A single infusion of engineered long-lived and multifunctional T cells confers durable remission of asthma in mice.

Asthma, the most prevalent respiratory disease, affects more than 300 million people and causes more than 250,000 deaths annually. Type 2-high asthma is characterized by interleukin (IL)-5-driven eosinophilia, along with airway inflammation and remodeling caused by IL-4 and IL-13. Here we utilize IL-5 as the targeting domain and deplete BCOR and ZC3H12A to engineer long-lived chimeric antigen receptor (CAR) T cells that can eradicate eosinophils. We call these cells immortal-like and functional IL-5 CAR T cells (5TIF) cells. 5TIF cells were further modified to secrete an IL-4 mutein that blocks IL-4 and IL-13 signaling, designated as 5TIF4 cells. In asthma models, a single infusion of 5TIF4 cells in fully immunocompetent mice, without any conditioning regimen, led to sustained repression of lung inflammation and alleviation of asthmatic symptoms. These data show that asthma, a common chronic disease, can be pushed into long-term remission with a single dose of long-lived CAR T cells.

Induction of immortal-like and functional CAR T cells by defined factors.

Long-term antitumor efficacy of chimeric antigen receptor (CAR) T cells depends on their functional persistence in vivo. T cells with stem-like properties show better persistence, but factors conferring bona fide stemness to T cells remain to be determined. Here, we demonstrate the induction of CAR T cells into an immortal-like and functional state, termed TIF. The induction of CARTIF cells depends on the repression of two factors, BCOR and ZC3H12A, and requires antigen or CAR tonic signaling. Reprogrammed CARTIF cells possess almost infinite stemness, similar to induced pluripotent stem cells while retaining the functionality of mature T cells, resulting in superior antitumor effects. Following the elimination of target cells, CARTIF cells enter a metabolically dormant state, persisting in vivo with a saturable niche and providing memory protection. TIF represents a novel state of T cells with unprecedented stemness, which confers long-term functional persistence of CAR T cells in vivo and holds broad potential in T cell therapies.

Cadmium-tolerant Bacillus cereus 2-7 alleviates the phytotoxicity of cadmium exposure in banana plantlets.

Bananas are the world's important fruit and staple crop in the developing countries. Cadmium (Cd) contamination in soils results in the decrease of crop yield and food safety. Bioremediation is an environmental-friendly and effective measure using Cd-tolerant plant growth promoting rhizobacteria (PGPR). In our study, a Cd-resistant PGPR Bacillus cereus 2-7 was isolated and identified from a discarded gold mine. It could produce multiple plant growth promoting biomolecules such as siderophores, indole-3-acetic acid (IAA), 1-aminocyclopropane-1-carboxylate (ACC)-deaminase and phosphatase. The extracellular accumulation was a main manner of Cd removal. Surplus Cd induced the expression of Cd resistance/transport genes of B. cereus 2-7 to maintain the intracellular Cd homeostasis. The pot experiment showed that Cd contents decreased by 50.31 % in soil, 45.43 % in roots, 56.42 % in stems and 79.69 % in leaves after the strain 2-7 inoculation for 40 d. Bacterial inoculation alleviated the Cd-induced oxidative stress to banana plantlets, supporting by the increase of chlorophyll contents, plant height and total protein contents. The Cd remediation mechanism revealed that B. cereus 2-7 could remodel the rhizosphere bacterial community structure and improve soil enzyme activities to enhance the immobilization of Cd. Our study provides a Cd-bioremediation strategy using Cd-resistant PGPR in tropical and subtropical area.

Epidemiological characteristics and transmissibility of HPV infection: A long-term retrospective study in Hokkien Golden Triangle, China, 2013-2021.

