Germline PRKACA amplification-associated primary pigmented nodular adrenocortical disease: a case report and literature review

SUMMARY Primary pigmented nodular adrenocortical disease (PPNAD) is a rare adrenocorticotropin hormone (ACTH)-independent Cushing's syndrome (CS). Pediatric patients with PPNAD typically have unusual skin lesions and slow growth with unknown causes. We present a case of a female Chinese patient with PPNAD caused by the germline PRKACA gene copy number gain of chromosome 19. The patient initially presented with kidney stones, short stature, and obesity. After further testing, it was discovered that the patient had diabetes, mild hypertension, low bone mass, a low ACTH level, and hypercortisolemia, and neither the low-dose or high-dose dexamethasone suppression test was able to inhibit hematuric cortisol, which paradoxically increased. PPNAD was pathologically diagnosed after unilateral adrenalectomy. Chromosome microarrays and whole exon sequencing analyses of the peripheral blood, as well as testing of sectioned adrenal tissue, showed a rise in the copy number of the duplication-containing PRKACA gene on chromosome 19p13.13p13.12, a de novo but not heritable gene defect that causes disease. The clinical signs and symptoms supported the diagnosis of Carney complex (CNC). One significant mechanism of CNC pathogenesis may be the rise in germline PRKACA copy number of chromosome 19. When assessing PPNAD patients for CNC, the possibility of PRKACA gene amplification should be considered. The effect of PRKACA gene amplification on the clinical manifestations of CNC needs to be confirmed by more cases.

Analysis of risk factors of radiation-induced toxicity in limited-stage small cell lung cancer treated with hypofractionated intensity-modulated radiotherapy / 中华肿瘤杂志

Objective: To compare the incidence of radiation-related toxicities between conventional and hypofractionated intensity-modulated radiation therapy (IMRT) for limited-stage small cell lung cancer (SCLC), and to explore the risk factors of hypofractionated radiotherapy-induced toxicities. Methods: Data were retrospectively collected from consecutive limited-stage SCLC patients treated with definitive concurrent chemoradiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from March 2016 to April 2022. The enrolled patients were divided into two groups according to radiation fractionated regimens. Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) was used to evaluate the grade of radiation esophagus injuries and lung injuries. Logistic regression analyses were used to identify factors associated with radiation-related toxicities in the hypofractionated radiotherapy group. Results: Among 211 enrolled patients, 108 cases underwent conventional IMRT and 103 patients received hypofractionated IMRT. The cumulative incidences of acute esophagitis grade ≥2 [38.9% (42/108) vs 35.0% (36/103), P=0.895] and grade ≥ 3 [1.9% (2/108) vs 5.8% (6/103), P=0.132] were similar between conventional and hypofractionated IMRT group. Late esophagus injuries grade ≥2 occurred in one patient in either group. No differences in the cumulative incidence of acute pneumonitis grade ≥2[12.0% (13/108) vs 5.8% (6/103), P=0.172] and late lung injuries grade ≥2[5.6% (6/108) vs 10.7% (11/103), P=0.277] were observed. There was no grade ≥3 lung injuries occurred in either group. Using multiple regression analysis, mean esophageal dose ≥13 Gy (OR=3.33, 95% CI: 1.23-9.01, P=0.018) and the overlapping volume between planning target volume (PTV) and esophageal ≥8 cm(3)(OR=3.99, 95% CI: 1.24-12.79, P=0.020) were identified as the independent risk factors associated with acute esophagitis grade ≥2 in the hypofractionated radiotherapy group. Acute pneumonitis grade ≥2 was correlated with presence of chronic obstructive pulmonary disease (COPD, P=0.025). Late lung injuries grade ≥2 was correlated with tumor location(P=0.036). Conclusions: Hypofractionated IMRT are tolerated with manageable toxicities for limited-stage SCLC patients treated with IMRT. Mean esophageal dose and the overlapping volume between PTV and esophageal are independently predictive factors of acute esophagitis grade ≥2, and COPD and tumor location are valuable factors of lung injuries for limited-stage SCLC patients receiving hyofractionated radiotherapy. Prospective studies are needed to confirm these results.

Effects of tumor-treating field arrays on the radiation position and dose of glioblastoma / 中华放射医学与防护杂志

Objective:To preliminarily investigate the effects of tumor treating field (TTF) arrays on the positioning accuracy of radiotherapy setup in the treatment of glioblastoma.Methods:The kilovolt cone-beam CT (CBCT) and an X-ray volumetric imaging (XVI) system were used to verify the radiotherapy setup of 29 patients treated with conventional radiotherapy and 12 patients treated with TTF concurrent radiotherapy, respectively. The errors of radiotherapy position isocenter and treatment plan isocenter were evaluated in six directions, namely lateral (Lat), head pin (Lng), dorsoventral (Vrt), roll, pitch, and rotation (Rtn). Then, the plan isocenter was redetermined according to the setup error data. Moreover, the dose distribution was recalculated without changing the radiation field parameters. Finally, the V40, Dmean, D98% and D2% of both PTV and CTV and the Dmean, D20 cm 3, and D30 cm 3 of scalp tissue were evaluated. Results:When patients were treated with TTF concurrent radiotherapy wearing TTF arrays, the setup errors increased by 2 mm and 1.3 mm on average (maximum: 3.5 mm and 2.7 mm) toward the foot and dorsal directions, respectively. In addition, the setup errors in both Roll and Rtn directions increased by about 1.1° toward one side. The V40 and D98% of PTV decreased by up to 4.78% and 6%, respectively. The Dmean, D20 cm 3, and D30 cm 3 to scalp tissue increased by up to 2.6%, 3.2%, and 3.5%, respectively. The errors of other dose parameters for both CTV and PTV were within 2%. Conclusions:TTF arrays have significant effects on the setup errors of patients in the Lng and Vrt directions and increase the setup difficulty in the Roll and Rtn directions, while there is no significant error in the Lat and Pitch directions. Moreover, too large setup errors can significantly reduce the dose to PTV.

