Application of Whole-Exome Sequencing in the Prenatal Diagnosis of Foetuses With Central Nervous System Abnormalities.

OBJECTIVE: To investigate the clinical value of whole-exome sequencing (WES) in the diagnosis of foetuses with central nervous system (CNS) abnormalities but having a normal karyotyping and chromosomal microarray result. METHOD: During the period of 2016-2022, there were a total of 149 foetuses with CNS abnormalities but having negative karyotyping and chromosomal microarray analysis results; WES was performed on these foetuses and their parents. Variants were classified according to ACMG guidelines, and the association of pathogenic variants with specific types of CNS abnormalities was explored. RESULTS: Among these 149 foetuses, three categories of abnormalities, namely, single CNS abnormality, multiple CNS abnormalities, CNS abnormalities along with other organ system abnormalities were identified, for which the detection rate of P/LP variants is 17.4% (12/69), 28.6% (14/49) and 54.8% (17/31), respectively. CONCLUSION: WES brought about an increase of 28.9% in diagnostic yield in the prenatal evaluation of foetuses with CNS abnormalities but having negative karyotyping and chromosome array results. WES may also be of benefit for the diagnosis of foetuses with isolated CNS abnormalities, as well as for making more informed interpretations of imaging findings and for providing better genetic counselling.

ß-glucan combined with Envafolimab and Endostar as immune rechallenge for metastatic non-small cell lung cancer.

BACKGROUND: Immune checkpoint inhibitor rechallenge has emerged as a prominent study area in non-small cell lung cancer (NSCLC). ß-glucan was reported to reverse resistance to anti-PD-1/PD-L1 inhibitors by regulating the tumor microenvironment. In this self-initiated clinical trial (ChiCTR2100054796), NSCLC participants who have previously failed anti-PD-1 therapy received ß-glucan (500 mg, bid, d1-21), Envafolimab (300 mg, d1) and Endostar (210 mg, civ72h) every 3 weeks until disease progression or unacceptable toxicity. The clinical efficacy and adverse events were observed, while serum samples were collected for proteomic analysis. RESULTS: Twenty Three patients were enrolled from January 2022 to March 2023 (median age, 65 years; male, n = 18 [78.3%]; squamous NSCLC, n = 9 [39.1%]; mutant type, n = 13 [56.5%]). The overall response rate (ORR) was 21.7% and disease control rate (DCR) was 73.9%. Median progression-free survival (mPFS) and median overall survival (mOS) was 4.3 months [95% CI: 2.0-6.6] and 9.8 months [95% CI: 7.2-12.4], respectively. The mPFS between PD-L1 positive and negative subgroup has significant difference (6.3 months vs. 2.3 months, p = 0.002). Treatment-related adverse events (TRAEs) occurred in 52.2% of patients. The most common TRAEs were hypothyroidism (26.1%) and fatigue (26.1%). 2 (8.7%) grade 3 adverse events were reported. No adverse reaction related deaths have been observed. Proteomic analysis revealed that the levels of CASP-8, ARG1, MMP12, CD28 and CXCL5 correlated with resistance to the treatment while the levels of CD40-L and EGF related to the favorable response. CONCLUSION: ß-glucan combined with Envafolimab and Endostar has considerable efficacy and safety for immune rechallenge in metastatic NSCLC patients who failed of anti-PD-1 treatment previously, especially for PD-L1 positive patients.

Association of frailty with adverse outcomes in surgically treated geriatric patients with hip fracture: A meta-analysis and trial sequential analysis.

OBJECTIVE: Some studies have associated frailty and prognostic outcomes in geriatric hip fracture patients, but whether frailty can predict postoperative outcomes remains controversial. This review aims to assess the relationship between frailty and adverse postoperative outcomes in geriatric patients with hip fracture. METHODS: Based on electronic databases, including PubMed, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Library, Chinese National Knowledge Infrastructure, and WanFang Data, we systematically searched for studies that investigated the association between frailty and adverse outcomes among patients aged 60 or over after hip fracture surgery. Stata 17.0 and Trial Sequential Analysis viewer software were used to obtain pooled estimates and verify whether the sample size was sufficient and the evidence robust. RESULTS: Twenty-one studies involving 49,196 patients were included for quantitative analysis. Compared with nonfrail patients, frail patients had a higher risk of inpatient mortality (risk ratio [RR] = 1.93, 95% confidence interval [CI]: 1.66-2.23), 30-day mortality (RR = 2.13, 95% CI: 1.23-3.70), and 1-year mortality (RR = 2.44, 95% CI: 1.47-4.04). Frailty can significantly predict postoperative complications (RR = 1.76, 95% CI: 1.38-2.23), including delirium, pneumonia, cardiac complications, urinary tract infection, and surgical site infection; the association between frailty and deep venous thrombosis/pulmonary embolism and acute kidney injury needs further analysis. Trial sequential analysis showed that the findings regarding mortality were reliable and robust. CONCLUSION: This meta-analysis provides detailed information indicating that frailty is a substantial predictor of mortality and selected postoperative complications.

