An interpretation of AAPOS uniform guidelines for instrument-based pediatric vision screen validation 2021 / 中华实验眼科杂志

In January 2022, after an eight-year hiatus, the American Association for Pediatric Ophthalmology and Strabismus (AAPOS) published the latest version of AAPOS uniform guidelines for instrument-based pediatric vision screen validation.Based on recent studies, the new guidelines have been updated and supplemented in many aspects, such as screening population, key points, methods and diagnosis criteria, including clinically significant refractive errors and myopia, simplified age subgroups, and adopted meridional refractive power.The updated guidelines will improve pediatric eye care, early detection of amblyopia and refractive screening, reduce excessive referral and ultimately improve the effectiveness of vision screening.In this article, the background and specific content of the updated guidelines were interpreted to guide clinical practice.

Evaluation of Renal Impairment in Patients with Diabetic Kidney Disease by Integrated Chinese and Western Medicine / 中国结合医学杂志

OBJECTIVE@#To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine.@*METHODS@#Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients.@*RESULTS@#Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD.@*CONCLUSIONS@#Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).

Specific DNA barcodes, germplasm resources, and genetic diversity of Eleutherococcus senticosus / 中国中药杂志

Eleutherococcus senticosus is one of the Dao-di herbs in northeast China. In this study, the chloroplast genomes of three E. senticosus samples from different genuine producing areas were sequenced and then used for the screening of specific DNA barcodes. The germplasm resources and genetic diversity of E. senticosus were analyzed basing on the specific DNA barcodes. The chloroplast genomes of E. senticosus from different genuine producing areas showed the total length of 156 779-156 781 bp and a typical tetrad structure. Each of the chloroplast genomes carried 132 genes, including 87 protein-coding genes, 37 tRNAs, and 8 rRNAs. The chloroplast genomes were relatively conserved. Sequence analysis of the three chloroplast genomes indicated that atpI, ndhA, ycf1, atpB-rbcL, ndhF-rpl32, petA-psbJ, psbM-psbD, and rps16-psbK can be used as specific DNA barcodes of E. senticosus. In this study, we selected atpI and atpB-rbcL which were 700-800 bp and easy to be amplified for the identification of 184 E. senticosus samples from 13 genuine producing areas. The results demonstrated that 9 and 10 genotypes were identified based on atpI and atpB-rbcL sequences, respectively. Furthermore, the two barcodes identified 23 genotypes which were named H1-H23. The haplotype with the highest proportion and widest distribution was H10, followed by H2. The haplotype diversity and nucleotide diversity were 0.94 and 1.82×10~(-3), respectively, suggesting the high genetic diversity of E. senticosus. The results of the median-joining network analysis showed that the 23 genotypes could be classified into 4 categories. H2 was the oldest haplotype, and it served as the center of the network characterized by starlike radiation, which suggested that population expansion of E. senticosus occurred in the genuine producing areas. This study lays a foundation for the research on the genetic quality and chloroplast genetic engineering of E. senticosus and further research on the genetic mechanism of its population, providing new ideas for studying the genetic evolution of E. senticosus.

Screening of specific DNA barcode, identification of germplasm resources, and analysis of genetic diversity of Atractylodes chinenesis / 药学学报

italic>Atractylodes chinensis has important medicinal and economic values. In this study, the chloroplast genome sequences of four A. chinensis samples from different producing areas were sequenced using the Illumina platform. The specific DNA barcodes were screened and the germplasm resources of A. chinensis samples from different producing areas and the genetic diversity of the population were analyzed basing on the specific barcodes. The whole chloroplast genomes of the four A. chinensis samples had a typical cyclic tetrad structure, with 112 genes annotated. The comparative genomics results indicated that ccsA and trnC-GCA_petN were potential specific DNA barcodes for intraspecific identification of A. chinensis. Polymerase chain reaction (PCR) analysis of ccsA and trnC-GCA_petN was performed on 256 samples from 14 areas in 9 provinces, and the amplification efficiency was 100%. Sequence analysis showed that ccsA and trnC-GCA_petN had 11 and 22 variant positions, which could identify 16 and 22 haplotypes, respectively. The combined sequence analysis identified 39 haplotypes, named Hap1-Hap39, of which the most abundant and widely distributed genotype was Hap9. Haplotype diversity (Hd) = 0.896 and nucleotide diversity (Pi) = 0.002 22 indicated high genetic diversity at the species level in A. chinensis. The genetic distances of the haplotypes were 0.000 00-0.004 88, indicating that there were small genetic differences among the haplotypes. The results of phylogenetic tree analysis showed that 39 haplotypes had very close genetic relationship, and formed two obvious branches with other groups of the same genus except Atractylodes macrocephala. This study plays an important role in the identification of the origin of A. chinensis and the protection and breeding of germplasm resources.