OBJECTIVE: Multiple human papillomavirus (HPV)-associated diseases have put a significant disease burden on the world. Therefore, we conducted a study to explore the epidemiological characteristics of HPV and the transmissibility of its genotypes. METHODS: HPV testing data was collected from Hospital. A transmission dynamics model of HPV was constructed to simulate and compare the transmissibility of different HPV genotypes, which was quantitatively described by the basic reproduction number (R0). RESULTS: The collected HPV subjects were mainly from Xiamen City, Zhangzhou City and Quanzhou City, together, they are known as the Hokkien golden triangle. There were variations in the distribution of HPV infections by age groups. Among all HPV genotypes, 13 of them had R0 > 1, with 10 of them being high-risk types. The top five were HPV56, 18, 58, 52 and 53, among which, HPV56, 18, 58 and 42 were of high risk, whereas HPV53 was not, and the R0 values for the five were 3.35 (CI: 0.00-9.99), 3.20 (CI: 0.00-6.46), 3.19 (CI: 1.27-6.94), 3.19 (CI: 1.01-8.42) and 2.99 (CI: 0.00-9.39), respectively. In addition, HPV52 had R0 > 1 for about 51 months, which had the longest duration. CONCLUSION: Most high-risk HPV types in the Hokkien golden triangle could transmit among the population. Therefore, there is a need of further optimization for developing HPV vaccines and better detection methods in the region.

Association between preoperative concurrent fibular pseudarthrosis and risk of postoperative ankle valgus in patients with congenital pseudarthrosis of the tibia.

BACKGROUND: This study evaluated the correlation of preoperative concurrent fibular pseudarthrosis with the risk of ankle valgus deformity in patients with congenital pseudarthrosis of the tibia (CPT) who underwent successful surgical treatment. METHOD: The children with CPT who were treated at our institution between 1 January 2013 and 31 December 2020 were retrospectively reviewed. The independent variable was preoperative concurrent fibular pseudarthrosis, and the dependent variable was postoperative ankle valgus. Multivariable logistic regression analysis was performed after adjusting for variables that might affect the risk of ankle valgus. Subgroup analyses with stratified multivariable logistic regression models were used to assess this association. RESULTS: Of the 319 children who underwent successful surgical treatment, 140 (43.89%) developed ankle valgus deformity. Moreover, 104 (50.24%) of 207 patients with preoperative concurrent fibular pseudarthrosis developed an ankle valgus deformity compared with 36 (32.14%) of 112 patients without preoperative concurrent fibular pseudarthrosis (p=0.002). After adjusting for sex, body mass index, fracture age, age of patient undergoing surgery, surgery method, type 1 neurofibromatosis (NF-1), limb-length discrepancy (LLD), CPT location and fibular cystic change, patients with concurrent fibular pseudarthrosis presented a higher risk of ankle valgus than those without concurrent fibular pseudarthrosis (OR 2.326, 95% CI 1.345 to 4.022). This risk further increased with CPT location at the distal one-third of the tibia (OR 2.195, 95% CI 1.154 to 4.175), age <3 years of patient undergoing surgery (OR 2.485, 95% CI 1.188 to 5.200), LLD <2 cm (OR 2.478, 95% CI 1.225 to 5.015) and occurrence of NF-1 disorder (OR 2.836, 95% CI 1.517 to 5.303). CONCLUSION: Our results indicate that patients with CPT and preoperative concurrent fibular pseudarthrosis have a significantly increased risk of ankle valgus compared with those without preoperative concurrent fibular pseudarthrosis, particularly in those with CPT location at the distal third, age <3 years at surgery, LLD <2 cm and NF-1 disorder.

Physical Activity among Rural Residents in Eastern, Central, and Western Provinces of China: A Cross-Sectional Survey.

