A biocompatible double-crosslinked gelatin/ sodium alginate/dopamine/quaterniazed chitosan hydrogel for wound dressings based on 3D bioprinting technology.

438Severe skin injuries can cause serious problems, which could affect the patient's normal life, if not dealt properly in a timely and effective manner. It is an urgent requirement to develop personalized wound dressings with excellent antibacterial activity and biocompatibility to match the shape of the wound to facilitate clinical application. In this study, a bioink (GAQ) based on gelatin (Gel)/sodium alginate (SA)/ quaternized chitosan (QCS) was prepared, and GAQ hydrogel dressing grafting with dopamine (GADQ) was fabricated by an extrusion three-dimensional (3D) printing technology. QCS was synthesized by modifying quaternary ammonium group on chitosan, and its structure was successfully characterized by nuclear magnetic resonance (1H NMR) and Fourier-transform infrared spectroscopy (FT-IR). Our results showed that the GADQ hydrogel dressing that was double-crosslinked by EDC/ NHS and Ca2+ had good tensile strength, considerable swelling ratio, and effective antioxidation properties. It also showed that GADQ1.5% had 93.17% and 91.06% antibacterial activity against Staphylococcus aureus and Escherichia coli, respectively. Furthermore, the relative survival ratios of fibroblast cells seeded on these hydrogels exceeded 350% after cultured for 7 days, which proved the biocompatibility of these hydrogels. Overall, this advanced 3D-printed GADQ1.5% hydrogels with effective antioxidation, excellent antibacterial activity and good biocompatibility had a considerable application potential for wound healing.

Bone marrow mesenchymal stem cells upregulate transient outward potassium currents in postnatal rat ventricular myocytes.

Bone marrow mesenchymal stem cell (BMSC) transplantation has been shown to effectively improve cardiac function in experimental animals and patients with myocardial infarction and heart hypertrophy. BMSCs exert potent effects on cardiomyocytes through the inhibition of cardiac apoptosis, the attenuation of cardiac inflammation, etc. However, novel biological actions of BMSCs on cardiomyocytes remain to be explored. The present study was designed to investigate whether BMSCs affect electrophysiological features of neonatal rat ventricular myocytes (NRVMs). BMSCs and NRVMs were indirectly co-cultured at a ratio of 1:10 with a semi-permeable membrane. We found that compared with mono-cultured NRVMs, co-cultured NRVMs exhibited an obvious increase of transient outward potassium current (I(to)), accompanied by significant changes in activation, inactivation and recovery of I(to). Meanwhile, K(V)4.2 mRNA which encodes the channel carrying I(to) was more abundant in co-cultured NRVMs than mono-cultured NRVMs. The increases in basic fibroblast growth factor (bFGF) and insulin growth factor-1 (IGF-1) levels were observed in culture medium of BMSCs. bFGF but not IGF-1 upregulated the K(V)4.2 mRNA expression and enhanced I(to) currents. Taken together, we conclude that BMSCs upregulate I(to) of NRVMs, at least partially, by secreting bFGF that in turn upregulates K(V)4.2 expression and alters the kinetics of I(to).

Characteristics of cerebral cortex activation in different swallowing periods based on near-infrared spectroscopy / 中国康复理论与实践

ObjectiveTo explore the cerebral cortex activation in different swallowing periods using functional near-infrared spectroscopy (fNIRS). MethodsFrom October to December 2023, a total of 18 healthy adults were recruited to perform four tasks of visual stimulation, chewing, tongue tip sliding and repeated swallowing during fNIRS acquisition, to calculate the cortical activation β values covering a total of 41 channels in frontal, parietal and occipital lobes. ResultsDuring the preoral period, the bilateral pre-motor and supplementary motor cortex (PSMC), bilateral inferior prefrontal gyrus, right visual association cortex (AVC), and left primary motor cortex (PMC) were significantly activated (P < 0.05). During oral preparation, the right pars triangularis (PTG), right frontal polar area (FPA), right dorsolateral prefrontal cortex (DPC), left primary somatosensory cortex (PSC), left PSMC and left PMC were significantly activated (P < 0.05). During the transition between oral and pharyngeal phases, bilateral PSMC and bilateral PMC were significantly activated (P < 0.05). Bilateral PSC, bilateral PTG, bilateral FPA, bilateral orbitofrontal area, bilateral PSMC, bilateral DPC and bilateral PMC were significantly activated during two consecutive periods of oral and pharyngeal phases (P < 0.05). ConclusionThe swallowing movement requires the coordination of the frontal, parietal and occipital cortex. The main activated brain areas are different in different swallowing stages, and the PSMC and PMC are involved in most swallowing stages.