Mechanism of HES1 regulating herceptin resistance in gastric cancer cells by ferroptosis / 药学学报

Drug resistance of cancer cells is the main causes of chemotherapy failure, and gene mutation or function loss is key factor to induce drug resistance. Previous studies have shown that hairy and enhancer of split 1 (HES1) is up-regulated in herceptin-resistant gastric cancer cells, and inhibition of its activity can reverse its resistance while the potential mechanism has not yet been elucidated. In this study, we employed CRISPR/Cas9 to establish HES1 knock-out cell line (△HES1/NCI N87R) to investigate the functions of HES1 in herceptin resistance of NCI N87R cells and its potential mechanisms. We investigated proteomics profiling of △HES1/NCI N87R cells based on quantitative proteomics. Gene ontology analysis was conducted by GeneSet Enrichment Analysis (GSEA) and Metascape database, and pathway enrichment analysis was done using GeneAnalytics database. The selected molecules were quantified by Western blot and some pathways were verified by using inhibitors. The results showed that the resistance to herceptin of △HES1/NCI N87R cells decreased compared to NCI N87R cells. Proteomic data demonstrated that the expression of 1 263 genes changed significantly in △HES1/NCI N87R cells, among which 761 genes were up-regulated while 502 ones down-regulated comparing with NCI N87R cells. Pathway analysis showed that ferroptosis, fatty acid β-oxidation, autophagy and glutathione metabolism, etc. exhibited notable changes in △HES1/NCI N87R cells. The functional studies showed that the levels of iron ion and malondialdehyde increased, and glutathione decreased in △HES1/NCI N87R cells. It was further found that Fer-1, a ferroptosis inhibitor, could reverse the expression of pTP53, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in △HES1/NCI N87R cell, and reduce the sensitivity of △HES1/NCI N87R cells to herceptin. It is suggested that HES1 regulated the resistance of NCI N87R cells to herceptin through TP53/SLC7A11/GPX4 signaling pathway, and targeting TP53/SLC7A11/GPX4 signal axis mediated by HES1 is a potential strategy to reverse herceptin resistance in gastric cancer.

Advances in the diagnosis and treatment of gallbladder carcinoma / 临床肝胆病杂志

Gallbladder carcinoma is a common malignant tumor of the biliary system characterized by poor specificity of early symptoms， a high degree of malignancy， and rapid progression， and it is difficult to make an early diagnosis. Gallstones and gallbladder polyps are considered the most common risk factors for gallbladder carcinoma. Ultrasound is the preferred examination， while CT， MRI， and PET also have their own advantages. There is a lack of radical treatment methods for gallbladder carcinoma， and surgical operation remains the preferred treatment method for gallbladder carcinoma； however， due to the rapid progression of this disease， most patients have lost the opportunity for surgery at the time of diagnosis. A combination of various treatment modalities， such as radiochemotherapy， targeted therapy， and immunotherapy， has improved the prognosis of patients to a certain extent， but with an unsatisfactory long-term therapeutic effect. Therefore， it is of particular importance to give priority to prevention rather than treatment and emphasize early identification and treatment.

