Construction of Switch Modules for CAR-T Cell Treatment Using a Site-Specific Conjugation System.

Chimeric antigen receptor T-cell (CAR-T cell) therapy has become a promising treatment option for B-cell hematological tumors. However, few optional target antigens and disease relapse due to loss of target antigens limit the broad clinical applicability of CAR-T cells. Here, we conjugated an antibody (Ab) fusion protein, consisting of an Ab domain and a SpyCatcher domain, with the FITC-SpyTag (FITC-ST) peptide to form a bispecific safety switch module using a site-specific conjugation system. We applied the safety switch module to target CD19, PDL1, or Her2-expressing tumor cells by constructing FMC63 (anti-CD19), antiPDL1, or ZHER (anti-Her2)-FITC-ST, respectively. Those switch modules significantly improved the cytotoxic effects of anti-FITC CAR-T cells on tumor cells. Additionally, we obtained the purified CD8+ T cells by optimizing a shorter version of the CD8-binding aptamer to generate anti-FITC CD8-CAR-T cells, which combined with the CD4-FITC-ST switch module (anti-CD4) to eliminate the CD4-positive tumor cells in vitro and in vivo. Overall, we established a novel safety switch module by site-specific conjugation to enhance the antitumor function of universal CAR-T cells, thereby expanding the application scope of CAR-T therapy and improving its safety and efficacy.

Translation, cultural adaptation, and validation of the Chinese standardized outcomes in nephrology-hemodialysis fatigue (C-SONG-HD fatigue) scale: a study of Chinese patients undergoing hemodialysis.

OBJECTIVE: This study aimed to translate and culturally adapt the standardized outcomes in nephrology-hemodialysis fatigue (SONG-HD fatigue) scale and to assess the psychometric properties of the Chinese version of the SONG-HD fatigue (C-SONG-HD fatigue) scale. METHODS: Forward and back translations were used to translate the SONG-HD fatigue scale into Chinese. We used the C-SONG-HD fatigue scale to survey Chinese patients undergoing hemodialysis (HD) in China. We examined the distribution of responses and floor and ceiling effects. Cronbach's alpha and McDonald's omega coefficient, intraclass coefficients, and Spearman correlations were used to assess internal consistency reliability, test-retest reliability, and convergent validity, respectively. Responsiveness was also evaluated. RESULTS: In total, 489 participants across southeast China, northwest China, and central China completed the study. The C-SONG-HD fatigue scale had good internal consistency (Cronbach's alpha coefficient 0.861, omega coefficient 0.916), test-retest reliability (intraclass correlation coefficient 0.695), and convergent validity (Spearman correlation 0.691). The analysis of all first-time HD patients did not show notable responsiveness, and only patients with temporary vascular access had good responsiveness with an effect size (ES) of 0.54, a standardized response mean (SRM) of 0.85, and a standard error of measurement (SEM) of 0.77. CONCLUSION: The Chinese version of the SONG-HD fatigue scale showed satisfactory reliability and validity in patients undergoing hemodialysis (HD) in China. It could be used as a tool to measure the fatigue of Chinese HD patients.

[Progress in Gene Polymorphisms Associated With Osteoporosis Susceptibility in Zhuang Ethnic Group in Guangxi].

The purpose of this paper is to systematically summarize the gene polymorphisms associated with osteoporosis(OP)susceptibility in Zhuang ethnic group in Guangxi.These genes mainly encode vitamin D receptor,estrogen receptor,calcitonin receptor,and adiponectin.The genotype and allele distribution frequency were compared between Zhuang ethnic group and other ethnic groups,which can clarify the existing genes and the potential gene polymorphism associated with OP in Zhuang ethnic group.The findings provide a representative solution for the subsequent research on the genes associated with OP susceptibility in ethnic minorities.

Proteome-wide analysis reveals potential therapeutic targets for Colorectal cancer: a two-sample mendelian randomization study.