MOF-derived low Ru-loaded high entropy alloy as an efficient and durable self-supporting electrode in rechargeable liquid/flexible Zn-air batteries.

Exploiting the high-entropy alloy (HEA) electrocatalysts with the synergistic effect of multi-metal components is an effective approach to address the slow kinetics and undesirable stability of the oxygen evolution reaction (OER) in Zn-air batteries (ZABs), but still faces many challenges. In this study, a multimetallic Metal-organic framework (MOF)-derived HEA catalyst was successfully fabricated on carbon fiber as a flexible self-supporting electrode (denoted as CC@FeCoNiMoRu-HEA/C) for high-performance liquid/flexible ZABs using a facile and cost-effective strategy. The three-dimensional (3D) highly open network framework and hierarchical porous structure accelerate the mass transport of OH-/O2 and charge transfer. The electronic structure adjustment, lattice defects and high entropy effects enable the CC@FeCoNiMoRu-HEA/C catalysts to perform high OER catalytic activity and strong durability while reducing the Ru content and lowering the economic cost. In situ Raman spectra and XPS results reveal the generation of metal-OOH intermediates on the HEA surface during the OER process. In a practical demonstration, the liquid ZAB assembled with CC@FeCoNiMoRu-HEA/C + Pt/C as the air electrode offers stable open-circuit voltage, large power density, excellent specific capacity and satisfactory cycle life, outperforming the commercial RuO2 + Pt/C-based reference ZAB. More attractively, the flexible solid-state ZAB also achieves fast dynamic response, high peak power density, robust cycling stability as well as favorable mechanical flexibility, indicating a promising application prospect in future flexible electronics and wearable devices. This work provides a viable pathway to develop low precious metal-loaded HEAs as advanced OER self-supporting electrocatalysts and realize high-performance flexible energy storage devices.

Development and validation of models for predicting mortality in intertrochanteric fracture surgery patients with perioperative blood transfusion: a prospective multicenter cohort study.

BACKGROUND: The association between allogenic blood transfusions and all-cause mortality in surgically treated hip fracture patients with perioperative transfusion (STHFPT) remained unknown. The authors aim to introduce transfusion-related factors, new variables to develop, and validate models to predict mortality in these patients. METHODS: A prospective multicenter cohort study was conducted with STHFPT hospitalized during January 2018 and June 2021. The database was divided into training cohort and validation cohort in a ratio of 70-30% using the randomization method. All participants received a minimum of 2-year follow-up and all participants' overall and eight time-specific survival status were recorded. Prediction models were developed using multivariate logistic regression and Cox regression for variable selection. Model performance was measured by determining discrimination, calibration, overall model performance or precision, and utility. Sensitivity analyses were performed to test robustness of the results. RESULTS: A total of 7074 consecutive patients were prospectively screened and assessed for eligibility to participate. Finally, 2490 patients met our inclusion and exclusion criteria and 1743 (70%) patients were randomized to the training cohort and 747 (30%) to the validation cohort. The median duration of follow-up was 38.4 months (IQR 28.0-62.0). Our novel models highlight that preoperative transfusion is of significance for short-term mortality while mid-term outcomes are predominantly determined by severe complications, pulmonary complications, and advanced age. Our models showed high discriminative power, good calibration, and precision for mortality prediction in both training and validation cohorts, especially in short-term mortality prediction. CONCLUSIONS: The authors introduce transfusion-related factors, new variables to develop, and validate models to predict mortality with STHFPT. The models can be further tested and updated with the ultimate goal of assisting in optimizing individual transfusion strategy.

Efficacy of surgical intervention over conservative management in intertrochanteric fractures among nonagenarians and centenarians: a prospective cohort study.