Analysis of expression of m 6A regulators in colorectal tumor samples based on TCGA and GEO databases / 中国基层医药

Objective:To detect the expression of N6-methyladenosine (m 6A) regulators in colorectal tumor samples and its clinical significance. Methods:From September to December 2021, the data regarding the expression of m 6A regulators in colorectal tumor samples were collected using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) and the expression of m 6A regulators was compared between different clinical pathological characteristics and between different molecular subtypes. Survival analysis was conducted in patients with colorectal cancer with different m 6A expression levels. Results:In TCGA, insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1), insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3), and YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) were higher in colorectal tumor samples than normal tissue samples (TCGA-COAD: IGF2BP3: 12.80 vs. 204.46, logFC = 4.00, P = 0.003; YTHDF1: 2 347.56 vs. 3712.77, logFC = 0.66, P < 0.001; TCGA-READ: IGF2BP1: 6.20 vs. 359.32, logFC = 5.82, P = 0.007; YTHDF1: 2 470.10 vs. 4 369.09, logFC = 0.82, P = 0.020). The intersection of TCGA and GEO databases showed that methyltransferase like 14 (METTL14), YTH domain m 6A RNA binding protein 3 (YTHDF3), and α-ketoglutarate dependent dioxygenase AlkB homolog 5 (ALKBH5) were downregulated in colorectal tumor samples compared with normal tissue samples (TCGA-COAD: METTL14: 1 051.56 vs. 711.40, logFC = -0.56, P < 0.001; YTHDF3:4 613.85 vs. 3 155.05, logFC = -0.55, P < 0.001, ALKBH5: 4 250.10 vs. 2 555.55, logFC = -0.73, P < 0.001; TCGA-READ vs. METTL14: 1 113.3 vs. 674.36, logFC = -0.72, P < 0.001; YTHDF3: 5 034.30 vs. 3 331.95, logFC = -0.60, P = 0.004; ALKBH5: 4 902.20 vs. 2 529.71, logFC = -0.95, P < 0.001; GEO-CRC vs. METTL14: 6.58 vs. 6.33, logFC = -0.06, P < 0.001; YTHDF3: 6.28 vs. 6.20, logFC = -0.02, P = 0.002; ALKBH5: 5.07 vs. 4.98, logFC = -0.02, P < 0.001). In colorectal tumor samples of different molecular subtypes, IGF2BP2, HNRNPC, TP53 and YTHDF2 expression was low in KRAS (IGF2BP2: 48.53 vs. 44.04, t = 2.64, P = 0.008; HNRNPC: 121.30 vs. 112.60, t = 2.32, P = 0.020; TP53: 65.30 vs. 60.26, t = 2.11, P = 0.034; YTHDF2: 54.07 vs. 51.19; t = 1.97, P = 0.048). Different clinical pathological characteristics showed that IGF2BP1 was higher in colorectal cancer with positive lymph nodes (8.97 vs. 6.11, W = 20 008, P = 0.002), distant metastasis (8.94 vs. 6.41, W = 19 104, P = 0.009), or stage Ⅲ-Ⅳ (7.46 vs. 7.13, W = 8 779, P = 0.025) than normal tissue. ALKBH5 overexpression, advanced age, presence of vascular invasion, and late pathological staging were significantly related to a short survival period (high ALKBH5 expression vs. low ALKBH5 expression: 5.85 years vs. not available, HR: 1.63, 95% CI: 1.071-2.491, P = 0.021; > 68 years vs. < 68 years: 6.78 years vs. not available, HR: 1.59, 95% CI: 1.049-2.422, P = 0.047; stage Ⅲ-Ⅳ vs. stage Ⅰ-Ⅱ: 4.55 years vs. 8.33 years, HR: 2.89, 95% CI: 1.895-4.425, P < 0.001; presence of vein invasion vs. absence of vein invasion: 5.48 years vs. not available, HR: 2.82, 95% CI: 1.672-4.783, P < 0.001). Conclusion:Some of the m 6A regulators are associated with the biological characteristics and prognosis of colorectal cancer.