Study on clinical characteristics of PALB2 gene-related breast cancer / 肿瘤研究与临床

Objective:To explore the clinical characteristics of breast cancer patients with PALB2 gene mutation.Methods:Data of 2030 female patients with early-stage breast cancer admitted to the Cancer Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College from July 2015 to July 2019 were retrospectively analyzed, and the patients were all from Genetic Investigation of Inherited & Familial Tumor Syndrome study cohort (GIFTS study, clinical trial registration number: ChiCTR1900024050). All these patients underwent the panel-based next-generation sequencing (NGS) on all the exons 50 cancer predisposition genes including BRCA1, BRCA2, PALB2, etc. The patients were divided into the PALB2 gene mutation group and the non-mutation carriers group according to the results of genetic testing. Furthermore, the clinicopathological characteristics were compared between the two groups, and their compliance of the National Comprehensive Cancer Network (NCCN) genetic testing criteria were also evaluated.Results:Among 2 030 patients with breast cancer, 184 patients (9.06%) harbored pathogenic germline variants, including 22 cases (1.08%) with PALB2 gene mutation and 1 666 cases (82.07%) without gene mutation. Patients with PALB2 gene mutation were at younger ages of onset than the non-mutation carriers group [(39±7) years old vs. (43±9) years old, t = -2.40, P = 0.016] and had higher proportion of early-onset breast cancer (age of onset < 35 years old) than the non-mutation carriers group [31.82% (7/22) vs. 14.83% (247/1 666), χ2 = 4.90, P = 0.036]. Patients with PALB2 gene mutation presented more positive family histories of pancreatic cancer than the non-mutation carriers group [9.09% (2/22) vs. 1.44% (24/1 666), χ2 = 8.38, P = 0.044], higher proportion of histological grade Ⅱ [85.00% (17/20) vs. 61.25% (811/1 324), χ2 = 4.70, P = 0.036], more hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative patients [86.36% (19/22) vs. 63.53% (1 040/1 637), χ2 = 4.90, P = 0.026], and less HR-positive and HER2-positive patients [0 (0) vs. 16.62% (272/1 637), P = 0.037]. Among 22 patients with PALB2 gene mutation, 18 (81.82%) met the NCCN genetic testing criteria for hereditary breast cancer; among 1 666 patients without gene mutation, 1 166 (69.99%) met the NCCN genetic testing criteria for hereditary breast cancer, and the difference was not statistically significant ( χ2 = 1.45, P = 0.347). Conclusions:The Chinese patients with PALB2 gene-related breast cancer have shown distinct clinical characteristics and genetic etiology. However, a more accurate screening criterion for identifying hereditary breast cancer is still needed in clinical practice.

Association between the severity of hypodontia and the characteristics of craniofacial morphology in a Chinese population: A cross-sectional study / 대한치과교정학회지

Objective@#To investigate craniofacial differences in individuals with hypodontia and explore the relationship between craniofacial features and the number of congenitally missing teeth. @*Methods@#A cross-sectional study was conducted among 261 Chinese patients (males, 124; females, 137; age, 7–24 years), divided into four groups (without hypodontia: no teeth missing, mild: one or two missing teeth, moderate: three to five missing teeth, severe: six or more missing teeth) according to the number of congenitally missing teeth. Differences in cephalometric measurements among the groups were analyzed. Further, multivariate linear regression and smooth curve fitting were performed to evaluate the relationship between the number of congenitally missing teeth and the cephalometric measurements. @*Results@#In patients with hypodontia, SNA, NA-AP, FH-NA, ANB, Wits, ANS-Me/N-Me, GoGn-SN, UL-EP, and LL-EP significantly decreased, while Pog-NB, AB-NP, N-ANS, and S-Go/N-Me significantly increased. In multivariate linear regression analysis, SNB, Pog-NB, and S-Go/N-Me were positively related to the number of congenitally missing teeth. In contrast, NA-AP, FH-NA, ANB, Wits, N-Me, ANS-Me, ANS-Me/N-Me, GoGn-SN, SGn-FH (Y-axis), UL-EP, and LL-EP were negatively related, with absolute values of regression coefficients ranging from 0.147 to 0.357. Further, NA-AP, Pog-NB, S-Go/N-Me, and GoGn-SN showed the same tendency in both sexes, whereas UL-EP and LL-EP were different. @*Conclusions@#Compared with controls, patients with hypodontia tend toward a Class III skeletal relationship, reduced lower anterior face height, flatter mandibular plane, and more retrusive lips. The number of congenitally missing teeth had a greater effect on certain characteristics of craniofacial morphology in males than in females.

