bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Soybean Lecithin on Growth Performance, Intestine Morphology, and Liver Tissue Metabolism in Rock Bream (Oplegnathus fasciatus) Larvae
Authors: Tan Peng , Zhang Pian , Zhang Lei , Zhu Wenliang , Wang Ligai , Chen Ruiyi , Zhu Qihui , Xu Dongdong
Published: July 2022

Investigations have demonstrated a strong and positive association between dietary intact phospholipid (PL) inclusion and aquatic larval growth, nevertheless, the precise molecular mechanism underlying PL inclusion on growth performance has not been well elucidated. This study aimed to investigate the effects of dietary soybean lecithin (SL) inclusion on growth performance, liver metabolism, resistance to hypoxia stress, and potential molecular mechanisms in rock bream (Oplegnathus fasciatus) larvae. Four types of equal-protein and equal-lipid content microdiets (MDs) were formulated with graded levels of SL to achieve phospholipid levels of (PLs, dry matter) 3.84% (SL0), 6.71% (SL4), 9.38% (SL8), and 12.21% (SL12). Rock bream larvae (25 days post-hatching) were fed the respective MDs for 30 days with three replicates. We found that dietary SL inclusion promoted growth performance, survival rate, and stress resistance to hypoxia stress. The increased dietary SL inclusion improved intestinal structure, as shown by the increased perimeter ratio, muscular thickness, and mucosal fold height of the mid-intestinal tissue. Moreover, a high SL inclusion diet (SL12) increased the activity of the key lipolysis-related enzyme (lipase [LP]) in liver tissue but decreased the activity of amino acid catabolism-related enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]). RNA sequencing results in liver tissue revealed that the SL12 diet increased the transcriptional level of fatty acid activation-related genes (acsl6 and acsbg2), phospholipid catabolism-related genes (acat2, lpin2, and crls), and amino acid synthesis-related genes (gs, csb, aldh18a1, and oct), but decreased the expression of amino acid catabolism-related gene gprt2. Notably, the SL12 diet significantly increased the expression of ribosome biogenesis-related genes (pes1, nop56, nop58, and rpf2) in liver tissue. The ribosome protein-related pathways were the most enriched pathways mapped in the GO database. Collectively, this study demonstrated the necessity of dietary SL for survival, growth performance, promotion of mid-intestinal morphology, and hypoxia stress during the rock bream larval stage. The SL-induced growth performance promotion was likely attributed to increasing nutrient acquisition by intestinal morphology improvement and to increasing SL catabolism and thereby sparing amino acids for protein synthesis.
Scaled Fracture Toughness Based on the Weibull Stress for the Ferritic Steel Used in Nuclear Power Plants
Authors: Jin Weiya , Li Yan , Li Yuebing , Zhou Mingjue
Published: July 2022

As an important material property in structural integrity assessment of nuclear power components, fracture toughness can be measured by single edge-notched bend (SENB) specimens or compact tension (CT) specimens. However, the tested values may be inhomogeneous with the crack size and specimen thickness. Some toughness scaling models (TSMs) were proposed to transfer the tested value to fracture toughness under small-scale yielding. Combined with the tested data by SENB specimens with different crack sizes and CT specimens with different thicknesses, the scaled fracture toughness is investigated on the global and local approaches to fracture. Using the scaled toughness values, the Weibull scale parameter K0 is estimated and compared for the ferritic steel DIN 22NiMoCr37 widely used in nuclear power plants. The results show that the estimated scale parameter K0 using the scaled toughness obtained by the global approach on the J-Q theory is reasonable in agreement with that of the local approach on the Weibull stress with a relative error of about 10%.
Pyruvate as a Potential Beneficial Anion in Resuscitation Fluids
Authors: Zhou Fang-Qiang
Published: July 2022

There have been ongoing debates about resuscitation fluids because each of the current fluids has its own disadvantages. The debates essentially reflect an embarrassing clinicalstatus quothat all fluids are not quite ideal in most clinical settings. Therefore, a novel fluid that overcomes the limitations of most fluids is necessary for most patients, particularly diabetic and older patients. Pyruvate is a natural potent antioxidant/nitrosative and anti-inflammatory agent. Exogenous pyruvate as an alkalizer can increase cellular hypoxia and anoxia tolerance with the preservation of classic glycolytic pathways and the reactivation of pyruvate dehydrogenase activity to promote oxidative metabolism and reverse the Warburg effect, robustly preventing and treating hypoxic lactic acidosis, which is one of the fatal complications in critically ill patients. In animal studies and clinical reports, pyruvate has been shown to play a protective role in multi-organ functions, especially the heart, brain, kidney, and intestine, demonstrating a great potential to improve patient survival. Pyruvate-enriched fluids including crystalloids and colloids and oral rehydration solution (ORS) may be ideal due to the unique beneficial properties of pyruvate relative to anions in contemporary existing fluids, such as acetate, bicarbonate, chloride, citrate, lactate, and even malate. Preclinical studies have demonstrated that pyruvate-enriched saline is superior to 0.9% sodium chloride. Moreover, pyruvate-enriched Ringer’s solution is advantageous over lactated Ringer’s solution. Furthermore, pyruvate as a carrier in colloids, such as hydroxyethyl starch 130/0.4, is more beneficial than its commercial counterparts. Similarly, pyruvate-enriched ORS is more favorable than WHO-ORS in organ protection and shock resuscitation. It is critical that pay attention first to improving abnormal saline with pyruvate for ICU patients. Many clinical trials with a high dose of intravenous or oral pyruvate were conducted over the past half century, and results indicated its effectiveness and safety in humans. The long-term instability of pyruvate aqueous solutions and para-pyruvate cytotoxicity is not a barrier to the pharmaceutical manufacturing of pyruvate-enriched fluids for ICU patients. Clinical trials with sodium pyruvate-enriched solutions are urgently warranted.
Assessing Public Health and Social Measures Against COVID-19 in Japan From March to June 2021
Authors: Hayashi Katsuma , Kayano Taishi , Anzai Asami , Fujimoto Marie , Linton Natalie , Sasanami Misaki , Suzuki Ayako , Kobayashi Tetsuro , Otani Kanako , Yamauchi Masato , Suzuki Motoi , Nishiura Hiroshi
Published: July 2022