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer-related mortality, highlighting an unmet clinical need for more effective therapies. This study aims to evaluate the causal relationship between 4,489 plasma proteins and CRC to identify potential therapeutic targets for CRC. METHODS: We conducted two-sample Mendelian randomization (MR) analysis to examine the causal effects of plasma proteins on CRC. Mediation analysis was performed to assess the indirect effects of plasma proteins on CRC through associated risk factors. In addition, we conducted a phenome-wide association study using the UK Biobank dataset to examine associations between these plasma proteins and other phenotypes. RESULTS: Out of 4,489 plasma proteins, MR analysis revealed causal associations with CRC for 23 proteins, including VIMP, MICB, TNFRSF11B, C5orf38 and SLC5A8. Our findings also confirm the associations between reported risk factors and CRC. Mediation analysis identified mediating effects of proteins on CRC outcomes through risk factors. Furthermore, MR analysis identified 154 plasma proteins are causally linked to at least one CRC risk factor. CONCLUSIONS: Our study evaluated the causal relationships between plasma proteins and CRC, providing a more complete understanding of potential therapeutic targets for CRC.

Effects of traditional Chinese culture-based bibliotherapy on the spiritual health of patients with liver cancer.

BACKGROUND: Liver cancer is a serious global health problem and is associated with poor spiritual health. Bibliotherapy is beneficial in improving health outcomes in cancer patients, yet there is a lack of empirical evidence of its effect on the spiritual health of liver cancer patients in China. The study aimed to investigate the effects of bibliotherapy based on Chinese traditional culture on the spiritual health of patients with liver cancer in China. This study was approved by the Ethics Committee of Hunan Normal University School of Medicine and registered with the Chinese Clinical Trial Registry with the registration (No: 2021260), which registration in June 30th 2021. METHODS: A total of 60 patients with liver cancer were divided into the intervention group (n = 30) and the control group (n = 30) through WeChat. The intervention group received bibliotherapy therapy based on traditional Chinese culture, while the control group received routine care. Spiritual health was assessed using the Spiritual Attitude and Involvement List (SAIL) and compared before and after the intervention between the two groups. The chi-square test and t-test were used to analyze the intervention effects. RESULTS: The two groups were comparable in all baseline characteristics including the SAIL score. After 5 weeks of intervention, the score of SAIL increased significantly from 96.76 ± 15.08 to 106.93 ± 13.82 in the intervention group (t = - 29.380, p < 0.001), while no significant difference in SAIL score was observed in the control group (from 95.27 ± 16.40 to 95.31 ± 16.24, t = - 0.189, p = 0.852). Similar patterns were also observed in its three dimensions of connecting with oneself, connecting with the environment, and connecting with transcendence. CONCLUSIONS: Our study showed that bibliotherapy based on traditional Chinese culture using the WeChat platform can greatly improve the spiritual health of patients with liver cancer and has the potential to be widely applied to cancer patients to improve their well-being.

A precise and efficient adenine base editor.

Adenine base editors (ABEs) are novel genome-editing tools, and their activity has been greatly enhanced by eight additional mutations, thus named ABE8e. However, elevated catalytic activity was concomitant with frequent generation of bystander mutations. This bystander effect precludes its safe applications required in human gene therapy. To develop next-generation ABEs that are both catalytically efficient and positionally precise, we performed combinatorial engineering of NG-ABE8e. We identify a novel variant (NG-ABE9e), which harbors nine mutations. NG-ABE9e exhibits robust and precise base-editing activity in human cells, with more than 7-fold bystander editing reduction at some sites, compared with NG-ABE8e. To demonstrate its practical utility, we used NG-ABE9e to correct the frequent T17M mutation in Rhodopsin for autosomal dominant retinitis pigmentosa. It reduces bystander editing by ∼4-fold while maintaining comparable efficiency. NG-ABE9e possesses substantially higher activity than NG-ABEmax and significantly lower bystander editing than NG-ABE8e in rice. Therefore, this study provides a versatile and improved adenine base editor for genome editing.

A clinically feasible circulating tumor cell sorting system for monitoring the progression of advanced hepatocellular carcinoma.