Physical activity (PA) in which physical exercise (PE) is an important component is probably the most important intervention for preventing noncommunicable diseases (NCDs). However, few studies on PA and PE of rural residents in China were reported. This study conducted the first population-based cross-sectional survey in three provinces of China in 2021 that examined both PA and PE as well as the associated factors of rural residents. The International Physical Activity Questionnaire Short Form (IPAQ-S) was used, and a total of 3780 rural residents were surveyed. The result showed that 22.2% of the rural residents were physical inactivity and rural residents reporting practice of PE was 54.4%. Binary logistic regression analyses showed that being female, people aged between 15 to 34 years or 60 years old and above, employees of governmental departments/retirees, school students, the unemployed, and people with NCDs were risk factors of PA while ethnic minority groups, smoking, and alcohol consumption were risk factors of PE. Health promotion programme aiming at increasing people's PA in rural China is urgently needed, and it should focus on the population groups of the female, people aged 60 years and above, school students, the unemployed, and people with NCDs.

[Construction of a Prognostic Model of Multiple Myeloma Based on Metabolism-Related Genes].

OBJECTIVE: To screen the prognostic biomarkers of metabolic genes in patients with multiple myeloma (MM), and construct a prognostic model of metabolic genes. METHODS: The histological database related to MM patients was searched. Data from MM patients and healthy controls with complete clinical information were selected for analysis.The second generation sequencing data and clinical information of bone marrow tissue of MM patients and healthy controls were collected from human protein atlas (HPA) and multiple myeloma research foundation (MMRF) databases. The gene set of metabolism-related pathways was extracted from Molecular Signatures Database (MSigDB) by Perl language. The biomarkers related to MM metabolism were screened by difference analysis, univariate Cox risk regression analysis and LASSO regression analysis, and the risk prognostic model and Nomogram were constructed. Risk curve and survival curve were used to verify the grouping effect of the model. Gene set enrichment analysis (GSEA) was used to study the difference of biological pathway enrichment between high risk group and low risk group. Multivariate Cox risk regression analysis was used to verify the independent prognostic ability of risk score. RESULTS: A total of 8 mRNAs which were significantly related to the survival and prognosis of MM patients were obtained (P<0.01). As molecular markers, MM patients could be divided into high-risk group and low-risk group. Survival curve and risk curve showed that the overall survival time of patients in the low-risk group was significantly better than that in the high risk group (P<0.001). GSEA results showed that signal pathways related to basic metabolism, cell differentiation and cell cycle were significantly enriched in the high-risk group, while ribosome and N polysaccharide biosynthesis signaling pathway were more enriched in the low-risk group. Multivariate Cox regression analysis showed that the risk score composed of the eight metabolism-related genes could be used as an independent risk factor for the prognosis of MM patients, and receiver operating characteristic curve (ROC) showed that the molecular signatures of metabolism-related genes had the best predictive effect. CONCLUSION: Metabolism-related pathways play an important role in the pathogenesis and prognosis of patients with MM. The clinical significance of the risk assessment model for patients with MM constructed based on eight metabolism-related core genes needs to be confirmed by further clinical studies.

Pregnancy associated cancer, timing of birth and clinical decision making-a NSW data linkage study.

BACKGROUND: The incidence of pregnancy-associated cancer (PAC), comprising cancer diagnosed during pregnancy or within one year postpartum, is increasing. We investigated the obstetric management and outcomes of women with PAC and their babies. METHODS: A population-based observational study of all women who gave birth between 1994 and 2013 in New South Wales, Australia. Women were stratified into three groups: those diagnosed during pregnancy (gestational cancer group), those diagnosed within one year of giving birth (postpartum cancer group), and a no-PAC group. Generalized estimating equations were used to examine the association between PAC and adverse maternal and neonatal outcomes. RESULTS: One million seven hundred eighty-eight thousand four hundred fifty-onepregnancies were included-601 women (614 babies) were in the gestational cancer group, 1772 women (1816 babies) in the postpartum cancer group, and 1,786,078 women (1,813,292 babies) in the no-PAC group. The overall crude incidence of PAC was 132.7/100,000 women giving birth. The incidence of PAC increased significantly over the twenty-year study period from 93.5/100,000 in 1994 to 162.5/100,000 in 2013 (2.7% increase per year, 95% CI 1.9 - 3.4%, p-value < 0.001). This increase was independent of maternal age. The odds of serious maternal complications (such as acute abdomen, acute renal failure, and hysterectomy) were significantly higher in the gestational cancer group (adjusted odds ratio (AOR) 5.07, 95% CI 3.72 - 6.90) and the postpartum cancer group (AOR 1.55, 95% CI 1.16 - 2.09). There was no increased risk of perinatal mortality in babies born to women with PAC. However, babies of women with gestational cancer (AOR 8.96, 95% CI 6.96 - 11.53) or postpartum cancer (AOR 1.36, 95% CI 1.05 - 1.81) were more likely to be planned preterm birth. Furthermore, babies of women with gestational cancer had increased odds of a severe neonatal adverse outcome (AOR 3.13, 95% CI 2.52 - 4.35). CONCLUSION: Women with PAC are more likely to have serious maternal complications. While their babies are not at increased risk of perinatal mortality, they are more likely to experience poorer perinatal outcomes associated with preterm birth. The higher rate of birth intervention among women with gestational cancers reflects the complexity of clinical decision-making in this context.