Background

Public health and social measures (PHSM) against COVID-19 in Japan involve requesting the public to voluntarily reduce social contact; these measures are not legally binding. The effectiveness of such PHSM has been questioned with emergence of the SARS-CoV-2 Alpha variant (B.1.1.7), which exhibited elevated transmissibility.

Materials and Methods

We investigated the epidemic dynamics during the fourth epidemic wave in Japan from March to June 2021 involving pre-emergency measures and declaration of a state of emergency (SoE). We estimated the effective reproduction number (Rt) before and after these interventions, and then analyzed the relationship between lower Rt values and each PHSM.

Results

With implementation of pre-emergency measures (PEM) in 16 prefectures, the Rt was estimated to be < 1 in six prefectures; its average relative reduction ranged from 2 to 19%. During the SoE, 8 of 10 prefectures had an estimated Rt < 1, and the average relative reduction was 26%–39%. No single intervention was identified that uniquely resulted in an Rt value < 1.

Conclusion

An SoE can substantially reduce the Rt and may be required to curb a surge in cases caused by future SARS-CoV-2 variants of concern with elevated transmissibility. More customized interventions did not reduce the Rt value to < 1 in this study, but that may be partly attributable to the greater transmissibility of the Alpha variant.
A Selective Medium for Screening Ceftazidime/Avibactam Resistance in Carbapenem-Resistant Enterobacterales
Authors: Zeng Weiliang , Liao Wenli , Zhao Yajie , Wang Lingbo , Shu Hongyun , Jia Huaiyu , Chen Tao , Zhang Ying , Zhou Tieli , Wu Qing
Published: July 2022

Ceftazidime/avibactam (CZA) is an alternative antibiotic used for the treatment of infections caused by carbapenem-resistant Enterobacterales (CRE). However, the CZA-resistant CRE strains have been detected worldwide. Therefore, it is critical to screen CZA-resistant CRE strains in colonized patients or a specific population so as to rapidly implement infection control measures to limit their transmission. In this study, we developed a Salmonella-Shigella (SS) CZA-selective medium and assessed its performance to screen for clinical CZA-resistant CRE isolates in both pure-strain specimens and stool samples. A total of 150 non-duplicated isolates, including 75 CZA-susceptible and 75 CZA-resistant CRE pathogens, were tested by using the broth microdilution method and the SS CZA medium, respectively. The bacterial suspensions were serially diluted in the SS CZA medium, which showed excellent screening performance in both pure CZA-resistant CRE strain and the stool samples with the lowest detection limit of 101-102 and 101-103 CFU/ml, respectively. Notably, none of the susceptible isolates showed growth even at the highest dilution concentration of 108 CFU/ml. Most importantly, the SS CZA medium demonstrated excellent performance in screening simulated clinical polymicrobial specimens. Moreover, its screening performance was unaffected by the different resistance determinants for tested isolates. Cumulatively, our data suggest that the SS CZA medium can be used as a promising selective medium to screen CZA-resistant CRE, irrespective of their resistance mechanisms.
Deoxythymidylate Kinase as a Promising Marker for Predicting Prognosis and Immune Cell Infiltration of Pan-cancer
Authors: Lan Tianfeng , Wang Yachao , Miao Jinxin , Guo Haoran , Wang Zheng , Wang Jianyao , Zhang Chunyang , Yang Panpan , Zhang Zhongxian , Dunmall Louisa Chard , Wang Yaohe
Published: July 2022

Background: Deoxythymidylate kinase (DTYMK) serves as a pyrimidine metabolic rate-limiting enzyme that catalyzes deoxythymidine monophosphate (dTMP) to generate deoxythymidine diphosphate (dTDP). It remains unclear whether DTYMK expression has the potential to predict outcome and immune cell infiltration in cancers.

Methods: DTYMK expression profile was analyzed using Oncomine, TIMER, GEPIA and UALCAN databases. The influence of DTYMK on immune infiltration was examined using TIMER and TISIDB databases. DTYMK interactive gene hub and co-expressing genes were obtained and analyzed by STRING and Linkedomics, respectively. The relationship between DTYMK expression and patient prognosis was validated using GEPIA, Kaplan-Meier plotter, and PrognoScan databases. The functions of DTYMK in cancer cells were also biologically validated in vitro.

Results: DTYMK expression was elevated in tumor tissues compared with their control counterparts. DTYMK expression varied in different stages and discriminatorily distributed in different immune and molecular subtypes. Higher expression of DTYMK predicted worse outcome in several cancer types such as liver hepatocellular carcinoma (LIHC) and lung adenocarcinoma (LUAD). High DTYMK expression was positively or negatively correlated with immune cell infiltration, including B cell, CD8+ cell, CD4+ T cell, macrophage, neutrophil and dendritic cell, depending on the type of cancers. Additionally, DTYMK co-expressing genes participated in pyrimidine metabolism as well as in T helper cell differentiation in LIHC and LUAD. In vitro, knockdown of DTYMK suppressed cell migration of liver and lung cancer cells.