BACKGROUND: Optimal treatment strategy for nonagenarians and centenarians with hip fractures (NCHF) remained unknown. The authors aimed to compare the outcomes of surgical and conservative management in NCHF. METHODS: A prospective cohort study was conducted based on CPMHF database with NCHF patients hospitalized during 2014-2020. Comorbidities were evaluated by mECM score and restricted cubic spline was utilized to visually assess the dose-effect relationship between the mECM and outcomes. Propensity score matching was performed to balance baseline characteristics between nonsurgical and surgical groups. Multivariate logistic regression, Cox proportional hazard analysis, and survival analysis were employed for unfavorable outcomes (UFO) evaluation. Competing risk of death were analyzed based on Fine and Gray's hazard model and then constructed nomogram models for predicting survival rates. Subgroup analyses were used to determine potential population heterogeneity and sensitivity analyses were performed to test robustness of the results. RESULTS: The authors found increasing trends for UFO with the increase in the mECM score, and that high mECM score (HMS, ≥3) was independently associated with a 2.42-fold (95% CI: 2.07-3.54; P =0.024) increased risk of UFO, which remained significant after considering the competing role of death and were more pronounced in nonsurgical treatment, women, no insurance, and patients with spouse (all P for interaction <0.05). Surgical intervention was identified to be significant protective factors for UFO (RR, 0.59; 95% CI: 0.46-0.75; P <0.001) and severe complications (RR, 0.63; 95% CI: 0.41-0.96; P =0.033) after propensity score matching, as well as survival (HR, 0.40, 95% CI: 0.28-0.58; P <0.001), which remained significant after considering the competing role of death and in all sensitivity analyses and were more pronounced in HMS participants ( P for interaction=0.006). Subgroup analyses revealed surgical patients with HMS had a significantly higher UFO rate (excluding death, P <0.001) while nonsurgical patients with HMS had higher mortality rate as compared to the others ( P =0.005). CONCLUSION: Surgical treatment for NCHF yields better outcomes compared to conservative treatment.

Construction of a knowledge graph for breast cancer diagnosis based on Chinese electronic medical records: development and usability study.

BACKGROUND: Electronic medical records (EMRs) contain a wealth of information related to breast cancer diagnosis and treatment. Extracting relevant features from these medical records and constructing a knowledge graph can significantly contribute to an efficient data analysis and decision support system for breast cancer diagnosis. METHODS: An approach was proposed to develop a workflow for effectively extracting breast cancer-related features from Chinese breast cancer mammography reports and constructing a knowledge graph for breast cancer diagnosis. Firstly, the concept layer of the knowledge graph for breast cancer diagnosis was constructed based on breast cancer diagnosis and treatment guidelines, along with insights from clinical experts. .Next, a BiLSTM-Highway-CRF model was designed to extract the mammography features, which formed the data layer of the knowledge graph. Finally, the knowledge graph was constructed by combining the concept layer and the data layer in a Neo4j graph data platform, and then applied in visualization analysis, semantic query and computer assisted diagnosis. RESULTS: Mammographic features were extracted from a total of 1171 mammography examination reports. The overall extraction performance of the model achieved an accuracy rate of 97.16%, a recall rate of 98.06%, and a F1 score of 97.61%. Additionally, 47,660 relationships between entities were identified based on the four different types of relationships defined in the concept layer. The knowledge graph for breast cancer diagnosis was constructed after inputting mammographic features and relationships into the Neo4j graph data platform. The model was assessed from the concept layer, data layer, and application layer perspectives, and showed promising results. CONCLUSIONS: The proposed workflow is applicable for constructing knowledge graphs for breast cancer diagnosis based on Chinese EMRs. This study serves as a reference for the rapid design, construction, and application of knowledge graphs for diagnosis and treatment of other diseases. Furthermore, it offers a potential solution to address the issues of limited data sharing and format inconsistencies present in Chinese EMR data.

Application of piezoelectric materials in the field of bone: a bibliometric analysis.

In the past 4 decades, many articles have reported on the effects of the piezoelectric effect on bone formation and the research progress of piezoelectric biomaterials in orthopedics. The purpose of this study is to comprehensively evaluate all existing research and latest developments in the field of bone piezoelectricity, and to explore potential research directions in this area. To assess the overall trend in this field over the past 40 years, this study comprehensively collected literature reviews in this field using a literature retrieval program, applied bibliometric methods and visual analysis using CiteSpace and R language, and identified and investigated publications based on publication year (1984-2022), type of literature, language, country, institution, author, journal, keywords, and citation counts. The results show that the most productive countries in this field are China, the United States, and Italy. The journal with the most publications in the field of bone piezoelectricity is the International Journal of Oral & Maxillofacial Implants, followed by Implant Dentistry. The most productive authors are Lanceros-Méndez S, followed by Sohn D.S. Further research on the results obtained leads to the conclusion that the research direction of this field mainly includes piezoelectric surgery, piezoelectric bone tissue engineering scaffold, manufacturing artificial cochleae for hearing loss patients, among which the piezoelectric bone tissue engineering scaffold is the main research direction in this field. The piezoelectric materials involved in this direction mainly include polyhydroxybutyrate valerate, PVDF, and BaTiO3.

The efficacy of different interventions in the treatment of sarcopenia in middle-aged and elderly people: A network meta-analysis.