Survey results of drinking water iodine level in some areas of Jiangsu Province in 2020 / 中华地方病学杂志

Objective:To dynamically observe the changes in iodine level in residents' drinking water after the change of regional water supply mode (2020) in Jiangsu Province.Methods:The survey of water iodine level was conducted from June to October 2020 in administrative villages of Jiangsu Province with a median water iodine ≥40 μg/L in 2017. The survey mainly covered 1 537 administrative villages in 21 counties (cities and districts) of 5 cities, including Huaian City, Lianyungang City, Suqian City, Yancheng City, and Xuzhou City. Based on the standard of "Definition and Demarcation of Iodine Deficient Areas and Iodine Adequate Areas" (WS/T 669-2020), the administrative villages with a median water iodine of 40 - 100 μg/L were classified as iodine adequate areas. Water iodine testing was conducted using the "Method for Water Iodine Testing in Iodine Deficient and High Iodine Areas" recommended by the National Reference Laboratory for Iodine Deficiency Disorders.Results:Totally 1 498 administrative villages in Jiangsu Province were monitored in 2020, all of which had centralized water supply. The minimum value of water iodine in all administrative villages was 1.2 μg/L and the maximum value was 606.7 μg/L, and the median water iodine was 35.2 μg/L. Among them, 206 administrative villages had median water iodine < 10 μg/L, accounting for 13.75% (206/1 498); 610 administrative villages had median water iodine from 10 to < 40 μg/L, accounting for 40.72% (610/1 498); 635 administrative villages had median water iodine from 40 to 100 μg/L, accounting for 42.39% (635/1 498); and 47 administrative villages with median water iodine > 100 μg/L, accounting for 3.14% (47/1 498). Except for Sucheng District in Suqian City, Xinyi City and Gulou District in Xuzhou City, Qingjiangpu District and Xuyi County in Huaian City, and Guannan County in Lianyungang City, the median water iodine in the administrative villages of the remaining 15 counties (cities and districts) in 2020 decreased significantly compared to 2017, and the differences were statistically significant ( P < 0.05). Conclusion:After change of regional water supply mode in 2020, in most monitored counties (cities and districts) of Jiangsu Province, the water iodine level of administrative villages has decreased significantly compared to 2017.

Analysis of surveillance results of drinking water-borne endemic fluorosis in Jiangsu Province in 2021 / 中华地方病学杂志

Objective:To learn about the implementation of prevention and control measures in drinking water-borne endemic fluorosis areas and the trend of the disease change in Jiangsu Province.Methods:In March to October 2021, a general survey was carried out in 1 972 villages with drinking water-borne endemic fluorosis in 27 counties (cities and districts) of Jiangsu Province, the operation of water improvement projects in the villages was monitored, and the water fluoride content was determined. The prevalence of dental fluorosis among children aged 8 to 12 years in all the villages was investigated.Results:The 1 972 villages with drinking water-borne endemic fluorosis had completed water improvement, and all water improvement projects were operating normally and the water was qualified. Among them, 1 774 villages in the disease affected areas had achieved the control goal, accounting for 89.96%; and there were 198 villages in the disease affected areas with control measures up to the standard, accounting for 10.04%. A total of 47 water improvement projects were monitored, including 2 small-scale water improvement projects, accounting for 4.26%. There were 45 large-scale water improvement projects, accounting for 95.74%. A total of 125 790 children aged 8 to 12 years were examined, and 12 625 cases of dental fluorosis were detected. The detection rate of dental fluorosis was 10.04%, and the dental fluorosis index was 0.19. The detection rate of dental fluorosis in children aged 8 to 12 years was 9.98% (1 854/18 579), 10.27% (2 704/26 323), 9.48% (2 765/29 152), 9.73% (2 835/29 145) and 10.92% (2 467/22 591), respectively, with statistically significant difference (χ 2 = 10.51, P = 0.015). Among the 198 villages with control measures up to standard, according to the historical water fluoride, the detection rate of dental fluorosis in children in each water fluoride range (1.20-2.00, 2.01-3.00, 3.01-4.00, > 4.00 mg/L) was 37.73% (698/1 850), 43.17% (1 176/2 724), 45.50% (769/1 690) and 55.20% (802/1 453), respectively, with a statistically significant difference (χ 2 = 104.15, P < 0.001). Conclusion:The water improvement measures in drinking water-borne endemic fluorosis areas in Jiangsu Province have achieved significant results, which still need to be further consolidated.

Analysis of influencing factors of dental fluorosis in children based on logistic regression and classification tree model / 中华地方病学杂志

Objective:To analyze the influencing factors of dental fluorosis of children in the drinking-water-borne endemic fluorosis (referred to as drinking-water-borne fluorosis) areas with qualified drinking water.Methods:In 2020 and 2021, the cluster sampling method was used to select the children aged 8 to 12 years old from the drinking-water-borne fluorisis areas with qualified drinking water in Tianjin City for water and urine fluoride detection, dental fluorosis examination and questionnaire survey, and logistic regression and classification tree model were used to analyze the influencing factors of dental fluorosis in children.Results:A total of 3 795 cases children aged 8 to 12 years old were investigated, and 1 001 cases of dental fluorosis were detected, and the detection rate of dental fluorosis was 26.38% (1 001/3 795). The results of logistic analysis showed that age [odds ratio ( OR) = 1.193, 95% confidence interval ( CI): 1.115 - 1.277], high urinary fluoride (1.84 - 19.40 mg/L, OR = 1.510, 95% CI: 1.169 - 1.952) and the number of permanent residents at home ≥6 ( OR = 1.377, 95% CI: 1.090 - 1.739) were risk factors of dental fluorosis in children; and the mother's with higher education level (college degree or above, OR = 0.664, 95% CI: 0.441 - 0.999), the years of water improvement ≥5 years (5 - < 10 years, OR = 0.193, 95% CI: 0.157 - 0.238; ≥10 years, OR = 0.254, 95% CI: 0.193 - 0.333) were protective factors of dental fluorosis in children. The results of classification tree model analysis showed that the years of water improvement contributed the most to the prevalence of dental fluorosis among children in the drinking-water-borne fluorisis areas with qualified drinking water, followed by age, number of permanent residents at home and urinary fluoride. The area under the receiver operating characteristic curve (AUC) of logistic regression model and classification tree model were 0.730 (95% CI: 0.711 - 0.748) and 0.721 (95% CI: 0.702 - 0.739), respectively, with good fitting effect. Conclusion:The detection rate of children's dental fluorosis in the drinking-water-borne fluorosis areas with qualified drinking water is mainly related to the years of water improvement, age, the number of permanent residents at home and urinary fluoride.