Conclusion: DTYMK might be taken as an useful prognostic and immunological marker in cancers and further investigation is warrented.
Dopamine D2-Subtype Receptors Outside the Blood-Brain Barrier Mediate Enhancement of Mesolimbic Dopamine Release and Conditioned Place Preference by Intravenous Dopamine
Authors: Obray J. Daniel , Small Christina A. , Baldwin Emily K. , Jang Eun Young , Lee Jin Gyeom , Yang Chae Ha , Yorgason Jordan T. , Steffensen Scott C.
Published: July 2022

Dopamine (DA) is a cell-signaling molecule that does not readily cross the blood-brain barrier. Despite this, peripherally administered DA enhances DA levels in the nucleus accumbens and alters DA-related behaviors. This study was designed to investigate whether DA subtype-2 receptors are involved in the enhancement of nucleus accumbens (NAc) DA levels elicited by intravenous DA administration. This was accomplished by using microdialysis in the NAc and extracellular single unit recordings of putative DA neurons in the ventral tegmental area (VTA). Additionally, the reinforcing properties of intravenous DA were investigated using a place conditioning paradigm and the effects of intravenous DA on ultrasonic vocalizations were assessed. Following administration of intravenous dopamine, the firing rate of putative DA neurons in the VTA displayed a biphasic response and DA levels in the nucleus accumbens were enhanced. Pretreatment with domperidone, a peripheral-only DA D2 receptor (D2R) antagonist, reduced intravenous DA mediated increases in VTA DA neuron activity and NAc DA levels. Pretreatment with phentolamine, a peripheral α-adrenergic receptor antagonist, did not alter the effects of IV DA on mesolimbic DA neurotransmission. These results provide evidence for peripheral D2R mediation of the effects of intravenous DA on mesolimbic DA signaling.
Electrophysiological Evidence of Local Sleep During Yoga Nidra Practice
Authors: Datta Karuna , Mallick Hruda Nanda , Tripathi Manjari , Ahuja Navdeep , Deepak K. K.
Published: July 2022

Background and Objectives

Yoga nidra is a technique sages use to self-induce sleep. Classically, sleep is characterized by three cardinal electrophysiological features, namely, electroencephalography (EEG), electromyography (EMG), and electrooculography (EOG). As the literature on electrophysiological characterization of Yoga nidra is lacking, it is not known whether it is a sleep or awake state. The objective of the study was to electrophysiologically characterize yoga nidra practice.

Materials and Methods

Thirty subjects underwent five initial supervised yoga nidra sessions and then continued practice on their own. The subjects completed their sleep diaries for 2 weeks before and during the intervention. The electrophysiological characterization was done after 2 weeks of yoga nidra practice using 19 EEG channels polysomnography for pre-yoga nidra, yoga nidra practice and post-yoga nidra. Polysomnographic data were scored for sleep-wake stages as per standard criteria. Power spectral density (PSD) was calculated from various frequency bands in different time bins. EEG data were grouped by areas, namely, central, frontal, prefrontal, parietal, temporal, and occipital in time bins. Sleep diary parameters were also compared for pre-post-yoga nidra training.

Results

After 2 weeks of yoga nidra practice, awake was scored throughout the session (n = 26). PSD results (mean difference in dB between different time bins; P value) showed significant changes. When compared to pre-yoga nidra, there was an increase in delta power in the central area (1.953; P = 0.033) and a decrease in the prefrontal area (2.713; P = 0.041) during yoga nidra. Sleep diary showed improvement in sleep duration (P = 0.0001), efficiency (P = 0.0005), quality (P = 0.0005), and total wake duration (P = 0.00005) after 2 weeks of practice.

Interpretations and Conclusions

Yoga nidra practice in novices is electrophysiologically an awake state with signs of slow waves locally, often referred to as local sleep.

Clinical Trial

Clinical Trial Registry of India, http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php? trialid = 6253, 2013/05/003682.
Real-World Experience Treating Pediatric Epilepsy Patients With Cenobamate
Authors: Makridis Konstantin L. , Bast Thomas , Prager Christine , Kovacevic-Preradovic Tatjana , Bittigau Petra , Mayer Thomas , Breuer Eva , Kaindl Angela M.
Published: July 2022

Introduction

In one third of all patients with epilepsy, seizure freedom is not achieved through anti-seizure medication (ASM). These patients have an increased risk of earlier death, poorer cognitive development, and reduced quality of life. Cenobamate (CNB) has recently been approved as a promising novel ASM drug for the treatment of adults with focal-onset epilepsy. However, there is little experience for its application in pediatric patients.

Methods

In a multicenter study we evaluated retrospectively the outcome of 16 pediatric patients treated “off label” with CNB.