BACKGROUND: In this study, a meta-analysis system was used to evaluate the effects of 7 methods of treating sarcopenia, including resistance exercise, aerobic exercise, mixed exercise, nutrition, resistance combined with nutrition, mixed exercise combined with nutrition, and electric stimulation combined with nutrition, and their effects on physical function. METHODS: According to the PRISMA guidelines, PubMed, Web of Science, Embase, and other foreign databases, as well as Chinese databases such as China National Knowledge Infrastructure and Wan Fang, the literatures of randomized controlled trials with different intervention measures were searched. ADDIS software was used to compare and rank the results of the network meta-analysis. RESULTS: A total of 2485 patients were included in the 30 randomized controlled trial items. According to the clinical manifestations of sarcopenia, 7 different forms of exercise and nutrition interventions can improve muscle strength, muscle mass, and physical function; in terms of improving muscle strength, resistance exercise has the most significant effect on improving grip strength (MD = 2.58, 95% confidence interval [CI] [1.06-4.07]); resistance exercise combined with nutrition lifting performed best in chair standing test (MD = -2.37, 95% CI [-4.73 to -0.33]). For muscle mass gains, resistance training increased appendicular skeletal muscle mass significantly (MD = 0.90, 95% CI [0.11-1.73]), while resistance exercise combined with nutrition significantly increased fat-free mass (MD = 5.15, 95% CI [0.91-9.43]). For physical activity, resistance training improved walk speed best (MD = 0.28, 95% CI [0.15-0.41]), and resistance exercise combined with nutrition in the best results were seen in the timed up and go test (MD = -2.31, 95% CI [-4.26 to -0.38]). CONCLUSION: Compared with aerobic exercise, mixed exercise, nutrition, resistance combined with nutrition, mixed exercise combined with nutrition, and electric stimulation combined with nutrition, resistance exercise has more advantages in improving muscle mass, strength, and physical function performance. The clinical treatment of sarcopenia with resistance exercise intervention has a better curative effect.

Exploration and Practice of the "One Combination, Two Highlights, Three Combinations, Four in One" Innovative Talents Training Mode in Forensic Medicine.

Talent is one of the basic and strategic supports for building a modern socialist country in all aspects. Since the 1980s, the establishment of forensic medicine major and the cultivation of innovative talents in forensic medicine have become hot topics in higher education in forensic medicine. Over the past 43 years, the forensic medicine team of Shanxi Medical University has adhered to the joint education of public security and colleges, and made collaborative innovation, forming a training mode of "One Combination, Two Highlights, Three Combinations, Four in One" for innovative talents in forensic medicine. It has carried out "5+3/X" integrated reform, and formed a relatively complete talent training innovation mode and management system in teaching, scientific research, identification, major, discipline, team, platform and cultural construction. It has made a historic contribution to China's higher forensic education, accumulated valuable experience for the construction of first-class major and first-class discipline of forensic medicine, and provided strong support for the construction of the national new forensic talent training system. The popularization of this training mode is conducive to the rapid and sustainable development of forensic science, and provides more excellent forensic talents for national building, regional social development and the discipline construction of forensic science.

The predictive value of microvascular obstruction for adverse left ventricular remodeling after primary percutaneous coronary intervention in patients with acute ST-elevation myocardial infarction: a prospective study / 中华内科杂志

Objectives:Microvascular obstruction (MVO) is a specific cardiac magnetic resonance (CMR) imaging feature in patients with acute myocardial infarction. The purpose of this study was to elucidate the predictive value of MVO in left ventricular adverse remodeling after primary percutaneous coronary intervention (PCI) in patients with acute ST-elevation myocardial infarction (STEMI).Methods:A total of 167 patients with STEMI undergoing primary PCI in the Chinese PLA General Hospital from 2016 to 2020 were enrolled in this prospective cohort study, the average age of study patients was 57±10 years old, with 151 males (90.4%) and 16 females (9.6%). The patients were divided into the MVO group ( n=81) and non-MVO group ( n=86) according to the presence or absence of MVO on CMR imaging, respectively. The primary endpoint of the study was the occurrence of left ventricular adverse remodeling, which was defined as an increase in left ventricular end diastolic volume (LVEDV) by >20% at 6 months after primary PCI compared with the baseline. Patients who completed follow-up were diagnosed as left ventricular adverse remodeling or no left ventricular adverse remodeling according to CMR. The baseline data, perioperative data, and related data of end points were compared between the MVO group and non-MVO group. Finally, the predictive value of MVO in left ventricular adverse remodeling was calculated by receiver operating characteristic curve analysis. Results:In the baseline data, preoperative thrombolysis in myocardial infarction (TIMI) flow ( χ2=13.74, P=0.003) and postoperative TIMI flow ( χ2=14.87, P=0.001) were both obviously decreased in the MVO group. After 6 months of follow-up, the incidence of left ventricular adverse remodeling in the MVO group was significantly higher than that in the non-MVO group [37.0%(27/73) vs. 18.9%(14/74), χ2=5.96, P=0.015]. The left ventricular end systolic volume at 6 months post infarction in the MVO group was significantly larger than that in the non-MVO group [(94±32) vs. (68±20) ml, t=-5.98, P<0.001], as well as the LVEDV [(169±38) vs. (143±29) ml, t=-4.74, P<0.001]. Receiver operating characteristic curve showed that the area under the curve of MVO size for predicting left ventricular adverse remodeling was 0.637. Conclusion:The risk of left ventricular adverse remodeling is significantly increased in patients with MVO after primary PCI for acute STEMI.