Referral criteria of the SPOT Vision Screener for children under 6 years old / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To revise the referral criteria for the SPOT Vision Screener in children under 6 years old and assessed its accuracy based on the American Association for Pediatric Ophthalmology and Strabismus(AAPOS)uniform guidelines for instrument-based pediatric vision screen validation 2021.METHODS: Children who visited the Maternal and Child Health Center of Yuhuatai District in Nanjing city from January 2022 to April 2023 were included in the study and underwent SPOT refractive screening, cycloplegic retinoscopy, and other examinations. Abnormal children were defined according to AAPOS guidelines with amblyopia risk factors(ARFs)and visually significant refractive error(VSRE). Receiver operating characteristic(ROC)curve was used to calculate the optimal referral criteria and compared with manufacturer criteria, Wu's criteria, and Peterseim's criteria.RESULTS: A total of 959 children were examined, with 342 in the &#x003C;4-year-old group and 617 in the ≥4-year-old group. The optimal referral criteria for the &#x003C;4-year-old group were myopia ≤-2.75 D, hyperopia ≥+2.25 D, astigmatism ≤-2.75 D, and anisometropia ≥1.00 D. For the ≥4-year-old group, the criteria were myopia ≤-1.75 D, hyperopia ≥+2.00 D, astigmatism ≤-2.25 D, and anisometropia ≥1.00 D. The Youden index was 0.38 and 0.52, respectively, which were higher than other criteria.CONCLUSION: The use of new referral criteria for refractive screening in children under 6 years old demonstrates higher accuracy compared to previous criteria. It provides valuable guidance for pediatric eye care and vision health in children.

Epidemiological analyses of 480 patients with electrical burn complicated by cerebral trauma / 中华创伤杂志

Objective:To explore the epidemiological characteristics of patients with electrical burn at different voltages complicated by cerebral trauma, so as to provide a basis for improving the treatment level of such injury.Methods:A retrospective cohort study was conducted to analyze the clinical data of 480 patients with electrical burn complicated by cerebral trauma treated in Qingdao Municipal Hospital affiliated to Qingdao University from January 2001 to December 2019. According to the voltage intensity, the patients were divided into low voltage group (injury voltage<1 kV, n=295) and high voltage group (injury voltage≥1 kV, n=185). Gender, age, status of burn and other general data of all patients were collected. The clinical manifestations, consciousness [Glasgow coma scale (GCS)], imaging findings, treatment, prognosis [Glasgow outcome scale (GOS)] and complications were compared between the two groups. Results:(1) Gender and age: the male to female ratio was 5.4∶1.0; the peak age of onset occurred at 18-60 years, accounting for 302 patients (62.9%); the status of burn: the burn area ranged from 1%-78% [(20.0±4.0)%] total body surface area (TBSA), with the current outlet located at the head in 321 patients. (2) Clinical manifestations: consciousness disorders accounted for the highest proportion, with 295 patients (100%) in low voltage group and 185 patients (100%) in high voltage group, followed by headache which occurred in 178 patients (60.3%) in low voltage group and 115 patients (62.2%) in high voltage group (all P>0.05). (3) Consciousness: 37 patients presented coma, with 17 patients (5.8%) in low voltage group and 20 patients (10.8%) in high voltage group ( P<0.05). (4) Imaging findings: CT and MRI examination found cerebral edema, skull fracture, intracranial hematoma, cerebral ischemia, subarachnoid hemorrhage, and other positive lesions. In patients with head wounds (current inlet and outlet located in the head), the incidence of cerebral trauma was 44.0% in low voltage group and 86.8% in high voltage group ( P<0.05). In patients with no head wound (the current outlet was not located in the head), the incidence of cerebral trauma was 5.3% in low voltage group and 6.3% in high voltage group ( P>0.05). In contrast with the patients without current outlet locating in the head, there were three more types of cerebral trauma in patients with current outlet locating in the head, including skull fracture, intracranial hematoma and subarachnoid hemorrhage. (5) Treatment, prognosis and complications: 478 patients (99.6%) received non-surgical treatment and 2 patients (0.4%) received surgical treatment. There was 1 death (0.2%) and 479 successfully treated patients (99.8%). The prognosis was good in 280 patients (94.9%), moderately disabled in 13(4.4%) and severely disabled in 2(0.7%) in low voltage group; while the prognosis was good in 143 patients (77.3%), moderately disabled in 30(16.2%), severely disabled in 11(5.9%) and death in 1(0.5%) in high voltage group (all P<0.01). After discharge, the incidence of numbness, paresthesia and anxiety was significantly higher in low voltage group than that in high voltage group (all P<0.01). Conclusions:Male patients with electrical burn complicated by cerebral trauma are more than female patients, with the young and middle-aged population being at high risk. Disturbance of consciousness and headache are the main clinical manifestations. The incidence of high voltage coma is relatively higher. Compared with low voltage-induced electrical burn, the patients with high voltage-induced electrical burn complicated by cerebral trauma (current inlet and outlet located at the head) sustain more severe and extensive injury. Early and active CT or MRI examination is conducive to definite diagnosis. Non-surgical treatment is the main treatment. Compared with high voltage-induced electrical burn, the patients with low voltage-induced electrical burn complicated by cerebral trauma have significantly better prognosis, but are more likely to develop complications of numbness, paresthesia and anxiety.