Clinical analysis of adult oculomoclonus-myoclonus syndrome with vertigo / 中华内科杂志

The clinical manifestation, physical and laboratory examination, electrophysiological, and imaging data of 2 female adult OMS patients with vertigo were analyzed at the Department of Neurology of the First Medical Center of Chinese PLA General Hospital from February 2021 to March 2022. The treatment strategy and clinical outcome were followed up. The two female patients were aged 42 and 66 years. Anti-NMDA receptor antibody and anti-GABAB receptor antibody were detected in serological screening, respectively. The two patients met the diagnostic criteria for OMS, and one was screened for breast tumor. The clinical symptoms of the two patients were relieved after immunomodulation therapy. OMS is a group of rare clinical syndromes; its clinical evaluation process should be standardized and the etiology should be actively searched for.

Effect of ixazomib combination treatment therapies on multiple myeloma and the prognostic influencing factors / 肿瘤研究与临床

Objective:To explore the efficacy of ixazomib combination treatment therapies for multiple myeloma (MM), and the influencing factors of prognosis.Methods:The clinical data of 80 MM patients admitted to Yancheng Third People's Hospital from January 2020 to January 2022 were retrospectively analyzed. All patients received 3 courses of ixazomib combination treatment therapies (28 d was 1 course). All combination treatment therapies included ID group (ixazomib + dexamethasone, 11 cases) and ID + immunomodulator group (ixazomib + dexamethasone + lenalidomide/thalidomide, 50 cases), ID + other chemotherapy drugs group (ixazzomib + dexamethasone + doxorubicin liposome/cyclophosphamide/bendamustine, 19 cases). The clinical efficacy of patients in different treatment regimens was compared, and the prognosis was followed up and recorded. The clinical characteristics between the survival and the dead patients were compared. Cox proportional risk model was used to make multivariate analysis of the overall survival of MM patients receiving ixazomib combination therapies.Results:The treatment was effective in 9 cases (81.82%) of the ID group, 32 cases (64.00%) of the ID + immunomodulator group, and 9 cases (47.37%) of the ID + other chemotherapy drugs group. There was no statistically significant difference in the effectiveness rate of 3 ixazomib combination regimens ( χ2 = 0.62, P = 0.432). All patients were followed up for 5 to 20 months, with an average follow-up time of (15±4) months. There were statistically significant differences in immunoglobulin type, Durie-Salmon stage, early treatment line and therapeutic efficacy between the survival group (49 cases) and the death group (31 cases) (all P < 0.05). Multivariate Cox regression analysis showed that the clinical effectiveness (effectiveness vs. ineffectiveness: OR = 0.242, 95% CI 0.103-0.567, P = 0.001) and the previous first-line treatment (the first-line vs. the other lines: OR = 0.577, 95% CI 0.452-0.736, P < 0.001) were independent protective factors for the overall survival of MM. Conclusions:The 3 ixazomib combination therapies have a certain efficacy in the treatment of MM; ID regimen has the best clinical efficacy and survival. The clinical effectiveness and the previous first-line treatment are independent protective factors for the survival of MM.