Non-Contrast Cine Cardiac Magnetic Resonance Derived-Radiomics for the Prediction of Left Ventricular Adverse Remodeling in Patients With ST-Segment Elevation Myocardial Infarction

Objective@#To investigate the predictive value of radiomics features based on cardiac magnetic resonance (CMR) cine images for left ventricular adverse remodeling (LVAR) after acute ST-segment elevation myocardial infarction (STEMI). @*Materials and Methods@#We conducted a retrospective, single-center, cohort study involving 244 patients (random-split into 170 and 74 for training and testing, respectively) having an acute STEMI (88.5% males, 57.0 ± 10.3 years of age) who underwent CMR examination at one week and six months after percutaneous coronary intervention. LVAR was defined as a 20% increase in left ventricular end-diastolic volume 6 months after acute STEMI. Radiomics features were extracted from the oneweek CMR cine images using the least absolute shrinkage and selection operator regression (LASSO) analysis. The predictive performance of the selected features was evaluated using receiver operating characteristic curve analysis and the area under the curve (AUC). @*Results@#Nine radiomics features with non-zero coefficients were included in the LASSO regression of the radiomics score (RAD score). Infarct size (odds ratio [OR]: 1.04 (1.00–1.07); P = 0.031) and RAD score (OR: 3.43 (2.34–5.28); P < 0.001) were independent predictors of LVAR. The RAD score predicted LVAR, with an AUC (95% confidence interval [CI]) of 0.82 (0.75–0.89) in the training set and 0.75 (0.62–0.89) in the testing set. Combining the RAD score with infarct size yielded favorable performance in predicting LVAR, with an AUC of 0.84 (0.72–0.95). Moreover, the addition of the RAD score to the left ventricular ejection fraction (LVEF) significantly increased the AUC from 0.68 (0.52–0.84) to 0.82 (0.70–0.93) (P = 0.018), which was also comparable to the prediction provided by the combined microvascular obstruction, infarct size, and LVEF with an AUC of 0.79 (0.65–0.94) (P = 0.727). @*Conclusion@#Radiomics analysis using non-contrast cine CMR can predict LVAR after STEMI independently and incrementally to LVEF and may provide an alternative to traditional CMR parameters.

Influence of liver metastasis on the effectiveness of immunotherapy in patients with gastric cancer: a retrospective cohort study / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨肝转移对晚期胃癌患者免疫治疗效果的影响。方法：收集2019年2月至2022年1月在南京医科大学附属常州第二人民医院肿瘤中心接受过免疫治疗的晚期胃癌患者的临床资料，进行回顾性分析，利用卡方检验或Fisher确切概率法进行基线特征比较，利用卡方检验和Kaplan-Meier生存分析方法进行有肝转移与无肝转移胃癌患者的疗效和生存期的比较。结果：共有48例晚期胃癌患者纳入分析，根据有无肝转移将患者分为肝转移队列（n=20）和无肝转移队列（n=28）。有肝转移较无肝转移胃癌患者体力状况更差。肝转移队列与无肝转移队列的ORR分别为15.0%和35.7%（P>0.05），DCR分别为65.0%和82.1%（P>0.05）；中位PFS在两组分别为5.0个月和11.2个月（HR=0.40，P<0.05），中位OS分别为12.0个月和19.0个月（P>0.05）。结论：胃癌肝转移患者免疫治疗的疗效差于无肝转移的患者。

Protection of side-branch ostium by the jailed balloon technique validated by three-dimensional optical coherence tomography / 中华心血管病杂志