BACKGROUND: Hematogenous metastasis is essential for the progression of advanced hepatocellular carcinoma (HCC) and can occur even after patients receive multidisciplinary therapies, including immunotherapy and hepatectomy; circulating tumor cells (CTCs) are one of the dominant components of the metastatic cascade. However, the CTC capture efficiency for HCC is low due to the low sensitivity of the detection method. In this study, epithelial cell adhesion molecule (EpCAM)/vimentin/Glypican-3 (GPC3) antibody-modified lipid magnetic spheres (LMS) were used to capture tumor cells with epithelial phenotype, mesenchymal phenotype and GPC3 phenotype, respectively, in order to capture more CTCs with a more comprehensive phenotype for monitoring tumor metastasis. RESULTS: The novel CTC detection system of Ep-LMS/Vi-LMS/GPC3-LMS was characterized by low toxicity, strong specificity (96.94%), high sensitivity (98.12%) and high capture efficiency (98.64%) in vitro. A sudden increase in CTC counts accompanied by the occurrence of lung metastasis was found in vivo, which was further validated by a clinical study. During follow-up, the rapid increase in CTCs predicted tumor progression in HCC patients. Additionally, genetic testing results showed common genetic alterations in primary tumors, CTCs and metastatic tissues. The proportion of patients predicted to benefit from immunotherapy with the CTC detection method was higher than that for the tissue detection method (76.47% vs. 41.18%, P = 0.037), guiding the application of clinical individualized therapy. CONCLUSIONS: The Ep-LMS/Vi-LMS/GPC3-LMS sequential CTC capture system is convenient and feasible for the clinical prediction of HCC progression. CTCs captured by this system could be used as a suitable alternative to HCC tissue detection in guiding immunotherapy, supporting the clinical application of CTC liquid biopsy.

Empowerment and quality of life: the mediating role of self-efficacy and health literacy among spousal caregivers in China.

The aim of this study was to explore the chain mediation model of self-efficacy and health literacy between empowerment and quality of life among spousal caregivers of disabled elderly based on 'Marriage Binding'. From December 2020 to June 2022, the cross-sectional study was conducted in hospitals and communities, in Guangdong, Fujian, Sichuan, Hunan, Jiangxi, Guangxi and Yunnan provinces, China. Descriptive statistics were used to describe the demographic data and four main variables, including empowerment, self-efficacy, health literacy and quality of life. Spearman correlation analysis was used to analyze the correlation between the four main research variables. Multiple Linear Regression and bootstrap analysis were used to analyze the direct and indirect effects among them. Any two variables of spousal caregivers were correlated among empowerment, self-efficacy, health literacy and quality of life. Self-efficacy and health literacy can separately and sequentially mediate the relationship between empowerment and quality of life. To improve the quality of life of spousal caregivers of disabled elderly, the mediating role of self-efficacy, the mediating role of health literacy and the chain mediating role of self-efficacy and health literacy should take effect. In the future, some intervention studies should be taken to enhance the effects of those variables that may be beneficial for improving quality of life of spousal caregivers of disabled elderly.

Improved Generative Adversarial Network for Super-Resolution Reconstruction of Coal Photomicrographs.

Analyzing the photomicrographs of coal and conducting maceral analysis are essential steps in understanding the coal's characteristics, quality, and potential uses. However, due to limitations of equipment and technology, the obtained coal photomicrographs may have low resolution, failing to show clear details. In this study, we introduce a novel Generative Adversarial Network (GAN) to restore high-definition coal photomicrographs. Compared to traditional image restoration methods, the lightweight GAN-based network generates more explicit and realistic results. In particular, we employ the Wide Residual Block to eliminate the influence of artifacts and improve non-linear fitting ability. Moreover, we adopt a multi-scale attention block embedded in the generator network to capture long-range feature correlations across multiple scales. Experimental results on 468 photomicrographs demonstrate that the proposed method achieves a peak signal-to-noise ratio of 31.12 dB and a structural similarity index of 0.906, significantly higher than state-of-the-art super-resolution reconstruction approaches.

The Effects of Theta/Beta-based Neurofeedback Training on Attention in Children with Attention Deficit Hyperactivity Disorder: A Systematic Review and Meta-analysis.

Neurofeedback training is a common treatment option for attention deficit hyperactivity disorder (ADHD). Given theta/beta-based neurofeedback (T/B NF) training targets at the electrophysiological characteristics of children with ADHD, benefits for attention may be expected. PsycINFO, PubMed, ScienceDirect, Scopus, and Web of Science were searched through December 31, 2020. Studies were evaluated with Risk of Bias tools. Within-group effects based on Pre- and Post-treatment comparisons of the Intervention Group, and Between-group effects based on the between-group differences from Pre-treatment to Post-treatment were calculated. Nineteen studies met selection criteria for systematic review, 12 of them were included in meta-analysis. Within-group effects were medium at Post-treatment and large at Follow-up. Between-group analyses revealed that T/B NF was superior to waitlist control and physical activities, but not stimulant medication. Results showed that T/B NF has benefits for attention in children with ADHD, however, cautions should be taken when interpreting the findings.