Investigating the association between infertility and psychological distress using Australian Longitudinal Study on Women's Health (ALSWH).

Infertility affects millions of people globally. Although an estimated 1 in 6 couples in Australia are unable to conceive without medical intervention, little is known about the mental health impacts of infertility. This study investigated how infertility impacts the mental health of women. The study used nationally representative Australian Longitudinal Study on Women's Health (ALSWH) data. We analysed data from survey periods 2-8 conducted every three years between 2000 and 2018 for 6582 women born in 1973-78. We used a Generalised Equation Modelling (GEE) method to investigate the association of primary, secondary and resolved fertility status and psychological distress over time. Multiple measures were used to measure psychological distress: the (1) the mental health index subscale of the 36-item short form survey (SF-36), (2) the Center for Epidemiological Studies Depression Scale (CESD-10), (3) the Goldberg Anxiety and Depression Scale (GADanx) anxiety subscale; and a (4) composite psychological distress variable. About a third (30%) of women reported infertility at any of the survey rounds; a steady increase over 18 years from 1.7% at round 2 to 19.3% at round 8. Half of the women reporting primary or secondary infertility reported psychological distress, with the odds of having psychological distress was higher in women reporting primary (odds ratio (OR) 1.24, 95% confidence interval (CI) 1.06-1.45), secondary (OR 1.27, 95% CI 1.10-1.46) or resolved infertility (OR 1.15, 95% CI 1.05-1.26) compared to women reporting normal fertility status. Women with partners, underweight or higher BMI, smoking, and high-risk alcohol use had higher odds of psychological distress, whereas women in paid work had significantly lower odds of psychological distress (p < 0.001). Diabetes, high blood pressure, asthma, and other chronic physical illness were independently associated with higher odds of psychological distress. Infertility has a significant impact on mental health even after it is resolved. Frequent mental health assessment and a holistic approach to address the lifestyle factors should be undertaken during the treatment of infertility.

Analysis of risk factors affecting union and refracture after combined surgery for congenital pseudarthrosis of the tibia: a retrospective study of 255 cases.

BACKGROUND: Congenital pseudarthrosis of the tibia (CPT) is a rare disease occurring in children. The aim of this study is to identify the factors affecting bone union and re-fracture after surgery for CPT and to provide reliable evidence for clinics. METHODS: We collected the detailed information of 255 cases with Crawford IV CPT treated by combined surgery in our hospital from 2013 to 2020. Basic characteristics were recorded. Univariate variance and logistic regression analysis were used to compare the correlations between factors and outcomes. RESULTS: 92.5% of patients achieved primary union, 7.5% of patients had non-union and 13.3% of patients had re-fracture. Logistic regression analysis showed that age at index surgery (Coef. = 0.171, 95%CI 0.015-0.327, P = 0.032), and CPT location (Coef. = - 1.337, 95%CI - 2.218-0.456, P = 0.003) had statistical differences, while no factors had significant correlation with re-fracture. Furthermore, ROC curve showed that the optimal age threshold for first surgery was 2.37 years old. CONCLUSIONS: For patients with Crawford IV CPT treated by combined surgery, the younger the age at index surgery and the closer the CPT location to the distal end, the easier to achieve bone union.