Objective: To evaluate the protective effect of jailed balloon technique on side branch (SB) ostium using three-dimensional optical coherence tomography(OCT). Methods: This is a retrospective study. Consecutive coronary disease patients with coronary artery bifurcation lesions who underwent percutaneous coronary intervention (PCI) and completed pre-and post-procedural OCT examinations at the Chinese People's Liberation Army General Hospital from September 2019 to March 2022 were enrolled. Patients were divided into the jailed balloon technique group and the unprotected group according to the options applied for the SB. The SB ostium area difference was calculated from OCT images (SB ostium area difference=post-PCI SB ostium area-pre-PCI SB ostium area). The SB ostium area differences were compared between the two groups and compared further in the subgroup of true bifurcation lesions and non-true bifurcation lesions. In the jailed balloon group, the SB ostium area difference was compared between the active jailed balloon technique and the conventional jailed balloon technique, between the jailed balloon>2.0 mm diameter and the jailed balloon≤2.0 mm diameter, and between the higher balloon pressure (>4 atm, 1 atm=101.325 kPa) and the lower balloon pressure (≤4 atm). Multivariate linear regression analysis was used to explore the correlation between the technical parameters of the jailed balloon technique and the SB protection effect. Results: A total of 176 patients with 236 bifurcation lesions were enrolled, aged (60.7±9.3) years, and there were 128 male patients (72.7%). There were 67 patients in the jailed balloon technique group with 71 bifurcation lesions and 123 patients in the unprotected group with 165 bifurcation lesions. Fourteen patients had 2 to 3 lesions, which were treated in different ways, so they appeared in the unprotected group and the jailed balloon technique group at the same time. The area difference in SB ostium was greater in the jailed balloon group than in the unprotected group (0.07 (-0.43, 1.05)mm2 vs.-0.33 (-0.83, 0.26)mm2, P<0.001), and the results were consistent in the true bifurcation lesion subgroup (0.29 (-0.35, 0.96)mm2 vs.-0.26 (-0.64, 0.29)mm2, P=0.004), while the difference between the two groups in the non-true bifurcation lesion subgroup was not statistically significant (P=0.136). In the jailed balloon technique group, the SB ostium area difference was greater in patients treated with the active jailed balloon technique than in those treated with the conventional jailed balloon technique ((0.43±1.36)mm2 vs. (-0.22±0.52)mm2, P=0.013). The difference in SB ostium area was greater in those using>2.0 mm diameter jailed balloons than in those using≤2.0 mm diameter jailed balloons (0.25 (-0.51, 1.31) mm2 vs.-0.01 (-0.45, 0.63) mm2, P=0.020), while SB ostium area difference was similar between those endowed with higher balloon pressure (>4 atm) compared to those with lower balloon pressure (≤4 atm) (P=0.731). Multivariate linear regression analysis showed that there was a positive correlation between jailed balloon diameter and SB ostium area difference (r=0.344, P=0.019). Conclusions: The jailed balloon technique significantly protects SB ostium, especially in patients with true bifurcation lesions. The active jailed balloon technique and larger diameter balloons may provide more protection to the SB.

Exploration and Practice of the "One Combination, Two Highlights, Three Combinations, Four in One" Innovative Talents Training Mode in Forensic Medicine / 法医学杂志

Talent is one of the basic and strategic supports for building a modern socialist country in all aspects. Since the 1980s, the establishment of forensic medicine major and the cultivation of innovative talents in forensic medicine have become hot topics in higher education in forensic medicine. Over the past 43 years, the forensic medicine team of Shanxi Medical University has adhered to the joint education of public security and colleges, and made collaborative innovation, forming a training mode of "One Combination, Two Highlights, Three Combinations, Four in One" for innovative talents in forensic medicine. It has carried out "5+3/X" integrated reform, and formed a relatively complete talent training innovation mode and management system in teaching, scientific research, identification, major, discipline, team, platform and cultural construction. It has made a historic contribution to China's higher forensic education, accumulated valuable experience for the construction of first-class major and first-class discipline of forensic medicine, and provided strong support for the construction of the national new forensic talent training system. The popularization of this training mode is conducive to the rapid and sustainable development of forensic science, and provides more excellent forensic talents for national building, regional social development and the discipline construction of forensic science.

Prenatal and postnatal diagnosis of Phelan-McDermid syndrome: A report of 21 cases from a medical center and review of the literature.