Reliability and validity of ultrasonography in evaluating the thickness, excursion, stiffness, and strain rate of respiratory muscles in non-hospitalized individuals: a systematic review.

OBJECTIVE: To summarize the reliability and validity of ultrasonography in evaluating the stiffness, excursion, stiffness, or strain rate of diaphragm, intercostals and abdominal muscles in healthy or non-hospitalized individuals. LITERATURE SEARCH: PubMed, Embase, SPORTDiscus, CINAHL and Cochrane Library were searched from inception to May 30, 2022. STUDY SELECTION CRITERIA: Case-control, cross-sectional, and longitudinal studies were included if they investigated the reliability or validity of various ultrasonography technologies (e.g., brightness-mode, motion-mode, shear wave elastography) in measuring the thickness, excursion, stiffness, or strain rate of any respiratory muscles. DATA SYNTHESIS: Relevant data were summarized based on healthy and different patient populations. The methodological quality by different checklist depending on study design. The quality of evidence of each psychometric property was graded by the Grading of Recommendations, Assessment, Development and Evaluations, respectively. RESULTS: This review included 24 studies with 787 healthy or non-hospitalized individuals (e.g., lower back pain (LBP), adolescent idiopathic scoliosis (AIS), and chronic obstructive pulmonary disease (COPD)). Both inspiratory (diaphragm and intercostal muscles) and expiratory muscles (abdominal muscles) were investigated. Moderate-quality evidence supported sufficient (intra-class correlation coefficient > 0.7) within-day intra-rater reliability of B-mode ultrasonography in measuring right diaphragmatic thickness among people with LBP, sufficient between-day intra-rater reliability of M-mode ultrasonography in measuring right diaphragmatic excursion in non-hospitalized individuals. The quality of evidence for all other measurement properties in various populations was low or very low. High-quality evidence supported sufficient positive correlations between diaphragm excursion and forced expiratory volume in the first second or forced vital capacity (r > = 0.3) in healthy individuals. CONCLUSIONS: Despite the reported sufficient reliability and validity of using ultrasonography to assess the thickness, excursion, stiffness, and strain rate of respiratory muscles in non-hospitalized individuals, further large-scale studies are warranted to improve the quality of evidence regarding using ultrasonography for these measurements in clinical practice. Researchers should establish their own reliability before using various types of ultrasonography to evaluate respiratory muscle functions. TRIAL REGISTRATION: PROSPERO NO. CRD42022322945.

[Traditional application and modern research progress on new foreign medicinal resources].

Chinese medicinal resources are the material basis for the survival and development of traditional Chinese medicine(TCM)and the sustainable development of Chinese medicinal resources is also an important project for the modernization of TCM in China. With the increasing demand for Chinese medicinal resources in China, over-exploitation has destroyed Chinese medicinal resources, resulting in a shortage of many natural medicinal resources in China and making the sustainable development of TCM in trouble. The introduced new foreign medicinal resources have become effective supplement and replacement for Chinese medicinal resources to some extent. However, the development and utilization of new foreign medicinal resources in China are different. To fully understand the development of new foreign medicinal resources in China, this paper, taking 43 new foreign medicinal resources such as Acacia nilotica as objects, sorted out the introduction forms and policies of new foreign medicinal resources, overviewed its current development status in China, summarized the application experience of new foreign medicinal resources in the place of origin, as well as the research progress and problems of new foreign medicinal resources in China and abroad, and analyzed the research situation, which can enrich Chinese medicinal resources and other uses, promote the sustainable development of Chinese medicinal resources, and provide ideas for further development and research of new foreign medicinal resources.

[Research progress in pathogenesis and traditional Chinese medicines treatment of ischemic stroke-related headache].

Headache is a common clinical complication of ischemic stroke. As a precursor of stroke, headache occurs repeatedly in the convalescent period of ischemic stroke, leading to secondary stroke and seriously hindering patients' rehabilitation. Currently, it is believed that the pathogenesis of ischemic stroke-related headache is associated with the abnormal release of vasoactive substances, high platelet aggregation, and stimulation of intracranial pain-sensitive structures. The active ingredients in traditional Chinese medicines(TCM) with the effects of activating blood to resolve stasis and clearing heat to release exterior can protect brain tissue and relieve headache by reducing the release of inflammatory cytokines, alleviating antioxidant stress, inhibiting neuronal apoptosis and so on. This paper introduces the research progress in the potential mechanism and TCM treatment of ischemic stroke-related headache, aiming to provide reference for further research and drug development of this complication.

