Structural and functional properties of whey protein isolate-inulin conjugates prepared with ultrasound or wet heating method.

BACKGROUND: Whey protein isolate (WPI) generally represents poor functional properties such as thermal stability, emulsifying activity and antioxidant activity near its isoelectric point or high temperatures, which limit its application in food industry. The preparation of WPI-polysaccharide covalent conjugates based on Maillard reaction is a promising method to improve the physical and chemical stability and functional properties of WPI. In this research, WPI-inulin conjugates were prepared through wet heating method and ultrasound method and their structural and functional properties were examined. RESULTS: In conjugates, the free amino acid content was reduced, the high molecular bands were emerged at SDS-PAGE, new C-N bonds were formed in FT-IR spectroscopy, and fluorescence intensity was reduced compared with WPI. Furthermore, the result of CD spectrum also showed that the secondary structure of conjugates was changed. Conjugates with ultrasound treatment had better structural properties compared with those prepared by wet heating treatment. The functional properties such as thermal stability, emulsifying activity index (EAI), emulsion stability (ES) and antioxidant activity of conjugates with wet heating treatment were significantly improved compared with WPI. The EAI and ES of conjugates with ultrasound treatment were the highest, but the thermal stability and antioxidant activity were only close to that of the conjugates with wet heating treatment for 2 h. CONCLUSION: This study revealed that WPI-inulin conjugates prepared with ultrasound or wet heating method not only changed the structural characteristics of WPI but also could promote its functional properties including thermal stability, EAI, ES and antioxidant activity. This article is protected by copyright. All rights reserved.

Recombinant bivalent subunit vaccine combining truncated VP4 from P[7] and P[23] induces protective immunity against prevalent porcine rotaviruses.

Porcine rotaviruses (PoRVs) cause severe economic losses in the swine industry. P[7] and P[23] are the predominant genotypes circulating on farms, but no vaccine is yet available. Here, we developed a bivalent subunit PoRV vaccine using truncated versions (VP4*) of the VP4 proteins from P[7] and P[23]. The vaccination of mice with the bivalent subunit vaccine elicited more robust neutralizing antibodies (NAbs) and cellular immune responses than its components, even at high doses. The bivalent subunit vaccine and inactivated bivalent vaccine prepared from strains PoRVs G9P[7] and G9P[23] were used to examine their protective efficacy in sows and suckling piglets after passive immunization. The immunized sows showed significantly elevated NAbs in the serum and colostrum, and the suckling piglets acquired high levels of sIgA antibodies from the colostrum. Challenging subunit-vaccinated or inactivated-vaccinated piglets with homologous virulent strains did not induce diarrhea, except in one or two piglets, which had mild diarrhea. Immunization with the bivalent subunit vaccine and inactivated vaccine also alleviated the microscopic lesions in the intestinal tissues caused by the challenge with the corresponding homologous virulent strain. However, all the piglets in the challenged group displayed mild to watery diarrhea and high levels of viral shedding, whereas the feces and intestines of the piglets in the bivalent subunit vaccine and inactivated vaccine groups had lower viral loads. In summary, our data show for the first time that a bivalent subunit vaccine combining VP4*P[7] and VP4*P[23] effectively protects piglets against the diarrhea caused by homologous virulent strains.IMPORTANCEPoRVs are the main causes of diarrhea in piglets worldwide. The multisegmented genome of PoRVs allows the reassortment of VP4 and VP7 genes from different RV species and strains. The P[7] and P[23] are the predominant genotypes circulating in pig farms, but no vaccine is available at present in China. Subunit vaccines, as nonreplicating vaccines, are an option to cope with variable genotypes. Here, we have developed a bivalent subunit candidate vaccine based on a truncated VP4 protein, which induced robust humoral and cellular immune responses and protected piglets against challenge with homologous PoRV. It also appears to be safe. These data show that the truncated VP4-protein-based subunit vaccine is a promising candidate for the prevention of PoRV diarrhea.

Isolation and characterization of a G9P[23] porcine rotavirus strain AHFY2022 in China.