Exploring the key anti-fatigue components of American ginseng based on metabolomics and zebrafish models / 药学学报

The aim of this paper is to explore the key anti-fatigue active components in the saponin-like composition of American ginseng. The anti-fatigue activity of western ginseng samples was evaluated using a zebrafish model; metabolomics techniques were used to identify the main saponins in western ginseng from different origins; the active substances and relevant targets of the anti-fatigue effect of western ginseng were initially screened by constructing a PPI protein interaction network between western ginseng saponins and disease targets, and the key active ingredients were screened using a molecular docking method; finally, the anti-fatigue activity of the key active ingredients was evaluated using a zebrafish, animal experiment was approved by the Ethics Committee of Shandong Academy of Medical Sciences (SYXK20220005). The anti-fatigue activity of the key active ingredients was evaluated using a zebrafish model. The results of the zebrafish activity evaluation showed that there were significant differences in the activities of the western ginseng samples from the two origins, and a total of 10 different saponins were identified as possibly related to the anti-fatigue activity after further metabolomic testing and pattern discrimination. The core anti-fatigue targets were screened with the help of component-disease target PPI, combined with pharmacophore-like parameters and molecular docking techniques, and pseudoginsenoside F11 was found to have good binding activity to five of the targets. Finally, the zebrafish model revealed that pseudoginsenoside F11 exhibited significant anti-fatigue activity. This study used metabolomics and zebrafish model to screen the key active substances of pseudoginsenoside F11 for its anti-fatigue activity, which will provide a reference for further research on the anti-fatigue of pseudoginsenosides.

Component analysis and network pharmacology of flavonoids in Sophora flavescens tissues at anthesis / 药学学报

italic>Sophora flavescens is a traditional Chinese medicine rich in flavonoids and has wide application potential in drug development and clinical practice. In this study, a total of 227 flavonoids were detected among five tissues of S. flavescens during anthesis using widely targeted metabolomics techniques. There were 137 flavonoids shared by five S. flavescens tissues and 18 root-specific flavonoids. There were 156, 155, 156 and 150 differentially accumulated metabolites identified in stem, leaf, flower, and young pod, respectively, compared with root. Forty-seven potentially active flavonoid components in S. flavescens were identified using the PubChem and SwissADME databases. The 58 potential target proteins for these potentially active components were predicted to be important in the treatment of type 2 diabetes mellitus (T2DM) based on the SwissTargetPrediction and GeneCards database. These 58 target proteins were used to construct a protein-protein interaction network through the STRING database, from which we performed GO and KEGG functional enrichment analysis. The mechanisms by which S. flavescens flavonoids may be useful in the treatment of T2DM was further explored in a multi-level and systematic way based on a "component-target-pathway" network. Finally, ten key potentially effective components were identified and found to be mainly distributed in the roots, flowers, and pods, and their content varied significantly between tissues. The results predict that the key targets of S. flavescens flavonoids in the treatment of T2DM are AKT1, ESR1, EGFR, PIK3R1, TNF and PTGS2, and that they play a hypoglycemic role through the regulation of endocrine resistance, AGE-RAGE, the PI3K-Akt signaling pathway, EGFR tyrosine kinase inhibitor resistance and other signaling pathways. This analysis of the tissue distribution and network pharmacology of S. flavescens flavonoids provides a theoretical basis for further studies on S. flavescens metabolites, the rational development and utilization of the S. flavescens aboveground parts, and initiates a comprehensive exploration of the mechanisms by which S. flavescens can be used in the treatment of T2DM.

Research progress in optimizing implantable collamer lens V4c implantation / 国际眼科杂志(Guoji Yanke Zazhi)

With the development of posterior chamber phakic intraocular lenses implantation and the constant improvement of the implantable collamer lens(ICL), ICL V4c implantation has become one of the main methods for correcting moderate and high myopia. Vault is an important indicator to evaluate the security of posterior chamber intraocular lens implantation. In recent years, optimizing surgical procedures to obtain the ideal vault in ICL V4c implantation surgery has become a research hotspot. This paper aims to provide help for improving surgical safety by summarizing and analyzing the optimized programs of ICL V4c implantation surgery. The focus will be on preoperative examination, intraoperative surgical design, and postoperative follow-up.