PSB0788 ameliorates maternal inflammation-induced periventricular leukomalacia-like injury.

Studies have shown that periventricular leukomalacia (PVL) is a distinctive form of cerebral white matter injury that pertains to myelination disturbances. Maternal inflammation is a main cause of white matter injury. Intrauterine inflammation cellular will be propagated to the developing brain by the entire maternal-placental-fetal axis, and triggers neural immune injury. As a low-affinity receptor, adenosine A2B receptor (A2BAR) requires high concentrations of adenosine to be significantly activated in pathological conditions. We hypothesized that in the maternal inflammation-induced PVL model, a selective A2BAR antagonist PSB0788 had the potential to prevent the injury. In this work, a total of 18 SD pregnant rats were divided into three groups, and treated with intraperitoneal injection of phosphate buffered saline (PBS), lipopolysaccharide (LPS), or LPS+PSB0788. Placental infection was determined by H&E staining and the inflammatory condition was determined by ELISA. Change of MBP, NG2 and CC-1 in the brain of the rats' offspring were detected by western blot and immunohistochemistry. Furthermore, LPS-induced maternal inflammation reduced the expression of MBP, which related to the decrease in the numbers of OPCs and mature oligodendrocytes in neonate rats. After treatment with PSB0788, the levels of MBP proteins increased in the rats' offspring, improved the remyelination. In conclusion, our study shows that the selective A2BAR antagonist PSB0788 plays an important role in promoting the normal development of OPCs in vivo by the maternal inflammation-induced PVL model. Future studies will focus on the mechanism of PSB0788 in this model.

Perinatal outcomes of women with gestational breast cancer in Australia and New Zealand: A prospective population-based study.

OBJECTIVE: To determine the epidemiology, clinical management, and outcomes of women with gestational breast cancer (GBC). METHODS: A population-based prospective cohort study was conducted in Australia and New Zealand between 2013 and 2014 using the Australasian Maternity Outcomes Surveillance System (AMOSS). Women who gave birth with a primary diagnosis of breast cancer during pregnancy were included. Data were collected on demographic and pregnancy factors, GBC diagnosis, obstetric and cancer management, and perinatal outcomes. The main outcome measures were preterm birth, maternal complications, breastfeeding, and death. RESULTS: Forty women with GBC (incidence 7.5/100 000 women giving birth) gave birth to 40 live-born babies. Thirty-three (82.5%) women had breast symptoms at diagnosis. Of 27 women diagnosed before 30 weeks' gestation, 85% had breast surgery and 67% had systemic therapy during pregnancy. In contrast, all 13 women diagnosed from 30 weeks had their cancer management delayed until postdelivery. There were 17 preterm deliveries; 15 were planned. Postpartum complications included the following: hemorrhage (n = 4), laparotomy (n = 1), and thrombocytopenia (n = 1). There was one late maternal death. Eighteen (45.0%) women initiated breastfeeding, including 12 of 23 women who had antenatal breast surgery. There were no perinatal deaths or congenital malformations, but 42.5% of babies were preterm, and 32.5% were admitted for higher-level neonatal care. CONCLUSIONS: Gestational breast cancer diagnosed before 30 weeks' gestation was associated with surgical and systemic cancer care during pregnancy and planned preterm birth. In contrast, cancer treatment was deferred to postdelivery for women diagnosed from 30 weeks, reflecting the complexity of managing expectant mothers with GBC in multidisciplinary care settings.

Efficacy of Repair for ACL Injury: A Meta­analysis of Randomized Controlled Trials.

