(+/+)and Aqp4~(-/-)) were randomly divided into control and low-, medium-and high-dose groups. The mice were exposed to 1,2-DCE at the dosages of 0.00, 100.00, 350.00 and 700.00 mg/m~3 for 6 hours per day for consecutive 28 days by systemic dynamic inhalation. After the end of 1,2-DCE exposure, the BBB permeability was evaluated by Evans blue staining. Real-time fluorescence quantitative polymerase chain reaction method was used to detect the mRNA expression of genes related to BBB tight junction protein(Tjp)1, Tjp2, Tjp3, claudin(Cldn)3, Cldn5, Cldn11, occludin(Ocln), matrix metalloproteinase(Mmp)2, Mmp9 and Na-K-Cl cotransporter-1(Nkcc1). RESULTS: The BBB permeability in mice showed significant change with 1,2-DCE dose and Aqp4 genotype(P<0.01). The BBB permeability of Aqp4~(+/+) genotype mice was higher in low-, medium-and high-dose groups than that of control group(all P values were <0.05). The permeability of BBB was lower in Aqp4~(+/+) genotype mice in the control group than that of Aqp4~(-/-) genotype mice in the same group(P<0.05), but BBB permeability was higher in Aqp4~(+/+) genotype mice in the three dose groups than that of Aqp4~(-/-) genotype mice in the same group(all P values were <0.05). The Cldn3 and Olcn mRNA relative expression in the brain cortex had statistical difference in mice with different genotype(all P values were <0.01). The mRNA relative expressions of Cldn3 and Olcn in the brain cortex were higher in Aqp4~(-/-) genotype mice than that of Aqp4~(+/+) genotype mice(all P values were <0.01). The relative mRNA expression levels of Tjp1, Tjp2, Tjp3, Cldn5, Cldn11, Mmp2, Mmp9 and Nkcc1 in the cerebral cortex of mice were not statistically significant in aspect of 1,2-DCE exposure dose and genotype(all P values were >0.05). CONCLUSION: Exposure to 1,2-DCE can increase BBB permeability in mice, and the mechanism may be associated with 1,2-DCE-induced down-regulation of Aqp4 and up-regulation of mRNA expression of the cerebral cortex TJP-related molecules Cldn3 and Ocln.

Application of digital positioning guide plate in extraction of impacted supernumerary teeth / 南方医科大学学报

OBJECTIVE@#To explore the application of digital positioning guide plate in extraction of impacted supernumerary teeth and evaluate its clinical efficacy.@*METHODS@#From March to August, 2019, 30 patients with labial impacted supernumerary teeth treated in the Department of Oral and Maxillofacial Surgery, Stomatological Hospital, Southern Medical University were enrolled in this study. Fifteen of the patients were treated with digital positioning guide plate to remove the impacted supernumerary teeth (test group). According to the CBCT data and the dentition model of the patients, the positioning guide plate was positioned by avoiding the important anatomical structure with the tooth-bone surface as the support to design the soft tissue incision line and bone tissue exposure range. The other 15 patients who were treated without the use of the guide plate for operation served as the control group. The design time, tooth searching time, operation time and complications were compared between the two groups.@*RESULTS@#The positioning guide plate was well attached during the operation and allowed quick location of the supernumerary teeth while helping to expose the supernumerary teeth and avoid the damage of the adjacent important anatomical structures. The pre-operative design time was 50 ± 5 min in the test group and 0 min in the control group. The average time of tooth finding in the test group was 5±2 min, as compared with 10±3 min in the control group (=15.40, < 0.01); the average time of operation was significantly shorter in the test group than in the control group (25±4 min 45±6 min; =35.50, < 0.01). No intraoperative complications occurred in the test group, and slight deviation occurred in one case in the control group.@*CONCLUSIONS@#The application of digital positioning guide plate in extraction of embedded supernumerary teeth can significantly shorten the time of tooth finding, reduce the difficulty of operation, and improve the quality of operation.

A multicenter survey of antibiotic use in very and extremely low birth weight infants in Hunan Province / 中国当代儿科杂志

OBJECTIVE@#To investigate the current status of antibiotic use for very and extremely low birth weight (VLBW/ELBW) infants in neonatal intensive care units (NICUs) of Hunan Province.@*METHODS@#The use of antibiotics was investigated in multiple level 3 NICUs of Hunan Province for VLBW and ELBW infants born between January, 2017 and December, 2017.@*RESULTS@#The clinical data of 1 442 VLBW/ELBW infants were collected from 24 NICUs in 2017. The median antibiotic use duration was 17 days (range: 0-86 days), accounting for 53.0% of the total length of hospital stay. The highest duration of antibiotic use was up to 91.4% of the total length of hospital stay, with the lowest at 14.6%. In 16 out of 24 NICUs, the antibiotic use duration was accounted for more than 50.0% of the hospitalization days. There were 113 cases with positive bacterial culture grown in blood or cerebrospinal fluid, making the positive rate of overall bacterial culture as 7.84%. The positive rate of bacterial culture in different NICUs was significantly different from 0% to 14.9%. The common isolated bacterial pathogens Klebsiella pneumoniae was 29 cases (25.7%); Escherichia coli 12 cases (10.6%); Staphylococcus aureus 3 cases (2.7%). The most commonly used antibiotics were third-generation of cephalosporins, accounting for 41.00% of the total antibiotics, followed by penicillins, accounting for 32.10%, and followed by carbapenems, accounting for 13.15%. The proportion of antibiotic use time was negatively correlated with birth weight Z-score and the change in weight Z-score between birth and hospital discharge (r=-0.095, -0.151 respectively, P<0.01), positively correlated with death/withdrawal of care (r=0.196, P<0.01).@*CONCLUSIONS@#Antibiotics used for VLBW/ELBW infants in NICUs of Hunan Province are obviously prolonged in many NICUs. The proportion of routine use of third-generation of cephalosporins and carbapenems antibiotics is high among the NICUs.