Identification and verification of α-11 giardin-interacting protein / 中国血吸虫病防治杂志

Objective To identify and verify the interacting protein of α-11 giardin, so as provide the experimental evidence for studies on the α-11 giardin function. Methods The yeast two-hybrid cDNA library of the Giardia lambia C2 strain and the bait plasmid of α-11 giardin were constructed. All proteins interacting with α-11 giardin were screened using the yeast two-hybrid system. α-11 giardin and all screened potential interacting protein genes were constructed into pBiFc-Vc-155 and pBiFc-Vn-173 plasmids, and co-transfected into the breast cancer cell line MDA-MB-231. The interactions between α-11 giardin and interacting proteins were verified using bimolecular fluorescence complementation (BiFC). Results The yeast two-hybrid G. lambia cDNA library which was quantified at 2.715 × 107 colony-forming units (CFU) and the bait plasmid containing α-11 giardin gene without an autoactivation activity were constructed. Following two-round positive screening with the yeast two-hybrid system, two potential proteins interacting with α-11 giardin were screened, including eukaryotic translation initiation factor 5A (EIF5A), calmodulin-dependent protein kinase (CAMKL) and nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase (NADP-GDH), hypothetical protein 1 (GL50803_95880), hypothetical protein 2 (GL50803_87261) and a protein from Giardia canis virus. The α-11 giardin and EIF5A genes were transfected into the pBiFc-Vc-155 and pBiFc-Vn-173 plasmids using BiFC, and the recombinant plasmids pBiFc-Vc-155-α-11 and pBiFc-Vn-173-EIF5A were co-tranfected into MDA-MB-231 cells, which displayed green fluorescence under a microscope, indicating the interaction between α-11 giardin and EIF5A protein in cells. Conclusion The yeast two-hybrid cDNA library of the G. lambia C2 strain has been successfully constructed, and six potential protein interacting with α-11 giardin have been identified, including EIF5A that interacts with α-11 giardin in cells.

Value of combined baseline serum HBV markers in predicting HBeAg seroconversion in chronic hepatitis B patients treated by nucleos(t)ide analogues / 临床肝胆病杂志

Objective To investigate the ability of combined baseline serum markers, i.e., HBV DNA, HBV RNA, HBsAg, and HBcrAg, to predict HBeAg seroconversion in patients with HBeAg-positive chronic hepatitis B (CHB) treated by nucleos(t)ide analogues. Methods A retrospective analysis was performed for 83 HBeAg-positive patients selected as subjects from the prospective CHB follow-up cohort established by Difficult & Complicated Liver Diseases and Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, from June 2007 to July 2008, and the baseline serum levels of HBV DNA, HBV RNA, HBsAg, and HBcrAg were analyzed. The t -test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Spearman method was used for correlation analysis. A Cox regression model was established to calculate HBeAg seroconversion prediction score, and the time-dependent receiver operating characteristic curve was used to evaluate the ability of combined markers in predicting HBeAg seroconversion. The Kaplan-Meier method was used to calculate cumulative seroconversion rate in each group, and the Log-rank test was used for comparison between groups. Results For the 83 HBeAg-positive patients, the median follow-up time was 108 months, and 44.58%(37/83) of these patients achieved HBeAg seroconversion. Compared with the non-seroconversion group, the HBeAg seroconversion group had significantly lower baseline serum levels of HBV DNA [6.23(1.99-9.28) log 10 IU/mL vs 7.69(2.05-8.96) log 10 IU/mL, Z =-2.345, P =0.019] and HBV RNA [4.81(1.40-7.53) log 10 copies/mL vs 6.22(2.00-8.49) log 10 copies/mL, Z =-1.702, P =0.010], and there were no significant differences in the levels of HBsAg and HBcrAg between the two groups ( P > 0.05). The Cox regression equation constructed based on the above serum markers showed a median score of 0.95(range 0.37-3.45) for predicting HBeAg seroconversion. In the total population, the combined score was negatively correlated with HBsAg, HBV DNA, HBV RNA, and HBcrAg ( r =-0.697, -0.787, -0.990, and -0.819, all P < 0.001). Based on the median prediction score, the patients were divided into high HBeAg seroconversion group and low HBeAg seroconversion group; as for the prediction of HBeAg seroconversion rate at 36, 60, and 84 months, the high HBeAg seroconversion group had a seroconversion rate of 43.90%, 51.20%, and 63.10%, respectively, while the low HBeAg seroconversion group had a seroconversion rate of 9.60%, 17.00%, and 19.8%, respectively, and there was a significant difference between the two groups ( χ 2 =11.6, P < 0.001). Conclusion The combined prediction score based on baseline serum HBV markers can predict HBeAg seroconversion in CHB patients treated by nucleos(t)ide analogues.

Multi-centre survey and analysis of individual therapy of antimicrobial agents in children / 中国药房

OBJECTIVE To investigate the development of individual therapy of antimicrobial agents in pediatric patients. METHODS A questionnaire survey was conducted to investigate the individual therapy of antimicrobial agents in 30 children’s hospitals and pediatric departments of general hospitals in China. The survey data was analyzed statistically by Microsoft Excel 2007 and SPSS 26.0 software. RESULTS In this survey， 75 questionnaires were collected， and 53 of them were valid with an effective rate of 70.7%. The results showed that 86.7% （26/30） of the hospitals carried out individual therapy of antimicrobial agents in different forms. Clinical needs primarily contributed to the individual therapy in these hospitals， while the insufficient personnel and equipment were the biggest obstacles for individual therapy. The proportions of hospitals， who implemented evidence- based pharmacy， therapeutic drug monitoring （TDM）， model-informed precision dosing （MIPD） and antimicrobial-related genetic tests were 70.0%， 80.0%， 30.0% and 33.3%， respectively. Various detection methods of TDM were carried out in various hospitals， and the antimicrobial agents which needed TDM focused on vancomycin and voriconazole. Moreover， nearly half of pharmacists did not know much about MIPD. CONCLUSIONS At present， TDM is the main way to develop individual therapy of antimicrobial agents in various hospitals， but its monitoring coverage and testing standards need to be improved. MIPD and antimicrobial-related gene tests still need to be further promoted in clinical practice.