We aim to compare the curative effect of primary repair for anterior cruciate ligament (ACL) injury with reconstruction and provide the reliable evidence for its clinical application. The literatures were searched in PubMed, EMBASE, Springer, and other medical literature databases published between January 1970 and June 2021. Basic characteristics, surgery technique, clinical outcome scores and physical examination results were recorded and evaluated. Seven randomized controlled trials (RCT) were eligible for inclusion. The results showed that there were no statistically significant differences between arthroscopic ACL repair and ACL reconstruction for Tegner, Lysholm, Lachman, KT-1000, range of motion (ROM), functional outcomes and reoperation rate (P>0.05), even the result of IKDC scores showed that arthroscopic repair was better than reconstruction (P=0.04). However, through the subgroup analysis, it was found that the short-term follow-up results of arthroscopic ACL repair were indeed better than those of open ACL repair. Therefore, we can assume that the arthroscopic ACL repair technique is an optional and promising surgical method to treat ACL injury.

Clinical Decision Making in the Management of Breast Cancer Diagnosed During Pregnancy: A Review and Case Series Analysis.

Purpose: To highlight the various options available for the management of breast cancer diagnosed during pregnancy by describing the investigations, treatment, and outcomes in relation to these women. Methods: This is a narrative review of the literature to describe the issues related to pregnancy and obstetric management in patients with breast cancer. It incorporates a description of six cases of women (aged 29-39 years) with a first-time diagnosis of breast cancer during pregnancy to illustrate a number of issues that need to be considered during different trimesters. Results: Of the six cases, two were diagnosed in each pregnancy trimester. A painless breast mass was the presenting symptom in five cases (83%). In all cases, breast ultrasound was the primary diagnostic imaging procedure. Chest X-ray was performed in 3 (50%) and computed tomography in 2 (33%). A core needle biopsy was performed in all cases, and sentinel lymph node biopsy in 3 (50%) cases. Four women had grade 3 tumor; five had estrogen receptor-positive tumors. Four women had breast surgery during pregnancy. Five women gave birth after the induction of labor and/or cesarean section. In all six cases, a multidisciplinary team was involved in the delivery of health care. Conclusion: Regular breast examinations are needed for all pregnant woman during prenatal visits. Breast ultrasonography should be offered if a breast lump or other symptoms are detected. Breast surgery can be safely performed during all pregnancy trimesters, and some systemic therapeutic agents can be administered safely in the second and third trimesters.

Gestational breast cancer in New South Wales: A population-based linkage study of incidence, management, and outcomes.

BACKGROUND: The incidence of gestational breast cancer (GBC) is increasing in high-income countries. Our study aimed to examine the epidemiology, management and outcomes of women with GBC in New South Wales (NSW), Australia. METHODS: A retrospective cohort study using linked data from three NSW datasets. The study group comprised women giving birth with a first-time diagnosis of GBC while the comparison group comprised women giving birth without any type of cancer. Outcome measures included incidence of GBC, maternal morbidities, obstetric management, neonatal mortality, and preterm birth. RESULTS: Between 1994 and 2013, 122 women with GBC gave birth in NSW (crude incidence 6.8/ 100,000, 95%CI: 5.6-8.0). Women aged ≥35 years had higher odds of GBC (adjusted odds ratio (AOR) 6.09, 95%CI 4.02-9.2) than younger women. Women with GBC were more likely to give birth by labour induction or pre-labour CS compared to women with no cancer (AOR 4.8, 95%CI: 2.96-7.79). Among women who gave birth by labour induction or pre-labour CS, the preterm birth rate was higher for women with GBC than for women with no cancer (52% vs 7%; AOR 17.5, 95%CI: 11.3-27.3). However, among women with GBC, preterm birth rate did not differ significantly by timing of diagnosis or cancer stage. Babies born to women with GBC were more likely to be preterm (AOR 12.93, 95%CI 8.97-18.64), low birthweight (AOR 8.88, 95%CI 5.87-13.43) or admitted to higher care (AOR 3.99, 95%CI 2.76-5.76) than babies born to women with no cancer. CONCLUSION: Women aged ≥35 years are at increased risk of GBC. There is a high rate of preterm birth among women with GBC, which is not associated with timing of diagnosis or cancer stage. Most births followed induction of labour or pre-labour CS, with no major short term neonatal morbidity.