Pulmonary perfusion defect index, pulmonary artery obstruction index and right heart function parameters for evaluating the severity of pulmonary embolism / 中国基层医药

Objective:To investigate the value of pulmonary perfusion defect index (PPDI), pulmonary artery obstruction index (PAOI) and right heart function parameters in the evaluation of severity of pulmonary embolism.Methods:The clinical data of 108 patients with pulmonary embolism who received treatment in The Second Hospital of Jiaxing from January 2019 to June 2021 were retrospectively analyzed. These patients were divided into high-risk ( n = 25), moderate-risk ( n = 32), and low-risk ( n = 51) groups according to the severity of pulmonary embolism. PAOI, PPDI, right ventricular short axis maximum diameter (RV), left ventricular short axis maximum diameter (LV), ratio of right/left right ventricular short axis maximum diameter (RV/LV) were determined in each group. PPDI, PAOI and right ventricular function parameters were correlated with the severity of pulmonary embolism. The area under the receiver operating characteristic curve, specificity and severity of PPDI, PAOI, RV, LV, RV/LV used alone and in combination to predict the severity of pulmonary embolism were analyzed. Results:PPDI, PAOI, RV, and RV/LV in the high-risk group were (32.52 ± 10.85)%, (45.01 ± 15.02)%, (50.32 ± 12.32) mm, (1.42 ± 0.45), respectively, which were significantly lower than (5.32 ± 1.85)%, (12.52 ± 3.25)%, (37.25 ± 8.52) mm, (0.96 ± 0.21) in the low-risk group, and LV was significantly lower in the high-risk group than that in the low-risk group [(35.14 ± 10.52) mm vs. (44.02 ± 15.21) mm, t = 13.95, 11.91, 2.62, 6.09, 5.44, all P < 0.05]. PPDI, PAOI, RV, and RV/LV in the moderate-risk group were (18.62 ± 6.02)%, (28.65 ± 8.65)%, (45.85 ± 10.02) mm, and (1.20 ± 0.32), respectively, which were significantly higher than those in the low-risk group ( t = 14.75, 12.06, 4.18, 4.13, all P < 0.05). There was no significant difference in LV between moderate-risk and low-risk groups ( t = 1.51, P > 0.05). Spearman correlation analysis showed that PPDI, PAOI, RV, RV/LV were positively correlated with the severity of pulmonary embolism ( r = 0.87, 0.84, 0.45, 0.41, all P < 0.001). LV was negatively correlated with the severity of pulmonary embolism ( r = -0.27, P < 0.001). The receiver operating characteristic curve (ROC curve) showed that the areas under the receiver operating characteristic curve of PPDI, PAOI, RV, LV, RV/LV used alone or in combination to predict the severity of pulmonary embolism were 0.941, 0.911, 0.721, 0.693, 0.726, and 0.951, respectively (all P < 0.001). Conclusion:PPDI, PAOI and right heart function parameters can be used as effective indexes to dynamically monitor the severity of pulmonary embolism.

Comparison of a bidirectional-traction reduction device versus a traction table in treatment of femoral neck fractures with femoral neck system / 中华创伤骨科杂志