Background: Phelan-McDermid syndrome (PMS), caused by deletions at 22q13.3 and pathogenic variants in the SHANK3 gene, is a rare developmental disorder characterized by hypotonia, developmental delay (DD), intellectual disability (ID), autism spectrum disorder (ASD), dysmorphic features, absence of or delayed language, and other features. Methods: Conventional karyotyping, chromosomal microarray analysis (CMA), and whole exome sequencing (WES) have been used to detect genetic defects causing PMS. We summarized the genetic and clinical findings from prenatal to postnatal stages of detected cases of PMS and mapped potential candidate haploinsufficient genes for deletions of 22q13. This study aimed to summarize the laboratory findings, genetic defects, and genotype-phenotype correlations for Chinese patients with PMS. Results: Seven prenatal cases and fourteen postnatal cases were diagnosed with PMS in our center. Thirteen cases had a deletion ranging in size from 69 to 9.06 Mb at 22q13.2-q13.33, and five cases had a pathogenic variant or an intragenic deletion in the SHANK3 gene. Three familial cases with a parental carrier of a balanced translocation were noted. A review of the literature noted another case series of 29 cases and a report of five cases of PMS in China. Genotype-phenotype correlations confirmed haploinsufficiency of the SHANK3 gene for PMS and suggested other candidate haploinsufficient genes TNFRSFI3C and NFAM1 genes for immunological features and TCF20, SULT4A1, PARVB, SCO2, and UPK3A genes for intellectual impairment and behavioral abnormality, neurological features, macrocephaly/hypotonia, oculopathy, and renal adysplasia, respectively. Conclusion: Indications for prenatal diagnosis of PMS are not specific, and approximately 85% prenatally diagnosed PMS elected termination of pregnancies after genetic counseling. For postnatal cases, 62.5% were caused by a deletion at 22q13 and 37.5% were caused by a pathogenic variant or an intragenic deletion in the SHANK3 gene. Approximately 6.7% of cases with a deletion were familial, and almost all pathogenic variants were de novo. Combined karyotype, CMA, and WES should be performed to increase the diagnostic yield. The identification of other candidate haploinsufficient genes in deletions of 22q13.2-q13.33 could relate to more severe dysmorphic features, neurologic defects, and immune deficiency. These results provided evidence for diagnostic interpretation, genetic counseling, and clinical management for the Chinese cases of PMS.

Risk of cardiovascular disease among cancer survivors: Protocol of a pooled analysis of population-based cohort studies.

Introduction: Cancer and cardiovascular disease remain leading causes of death and disability worldwide, which places a heavy burden on public health systems and causes widespread suffering. Because these entities have highly overlapping risk factors, including hyperlipidemia, hypertension, diabetes, obesity, smoking and other lifestyle factors, many studies have reported that they have similar etiological mechanisms. Accumulating evidence indicates that there is an increased risk of cardiovascular disease among cancer survivors compared with the general population. However, whether cancer is associated with an increased risk of cardiovascular disease remains controversial. Methods and analysis: We will conduct and report the meta-analysis strictly based on the Cochrane Handbook for Systematic Reviews and the Meta-analysis of Observational Studies in Epidemiology guidelines combined with the Preferred Reporting Items for Systematic Reviews and Meta-analysis for Protocols (PRISM-P). This meta-analysis was registered with PROSPERO (registration number CRD42022307056). We will search for studies published from database inception to December 1, 2021, regardless of language or date, in three electronic databases (PubMed, EMBASE, and Cochrane Library) to identify and appraise cohort studies examining the relationship between cancer and subsequent cardiovascular disease risk. The literature screening, inclusion and data extraction will be conducted independently by two investigators using pre-designed standardized data extraction forms. A senior investigator will be consulted in cases of disagreement. We will assess risk of bias in the included cohort studies using the Newcastle-Ottawa Scale (NOS). Quantitative synthesis will be conducted using a random-effects model. To explore potential sources of heterogeneity, we will carry out multiple sensitivity analysis, meta-regression and subgroup analysis according to baseline characteristics. Publication bias will be evaluated through visual inspection of funnel plot asymmetry as well as by Begg's rank correlation test and Egger's weighted linear regression test.

Novel recombinant human thyroid-stimulating hormone in aiding postoperative assessment of patients with differentiated thyroid cancer-phase I/II study.