Rotavirus group A (RVA) is a main pathogen causing diarrheal diseases in humans and animals. Various genotypes are prevalent in the Chinese pig herd. The genetic diversity of RVA lead to distinctly characteristics. In the present study, a porcine RVA strain, named AHFY2022, was successfully isolated from the small intestine tissue of piglets with severe diarrhea. The AHFY2022 strain was identified by cytopathic effects (CPE) observation, indirect immunofluorescence assay (IFA), electron microscopy (EM), high-throughput sequencing, and pathogenesis to piglets. The genomic investigation using NGS data revealed that AHFY2022 exhibited the genotypes G9-P[23]-I5-R1-C1-M1-A8-N1-T1-E1-H1, using the online platform the Bacterial and Viral Bioinformatics Resource Center (BV-BRC) (https://www.bv-brc.org/). Moreover, experimental inoculation in 5-day-old and 27-day-old piglets demonstrated that AHFY2022 caused severe diarrhea, fecal shedding, small intestinal villi damage, and colonization in all challenged piglets. Taken together, our results detailed the virological features of the porcine rotavirus G9P[23] from China, including the whole-genome sequences, genotypes, growth kinetics in MA104 cells and the pathogenicity in suckling piglets.

Betel-nut chewing does not influence PD-L1 expression rates in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC): A prospective biomarker prevalence study.

This study explored the relationship between betel-nut chewing and programmed death-ligand 1 (PD-L1) expression in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients in Taiwan. A total 280 R/M HNSCC patients, predominantly male, were evaluated; 75.4 % of whom chewed betel-nut. The prevalence of PD-L1 expression (combined positive score ≥1) was 94.3 % with similar PD-L1 expression rates between betel-nut-exposed and non-exposed groups. PD-L1 prevalence did not differ in those who received prior first-or second-line systemic therapy. In summary, betel-nut exposure did not notably affect PD-L1 expression rates in R/M HNSCC patients in Taiwan.

Asiaticoside Attenuates Blood-Spinal Cord Barrier Disruption by Inhibiting Endoplasmic Reticulum Stress in Pericytes After Spinal Cord Injury.

The blood-spinal cord barrier (BSCB) plays a vital role in the recovery of spinal cord function after spinal cord injury (SCI). Pericytes, pluripotent members of the neurovascular unit (NVU), receive signals from neighboring cells and are critical for maintaining CNS function. Therapeutic targets for the BSCB include endothelial cells (ECs) and glial cells, but few drugs target pericytes. This study was designed to explore whether asiaticoside has a positively effect on pericytes and the integrity of the BSCB. In this study, we found that asiaticoside could inhibit the loss of junction proteins just 1 day after SCI in vivo, but our in vitro study showed no significant differences in the expression of endothelial junction proteins between the control and asiaticoside treatment groups. We also found that asiaticoside could inhibit endoplasmic reticulum (ER) stress and pericyte apoptosis, which might be associated with the inhibition of junction protein reduction in ECs. Thus, we investigated the interactions between pericytes and ECs. Our results showed that asiaticoside could decrease the release of matrix metalloproteinase (MMP)-9 in pericytes and therefore upregulate the expression of junction proteins in ECs. Furthermore, the protective effect of asiaticoside on pericytes is related to the inhibition of ER stress via the MAPK signaling pathway. Taken together, our results demonstrate that asiaticoside treatment inhibits BSCB disruption and enhances functional recovery after SCI.

Organic photoredox catalyzed C(sp3)-H functionalization of saturated aza-heterocycles via a cross-dehydrogenative coupling reaction.

Herein we present a novel protocol to access α-functionalized saturated aza-heterocycles, and a variety of nucleophilic groups, such as indole, naphthol, phenol, pyrrole, furyl, nitromethyl, and cyano, could be easily installed into saturated aza-heterocycles. Furthermore, a range of biologically valuable 3,3'-diindolylmethane derivatives could also be readily accessed under mild photocatalytic conditions.

GTR: An SQL Generator With Transition Representation in Cross-Domain Database Systems.

Recent studies have focused on using natural language (NL) to automatically retrieve useful data from database (DB) systems. As an important component of autonomous DB systems, the NL-to-SQL technique can assist DB administrators in writing high-quality SQL statements and make persons with no SQL background knowledge learn complex SQL languages. However, existing studies cannot deal with the issue that the expression of NL inevitably mismatches the implementation details of SQLs, and the large number of out-of-domain (OOD) words makes it difficult to predict table columns. In particular, it is difficult to accurately convert NL into SQL in an end-to-end fashion. Intuitively, it facilitates the model to understand the relations if a "bridge" transition representation (TR) is employed to make it compatible with both NL and SQL in the phase of conversion. In this article, we propose an automatic SQL generator with TR called GTR in cross-domain DB systems. Specifically, GTR contains three SQL generation steps: 1) GTR learns the relation between questions and DB schemas; 2) GTR uses a grammar-based model to synthesize a TR; and 3) GTR predicts SQL from TR based on the rules. We conduct extensive experiments on two commonly used datasets, that is, WikiSQL and Spider. On the testing set of the Spider and WikiSQL datasets, the results show that GTR achieves 58.32% and 71.29% exact matching accuracy which outperforms the state-of-the-art methods, respectively.