Steroids and dihydroisocoumarin glycosides from Xylaria sp. by the one strain many compounds strategy and their bioactivities / 中国天然药物

The fungus Xylaria sp. KYJ-15 was isolated from Illigera celebica. Based on the one strain many compounds (OSMAC) strategy, the strain was fermented on potato and rice solid media, respectively. As a result, two novel steroids, xylarsteroids A (1) and B (2), which are the first examples of C28-steroid with an unusual β- and γ-lactone ring, respectively, along with two new dihydroisocoumarin glycosides, xylarglycosides A (3) and B (4), were identified. Their structures were elucidated by spectroscopic methods, X-ray diffraction and electronic circular dichroism (ECD) experiments. All isolated compounds were evaluated for cytotoxicity, DPPH radical scavenging activity, acetylcholinesterase inhibitory and antimicrobial effect. Compound 1 exhibited potent AChE inhibitory activity with an IC50 value of 2.61 ± 0.05 μmol·L-1. The β-lactone ring unit of 1 is critical for its AChE inhibitory activity. The finding was further confirmed through exploring the interaction of 1 with AChE by molecular docking. In addition, both compounds 1 and 2 exhibited obvious antibacterial activity against Bacillus subtilis with a minimum inhibitory concentration (MIC) of 2 μg·mL-1. Compounds 3 and 4 exhibited antibacterial activities against Staphylococcus aureus with MICs of 4 and 2 μg·mL-1, respectively, which also exhibited DPPH radical scavenging activity comparable to the positive control with IC50 values of 9.2 ± 0.03 and 13.3 ± 0.01 μmol·L-1, respectively.

CRISPR-assisted transcription activation by phase-separation proteins

The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system has been widely used for genome engineering and transcriptional regulation in many different organisms. Current CRISPR-activation (CRISPRa) platforms often require multiple components because of inefficient transcriptional activation. Here, we fused different phase-separation proteins to dCas9-VPR (dCas9-VP64-P65-RTA) and observed robust increases in transcriptional activation efficiency. Notably, human NUP98 (nucleoporin 98) and FUS (fused in sarcoma) IDR domains were best at enhancing dCas9-VPR activity, with dCas9-VPR-FUS IDR (VPRF) outperforming the other CRISPRa systems tested in this study in both activation efficiency and system simplicity. dCas9-VPRF overcomes the target strand bias and widens gRNA designing windows without affecting the off-target effect of dCas9-VPR. These findings demonstrate the feasibility of using phase-separation proteins to assist in the regulation of gene expression and support the broad appeal of the dCas9-VPRF system in basic and clinical applications.

Establishment and validation of a multigene model to predict the risk of relapse in hormone receptor-positive early-stage Chinese breast cancer patients / 中华医学杂志(英文版)

BACKGROUND@#Breast cancer patients who are positive for hormone receptor typically exhibit a favorable prognosis. It is controversial whether chemotherapy is necessary for them after surgery. Our study aimed to establish a multigene model to predict the relapse of hormone receptor-positive early-stage Chinese breast cancer after surgery and direct individualized application of chemotherapy in breast cancer patients after surgery.@*METHODS@#In this study, differentially expressed genes (DEGs) were identified between relapse and nonrelapse breast cancer groups based on RNA sequencing. Gene set enrichment analysis (GSEA) was performed to identify potential relapse-relevant pathways. CIBERSORT and Microenvironment Cell Populations-counter algorithms were used to analyze immune infiltration. The least absolute shrinkage and selection operator (LASSO) regression, log-rank tests, and multiple Cox regression were performed to identify prognostic signatures. A predictive model was developed and validated based on Kaplan-Meier analysis, receiver operating characteristic curve (ROC).@*RESULTS@#A total of 234 out of 487 patients were enrolled in this study, and 1588 DEGs were identified between the relapse and nonrelapse groups. GSEA results showed that immune-related pathways were enriched in the nonrelapse group, whereas cell cycle- and metabolism-relevant pathways were enriched in the relapse group. A predictive model was developed using three genes ( CKMT1B , SMR3B , and OR11M1P ) generated from the LASSO regression. The model stratified breast cancer patients into high- and low-risk subgroups with significantly different prognostic statuses, and our model was independent of other clinical factors. Time-dependent ROC showed high predictive performance of the model.@*CONCLUSIONS@#A multigene model was established from RNA-sequencing data to direct risk classification and predict relapse of hormone receptor-positive breast cancer in Chinese patients. Utilization of the model could provide individualized evaluation of chemotherapy after surgery for breast cancer patients.