Epidemiological Characteristics and Transmissibility of Human Immunodeficiency Virus in Nanning City, China, 2001-2020.

Background: Human immunodeficiency virus (HIV) is a single-stranded RNA virus that can weaken the body's cellular and humoral immunity and is a serious disease without specific drug management and vaccine. This study aimed to evaluate the epidemiologic characteristics and transmissibility of HIV. Methods: Data on HIV follow-up were collected in Nanning City, Guangxi Zhuang Autonomous, China. An HIV transmission dynamics model was built to simulate the transmission of HIV and estimate its transmissibility by comparing the effective reproduction number (Reff ) at different stages: the rapid growth period from January 2001 to March 2005, slow growth period from April 2005 to April 2011, and the plateau from May 2011 to December 2019 of HIV in Nanning City. Results: High-risk areas of HIV prevalence in Nanning City were mainly concentrated in suburbs. Furthermore, high-risk groups were those of older age, with lower income, and lower education levels. The Reff in each stage (rapid growth, slow growth, and plateau) were 2.74, 1.62, and 1.15, respectively, which suggests the transmissibility of HIV in Nanning City has declined and prevention and control measures have achieved significant results. Conclusion: Over the past 20 years, the HIV incidence in Nanning has remained at a relatively high level, but its development trend has been curbed. Transmissibility was reduced from 2.74 to 1.15. Therefore, the prevention and treatment measures in Nanning City have achieved significant improvement.

Bibliometric Analysis of the 100 Most Cited Articles on Intervertebral Disk Research: From 1900 to 2017 Year.

STUDY DESIGN: A bibliometric review of the literature. OBJECT: To analyze and quantify the most frequently cited papers in intervertebral disk research. SUMMARY OF BACKGROUND DATA: The number of citations that a paper has received reflects its impact in related research area. In the field of disk research, however, it remains unknown which papers are most cited. By searching related literature databases, we identified the most cited 100 articles that advanced the understanding of the intervertebral disk to provide a historic view of scientific research of the disk. MATERIALS AND METHODS: Intervertebral disk original research-related publications from January 1, 1900 to December 31, 2017 were retrieved from the Web of Science database. Each retrieved article was analyzed using the Cited Reference Search tool to identify the most cited articles. The number of citations, year of publication, publishing journal, authorship, country of publication, and the knowledge maps of keywords were gathered and generated. RESULTS: The number of citations of the 100 selected articles ranges from 209 to 1269, and they were published from 1953 to 2009. Basic research is the most common type of study (n=60), followed by epidemiological study (n=40). Spine published 57 of the most cited 100 papers. The greatest contribution came from the United States of America (n=41), followed by the United Kingdom (n=18) and Japan (n=9). Frequently appearing keywords classified into 3 clusters: "biological study," "clinical study," and "imageological study." The keyword "degeneration" was mentioned the most, 51 items, and the word "development" was the latest hot spot in the most cited articles. CONCLUSIONS: In the field of disk research, some papers were heavily cited more than 100 times, suggesting these studies have substantially contributed to the body of knowledge of the intervertebral disk and findings were widely accepted by related clinicians and scientists.

In utero exposure to breast cancer treatment: a population-based perinatal outcome study.

Chemotherapy during a viable pregnancy may be associated with adverse perinatal outcomes. We conducted a prospective cohort study to examine the perinatal outcomes of babies born following in utero exposure to chemotherapy in Australia and New Zealand. Over 18 months we identified 24 births, of >400 g and/or >20-weeks' gestation, to women diagnosed with breast cancer in the first or second trimesters. Eighteen babies were exposed in utero to chemotherapy. Chemotherapy commenced at a median of 20 weeks gestation, for a mean duration of 10 weeks. Twelve exposed infants were born preterm with 11 by induced labour or pre-labour caesarean section. There were no perinatal deaths or congenital malformations. Our findings show that breast cancer diagnosed during mid-pregnancy is often treated with chemotherapy. Other than induced preterm births, there were no serious adverse perinatal outcomes.