Targeting alternative splicing in cancer immunotherapy.

Tumor immunotherapy has made great progress in cancer treatment but still faces several challenges, such as a limited number of targetable antigens and varying responses among patients. Alternative splicing (AS) is an essential process for the maturation of nearly all mammalian mRNAs. Recent studies show that AS contributes to expanding cancer-specific antigens and modulating immunogenicity, making it a promising solution to the above challenges. The organoid technology preserves the individual immune microenvironment and reduces the time/economic costs of the experiment model, facilitating the development of splicing-based immunotherapy. Here, we summarize three critical roles of AS in immunotherapy: resources for generating neoantigens, targets for immune-therapeutic modulation, and biomarkers to guide immunotherapy options. Subsequently, we highlight the benefits of adopting organoids to develop AS-based immunotherapies. Finally, we discuss the current challenges in studying AS-based immunotherapy in terms of existing bioinformatics algorithms and biological technologies.

FiNuTyper: Design and validation of an automated deep learning-based platform for simultaneous fiber and nucleus type analysis in human skeletal muscle.

AIM: While manual quantification is still considered the gold standard for skeletal muscle histological analysis, it is time-consuming and prone to investigator bias. To address this challenge, we assembled an automated image analysis pipeline, FiNuTyper (Fiber and Nucleus Typer). METHODS: We integrated recently developed deep learning-based image segmentation methods, optimized for unbiased evaluation of fresh and postmortem human skeletal muscle, and utilized SERCA1 and SERCA2 as type-specific myonucleus and myofiber markers after validating them against the traditional use of MyHC isoforms. RESULTS: Parameters including cross-sectional area, myonuclei per fiber, myonuclear domain, central myonuclei per fiber, and grouped myofiber ratio were determined in a fiber-type-specific manner, revealing that a large degree of sex- and muscle-related heterogeneity could be detected using the pipeline. Our platform was also tested on pathological muscle tissue (ALS and IBM) and adapted for the detection of other resident cell types (leucocytes, satellite cells, capillary endothelium). CONCLUSION: In summary, we present an automated image analysis tool for the simultaneous quantification of myofiber and myonuclear types, to characterize the composition and structure of healthy and diseased human skeletal muscle.

Organic photoredox catalyzed dealkylation/acylation of tertiary amines to access amides.

A mild metal-free C-N bond activation strategy for the direct conversion of inert tertiary amines with acyl chlorides into tertiary amides via organic photoredox catalysis is presented. In this protocol, a novel organic photocatalyst (Cz-NI-Ph) that showed excellent catalytic performance during C-N bond cleavage is developed. Moreover, this reaction features green and mild conditions, broad substrate scope, and readily available raw materials.

ortho-C(sp3)-H arylation of aromatic aldehydes using 2-amino-N-methyl-acetamide as a L,L-type transient directing group.

Pd-catalyzed ortho-C(sp3)-H arylation of aromatic aldehydes using 2-amino-N-methyl-acetamide as a simple, efficient and commercially available L,L-type transient directing group (TDG) is reported. The reaction exhibited excellent substrate compatibility and generated the desired products in moderate-to-high yields up to 78%. Further acid-catalyzed cyclization and dehydrative aromatization were also tested, and furnished some polycyclic aromatic hydrocarbons with excellent yields up to 96%. The X-ray crystal structure of a 2-methylbenzaldehyde ortho-C(sp3)-H palladation intermediate was obtained. Then, a plausible reaction mechanism involving the formation of a [5,6]-fused palladacycle was proposed. This approach offers valuable insights for exploiting novel L,L-type TDGs.

Taxifolin attenuates neuroinflammation and microglial pyroptosis via the PI3K/Akt signaling pathway after spinal cord injury.

Spinal cord injury (SCI) is a severe injury characterized by neuroinflammation and oxidative stress. Taxifolin is exhibits anti-inflammatory and antioxidative activities in neurologic diseases. However, the roles and mechanisms of taxifolin in neuroinflammation and microglial pyroptosis after SCI remain unclear. The present study aims to investigate the effect of taxifolin on SCI and its potential underlying mechanisms in in vivo and in vitro models. In this study, taxifolin markedly reduced microglial activation mediated oxidative stress, and inhibited the expression of pyroptosis-related proteins (NLRP3, GSDMD, ASC, and Caspase-1) and inflammatory cytokines (IL-1ß and IL-18) after SCI, as shown by immunofluorescence staining and western blot assays. In addition, taxifolin promoted axonal regeneration and improved functional recovery after SCI. In vitro studies showed that taxifolin attenuated the activation of microglia and oxidative stress after lipopolysaccharide (LPS) + adenosine-triphosphate (ATP) stimulation in BV2 cells. We also observed that taxifolin inhibited the pyroptosis-related proteins and reduced the release of inflammatory cytokines. Moreover, to explore how taxifolin exerts its effects on microglial pyroptosis and axonal regeneration of neurons, we performed an in vitro study in BV-2 cells and PC12 cells co-culture. The results revealed that taxifolin facilitated axonal regeneration of PC12 cells in co-culture with LPS + ATP-induced BV-2 cells. Mechanistically, taxifolin regulated microglial pyroptosis via the PI3K/AKT signaling pathway. Taken together, these results suggest that taxifolin alleviates neuroinflammation and microglial pyroptosis through the PI3K/AKT signaling pathway after SCI, and promotes axonal regeneration and improves functional recovery, suggesting that taxifolin may represent a potential therapeutic agent for SCI.