Study on environmental residues detection and cleaning method of 15 cytotoxic antineoplastic drugs in PIVAS of our hospital / 中国药房

OBJECTIVE To provide a method to reduce environmental residues for pharmacy intravenous admixture service （PIVAS）， and ensure the occupational health of medical staff. METHODS The residues of 15 cytotoxic antineoplastic drugs such as gemcitabine were detected by UPLC-Q-Orbitrap-HRMS. The cleaning process was optimized with the residual quantity as the index. Nitrogen blowing method was used for alcohol volatilization experiment. CCK-8 assay was used to detect the effect of chlorine-containing disinfectant on the toxicity of cytotoxic antitumor drugs. RESULTS The linear range of 15 cytotoxic antineoplastic drugs such as gemcitabine were 0.5-1 000 ng/mL. RSDs of intra-day and intra-day precision were no higher than 20.00%. Six drugs including gemcitabine， isocyclophosphamide and cyclophosphamide were detected in the PIVAS environment of our hospital， and the residue of cyclophosphamide was relatively high. The optimal cleaning procedure was cleaning once with water + cleaning once with 1 000 mg/L chlorine-containing disinfectant + cleaning once with 75% alcohol， wiping with dry gauze method. The results of alcohol volatilization test showed that there was no significant difference in drug residues between control group and 75% alcohol group （P＞0.05）. The results of CCK-8 test showed that compared with control group， the survival rates of the cells treated with 15 cytotoxic antineoplastic drugs were decreased significantly （P＜0.01）； the survival rates of the cells treated with 15 cytotoxic antineoplastic drugs+chlorine-containing disinfectant were significantly higher than those treated with 15 cytotoxic antineoplastic drugs （P＜0.01）. CONCLUSIONS A method for the simultaneous determination for residues of 15 cytotoxic antineoplastic drugs such as gemcitabine in PIVAS is successfully established； the optimal cleaning procedure can significantly reduce the residues of drugs， the use of chlorine- containing disinfectant can significantly reduce the toxicity of drug， and the residual drugs will not cause secondary contamination of the operating area with alcohol volatilization.

Value of hepatic venous pressure gradient in preoperative evaluation and prognosis prediction in liver transplant recipients / 器官移植

Hepatic venous pressure gradient (HVPG) is the "gold standard" for the diagnosis of portal hypertension, which could be applied in the evaluation of liver cirrhosis. Combined use of HVPG with model for end-stage liver disease (MELD) scoring system may more accurately match the donors and recipients undergoing liver transplantation for liver cirrhosis, select the appropriate timing of surgery, and provide guidance for bridging treatment for patients on the waiting list for liver transplantation. Besides, HVPG may also predict clinical prognosis of liver transplant recipients, and provide evidence for early detection and intervention of potential complications. Therefore, the value of HVPG in preoperative evaluation and prognosis prediction of liver transplant recipients was reviewed, aiming to provide guidance for clinical diagnosis and treatment of liver transplant recipients before and after surgery.

Microvascular perfusion characteristics of breast cancer by contrast-enhanced ultrasound and its comparison with pathology / 中国医师进修杂志

Objective:To study the characteristics of tumor microvascular perfusion by contrast-enhanced ultrasound (CEUS) in patients with breast cancer, and to analyze its relationship with pathology.Methods:The clinical data of 180 breast cancer patients admitted to Tangshan People′s Hospital from February 2019 to March 2021 were retrospectively analyzed. They were examined by contrast-enhanced ultrasound before surgery, and the specimens were sent for pathological biopsy after surgery. The characteristics of tumor microvascular perfusion under CEUS were observed, and the correlation between the characteristics and pathological classification and grade were analyzed.Results:The results of the CEUS showed that the contrast agentrapid infusion was 47.78%(86/180), slowly filled was 60.00%(108/180), the mass showed hyperenhancement when the contrast agent reached its peak was 42.78%(77/180), the contrast agent slowly withdrew was 42.78% (77/180), and the contrast agent retention in clearance was 65.56% (118/180). Pathological biopsy revealed that among 180 patients, 16 patients (8.89%) were non-invasive carcinoma, 41 patients (22.78%) were invasive lobular carcinoma, 88 patients (48.89%) were invasive ductal carcinoma, 10 patients (5.56%) were mucinous adenocarcinoma, 11 patients (6.11%) were medullary carcinoma, 8 patients (4.44%) were squamous carcinoma, 6 patients (3.33%) were hard carcinoma (3.33%). There was no correlation between tumor microvascular perfusion characteristics and pathological classification under CEUS ( P>0.05). Pathological biopsy showed that 95 patients (52.78%) were grade Ⅰ, 49 patients (27.22%) were gradeⅡand 36 patients (20.00%) were grad Ⅲ. There was a certain correlation between tumor microvascular perfusion characteristics and pathological grade under CEUS ( P<0.05). Conclusions:There is a certain relationship between tumor microvascular perfusion characteristics detected by CEUS and pathological grading in patients with breast cancer. Analysis of the microvascular perfusion characteristics can provide an important basis for pathological grading.