Progress in the genetics of uveitis.

Uveitis is the most common form of intraocular inflammatory disease and is a significant cause of visual impairment worldwide. Aetiologically, uveitis can also be classified into infectious uveitis and non-infectious uveitis. The common non-infectious forms of uveitis include acute anterior uveitis (AAU), Behçet's disease (BD), Vogt-Koyanagi-Harada (VKH) disease, birdshot chorioretinopathy (BSCR), sarcoid uveitis. In addition, a few monogenic autoinflammatory disorders can also cause uveitis, such as Blau Syndrome and haploinsufficiency of A20 (HA20). Although the exact pathogenesis of non-infectious uveitis is still unclear, it is well-recognised that it involves both genetic and environmental risk factors. A hallmark of uveitis is its strong associations with human leucocyte antigens (HLA). For examples, AAU, BD and BSCR are strongly associated with HLA-B27, HLA-B51, and HLA-A29, respectively. In uveitis studies, multiple GWAS have successfully been conducted and led to identification of novel susceptibility loci, for example, IL23R has been identified in BD, VKH and AAU. In this review, we summarize the latest progress on the genetic associations of both HLA and non-HLA genes with major forms of uveitis, including AAU, BD, VKH, BSCR, sarcoid uveitis, Blau Syndrome and HA20, and potential future research directions.

Age increased the cancer-specific mortality risk of thyroid cancer with lung metastasis.

OBJECTIVE: To investigate the relationship between age and cancer-specific mortality in thyroid cancer (TC) with lung-metastasis. PATIENTS AND METHODS: A total of 1418 patients with initial distant metastases from Surveillance, Epidemiology, and End Results databases were investigated. Patients with a median follow-up time of 8 months (interquartile range [IQR]: 2-27] and a median age of 66 years (IQR: 55-76) were divided into five groups by age and the association between age and TC-specific mortality was analysed. RESULTS: The TC-specific mortality rates were 32.78% (118/360), 46.71% (156/334), 53.93% (199/369), 58.96% (158/268) and 82.76% (72/87) in patients aged ≤55 years, >55 but ≤65 years, >65 but ≤75 years, >75 but ≤85 years and >85 years. Kaplan-Meier curves showed that TC-specific mortality rate was associated with increased age (p < .001). Compared with patients ≤55 years, patients aged >55 but ≤65 years, >65 but ≤75 years, >75 but ≤85 years and >85 years had significantly higher hazard ratios (HRs) of 1.69 (1.26-2.26), 1.97 (1.47-2.64), 2.18 (1.59-2.99) and 3.24 (2.08-5.06) after adjustments for sex, tumour size and radiation therapy (all p < .001). In TC with initial lung-metastasis, compared with patients ≤55 years, patients aged >55 but ≤65 years, >65 but ≤75 years, >75 but ≤85 years and >85 years had significantly higher adjusted HRs of 1.68 (1.20-2.36; p = .003), 2.18 (1.57-3.02), 2.16 (1.51-3.08) and 2.91 (1.79-4.75; p < .001). Similar results were obtained in papillary TC. CONCLUSIONS: The TC-specific mortality was increased with age in TC patients with initial lung-metastasis, indicating that further risk stratification based on age was necessary for TC over 55 years with lung-metastasis. Individual treatment strategies maybe recommended for such patients.

Application of Multiparametric Magnetic Resonance Imaging to Monitor the Early Antitumor Effect of CuS@GOD Nanoparticles in a 4 T1 Breast Cancer Xenograft Model.