PURPOSE: Thyroid hormone withdrawal (THW) inevitably induced hypothyroidism in patients with differentiated thyroid cancer (DTC), and we aimed to evaluate the safety and efficacy of a novel recombinant human thyroid-stimulating hormone (rhTSH, ZGrhTSH) as an alternative of THW in China. METHODS: Totally, 64 DTC patients were enrolled with 24 in the dose-escalation cohort equally grouped into 0.9 mg × 1 day, 0.9 mg × 2 day, 1.8 mg × 1 day, and 1.8 mg × 2 day dosage, and 40 further enrolled into 0.9 mg × 2 day dose-expansion cohort. All patients underwent both ZGrhTSH phase and levothyroxine (L-T4) withdrawal phase for self-comparison in terms of TSH levels, the radioactive iodine (RAI) uptake, stimulated thyroglobulin level, and the quality of life (QoL). RESULTS: In ZGrhTSH phase, no major serious adverse events were observed, and mild symptoms of headache were observed in 6.3%, lethargy in 4.7%, and asthenia in 3.1% of the patients, and mostly resolved spontaneously within 2 days. Concordant RAI uptake was noticed in 89.1% (57/64) of the patients between ZGrhTSH and L-T4 withdrawal phases. The concordant thyroglobulin level with a cut-off of 1 µg/L was noticed in 84.7% (50/59) of the patients without the interference of anti-thyroglobulin antibody. The QoL was far better during ZGrhTSH phase than L-T4 withdrawal phase, with lower Billewicz (- 51.30 ± 4.70 vs. - 39.10 ± 16.61, P < 0.001) and POMS (91.70 ± 16.70 vs. 100.40 ± 22.11, P = 0.011) scores which indicate the lower the better. Serum TSH level rose from basal 0.11 ± 0.12 mU/L to a peak of 122.11 ± 42.44 mU/L 24 h after the last dose of ZGrhTSH. In L-T4 withdrawal phase, a median of 23 days after L-T4 withdrawal was needed, with the mean TSH level of 82.20 ± 31.37 mU/L. The half-life for ZGrhTSH clearance was about 20 h. CONCLUSION: The ZGrhTSH held the promise to be a safe and effective modality in facilitating RAI uptake and serum thyroglobulin stimulation, with better QoL of patients with DTC compared with L-T4 withdrawal.

Upregulation of Runt related transcription factor 1 (RUNX1) contributes to tendon-bone healing after anterior cruciate ligament reconstruction using bone mesenchymal stem cells.

BACKGROUND: Anterior cruciate ligament (ACL) injury could lead to functional impairment along with disabilities. ACL reconstruction often fails owing to the regeneration failure of tendon-bone interface. Herein, we aimed to investigate the effects of Runt related transcription factor 1 (RUNX1) on tendon-bone healing after ACL reconstruction using bone mesenchymal stem cells (BMSCs). METHODS: BMSCs were isolated from the marrow cavity of rat femur, followed by the modification of RUNX1 with lentiviral system. Then, an ACL reconstruction model of rats was established with autografts. RESULTS: Results of flow cytometry exhibited positive-antigen CD44 and CD90, as well as negative-antigen CD34 and CD45 of the BMSCs. Then, we found that RUNX1-upregulated BMSCs elevated the decreased biomechanical strength of the tendon grafts after ACL reconstruction. Moreover, based on the histological observation, upregulation of RUNX1 was linked with better recovery around the bone tunnel, a tighter tendon-bone interface, and more collagen fibers compared to the group of BMSCs infected with LV-NC. Next, RUNX1-upregulated BMSCs promoted osteogenesis after ACL reconstruction, as evidenced by the mitigation of severe loss and erosion of the cartilage and bone in the tibial and femur area, as well as the increased number of osteoblasts identified by the upregulation of alkaline phosphatase, osteocalcin, and osteopontin in the tendon-bone interface. CONCLUSION: Elevated expression of RUNX1 contributed to tendon-bone healing after ACL reconstruction using BMSCs.

Efficacy and Safety of Low-Dose Nab-Paclitaxel Plus Tislelizumab in Elderly Patients With Previously Treated Metastatic Non-Small Cell Lung Cancer.

The combination of immunotherapy and chemotherapy has a synergic effect in non-small cell lung cancer (NSCLC). However, the elderly are often excluded from clinical trails due to their poor health status and more comorbidities. We sought to assess the efficacy and safety of low-dose nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus tislelizumab (an anti-PD-1 antibody) in elderly patients with advanced NSCLC. In this phase 2 clinical trail, eligible patients were those aged ≥65 years with metastatic NSCLC who had disease progression after treatment with ≥1 line of chemotherapy or targeted therapy. Patients with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) variations were eligible if they demonstrated disease progression after treatment with ≥1 corresponding inhibitor. Primary endpoints were progression-free survival and safety/tolerability. Secondary endpoints included objective response rate and overall survival. Among 29 patients enrolled from May 2019 through August 2020, 21 (72.4%) had adenocarcinoma, 17 (58.6%) had a performance status of 2, 8 (27.6%) had asymptomatic brain metastases, and 13 (44.8%) had EGFR/ALK variations. As of the data cutoff point on April 1, 2021, median progression-free survival and overall survival were 9.5 months and 16.5 months, respectively. Ten patients achieved a partial response (objective response rate of 34.5%). Seventeen (58.6%) patients had ≥1 treatment-related adverse event, with grade 3 events seen in 3 patients (10.3%). The most common adverse events were fatigue (20.7%), fever (17.2%), abnormal liver function (17.2%), and rash (17.2%). These results suggest that low-dose nab-paclitaxel plus tislelizumab is well tolerated and effective in elderly patients with advanced NSCLC, including those with EGFR/ALK variations.