Results

In 16 patients with a mean age of 15.38 years, CNB was started at an age of 15.05 years due to DRE. Prior to initiation of therapy, an average of 10.56 (range 3–20) ASM were prescribed. At initiation, patients were taking 2.63 (range 1–4) ASM. CNB was increased by 0.47 ± 0.27mg/kg/d every 2 weeks with a mean maximum dosage of 3.1 mg/kg/d (range 0.89–7) and total daily dose of 182.81 mg (range 50–400 mg). Seizure freedom was achieved in 31.3% and a significant seizure reduction of >50% in 37.5%. Adverse events occurred in 10 patients with fatigue/somnolence as the most common. CNB is taken with high adherence in all but three patients with a median follow-up of 168.5 days

Conclusion

Cenobamate is an effective ASM for pediatric patients suffering from drug-resistant epilepsy. In addition to excellent seizure reduction or freedom, it is well-tolerated. Cenobamate should be considered as a novel treatment for DRE in pediatric patients.
Relationship Between Gross Motor Skills and Inhibitory Control in Preschool Children: A Pilot Study
Authors: Liu Jiajia , Li Yiyan , Zhou Tang , Lu Yanhua , Sang Menghao , Li Longkai , Fang Chunyi , Hu Wenwen , Sun Xiaojiao , Quan Minghui , Liu Jinyan
Published: July 2022

Purpose

Gross motor skills (GMS) and inhibitory control (IC) which are both development in preschool stage is significant for preschooler to healthy growth. However, the evidence of relationship between them in preschoolers are still insufficient, most of studies only focus on youth. Thus, the aim of this research is to examine the association between GMS and IC in preschool children.

Methods

This cross-sectional study used baseline data from a previous intervention study of preschoolers conducted in 2018. GMS were assessed by using the Test for Gross Motor Development (2nd edition) in preschoolers, which includes two subtests of locomotor and object control skills. Total GMS is calculated from the sum of these two subtests. The Fish Flanker task was used to evaluate both accuracy and reaction time of IC. Multivariate linear regression models were established to analyze the relationships between GMS and IC.

Results

A total of 123 preschool-age children (55 girls, 68 boys) were included in the final analysis. After adjusting for confounders, GMS (β = −8.27 ms, 95%CI: −14.2, −2.34), locomotor (β = −11.2 ms, 95%CI: −21.43, −0.97), and object control skills (β = −12.15 ms, 95%CI: −22.07, −2.23) were all negatively related with reaction time of IC.

Conclusion

There was a significant negative correlation between gross motor skills and the reaction time of inhibitory control in preschool children. Further research is needed to verify this finding in prospective and experimental studies.
Infra-Low Frequency Neurofeedback: A Systematic Mixed Studies Review
Authors: Bazzana Fabian , Finzi Sarah , Di Fini Giulia , Veglia Fabio
Published: July 2022

Introduction

Neurofeedback training is increasingly applied as a therapeutic tool in a variety of disorders, with growing scientific and clinical interest in the last two decades. Different Neurofeedback approaches have been developed over time, so it is now important to be able to distinguish between them and investigate the effectiveness and efficiency characteristics of each specific protocol. In this study we intend to examine the effects of Neurofeedback based on slow brain activity, the so-called Infra-Low Frequency (ILF) training a recently developed methodology that seems promising for the regulation of the central nervous system.

Aims

With this review we intend to summarize the currently existing literature on ILF-Neurofeedback, examine its quality and formulate indications about the clinical effectiveness of ILF-Neurofeedback.

Methods

Literature search was first conducted according to PRISMA principles, described, and then assessed using the MMAT appraisal tool. 18 well-documented studies of ILF-Neurofeedback training in human subjects were picked up and analyzed. Reports include group interventions as well as single case studies.

Results

Research data indicates good potential for ILF-Neurofeedback to influence brain activity and neurovegetative parameters. From the clinical profile, a salient common observation is a high level of individualization as a specific characteristic of ILF-Training: this feature seems to correlate with effectiveness of ILF-Neurofeedback, but also poses a challenge for researchers in terms of producing controlled and comparable findings; according to this point, some recommendation for future research on ILF-Neurofeedback are proposed. In conclusion, ILF-neurofeedback shows great potential for application for all those conditions in which the regulation of brain activity and neurophysiological processes are crucial. Further research will make it possible to complete the available data and to have a broader overview of its possible applications.
Motor Cortex Response to Pleasant Odor Perception and Imagery: The Differential Role of Personality Dimensions and Imagery Ability
Authors: Infortuna Carmenrita , Gualano Francesca , Freedberg David , Patel Sapan P. , Sheikh Asad M. , Muscatello Maria Rosaria Anna , Bruno Antonio , Mento Carmela , Chusid Eileen , Han Zhiyong , Thomas Florian P. , Battaglia Fortunato
Published: July 2022

Background

Neuroimaging studies have shown a complex pattern of brain activation during perception of a pleasant odor and during its olfactory imagery. To date, little is known regarding changes in motor cortex excitability during these tasks. Bergamot essential oil (BEO) is extensively used in perfumes and cosmetics for its pleasantness. Therefore, to further our understanding of the human sense of smell, this study aimed to investigate the effect of perception and imagery of a pleasant odor (BEO) on motor cortex using Transcranial magnetic stimulation (TMS).

Materials and Methods

We examined the primary motor cortex (M1) excitability during perception of a pleasant odor (BEO) or perception of odorless saline (experiment 1). Furthermore, we tested the effect of olfactory imagery (OI) of BEO on corticospinal excitability (experiment 2). The increase in motor evoked potential (MEP) amplitude was correlated with personality dimensions scores, pleasantness, vividness, and general imagery ability.

Results

The results indicate that the corticospinal excitability changed after both perception and imagery of a pleasant odor (BEO). The correlation analysis shows an association with neuroticism personality trait (experiment 1) and with general olfactory imagery ability (experiment 2).