Recent advance in circulating micro RNAs as biomarkers in intracranial aneurysm / 中华神经医学杂志

Micro RNAs in body fluids, enjoying convenient collection and less invasion, have the potential of being biomarkers of intracranial aneurysm (IA), and are suitable for early screening and rupture prediction of IA. The stable micro-RNAs (circulating micro RNAs) in serum, plasma and other body fluids are involved in regulating the functions of vascular smooth muscle cells and endothelial cells, and play important roles in pathophysiological process of IA progression. In this paper, the current research progress of circulating micro RNAs as biomarkers in the early diagnosis, rupture prediction and prognoses of IA are summarized as follows.

Clinical observation of diaphragm plication after pediatric congenital heart disease surgery / 中国小儿急救医学

Objective:To analyze the risk factors of performing diaphragm plication(DPL) after congenital heart disease(CHD) surgery as well as the timing and clinical efficacy.Methods:Data regarding children underwent open heart surgery at Shanghai Children′s Medical Center from January 2017 to December 2019 were reviewed.According to whether DPL was performed after CHD operation or not, the children were divided into DPL group and non-diaphragm plication(NDPL)group.Clinical data including age, surgery, cardiopulmonary bypass(CPB)temperature and time of two groups were compared, meanwhile the risk factors of DPL surgery were analyzed.Based on the median of 8 days between open heart surgery and DPL, children in DPL group were divided into early surgery group(less than 8 days), and delayed operation group(no less than 8 days). The parameters of comparison included ventilator using time, hospital stay time, hospitalization expenditure, postoperative infection to evaluate the timing of DPL and effect.Results:There were 10 309 children after CHD, including 95 in DPL group and 10 214 in NDPL group.In DPL group, there were 52 males(54.7%) and 43 females(45.3%), with age 147(52, 318) d, weight(5.5±4.1) kg, height(56.8±25.6) cm, CPB time(136.8±93.4) min and aortic occlusion time(62.5±50.2) min.Compared with NDPL group, DPL group had younger age, shorter height, lighter weight, higher incidence of preoperative special treatment, higher proportion of reoperation, lower CPB temperature, longer CPB time and longer aortic occlusion time.There were significant differences between two groups( P<0.05). Multivariate Logistic regression analysis showed that younger operative age( OR=0.998, 95% CI 0.998~0.999, P<0.001), staging operation( OR=72.977, 95% CI 39.096~136.211, P<0.001), long CPB time( OR=1.006, 95% CI 1.002~1.011, P=0.008), and pulmonary venoplasty( OR=4.219, 95% CI 2.132~8.350, P<0.001) were independent risk factors for DPL after CHD.Early surgery group had lower postoperative infection rate(43.59% vs. 88.38%, P=0.007), shorter ventilator duration[168.0(99.5, 280.5) h vs.309.9(166.2, 644.5) h, P=0.029], shorter hospital stay duration[27.00(20.75, 35.00)d vs.37.00(28.00, 53.00)d, P<0.001], and lower hospitalization cost[158.36(128.99, 203.11) thousand yuan vs.232.95(174.54, 316.47) thousand yuan, P<0.001] than delayed operation group. Conclusion:Younger age, staging operation, long CPB time, and pulmonary venoplasty are independent risk factors for DPL due to diaphragmatic paralysis after pediatric CHD surgery.Early surgical intervention is beneficial for the recovery of children.

Correlation between abnormal left atrial appendage function and thrombotic events in patients with non-valvular atrial fibrillation / 中华内科杂志

Objective:To investigate the association between abnormal left atrial appendage function and thrombotic events in patients with non-valvular atrial fibrillation, and the independent risk factors affecting left atrial appendage function.Methods:Patients with non-valvular atrial fibrillation, who visited the Atrial Fibrillation Center of the First Affiliated Hospital of Xinjiang Medical University from June 1, 2019 to June 1, 2021, were selected. According to left atrial appendage flow velocity (LAAFV), they were divided into normal left atrial appendage function group (297 patients with LAAFV ≥ 40 cm/s) and abnormal left atrial appendage function group (85 patients with LAAFV<40 cm/s). Baseline data and transesophageal echocardiography images were collected from all the patients. The occurrence of thrombotic events was recorded. Univariate and multivariate unconditional logistic regression analyses were conducted to investigate the correlation between abnormal left atrial appendage function and the occurrence of thrombotic events.Results:There were significant differences in gender, type of atrial fibrillation, CHA 2DS 2-VASc score, anticoagulant therapy, total cholesterol, low-density lipoprotein cholesterol, international normalized ratio (INR), left atrial diameter, proportion of patients with right atrial enlargement, left ventricular ejection fraction, inner diameter, sum of inner diameter, depth, and sum of depth of all angles of the left atrial appendage, and incidence of thrombotic events between the two groups (all P<0.05). After adjusting for confounders, multivariate unconditional logistic regression analyses showed that abnormal left atrial appendage function was closely associated with thrombotic events (β=1.168 P=0.002), and left atrial diameter ( OR=1.084, 95% CI 1.019-1.153, P=0.011) and persistent atrial fibrillation ( OR=2.323, 95% CI 1.226-4.403, P=0.010) were independent risk factors affecting left atrial appendage function. Conclusions:Abnormal left atrial appendage function is closely associated with thrombosis. The left atrial diameter and persistent atrial fibrillation were independent risk factors affecting left atrial appendage function.