BACKGROUND: We have developed hybrid nanoparticles (NPs) by co-loading copper sulfide (CuS) NPs and glucose oxidase (GOD) (CuS@GOD NPs) to explore their antitumor properties. PURPOSE: To investigate the feasibility of using multiparametric magnetic resonance imaging (MRI) including intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and R2 * mapping to quantitatively assess the early antitumor effect of CuS@GOD NPs. STUDY TYPE: Prospective. ANIMAL MODEL: The orthotopic BALB/c mice 4 T1 breast cancer model. The 4 T1 xenografts in group 1 mice received normal saline, group 2 received CuS@GOD NPs, group 3 received CuS NPs plus laser, and group 4 received CuS@GOD NPs plus laser (n = 28 for each group). FIELD STRENGTH/SEQUENCE: A 3.0 T/IVIM-DWI MRI single-shot echo-planar imaging, R2 * mapping spoiled gradient recalled echo (SPGR) sequence, T2-weighted images (T2WI) and T1-weighted images (T1WI) fast spin echo (FSE) sequence. ASSESSMENT: The IVIM-DWI and R2 * mapping were performed before and after treatment at 0 hour, 0.5 hour, 1 hour, 2 hours, 4 hours, and 24 hours in four groups and the MRI parameters were obtained. Correlation analysis between the MRI parameters and histological analyses was conducted. STATISTICAL TESTS: One-way ANOVA, Pearson's correlation analysis, two independent samples t test, intraclass correlation coefficient. P < 0.05 was considered to be statistically significant. RESULTS: In group 4, the tumoral D value was significantly higher than that of group 2 at 24 hours (0.541 ± 0.065 vs. 0.492 ± 0.051). The f value of group 4 was significantly lower than that of groups 1 and 2 at 2 hours (10.83 ± 2.16 vs. 14.28 ± 1.86, 16.67 ± 3.53, respectively). The R2 * value was significantly increased at 0 hour in group 4 compared to that of groups 1 and 2 (64.552 ± 4.663 vs. 42.441 ± 1.516, 43.165 ± 1.709, respectively). D, f, and R2 * were correlated with the histological staining results (r = 0.695-0.970). DATA CONCLUSION: The IVIM-DWI-derived D and f and R2 * mapping-derived R2 * could monitor early response to CuS@GOD NPs treatment in vivo. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Clinical performance of quantitative PCR for the molecular identification of skeletal tuberculosis from formalin-fixed paraffin-embedded tissues.

BACKGROUND: At present, skeletal tuberculosis (TB) diagnosis is mostly by histopathology, but the positivity rate is low. There is a need to develop new methods for the molecular identification of this disorder. Therefore, we aimed to investigate the clinical utility of quantitative PCR (qPCR)-based diagnosis of skeletal TB from formalin-fixed paraffin-embedded (FFPE) tissues and its comparative evaluation with acid-fast bacillus staining (AFS). METHODS: We detected Mycobacterium tuberculosis (M. tuberculosis/MTB) DNA using qPCR and AFS in FFPE tissue samples from 129 patients suspected of having skeletal TB. The sensitivity, specificity as well as area under the curve (AUC) of qPCR and AFS were calculated. Meanwhile, some factors potentially affecting qPCR and AFS results were investigated. RESULTS: Overall, qPCR outperformed AFS in detecting M. tuberculosis. The AUC of qPCR was higher than that of AFS (0.744 vs.0.561, p < 0.001). Furthermore, decalcification of bone tissues did not affect the sensitivity and specificity of qPCR tests. Whereas it impacted the performance of AFS, decalcification increased AFS's specificity and decreased its sensitivity (p < 0.05). Moreover, qPCR had a significantly larger AUC than AFS in decalcified and non-decalcified groups (0.735/0.756 vs. 0.582/0.534, p < 0.001) respectively. Similarly, the AUC of PCR was more extensive than that of AFS regardless of skeletal TB patients with concomitant pulmonary TB or not (0.929 vs. 0.762; 0.688 vs. 0.524, p < 0.01). CONCLUSIONS: Our data demonstrate that qPCR offers superior accuracy for the detection of mycobacteria in FFPE tissues compared to traditional AFS, indicating its clinical value in osteoarticular TB diagnosis.

Burkholderia cepacia-A rare but important cause of refractory peritonitis in patients with continuous ambulatory peritoneal dialysis: A case report and literature review.

Refractory peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) caused by Burkholderia cepacia is very rare. Herein, we describe a case of B. cepacia-related refractory peritonitis and present a literature review of similar cases. A 62-year-old male patient presented with diffuse abdominal pain, bloating, and turbid peritoneal effluent. Initial dialysis effluent culture was negative for any microorganism. The patient initially underwent treatment with piperacillin-sulbactam. The second dialysis effluent culture was positive for gram stain and later tested positive for B. cepacia. Peritoneal dialysis (PD) catheter removal was recommended, and the patient agreed to undergo regular hemodialysis. To the best of our knowledge, this is the first case of B. cepacia-related refractory peritonitis in a patient undergoing CAPD with no history of a recent hospitalization. B. cepacia infections can result in death in some areas. Therefore, timely catheter removal and switching treatment to hemodialysis is recommended for patients with B. cepacia-related refractory peritonitis.