Conclusion

Both perception of a pleasant odor and its olfactory imagery modulate motor cortex excitability. The enhanced brain activation is affected by specific individual characteristics. Overall, our findings provide physiological evidence for a complex interaction between the olfactory and motor systems.
Cochlear Implantation in Hearing-Impaired Elderly: Clinical Challenges and Opportunities to Optimize Outcome
Authors: Illg Angelika , Lenarz Thomas
Published: July 2022

Cochlear implant (CI) overall provides a very good outcome, but speech comprehension outcome in the elderly is more variable. Several clinical factors play an important role. The management of residual hearing, the presence of comorbidities, and especially the progression of cognitive decline seem to be the clinical parameters that strongly determine the outcome of cochlear implantation and need to be discussed prospectively in the consultation process with the elderly hearing impaired. In the context of this review article, strategies for dealing with these will be discussed. Timely cochlear implantation should already be considered by hearing aid acousticians or practicing otolaryngologists and communicated or initiated with the patient. This requires intensive cooperation between hearing aid acousticians and experts in the clinic. In addition, residual hearing and comorbidities in the elderly need to be considered to make realistic predictions about speech comprehension with CI. Long-term aftercare and its different implementations should be discussed preoperatively, so that the elderly person with hearing impairments feels well taken care of together with his or her relatives. Elderly patients with hearing impairments benefit most from a CI in terms of speech comprehension if there is a large cochlear coverage (electrical or acoustic electrical) and the therapy is not hampered by comorbidities, especially cognitive decline.
CNN1 Represses Bladder Cancer Progression and Metabolic Reprogramming by Modulating HIF-1α Signaling Pathway
Authors: Zhang Zheng , Li Xiaoqing , Ren Shaokun , Zhang Wei
Published: July 2022

Bladder cancer (BC) is the second most common urinary system malignant tumor around the whole world. It has been reported that CNN1 was lowly expressed in BC tissues. However, the mechanisms of CNN1 on BC cells were unclear. Herein, we aimed to probe the specific influences of CNN1 on BC pathogenesis. First, the expression level and prognostic ability of CNN1 in BC patients were surveyed. Then, CNN1 overexpression was executed to exhibit the influences of CNN1 on BC cells. The real-time PCR and Western blotting were employed to detect by the mRNA and protein expression levels. CCK8 assay was utilized to examine cell proliferation, and transwell assay was executed to test cell invasion and migration. The corresponding kits were utilized to detect glucose absorption, lactate secretion, and ATP level. BC cells overexpressing CNN1 were utilized to establish a nude mouse xenograft tumor model, and the tumor volume and tumor weight were detected. Nude mouse tumor tissues were used for immunohistochemical experiments to test the expression levels of Ki-67 and CNN1. The outcomes indicated that CNN1 was significantly lowly expressed in BC tissues and cells. Besides, low expression of CNN1 might be concerned with poor prognosis. Moreover, overexpression of CNN1 repressed the proliferation, invasion, and migration of BC cells. Furthermore, CNN1 overexpression decreased the protein levels of glycolysis-related protein GLUT1 (glucose transporter 1), pyruvate kinase M2 (PKM2), and LDHA (lactate dehydrogenase A). Then, the decreased mRNA and protein levels of HIF-1α and PDK1 were identified after CNN1 overexpression. The in vivo assays verified the effects of aberrant expression of CNN1 in mice with BC. In conclusion, these findings suggested that CNN1 might modulate BC progression through activating HIF-1α pathway and CNN1 might be a promising marker for BC diagnosis.
Percutaneous Microcoil Localization of a Small, Totally Endophytic Renal Mass for Nephron-Sparing Surgery: A Case Report and Literature Review
Authors: Su Tianhao , Zhang Zhiyuan , Zhao Meishan , Hao Gangyue , Tian Ye , Jin Long
Published: July 2022

Small, totally endophytic renal masses present a technical challenge for surgical extirpation due to poor identifiability during surgery. The method for the precise localization of totally endophytic tumours before nephron-sparing surgery could be optimized. An asymptomatic 70-year-old male presented with a right-sided, 16-mm, totally endophytic renal mass on computed tomography (CT). CT-guided percutaneous microcoil localization was carried out prior to laparoscopy to provide a direction for partial nephrectomy. During the 25 minutes of the localization procedure, the patient underwent five local CT scans, and his cumulative effective radiation dosage was 5.1 mSv. The span between localization and the start of the operation was 15 hours. The laparoscopic operation time was 105 minutes, and the ischaemia time was 25 minutes. The postoperative recovery was smooth, and no perioperative complications occurred. Pathology showed the mass to be renal clear cell carcinoma, WHO/ISUP grade 2, with a 2-mm, clear surgical margin. The patient remained free of recurrence on follow-up for eleven months. To our knowledge, this application of microcoil implantation prior to laparoscopic partial nephrectomy towards an intrarenal mass could be an early reported attempt for the localized method applied in renal surgery. The percutaneous microcoil localization of endophytic renal tumours is potentially safe and effective prior to laparoscopic partial nephrectomy.
Case Report: A Durable Response to Camrelizumab and Apatinib Combination Therapy in a Heavily Treated Small Cell Carcinoma of the Ovary, Hypercalcemic Type
Authors: Li Guiling , Jiang Yao
Published: July 2022