Customized maxillary incisor position relative to dentoskeletal and soft tissue patterns in Chinese women: A retrospective study / 대한치과교정학회지

Objective@#To provide reliable prediction models based on dentoskeletal and soft tissue variables for customizing maxillary incisor positions and to optimize digitalized orthodontic treatment planning. @*Methods@#This study included 244 Chinese women (age, 18–40 years old) with esthetic profiles after orthodontic treatment with fixed appliances (133 in group I: 1° ≤ The angle between the nasion [N]-A point [A] plane and the N-B point [B] plane [ANB] ≤ 4°; 111 in group II: 4° < ANB ≤ 7°). Dental, skeletal, and soft tissue measurements were performed on lateral cephalograms of the participants. Correlation and multiple linear regression analyses were used to determine the influence of dentoskeletal and soft tissue variables on maxillary incisor position. @*Results@#The ideal anteroposterior position of the maxillary incisor varied between sagittal skeletal patterns. The position of the maxillary incisor correlated with the sagittal discrepancy between the maxilla and the mandible (ANB), protrusion of the midface, nasal tip projection, development of the chin, and inclination of both the maxillary and mandibular incisors. Distance from the maxillary central incisor to nasion-pogonion plane predicted using multiple linear regression analysis was accurate and could be a practical measurement in orthodontic treatment planning. @*Conclusions@#Instead of using an average value or norm, orthodontists should customize a patient’s ideal maxillary incisor position using dentoskeletal and soft tissue evaluations.

Effect of exposure to chrysotile on ribosomal DNA copy number variation and DNA damage response / 预防医学

Objective@#To investigate the effect of chrysotile exposure on ribosomal DNA (rDNA) copy number and DNA damage response, so as to provide insights into the mechanism of asbestos-induced carcinogenesis. @*Methods@#Human pleural mesothelial MeT-5A cells were treated with chrysotile suspensions at doses of 1.25, 2.5 and 5 μg/cm2 (low-, medium-, high-dose group), while PBS served as controls. MeT-5A cells were harvested 6, 24, 48 and 72 h post-treatment, and the rDNA copy numbers and the BIRC5, HRAS, GINS4 and RRM2 mRNA expression were determined using a quantitative real-time PCR (qPCR) assay. The apoptosis of MeT-5A cells and DNA damage were detected using Muse cell analyzer. The rDNA copy numbers, DNA damage responses and BIRC5, HRAS, GINS4 and RRM2 mRNA expression were compared in MeT-5A cells treated with different doses of chrysotile suspensions.@*Results@#There were significant differences in 45S rDNA copy numbers among low-, medium-, high-dose groups and the control groups 6, 48 and 72 h post-treatment with chrysotile suspensions, and significantly lower 45S rDNA copy numbers were measured in low-, medium- and high-dose groups than in the control group 6 h post-treatment, while significantly higher 45S rDNA copy numbers were found in the high-dose group than in low- and medium-dose groups 48 and 72 h post-treatment (all P<0.05). There were significant differences in 5S rDNA copy numbers among low-, medium-, high-dose groups and the control groups 24, 48 and 72 h post-treatment with chrysotile suspensions, and significantly lower 5S rDNA copy numbers were measured in medium- and high-dose groups than in the control group 24 and 48 h post-treatment, while significantly lower 5S rDNA copy numbers were found in medium- and high-dose groups than in the low-dose group 24, 72 h post-treatment (all P<0.05). There were significant differences in the overall apoptotic rate of MeT-5A cells among groups at different time points, and the overall apoptotic rate of MeT-5A cells were significantly higher in medium- and high-dose groups than in the control group (all P<0.05), with late-stage apoptosis predominantly detected. There were significant differences in the rates of ATM activation and DNA double-strand break in MeT-5A cells among groups 72 h post-treatment, and higher rates of ATM activation and DNA double-strand break were measured in medium- and high-dose groups than in the control group (all P<0.05). In addition, there were significant differences in the relative mRNA expression of BIRC5, HRAS, GINS4 and RRM2 genes among groups 24 and 48 h post-treatment, and significantly lower BIRC5, HRAS, GINS4 and RRM2 mRNA expression was quantified in medium- and high-dose groups than in the control group (all P<0.05).@*Conclusion@#Exposure to chrysotile may induce rDNA copy number variations and altered expression of nucleolar proteins in human pleural mesothelial cells, which may be involved in the regulation of DNA damage responses.