Objective:To compare the clinical efficacy between a bidirectional-traction reduction device and a traction table in the treatment of femoral neck fracture with femoral neck system (FNS).Methods:A retrospective study was conducted in the 46 patients with femoral neck fracture who had been treated at Department of Orthopedics, The First Central Hospital of Baoding from January 2020 to January 2021. There were 19 males and 27 females, aged from 30 to 64 years (average, 47.1 years). According to the Garden classification, 29 cases were type Ⅲ and 17 type Ⅳ. By the reduction method, the patients were assigned into an observation group ( n=24) in which the reduction was assisted by a bidirectional-traction reduction device and a control group ( n=22) in which the reduction was assisted by a traction table. FNS fixation was conducted in both groups. The 2 groups were compared in terms of operation time, reduction time, fluoroscopy frequency, intraoperative blood loss, femoral neck shortening at immediate postoperation and 12 months postoperation, Harris scores of the affected hip at 3, 6, and 12 months postoperation, and incidence of lower extremity venous thrombosis. Results:There were no significant differences in age, gender or fracture type between the 2 groups, showing they were comparable ( P>0.05). The observation group needed significantly less operation time [57.5 (54.0, 64.5) min], reduction time [(16.3±3.0) min] and fluoroscopy frequency [(20.5±4.6) times] than the control group did [85.0 (71.3, 92.0) min, (21.0±6.0) min and (29.7±4.7) times, respectively] (all P<0.05). There was no significant difference in intraoperative blood loss between 2 groups ( P>0.05). All patients were followed up for 12 to 22 months (average, 15.5 months). There was no significant difference in femoral neck shortening between the 2 groups at immediate postoperation or 12 months postoperation ( P>0.05). The Harris score of the affected hip in the observation group was significantly better than that in the control group at 3 months after surgery ( P<0.05), but such a significant difference was not observed at 6 or 12 months postoperation ( P>0.05). The incidence of thrombotic complications in the observation group (12.5%, 3/24) was significantly lower than that in the control group (40.9%, 9/22) ( P<0.05). Conclusions:In the FNS treatment of femoral neck fracture, compared with a traction table, reduction assisted by a bidirectional-traction reduction device is more advantageous because it is simpler and less time-consuming, incurs less fluoroscopy and leads to better early functional recovery of the affected hip and lower incidence of thrombotic complications.

RUNX3 regulates trastuzumab resistance of gastric cancer cells: a metabolomic analysis based on UPLC-Q Exactive Focus Orbitrap mass spectrometry / 南方医科大学学报

OBJECTIVE@#To explore the role of Runt-related transcription factor 3 (RUNX3) in metabolic regulation of trastuzumab-resistant gastric cancer cells and investigate the mechanism of RUNX3 knockdown-mediated reversal of trastuzumab resistance.@*METHODS@#We performed a metabolomic analysis of trastuzumab-resistant gastric cancer cells (NCI N87R) and RUNX3 knockdown cells (NCI N87R/RUNX3) using ultra performance liquid chromatography (UPLC) coupled with Q Exactive Focus Orbitrap mass spectrometry (MS). Multivariate combined with univariate analyses and MS/MS ion spectrums were used to screen the differential variables. MetaboAnalyst 5.0 database was employed for pathway enrichment analysis. Differential metabolites-genes regulatory relationships were constructed based on OmicsNet database. The changes in GSH/GSSG and NADPH/NADP ratios in NCI N87R/RUNX3 cells were measured using detection kits.@*RESULTS@#The metabolic profile of NCI N87R cells was significantly altered after RUNX3 knockdown, with 81 differential metabolites identified to contribute significantly to the classification, among which 43 metabolites were increased and 38 were decreased (P < 0.01). In NCI N87R cells, RUNX3 knockdown resulted in noticeable alterations in 8 pathways involving glutamine metabolism, glycolysis, glycerophospholipid, nicotinate-nicotinamide and glutathione metabolism, causing also significant reduction of intracellular GSH/GSSG and NADPH/NADP ratios (P < 0.01). The differential metabolites-genes network revealed a regulatory relationship between the metabolic molecules and genes.@*CONCLUSION@#RUNX3 reverses trastuzumab resistance in gastric cancer cells by regulating energy metabolism and oxidation-reduction homeostasis and may serve as a potential therapeutic target for trastuzumab-resistant gastric cancer.

Identification and quality evaluation of germplasm resources of commercial Scutellaria baicalensis based on DNA barcode and HPLC / 中国中药杂志