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and highly aggressive malignancy with a poor prognosis. Most patients experience recurrence even after surgery and chemotherapy, and there are no standard treatment options for recurrent disease. Here, we report the case of a 36-year-old woman with SCCOHT who underwent primary cytoreductive surgery without adjuvant chemotherapy and remained disease-free for 9 months. She then developed retroperitoneal lymph node metastasis and was treated with two cycles of bleomycin/etoposide/cisplatin chemotherapy. However, the disease progressed and the patient received four cycles of liposomal doxorubicin/ifosfamide chemotherapy, followed by local radiation to the enlarged retroperitoneal lymph nodes. She achieved partial remission for 13 months, after which the disease progressed again. Tumor tissues and blood samples were sent for next-generation sequencing. The results indicated a somatic SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4) mutation, microsatellite stability, and a tumor mutation burden of 1.0 muts/Mb without any germline mutations. An anti-PD-1 antibody, camrelizumab, and an antiangiogenic agent, apatinib, were administered, and the patient achieved partial remission for 28 months. Our study provides the first clinical evidence that the combination therapy of camrelizumab and apatinib could be an effective treatment for recurrent SCCOHT.
Plasma Dermatology: Skin Therapy Using Cold Atmospheric Plasma
Authors: Tan Fei , Wang Yang , Zhang Shiqun , Shui Runying , Chen Jianghan
Published: July 2022

Cold atmospheric plasma-based plasma medicine has been expanding the diversity of its specialties. As an emerging branch, plasma dermatology takes advantage of the beneficial complexity of plasma constituents (e.g., reactive oxygen and nitrogen species, UV photons, and electromagnetic emission), technical versatility (e.g., direct irradiation and indirect aqueous treatment), and practical feasibility (e.g., hand-held compact device and clinician-friendly operation). The objective of this comprehensive review is to summarize recent advances in the CAP-dominated skin therapy by broadly covering three aspects. We start with plasma optimisation of intact skin, detailing the effect of CAP on skin lipids, cells, histology, and blood circulation. We then conduct a clinically oriented and thorough dissection of CAP treatment of various skin diseases, focusing on the wound healing, inflammatory disorders, infectious conditions, parasitic infestations, cutaneous malignancies, and alopecia. Finally, we conclude with a brief analysis on the safety aspect of CAP treatment and a proposal on how to mitigate the potential risks. This comprehensive review endeavors to serve as a mini textbook for clinical dermatologists and a practical manual for plasma biotechnologists. Our collective goal is to consolidate plasma dermatology’s lead in modern personalized medicine.
Driver Gene Alterations in Malignant Progression of Gastric Cancer
Authors: Dong Yuanqiang , Song Ning , Wang Jun , Shi Liubin , Zhang Ziqiang , Du Jianjun
Published: July 2022

The identification of driver genes is of great importance in modern medical research. It is also an essential factor in the development of individualization and has a positive effect on understanding the causes of cancer. Gene mutations are the primary cause of the outcomes of the process of tumorigenesis. Driver genes can be used as therapeutic targets for tumor-specific mutation-dependent overexpression. This study sought to identify mutation-based driver genes in gastric cancer (GC) by applying comprehensive gene expression and copy number analysis. Multiplatform analysis was used to identify four major genomic subtypes of GC. The most prominent cancer-related variations observed in this cohort were TTN mutations (found in 56% of tumors), followed by TP53 (51%), MUC16 (7%), and LRP1B (6%) mutations. In our analysis, mutation characteristics were mainly related to the DNA mismatch repair system. In addition, 34 candidate driver oncogenes were identified in GC. Further research identified six GC-related driver genes associated with the levels of immune infiltration of different immune cells and the majority of immune markers. Our mutation-based study of driver oncogenes identified potential drug targets in GC.
GPR12 Inhibits Apoptosis in Epithelial Ovarian Cancer via the Activation of ERK1/2 Signaling
Authors: Wang Lu , Yang Da , Zhang Yao , Jiao Yisheng
Published: July 2022

Epithelial ovarian cancer (EOC) is one of the most lethal gynecological malignancies in women worldwide. G protein–coupled receptor 12 (GPR12) is a member of G protein–coupled receptors (GPCRs) and plays an important role in the regulation of cell proliferation and survival. However, its role in EOC is underappreciated. In this study, we found that GPR12 is highly expressed in the EOC tissues and can be an ideal biomarker to predict the prognosis of patients with EOC. GPR12 knockdown obviously inhibits the proliferation of EOC cells by inducing cellular apoptosis in vitro and in vivo. Meanwhile, bioinformatic analysis showed that the inhibitory effect of GPR12 knockdown on the cell viability is closely related with Extracellular signal-regulated kinases 1/2 (ERK1/2) pathway, which has been confirmed by the fact that the activity of ERK1/2 pathway has been significantly blocked in the GPR12 knockdown cells. LM22B-10, ERK1/2 pathway activator, could reverse the inhibited proliferation caused by GPR12 knockdown in the EOC cells. Our findings suggest that GPR12 is involved in the EOC process and is a potential therapeutic target for EOC.
Lymphocyte-to-Monocyte Ratio (LMR) During Induction Is a Better Predictor Than Preoperative LMR in Patients Receiving Intravesical Bacillus Calmette -Guerin for Non-Muscle-Invasive Bladder Cancer
Authors: Li Deng-xiong , Wang Xiao-ming , Feng De-chao , Zhang Fa-cai , Wu Rui-cheng , Shi Xu , Chen Kai , Bai Yunjin , Han Ping
Published: July 2022