Practice of the Qualification and Recognition for Orphan Drugs in the World and its Inspiration / 罕见病研究

We have analyzed the current status of recognization and qualification of orphan drugs in China and abroad, looking at the aspects of the authority institutions, identification and qualification process, and the number of orphan drugs identified and available in the market. By comparing and analyzing horizontally the differences in orphan drugs identification between representative developed countries vs. some developing countries, we discuss the inadequacy of orphan drugs supervision in China. We introduce the advanced experience from the developed countries and some developing countries to provide suggestions for the identification and management of orphan drugs, hoping to speed up the process of development and market availability of orphan drugs and to maximize patient's accessibility to treatment in China.

Managing nipple necrosis secondary to inverted nipple repair / 中华医学美学美容杂志

Objective:Nipple inversion is relatively common, occurring in up to 10% of females, various techniques have been described for correction of inverted nipples. However, data are limited on the associated complications. The presented study aimed to assess the management of nipple necrosis after inverted nipple repair.Methods:A retrospective chart review was performed on 25 cases of nipple necrosis after correction of nipple inversion between January 2018 and June 2020. All patients were female. Age ranged from 10 to 37 years with the average of 24.4 years. 13 cases were partial nipple necrosis with retract recurrence, and 12 cases were complete nipple necrosis.Results:The follow-up period was 6 months. All cases achieved primary healing. No infection or nipple necrosis occurred. All patients had satisfactory appearance.Conclusions:Appropriate intervention time, accurate preoperative evaluation and well-performed operation are important factors for the management of nipple necrosis after inverted nipple repair.

Evaluation of methods for monitoring transpulmonary gradien after total cavopulmonary connection surgery / 中国小儿急救医学

Objective:To explore the reliability of estimated transpulmonary gradient(TPG)by comparing the measured TPG with the estimated TPG in echocardiography.Methods:The cardiothoracic surgery database of Shanghai Children′s Medical Center was reviewed.Children with hemodynamic monitoring and ultrasound findings who underwent total cavopulmonary connection between January 2015 and December 2018 were included.TPG was calculated separately according to the formula.Intraclass correlation efficient was used for consistency test.Results:Finally, 27 patients were selected, including 16 males and 11 females with age(4.0±1.6)years old, weight(15.2±3.3)kg and height(99.1±11.2)cm.There were nine cases (33.3%) of right ventricular double outlet and seven cases (25.9%) of pulmonary atresia.For hemodynamic blood monitoring, TPG was 5-16(10.1±3)mmHg, and its echocardiography parameters were estimated as 5.8-20.3(11±3.3)mmHg.The ICC value was 0.117 which was less than 0.4( P=0.277). Conclusion:TPG estimated by total cavopulmonary connection pipe window during perioperative period is inaccurate and higher than actual value, so invasive hemodynamic monitoring is still recommended during perioperative period.