Scutellaria baicalensis is a commonly used Chinese medicinal herb. In this study, we identified the germplasm resources of commercial S. baicalensis samples based on trnH-psbA, petA-psbJ, and ycf4-cemA sequences according to the available chloroplast genome sequencing results, and measured the content of baicalin by HPLC. Through the above means we determined the best DNA barcode that can be used to detect the germplasm resources and evaluate the quality of commercial S. baicalensis samples. A total of 104 samples were collected from 24 provinces, from which DNA was extracted for PCR amplification. The amplification efficiencies of trnH-psbA, petA-psbJ, and ycf4-cemA sequences were 100%, 59.62%, and 25.96%, respectively. The results of sequence analysis showed that 5, 4, and 2 haplotypes were identified based on trnH-psbA, petA-psbJ, and ycf4-cemA sequences, respectively. However, the sequences of haplotypes in commercial samples were different from that of the wild type, and the joint analysis of three fragments of S. baicalensis only identified 6 haplotypes. Furthermore, the phylogenetic analysis and genetic distance analysis indicated that trnH-psbA could be used to identify S. baicalensis from adulterants. The above analysis showed that trnH-psbA was the best fragment for identifying the germplasm resources of commercial S. baicalensis samples. We then analyzed the haplotypes(THap1-THap5) of commercial S. baicalensis samples based on trnH-psbA and found that THap2 was the main circulating haplotype of the commercial samples, accounting for 86.55% of the total samples, which indicated the scarce germplasm resources of commercial S. baicalensis samples. The content of baicalin in all the collected commercial S. baicalensis samples exceeded the standard in Chinese Pharmacopoeia and had significant differences(maximum of 12.21%) among samples, suggesting that the quality of commercial S. baicalensis samples varied considerably. However, there was no significant difference in baicalin content between different provinces or between different haplotypes. This study facilitates the establishment of the standard identification system for S. baicalensis, and can guide the commercial circulation and reasonable medication of S. baicalensis.

Label-free quantitative proteomic study of RUNX3 regulating Herceptin resistance in gastric cancer cells / 药学学报

Resistance of tumor cells is a complex biological process involving multiple mechanisms and factors, in which anti-apoptosis is the most important cause of drug resistance. Previous studies have shown that the DNA binding activity of Runt related transcription factor 3 (RUNX3) increased prominently in Herceptin resistant gastric cancer cells (NCI N87R) while the relevance of which to drug resistance has not yet been confirmed. In this study, we employed CRISPR/Cas9 to establish RUNX3 knock-out cell line (△RUNX3/NCI N87R) to investigate the functions of RUNX3 in Herceptin resistance of NCI N87R cells and its potential mechanisms. We investigated proteomics profiling of △RUNX3/NCI N87R cells based on label free quantitative proteomics. Differentially expressed proteins were screened out according to fold change and significance level between △RUNX3/NCI N87R and NCI N87R cells. Pathway enrichment analysis was done using GeneAnalytics database, and gene ontology analysis was conducted by DAVID Bioinformatics Resources database. Protein-protein interaction networks were constructed based on STRING database. The results showed that △RUNX3/NCI N87R cells increased the sensitivity to Herceptin. Proteomic data demonstrated that the expression of 577 genes changed significantly in △RUNX3/NCI N87R cells, among which 191 genes were up-regulated while 386 ones down-regulated comparing with NCI N87R cells. Pathway analysis showed that autophagy, cell cycle, apoptosis, mitochondrial fatty acid β oxidation, neurogenic locus notch homolog protein 1 (NOTCH1), mammalian target of rapamycin (mTOR), Hedgehog and DNA damage response pathways exhibited notable changes based on pathway enrichment ratio and significance level (P < 0.05). These results indicated that RUNX3 knock-out altered multiple signaling pathways of NCI N87R cells. Western blotting manifested that the expression of autophagy regulatory molecules autophagy-related protein (ATG) 13, 7 and BECN1 increased remarkably while cell cycle molecules serine/threonine-protein kinase Chk2 (CHEK2) and apoptosis regulator Bcl-2 (BCL2) decreased prominently in △RUNX3/NCI N87R cells. The p-AKT expression decreased significantly in △RUNX3/NCI N87R cells compared with NCI N87R cells (P < 0.01) and was suppressed by Herceptin. These results indicated that RUNX3 knock-out altered cell cycle, increased inhibition to p-AKT by Herceptin, promoted autophagy and induced cell apoptosis of NCI N87R cells. These results suggested that RUNX3 may be a potential therapeutic target for reversing or reducing Herceptin resistance in gastric cancer cells.

Application of nano-bionic drug delivery system based on macrophages in tumor therapy / 药学学报

The construction of nano-bionic drug delivery system based on cells or cellular components is a research hotspot of novel drug delivery systems at present. The nano-bionic drug delivery system can integrate the characteristics not only high drug loading and controlled release of nano-carriers, but also good biocompatibility, low immunogenicity and natural targeting from bionic components of cell, and it can also integrate with flexible morphology from living cells. Among them, nano-bionic drug delivery system based on macrophages possesses a good prospect of clinical application because of phagocytic function, inherent tendency, deep penetration ability and potential in cell therapy of macrophages in the treatment of tumors. Based on this, this paper reviews the drug loading strategies of nano-bionic drug delivery system based on macrophages and its application in tumor therapy, so as to provide reference for the development of novel drug delivery systems.