The prognostic value of the lymphocyte-to-monocyte ratio during induction (ILMR) remains unclear in non-muscle-invasive bladder cancer (NMIBC) patients receiving Bacillus Calmette-Guérin (BCG). We aimed to determine and compare the prognostic value of the ILMR, preoperative lymphocyte-to-monocyte ratio (PLMR) and their dynamic changes (PILMR). This study collected the data from NMIBC patients receiving BCG treatment in our institution. The prognostic value of the PLMR, ILMR and PILMR was analyzed by the Kaplan−Meier method and Cox proportional hazard regression models. The concordance index and receiver operating characteristic curve analysis were employed to compare the prognostic value of these three factors. Our study enrolled 197 patients. These patients included 170 male patients, and the mean age was 64.17 years. During the follow-up time, 85 patients experienced recurrence, and 55 patients experienced progression. According to the results of COX multivariable analysis, PLMR (P=0.011) and ILMR (P<0.001) could independently predict the recurrence of NMIBC patients receiving BCG. Meanwhile, ILMR (P=0.001) and PILMR (P=0.036) were also the independent prognostic factors of progression. Compared with PLMR and PILMR, ILMR was associated with better accuracy for NMIBC patients receiving BCG. This study first found that the ILMR could independently predict the prognosis of NMIBC patients receiving BCG. Furthermore, we also identified that ILMR was associated with higher prognostic value than PLMR and PILMR, which might help to select an optimal treatment schedule for patients with NMIBC.
Frequency of Hereditary Hemochromatosis Gene (HFE) Variants in Sri Lankan Transfusion-Dependent Beta-Thalassemia Patients and Their Association With the Serum Ferritin Level
Authors: Padeniya Padmapani , Goonasekara Hemali , Abeysekera Gayan , Jayasekara Rohan , Dissanayake Vajira
Published: July 2022

Introduction

Co-inheritance of hereditary hemochromatosis (HFE) gene variants p. C282Y and p.H63D worsen iron overload in transfusion-dependent thalassemia. Data on the HFE gene variants in Sri Lankan patients with thalassemia have not been extensively studied. This study aimed to analyze the p.C282Y and p.H63D variants in transfusion-dependent beta (β) and HbE/β-thalassemia patients and establish an association between these variants and their serum ferritin levels.

Materials and Methods

A total of 125 transfusion-dependent β-thalassemia major and HbE/β thalassemia patients were tested for the c.845G>A (p.C282Y) and c.187C>G (p.H63D) HFE gene variants using the multiplex Amplification Refractory Mutation System Polymerase Chain Reaction method. For phenotype-genotype correlation, serum ferritin levels, the erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels were measured. The standard descriptive statistics were used for data analysis.

Results

The study cohort consisted of transfusion-dependent 123 β-thalassemia and 2 HbE/β-thalassemia patients. The p.C282Y variant was not detected in any patient; allele frequency for the wild type (c.845GG) was 100%. Twenty-three patients were heterozygous for the p.H63D variant allele, and the allele frequencies were c.187CC 91.8%, c.187CG 9.2%, and c.187GG 0%. The mean serum ferritin level was relatively higher (mean level 4,987 ng/ml) in the p.H63D heterozygous (c.187CG) group compared to the wild type (c.187CC) group (mean level 4,571 ng/ml), but the difference was statistically not significant (p = 0.865). Among the total study population, CRP, ESR, and serum glutamine aspartate transaminase (SGPT) were elevated in 9 (7.2%), 65 (52%), and 82 (65.6%) patients, respectively. Among the p.H63D c.187CG group, elevated CRP, ESR, and SGPT were present in 5 (5%), 15 (12%), and 18 (14.4%) patients, respectively. The detected sample number was low to correlate with the confounding effect of inflammatory disorders and liver damage on the serum ferritin levels.

Conclusions

The HFE gene variant p.C282Y is unlikely to cause iron overload in the Asian β-thalassemia patients; the rarity of this variant in the study cohort replicates the findings of other South Asian population studies of this variant. The presence of the p.H63D variant could be a potential risk factor for iron overload in the β-thalassemia patients. A more extensive cohort study is required to validate this finding.
Case Report: A Case of Late-Onset Combined Methylmalonic Acidemia and Hyperhomocysteinemia Induced by a Vegetarian Diet
Authors: Xu Bei , Zhang Lihong , Chen Qiang , Wang Yajuan , Peng Yahong , Tang Hui
Published: July 2022

Methylmalonic acidemia is a rare autosomal recessive metabolic disease. However, because of the atypical clinical symptoms, the type of late-onset methylmalonic academia is often misdiagnosed. Especially when the blood vitamin B12 and folic acid levels are normal, it is not easy to think of this disease. Herein we report a 9-year-old girl who developed normally on a relatively balanced diet before 7 years of age. However, she presented with fatigue and attention deficit when she followed a vegetarian diet. Laboratory examination showed moderate macrocytic anemia, high levels of homocysteine, high level of propionylcarnitine/acetylcarnitine, urinary methylmalonic acid and methyl citrate. Gene mutation analysis showed c.609G > A and c.80A > G compound heterozygous mutations in the MMACHC gene, supported late-onset combined methylmalonic academia with homocysteinemia. Then treatment performed with add meat to the diet, vitamin B12, folic acid betaine and L-carnitine supplement. One week later, the child's clinical symptoms and the laboratory examinations were significantly improved.
Treatment Outcomes of HIV Infected Children After Initiation of Antiretroviral Therapy in Southwest China: An Observational Cohort Study
Authors: Zeng Xiaoliang , Chen Huanhuan , Zhu Qiuying , Shen Zhiyong , Lan Guanghua , Liang Jiangming , Liang Fuxiong , Zhu Jinhui , Xing Hui , Shao Yiming , Ruan Yuhua , Zhang Jianfeng , Zhang Xiangjun
Published: July 2022

Background

The number of HIV infected children receiving antiviral treatment in Guangxi is increasing. Understanding factors and trends of mortality and attrition in HIV-infected children under antiretroviral therapy (ART) was an urgent need to improve treatment outcomes. This study aimed to estimate mortality and attrition rates and identify factors that were associated with mortality and attrition after ART initiation among children with HIV in Guangxi, China between 2004 and 2018.