Bupivacaine at clinically relevant concentrations induces toxicity in human intervertebral disc cells via the induction of autophagy in vitro.

It has been reported that bupivacaine, the most widely used local anesthetic to relieve discogenic back pain in clinical settings, is cytotoxic to intervertebral disc (IVD) cells in vitro; however, the precise mechanisms of cytotoxicity induced by bupivacaine remain unclear. Autophagy is an intracellular lysosomal degradation process that is important for cellular survival. The present study investigated the role of autophagy in the survival of IVD cells subjected to bupivacaine treatment. Human nucleus pulposus (NP) cells isolated from IVD cells were exposed to various concentrations of bupivacaine for 2, 6 and 12 h, and analyzed for cellular viability using MTT assay and western blotting. Additionally, autophagosome formation and autophagy­associated biomarkers were evaluated by electron microscopy and western blotting to determine the autophagic activity and signaling alterations in NP cells under bupivacaine treatment. Furthermore, autophagic activity was inhibited in vitro using 3­methyladenine to further analyze the association between autophagy and apoptosis in bupivacaine­treated NP cells. Bupivacaine exhibited time­ and dose­dependent cytotoxic effects on human IVD cells at clinically relevant concentrations. Bupivacaine increased autophagic activity by promoting autophagosome formation, and LC3­II and Beclin­1 production. Additionally, bupivacaine inhibited protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/S6 kinase (S6K) signaling, which is a negative regulator of autophagic activity. Of note, pharmacological inhibition of autophagy alleviated bupivacaine­induced cytotoxicity of IVD cells. The findings indicated that application of clinically relevant concentrations of bupivacaine upregulated autophagic activity via inhibition of Akt/mTOR/S6K signaling. In addition, the inhibition of autophagic activation served as a protective mechanism against bupivacaine­induced cytotoxicity. Collectively, these findings may provide novel insight into the mechanisms underlying cytotoxicity induced by bupivacaine when controlling spine­associated pain.

Efficacy of magnetic resonance imaging with an SPGR sequence for the early evaluation of knee cartilage degeneration and the relationship between cartilage and other tissues.

RATIONALE AND OBJECTIVES: The aim of this study was to investigate the efficacy of magnetic resonance imaging (MRI) with a spoiled gradient-recalled (SPGR) sequence to evaluate early knee cartilage degeneration and the relationship between cartilage and other tissues using a modified Whole-Organ Magnetic Resonance Imaging Score (WORMS). MATERIALS AND METHODS: Eighty-four patients with knee joint pain were evaluated by X-ray and MRI with an SPGR sequence from June 2015 to December 2016. Joint degeneration was graded by two experienced radiologists using the Kellgren-Lawrence (K-L) grading scale. The modified WORMS was used to evaluate cartilage lesions, bone marrow abnormalities, bone cysts, osteophytes, joint effusion and synovitis. The difference between the WORMS of the SPGR and the T2 sequences evaluated by the Wilcoxon signed-rank test was determined, and the relationships between the WORMS features were evaluated by a Spearman correlation. RESULTS: The modified WORMS for the cartilage lesion evaluation was significantly higher with the SPGR sequence than with the T2 sequence (P < 0.05). The cartilage lesions showed a moderate correlation with osteophytes, synovitis and joint effusion (Rs > 0.40, P < 0.05) and weak correlations with bone marrow abnormalities and bone cysts (Rs < 0.4, P < 0.05). CONCLUSION: The modified WORMS evaluation using MRI with the SPGR sequence was much better than the normal sequence for early knee osteoarthritis (OA). The cartilage lesions are associated with bone marrow abnormalities and the other features of OA.