Inhibitory effect of miR-497 on the repair of diabetic mice corneal epithelial damage by targeting wnt3a / 中华实验眼科杂志

Objective:To investigate the inhibitory effect of miR-497 on the corneal epithelial healing in diabetic mice and its possible mechanism.Methods:Forty healthy clean-grade wild-type C57BL/J6 mice were randomly divided into a blank control group and a model control group, with 20 mice in each group.Another 20 CRISPR/Cas9-mediated miR-497 knockout mice and miR-497 overexpression mice were taken as miR-497 knockout and miR-497 overexpression groups, respectively.The diabetes model was constructed by continuous intraperitoneal injection of streptozotocin (STZ) to the mice in model control, miR-497 knockout and miR-497 overexpression groups, and the mice in blank control group were injected with an equal amount of citrate buffer, followed by 8-week normal feeding.After the establishment of diabetes model, the corneal epithelial injury model was further constructed by scraping off part of the corneal epithelium with a central diameter of 2 mm.The corneal epithelial defect area of mice in 0, 12, 24 and 36 hours after corneal epithelial injury was observed by corneal fluorescein sodium staining.The expression of Wnt3a and β-catenin proteins in mice corneal tissues was detected by Western blot.The expression of miR-497 as well as the mRNA expression levels of cell proliferation-associated factor genes CyclinD1, c-Myc, and Ki-67 mRNA was detected by real-time quantitative fluorescence PCR.The targeting relationship between miR-497 and wnt3a was detected by a dual luciferase reporter gene assay.Human corneal epithelial cells (HCEC) were cultured in vitro and transfected with miR-497 mimics, miR-497 mimics negative control, miR-497 inhibitor, and miR-497 inhibitor negative control by Lipo8000 as miR-497 mimics group, mimics negative control group, miR-497 inhibitor group, andmiR-497 inhibitor negative control group, respectively, all of which were cultured in high glucose medium containing 25% glucose.Another two groups of HCEC were taken and cultured in medium containing 5% and 25% glucose as control and high glucose groups, respectively.The cell proliferation viability was determined by CCK8 method.The use and care of animals complied ith the ARVO statement.The study protocol was approved by the Ethics Committee of Renmin Hospital of Wuhan University (2019K-K010). Results:Eight weeks after STZ injection, the blood glucose of mice was significantly higher and the weight was significantly lower in each diabetic model group than those of blank control group (all at P<0.05). At 12, 24 and 36 hours after the corneal epithelial injury, the percentages of corneal epithelial defect area observed by slit-lamp microscopy in model control group were significantly higher than those in blank control group and miR-497 knockout group and lower than those in miR-497 overexpression group, and the differences were statistically significant (all at P<0.05). The relative expressions of wnt3a and β-catenin proteins in the corneal tissues of model control group were significantly lower than those of blank control group and miR-497 knockout group, but higher than those of miR-497 overexpression group, and the differences were statistically significant (all at P<0.05). The relative expressions of CyclinD1, c-Myc and Ki-67 mRNA in model control group were lower than those in miR-497 knockout group, but higher than those in miR-497 overexpression group, and the differences were statistically significant (all at P<0.05). The relative expression of miR-497 in model control group, miR-497 knockout group and miR-497 overexpression group was 1.00±0.02, 0.63±0.06 and 1.48±0.03, respectively, with a statistically significant difference ( F=19.62, P<0.01). The luciferase activity of miR-497-5p mimics group in wild-type wnt3a transfected cells was lower than that of miR-497-5p negative control group and empty vector group, and the differences were statistically significant (all at P<0.05). In the mutant wnt3a transfected cells, there was no significant difference in the luciferase activity among various groups ( F=0.73, P=0.59). The cell proliferation A value of high glucose group was 0.59±0.03, which was significantly lower than 0.59±0.03 of normal control group and 0.88±0.08 of miR-497 inhibitor group, but significantly higher than 0.48±0.11 of miR-497 mimics group (all at P<0.05). Conclusions:The silencing of miR-497 may promote the repair of diabetic corneal epithelial defects by targeting wnt/β-catenin pathway.

Inhibitory effect of miR-497 on corneal neovascularization and its regulation mechanism targeting STAT3 / 中华实验眼科杂志