Methods

Cohort study data were extracted from the National Free Antiretroviral Treatment Program (NFATP) database, which has standard guidelines for core treatment indicators and other data at all HIV/AIDS treatment facilities in Guangxi. A total of 901 HIV-infected children who have started ART were included in the study. The study collected the following data: age, gender, WHO clinic stages before ART, CD4 cell count before ART, Cotrimoxazole prophylaxis (CTX) use before ART, initial ART regimen, malnutrition before ART, abnormal liver function before ART, abnormal kidney function before ART, severe anemia before ART, and the time lag between an HIV diagnosis and ART initiation.

Results

HIV-infected children under ART had a mortality rate of 0.87 per 100 person-years [95% Confidence Interval (CI) 0.63–1.11], and an attrition rate of 3.02 per 100 person-years (95% CI 2.57–3.47). Mortality was lower among children with a CD4 count between 200 and 500 copies/ml [Adjusted Hazard Ratio (AHR) 0.22, 95% CI 0.09–0.55], and CD4 count ≥500 copies/ml (AHR 0.10, 95% CI 0.03–0.29); but higher among children with late ART initiation at 1–3 months (AHR 2.30, 95% CI 1.07–4.94), and at ≥3 months (AHR 2.22, 95% CI 1.04–4.74). Attrition was lower among children with a CD4 count ≥500 copies/ml (AHR 0.62, 95% CI 0.41–0.95), but higher among children with late ART initiation at 1–3 months (AHR 1.55, 95% CI 1.05–2.30).

Conclusion

Supportive programs are needed to educate children's families and parents on early ART, link HIV-infected children to care and retain them in care among other programs that treat and manage the medical conditions of HIV-infected children before ART initiation.
Therapeutic Potential of Polyphenol and Nanoparticles Mediated Delivery in Periodontal Inflammation: A Review of Current Trends and Future Perspectives
Authors: Jayusman Putri Ayu , Nasruddin Nurrul Shaqinah , Mahamad Apandi Nurul Inaas , Ibrahim Norliwati , Budin Siti Balkis
Published: July 2022

Periodontitis is an oral inflammatory process involving the periodontium, which is mainly caused by the invasion of periodontopathogenic microorganisms that results in gingival connective tissue and alveolar bone destruction. Metabolic products of the oral pathogens and the associated host immune and inflammatory responses triggered are responsible for the local tissue destruction. Numerous studies in the past decades have demonstrated that natural polyphenols are capable of modulating the host inflammatory responses by targeting multiple inflammatory components. The proposed mechanism by which polyphenolic compounds exert their great potential is by regulating the immune cell, proinflammatory cytokines synthesis and gene expression. However, due to its low absorption and bioavailability, the beneficial effects of these substances are very limited and it hampers their use as a therapeutic agent. To address these limitations, targeted delivery systems by nanoencapsulation techniques have been explored in recent years. Nanoencapsulation of polyphenolic compounds with different carriers is an efficient and promising approach to boost their bioavailability, increase the efficiency and reduce the degradability of natural polyphenols. In this review, we focus on the effects of different polyphenolic substances in periodontal inflammation and to explore the pharmaceutical significance of polyphenol-loaded nanoparticles in controlling periodontitis, which may be useful for further enhancement of their efficacy as therapeutic agents for periodontal disease.
From Rate-Limiting Enzyme to Therapeutic Target: The Promise of NAMPT in Neurodegenerative Diseases
Authors: Zhu Yumeng , Xu Ping , Huang Xuan , Shuai Wen , Liu Li , Zhang Shuai , Zhao Rui , Hu Xiuying , Wang Guan
Published: July 2022

Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in the nicotinamide adenine dinucleotide (NAD) salvage pathway in mammals. It is of great significance in the metabolic homeostasis and cell survival via synthesizing nicotinamide mononucleotide (NMN) through enzymatic activities, serving as a key protein involved in the host’s defense mechanism. The NAMPT metabolic pathway connects NAD-dependent sirtuin (SIRT) signaling, constituting the NAMPT–NAD–SIRT cascade, which is validated as a strong intrinsic defense system. Neurodegenerative diseases belong to the central nervous system (CNS) disease that seriously endangers human health. The World Health Organization (WHO) proposed that neurodegenerative diseases will become the second leading cause of human death in the next two decades. However, effective drugs for neurodegenerative diseases are scant. NAMPT is specifically highly expressed in the hippocampus, which mediates cell self-renewal and proliferation and oligodendrocyte synthesis by inducing the biosynthesis of NAD in neural stem cells/progenitor cells. Owing to the active biological function of NAMPT in neurogenesis, targeting NAMPT may be a powerful therapeutic strategy for neurodegenerative diseases. This study aims to review the structure and biological functions, the correlation with neurodegenerative diseases, and treatment advance of NAMPT, aiming to provide a novel idea for targeted therapy of neurodegenerative diseases.