Synthesis of 8-Fluoroneocryptolepine and Evaluation for Cytotoxic Activity against AGS Cancer Cells.

Neocryptolepine derivatives have attracted great interest because of their unique cytotoxic activity. 8-Fluoroneocryptolepine (8FNC) was synthesized, and its cytotoxicity was evaluated by MTT assay in AGS gastric cancer cells and gastric mucosa GES-1 cells. 8-Fluoroneocryptolepine showed greater selectivity and cytotoxicity to AGS cells than the cisplatin (CIS) and fluorouracil (5-Fu) commonly used in clinical treatment of gastric cancer. Most importantly, we significantly improved the cytotoxic effect of 8FNC against AGS cells by structural modification and reduced the cytotoxicity against GES-1 cells compared with neocryptolepine. We further evaluated the activity of 8FNC against AGS cells in vitro. Our results indicate that 8FNC arrests the AGS cell cycle in the G2/M phase, reduces the mitochondrial membrane potential of AGS cells, and drives the initiation of apoptotic body formation in 8FNC-induced apoptosis. Moreover, 8FNC exhibits strong inhibitory effects on AGS cell migration. Studies on the molecular mechanisms of the cytotoxic activities of 8FNC revealed that it may play a significant role in the inhibitory effect on AGS human gastric cancer cells through the PI3K/AKT signaling pathway. In conclusion, 8FNC may become a promising lead compound in the development of potential clinical drug candidates for the treatment of gastric cancer.

Examining the effects of second-and third-trimester gestational weight gain rates on the perinatal outcomes among Chinese twin pregnancies: a retrospective cohort study.

BACKGROUND: This paper investigated how second- and third-trimester gestational weight gain relates to perinatal outcomes among normal weight women with twin pregnancies in Fujian, China. METHODS: A retrospective study examining the medical records of 931 normal weight twin-pregnant women was conducted in Fujian Maternity and Child Health Hospital from 2014 to 2018.The 2nd and 3rdtrimester weekly weight gain rates were calculated, and women were categorized as gaining below, within, or above the 2009 Institute of Medicine (IOM) recommended rates. The association between the trimester-specific weight gain rate and perinatal outcome was determined by traditional regression analysis among groups. RESULTS: A total of 25.9%, 19.8% and 54.3% of women had rates of weight gain across the 2nd and 3rd trimesters less than, greater than or within the recommended rates respectively. Multivariate logistic regression analysis showed that weight gain greater than the recommended rate in the 2nd trimester was associated with a decreased risk of preeclampsia (aOR:0.489,95%CI:0.289 ~ 0.974). Weight gain less than the recommended rate of weight gain in the 3rd trimester was associated with increased risks of premature delivery(aOR:2.079, 95%CI:1.467 ~ 2.968), gestational diabetes mellitus (aOR: 2.048, 95%CI:1.411 ~ 2.971), intrahepatic cholestasis syndrome (aOR:3.015,95%CI: 1.058 ~ 8.587), pre-labour rupture of membrane (aOR: 1.708,95%CI: 1.169 ~ 2.493), average twin birth weight < 2500 g(aOR:1.532,95%CI: 1.125 ~ 2.084) and neonatal respiratory distress syndrome (aOR:4.934,95%CI:1.626 ~ 15.083) and was associated with decreased risks of caesarean section (aOR:0.589,95%CI:0.386 ~ 0.898) and preeclampsia (aOR:0.471, 95%CI:0.274 ~ 0.808). In addition, weight gain greater than the recommended rate of weight gain in the 3rd trimester was associated with increased risks of premature delivery (aOR:1.589,95%CI:1.428 ~ 2.951) and gestational hypertension (aOR:2.137,95% CI:1.034 ~ 4.415) as well as preeclampsia (aOR:2.246, 95%CI:1.462 ~ 3.452). The stratified analysis of weight gain in the 3rd trimester showed that there was no significant difference in the incidence of adverse pregnancy outcomes compared to the 2nd trimester weight gain groups. CONCLUSIONS: While this study showed that a gestational weight gain rate above or below the recommendation in the 3rd trimester was associated with some adverse maternal and neonatal outcomes, further prospective and multicentre studies are required to explore alternate ranges of gestational weight gain rates in twin pregnancies.