Objective:To investigate the role of microRNA (miR)-497 in the formation of corneal neovascularization (CNV) induced by alkali burn and its mechanism.Methods:Forty-two wild type (WT) C57BL/6 mice aged 6 to 8 weeks, 42 CRISPR/Cas9 mediated miR-497 knockout (KO) and 42 CRISPR/Cas9 mediated overexpression transgenic (TG) C57BL/6 mice were selected and assigned as WT group, KO group and TG group, respectively.The corneal alkali burn model was established.At 3, 7, 14 and 21 days after modeling, corneal epithelium damage and stromal turbidity were scored according to slit lamp microscopy.The area of neovascularization was measured.Corneal structural changes and expression of inflammatory cells were observed by histopathological staining.The expression of CD31 in corneal tissues was detected by immunohistochemistry staining.The targeted binding relationship between miR-497 and signal transducer and activator of transcription 3 (STAT3) was detected by luciferase reporter assay.The relative expressions of miR-497, vascular endothelial growth factor A (VEGFA), tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β and macrophage inflammatory protein (MCP)-1 mRNA were detected by real-time quantitative PCR.At 14 days following modeling, the expression of STAT3 and p-STAT3 proteins in mice corneal tissues was detected by Western blot.The use and care of animals complied with the ARVO statement.The study protocol was approved by the Ethics Committee of Renmin Hospital of Wuhan University (No.2019K-K010).Results:Corneal injury, inflammatory cell infiltration and CNV occurred in mice cornea after alkali burn.Corneal epithelial injury score, corneal stromal turbidity score and CNV area increased first and reached the peak on the 14th day after modeling, and then decreased.There were significant differences in corneal epithelial injury score, corneal stromal turbidity score, CNV area and number of CD31-positive cells among various time points after alkali burn ( Fgroup=49.19, 34.56, 44.56, 77.56; all at P<0.01; Ftime=51.62, 65.62, 71.32, 46.12; all at P<0.01). Corneal epithelial injury score, corneal stromal turbidity score, CNV area and the number of CD31-positive cells were greater in KO group at various time points than in WT and TG groups, and those in WT group were greater than in TG group (all at P<0.05). In WT STAT3 co-transfected cells, the luciferase activity of the miR-497 group was significantly lower than that of the miR-negative control group and normal control group (both at P<0.05). In mutant STAT3-transfected cells, there was no significant difference in luciferase activity among all groups ( F=0.69, P=0.56). On the 14th day after modeling, the relative expression levels of miR-497 in corneal tissue of WT, KO and TG groups were 0.68±0.11, 0.41±0.06 and 1.05±0.14, respectively, which were significantly lower than 1.00±0.04, 0.56±0.07 and 1.34±0.11 before modeling (all at P<0.01). The relative expressions of STAT3 and p-STAT3 were higher in KO group than in WT and TG groups, and were lower in TG group than in WT group, and the differences were statistically significant (all at P<0.05). The expressions of VEGFA, TNF-α, IL-6, IL-1β and MCP-1 mRNA at various time points after modeling in various groups were significantly higher than before modeling, which were higher in KO group than in WT and TG groups and were lower in TG group than in WT group, and the differences were statistically significant (all at P<0.01). Conclusions:MiR-497 inhibits corneal inflammation and CNV formation induced by alkali burn.It might inhibit the activation of the inflammation signal pathway via targeting STAT3.

Thoughts of syndrome differentiation and treatment of precancerous lesions of chronic atrophic gastritis based on the theory on hidden pathogen / 国际中医中药杂志

Precancerous lesions of gastric cancer (PLGC) is a pathological change accompanied by intestinal metaplasia and dysplasia on the basis of chronic atrophic gastritis. It is also an important stage of "inflammation-cancer transformation" on gastric mucosa. Paying attention to the intervention of PLGC has important value and significance for the secondary prevention of gastric cancer. PLGC has the characteristics of occult onset, toxin damaging collaterals, and long course of disease, which is highly consistent to the pathogenesis characteristics of incubative pathogenic factors. Based on the relevance of incubative pathogenic factors and PLGC, treatment of PLGC from the perspective of incubative pathogenic factors should be mainly strengthening the spleen and stomach, and combined with the methods of regulating qi and dissipating dampness, and removing blood stasis and detoxification. It should also pay attention to the prognosis.Paying attention to the body-mind treatment can reduce the re-occurrence , so as to provide a new way of thinking for treating PLGC from incubative pathogenic factors.

Analysis of the molecular mechanism of Indigo Naturalis in the treatment of ulcerative colitis based on GEO Chip and network pharmacology / 国际中医中药杂志

Objective:The mechanism of Indigo Naturalis in the treatment of ulcerative colitis (UC) was predicted by GEO chip combined with network pharmacology, and preliminarily verified by molecular docking. Methods:The main active components and targets of Indigo Naturalis were obtained by searching TCMSP, SymMap database, SwissTargetPrediction and Pharmmapper. The UC disease targets were obtained from DrugBank database, OMIM database, TTD database, Disgenet database and GEO gene chips. Venn diagram was used to show drug-disease common targets. The protein-protein interaction (PPI) network of intersection targets was analyzed by String platform, and Cytoscape 3.8.2 software was used to construct the PPI network of components and disease targets. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed on the core targets. AutoDock Vina 1.2.1 was used for molecular docking, and the results were visualized by Discovery studio Visualizer. Results:A total of 10 active components and 184 compound targets of IN-UC, of which 42 were core targets, were enriched and analyzed by GO and KEGG. The therapeutic effect of Indigo Naturalis on UC may involve activation of various process, such as reactive oxygen species metabolism, heme binding, protein phosphatase binding, secretory granule exocytosis, cytoplasmic vesicles, cell focal adhesion and cell substrate connection, and regulates PI3K/Akt signal pathway, human cytomegalovirus infection signal pathway, EB virus infection signal pathway HF1 signaling pathway and insulin resistance signaling pathway to treat UC. Conlusion:Indigo Naturalis has the characteristics of multi-component, multi target and multi pathway in the treatment of ulcerative colitis. Through PTGS2, CAT and other core targets, it can regulate PI3K/Akt signal pathway, human giant cell signal pathway, HIF-1 signal pathway to play a therapeutic role.