Discovery of a potent FKBP38 agonist that ameliorates HFD-induced hyperlipidemia

The mammalian target of rapamycin (mTOR)-sterol regulatory element-binding proteins (SREBPs) signaling promotes lipogenesis. However, mTOR inhibitors also displayed a significant side effect of hyperlipidemia. Thus, it is essential to develop mTOR-specific inhibitors to inhibit lipogenesis. Here, we screened the endogenous inhibitors of mTOR, and identified that FKBP38 as a vital regulator of lipid metabolism. FKBP38 decreased the lipid content

Bloodletting Puncture at Hand Twelve Jing-Well Points Relieves Brain Edema after Severe Traumatic Brain Injury in Rats via Inhibiting MAPK Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate whether blood-brain barrier (BBB) served a key role in the edema-relief effect of bloodletting puncture at hand twelve Jing-well points (HTWP) in traumatic brain injury (TBI) and the potential molecular signaling pathways.@*METHODS@#Adult male Sprague-Dawley rats were assigned to the sham-operated (sham), TBI, and bloodletting puncture (bloodletting) groups (n=24 per group) using a randomized number table. The TBI model rats were induced by cortical contusion and then bloodletting puncture were performed at HTWP twice a day for 2 days. The neurological function and cerebral edema were evaluated by modified neurological severity score (mNSS), cerebral water content, magnetic resonance imaging and hematoxylin and eosin staining. Cerebral blood flow was measured by laser speckles. The protein levels of aquaporin 4 (AQP4), matrix metalloproteinases 9 (MMP9) and mitogen-activated protein kinase pathway (MAPK) signaling were detected by immunofluorescence staining and Western blot.@*RESULTS@#Compared with TBI group, bloodletting puncture improved neurological function at 24 and 48 h, alleviated cerebral edema at 48 h, and reduced the permeability of BBB induced by TBI (all P<0.05). The AQP4 and MMP9 which would disrupt the integrity of BBB were downregulated by bloodletting puncture (P<0.05 or P<0.01). In addition, the extracellular signal-regulated kinase (ERK) and p38 signaling pathways were inhibited by bloodletting puncture (P<0.05).@*CONCLUSIONS@#Bloodletting puncture at HTWP might play a significant role in protecting BBB through regulating the expressions of MMP9 and AQP4 as well as corresponding regulatory upstream ERK and p38 signaling pathways. Therefore, bloodletting puncture at HTWP may be a promising therapeutic strategy for TBI-induced cerebral edema.

Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine：Membranous Nephropathy / 中国实验方剂学杂志

Traditional Chinese medicine （TCM） is a great treasure house， exhibiting unique advantages in the treatment of some difficult and critical diseases. The incidence rate of membranous nephropathy has increased year by year in recent years， and has become the first cause of primary glomerular diseases. However， its pathogenesis is not clear. Modern medicine often uses immunosuppressive therapy， but it often faces the problems of high side effects and high recurrence rate. The China Association of Chinese Medicine （CACM） invited clinical experts of TCM and western medicine to fully discuss membranous nephropathy， which was later confirmed to be one of the clinical diseases responding specifically to TCM. Apart from summarizing the pathogenesis and clinical diagnosis and treatment of membranous nephropathy in both TCM and western medicine， this paper also detailed TCM cognition， syndrome differentiation， and therapeutic schemes of membranous nephropathy， aiming to improve the clinical remission rate of membranous nephropathy and provide reference for its clinical treatment.

Efficacy and safety of Shenyankangfu Tablet, a Chinese patent medicine, for primary glomerulonephritis: A multicenter randomized controlled trial / 中西医结合学报

BACKGROUND@#Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease.@*OBJECTIVE@#This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium.@*DESIGN, SETTING, PARTICIPANTS AND INTERVENTION@#This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m@*MAIN OUTCOME MEASURES@#The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment.@*RESULTS@#A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group.@*CONCLUSION@#SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone.@*TRIAL REGISTRATION NUMBER@#NCT02063100 on ClinicalTrials.gov.