Outcome of extracorporeal membrane pulmonary oxygenation after congenital heart diseases in pediatric: experience from single center / 中国小儿急救医学

Objective:To review the clinical prognosis and causes of death in children with extracorporeal membrane pulmonary(ECMO) assistance after congenital heart disease(CHD) operation in our center, so as to improve the survival rate of ECMO.Methods:All clinical data of 105 children with VA-ECMO assisted after CHD operation who were admitted to the Department of Cardiothoracic Surgery at Shanghai Children′s Medical Center from January 2017 to December 2019 were collected, and the clinical characteristics and causes of death were retrospectively analyzed.Results:The age of 105 children with ECMO was 110(38, 341)days, the weight was 5.30(3.75, 8.45)kg, and the risk adjustment for congenital heart surgery score was 3(2-3)points.There were no statistically significant differences in gender, age, weight, height, risk adjustment for congenital heart surgery score, the number of ECMO installed in the operating room, the number of ECMO installed after cardiopulmonary resuscitation and ECMO duration between the surviving group ( n=51) and the death group ( n=54)( P>0.05). While there was a significant difference in utilization of continuous renal replacement therapy[7.8% (4/51) vs.38.9% (21/54), P<0.001]. The death mainly occurred within one week after evacuating ECMO(83.3%, 45/54). ECMO installation was most in children aged 1 month to 1 year old(52.4%, 55/105), and the survival rate showed a rise over three years(2017 to 2019), increased from 31.6% (6/19) to 65.0% (13/20). Children with 3 to 5 kg were the most affected (39.0%, 41/105) when ECMO was installed, and the survival rate from 2017 to 2019 increased from 28.6%(4/14) to 75.0%(9/12). The main cause of death was heart failure(48.1%, 26/54), followed by bleeding(18.5%, 10/54)and pulmonary hypertension(13.0%, 7/54). Conclusion:With the progress of surgical technology and cardiopulmonary bypass, and the improvement of postoperative management, the mortality of children with CHD in our hospital after ECMO has decreased year by year during the last three years.However, the mortality of children requiring continuous renal replacement therapy assistance during ECMO is higher.Therefore, it is still necessary to strengthen the maintenance of each organ function during ECMO.

Nomogram for predicting axillary lymph node pathological response in node-positive breast cancer patients after neoadjuvant chemotherapy / 中华医学杂志(英文版)

BACKGROUND@#Pathological complete response (pCR) of axillary lymph nodes (ALNs) is frequently achieved in patients with clinically node-positive breast cancer after neoadjuvant chemotherapy (NAC), and ALN status is an important prognostic factor for breast cancer patients. This study aims to develop a new predictive clinical model to assess the ALN pCR rate after NAC.@*METHODS@#This was a retrospective series of 467 patients who had biopsy-proven positive ALNs at diagnosis and underwent ALN dissection from 2007 to 2014 at the National Cancer Center/Cancer Hospital of the Chinese Academy of Medical Sciences. We analyzed the clinicopathologic features of the patients and developed a nomogram to predict the probability of ALN pCR. A multivariable logistic regression stepwise model was used to construct a nomogram to predict ALN pCR in node-positive patients. The adjusted area under the receiver operating characteristic curve (AUC) was calculated to quantify the ability to rank patients by risk. Internal validation was performed using the 50/50 hold-out validation method. The nomogram was externally validated with prospective cohorts of 167 patients from 2016 to 2018 at the Cancer Hospital of the Chinese Academy of Medical Sciences and 114 patients from 2018 to 2020 at Beijing Tiantan Hospital.@*RESULTS@#In this retrospective study, 115 (24.6%) patients achieved ALN pCR after NAC. Multivariate analysis showed that clinical tumor stage (Odds ratio [OR]: 0.321, 95% confidence interval [CI]: 0.121-0.856; P = 0.023); primary tumor response (OR: 0.189; 95% CI: 0.123-0.292; P < 0.001), and estrogen receptor status (OR: 0.530, 95% CI: 0.304-0.925; P = 0.025) were independent predictors of ALN pCR. The nomogram was constructed based on the result of multivariate analysis. In the internal validation of performance of nomogram, the AUCs for the training and test sets were 0.719 and 0.753, respectively. The nomogram was validated in external cohorts with AUCs of 0.720, which demonstrated good discriminatory power in these data sets.@*CONCLUSION@#We developed a nomogram to predict the likelihood of axillary pCR in node-positive breast cancer patients after NAC. The predictive model performed well in multicenter prospective external validation. This practical tool could provide information to surgeons regarding whether to perform additional ALN dissection after NAC.@*TRIAL REGISTRATION@#ChiCTR.org.cn, ChiCTR1800014968.