Quantitative measurement of iodine concentration in the liver using dual-energy CT in patients with oral amiodarone：a feasibility study / 中华放射学杂志

Objective:To explore the feasibility of dual-energy CT (DECT) in the evaluation of liver iodine concentration in patients on long-term oral amiodarone treatment (≥12 months).Methods:Eighteen subjects undergoing abdominal dual-energy CT who met the criterion in January 2017 were collected as a control group. Twenty-seven patients who received oral amiodarone treatment for more than 12 months from January 2017 to May 2019 were enrolled as an experimental group. The difference of CT value and iodine concentration of liver, pancreas and spleen in 140 kV, 100 kV and VNC images between experimental and control groups were measured and analyzed. The correlation between liver CT value and liver iodine concentration was analyzed by Spearman correlation.Results:The concentrations of iodine in the liver, pancreas and spleen of the experimental group were 0.2 (0.2, 0.4), 0.1 (0.1, 0.2) and 0.2 (0.1, 0.2) mg/ml, and those in the control group were 0.2 (0.1， 0.2), 0.1 (0.1, 0.2) and 0.1 (0.1, 0.2) mg/ml. The difference in the concentration of iodine of the liver was statistically significant ( Z=-3.354, P<0.05), however there was no significant difference in the concentration of pancreas and spleen between the two groups ( Z=-0.179 and -1.590, P>0.05). The CT values of 100 kV, 140 kV, VNC images in the experimental group [(74±18)， (70±10) and (71±5) HU] were higher than those in the control group [(60±6)， (59±6) and (62±6) HU], and the differences were statistically significant ( t=3.310, 4.205 and 5.241, P<0.05). There was a positive correlation between the CT value of 140 kV image and iodine concentration ( r=0.410, P<0.05). In the experimental group, the time difference of taking amiodarone was statistically significant ( P<0.05). Conclusions:DECT can be used to quantitatively measure the liver iodine concentration of patients with long-term oral amiodarone, and provides some biological indicators for the assessment of amiodarone induced liver injury.

Small airway immunoglobulin A profile in emphysema-predominant chronic obstructive pulmonary disease / 中华医学杂志(英文版)

BACKGROUND@#Due to airway remodeling and emphysematous destruction in the lung, the two classical clinical phenotypes of chronic obstructive pulmonary disease (COPD) are emphysema and bronchiolitis. The present study was designed to investigate the levels of small airway immunoglobulin A (IgA) in COPD with "emphysema phenotype." The study also evaluated the associations between the small airway IgA levels and the severity of disease by the extent of emphysema versus airflow limitation.@*METHODS@#Thirty patients (20 with COPD and ten healthy smokers) undergoing lung resection surgery for a solitary peripheral nodule were included. The study was conducted from January 2015 to December 2018 in the Shanxi Dayi Hospital. The presence of small airway IgA expression was determined in the lung by immunohistochemistry. In vivo, Wistar rats were exposed to silica by intratracheal instillation. Rats were sacrificed at 15 and 30 days after exposure of silica (n = 10 for each group). We also evaluated airway IgA from rats.@*RESULTS@#Small airway secretory IgA (sIgA), dimeric IgA (dIgA), and dIgA/sIgA of Global Initiative for Chronic Obstructive Lung Disease grade 1-2 COPD patients showed no difference compared with smoking control subjects (5.15 ± 1.53 vs. 6.03 ± 0.85; 1.94 ± 0.66 vs. 1.67 ± 0.04; 41.69 ± 21.02 vs. 28.44 ± 9.45, all P > 0.05). dIgA/sIgA level in the lung of COPD patients with emphysema showed higher levels than that of COPD patients without emphysema (51.89 ± 24.81 vs. 31.49 ± 9.28, P = 0.03). The percentage of low-attenuation area below 950 Hounsfield units was positively correlated with dIgA/sIgA levels (r = 0.45, P = 0.047), but not associated with the severity of disease by spirometric measurements (forced expiratory volume in the first second %pred, P > 0.05). Likewise, in the rat study, significant differences in sIgA, dIgA, dIgA/sIgA, mean linear intercept, mean alveoli number, and mean airway thickness of bronchioles (VV airway, all P  0.05).@*CONCLUSION@#Airway IgA concentrations in mild and moderate COPD patients are directly associated with the severity of COPD with "emphysema phenotype" preceding severe airway limitation. This finding suggests that small airway IgA might play an important role in the pathophysiology of COPD, especially emphysema phenotype.