Efficacy and safety of preoperative versus postoperative NSAIDs on pain relief in patients undergoing hip arthroscopy surgery: A multicentre, randomized, controlled trial.

WHAT IS KNOWN AND OBJECTIVE: Postoperative pain relief is a critical issue for hip arthroscopy surgery (HAS). This study aimed to investigate the effect of preemptive non-steroidal anti-inflammatory drugs (NSAIDs) for postoperative analgesia in femoroacetabular impingement (FAI) patients receiving HAS. METHODS: This multicenter, randomized, controlled study enrolled 204 FAI patients receiving HAS, then assigned them to preoperative (PRE, N = 103) or postoperative (POS, N = 101) group as a 1:1 ratio; the PRE group administrated NSAIDs from 24 h pre-surgery to day 7 (D7) post-surgery, while the POS group administrated NSAIDs from 12 h post-surgery to D7 post-surgery. RESULTS AND DISCUSSION: Pain at rest was reduced at D1 (p = 0.016) and D2 (p = 0.023); pain at movement was decreased at D1 (p = 0.002), D2 (p = 0.020), and D3 (p = 0.030) in the PRE group compared with POS group, but not at other time points (all p > 0.05). Patient's satisfaction was increased at D1 (p = 0.013) and D3 (p = 0.029) in the PRE group compared to the POS group, but not at D7 (p = 0.145). Pethidine was less consumed at D3 (p = 0.038) and D7 (p = 0.017) in the PRE group in contrast with the POS group. Harris hip scores were similar at D7 (p = 0.124), month 1 (M1) (p = 0.273), and M3 (p = 0.360) between groups. Adverse events incidence was similar between groups (all p > 0.05). Besides, subgroup analysis discovered that pain was not influenced by the types of NSAID in both groups (all p > 0.05). WHAT IS NEW AND CONCLUSION: Starting NSAIDs before HAS provides better short-term pain relief and improves patient's satisfaction compared with its postoperative utilization, while does not induce additional adverse events in FAI patients.

Effects of group mindfulness-based cognitive therapy and group cognitive behavioural therapy on symptomatic generalized anxiety disorder: a randomized controlled noninferiority trial.

BACKGROUND: Mindfulness-based cognitive therapy (MBCT) is a promising alternative treatment for generalized anxiety disorder (GAD). The objective of this study was to examine whether the efficacy of group MBCT adapted for treating GAD (MBCT-A) was noninferior to group cognitive behavioural therapy (CBT) designed to treat GAD (CBT-A), which was considered one of first-line treatments for GAD patients. We also explored the efficacy of MBCT-A in symptomatic GAD patients compared with CBT-A for a variety of outcomes of anxiety symptoms, as well as depressive symptoms, overall illness severity, quality of life and mindfulness. METHODS: This was a randomized, controlled, noninferiority trial with two arms involving symptomatic GAD patients. Adult patients with GAD (n = 138) were randomized to MBCT-A or CBT-A in addition to treatment as usual (TAU). The primary outcome was the anxiety response rate assessed at 8 weeks after treatment as measured using the Hamilton Anxiety Scale (HAMA). Secondary outcomes included anxiety remission rates, scores on the HAMA, the state-trait anxiety inventory (STAI), the Hamilton Depression Scale (HAMD), the Severity Subscale of the Clinical Global Impression Scale (CGI-S), and the 12-item Short-Form Health Survey (SF-12), as well as mindfulness, which was measured by the Five Facet Mindfulness Questionnaire (FFMQ). Assessments were performed at baseline, 8 weeks after treatment, and 3 months after treatment. Both intention-to-treat (ITT) and per-protocol (PP) analyses were performed for primary analyses. The χ2 test and separate two-way mixed ANOVAs were used for the secondary analyses. RESULTS: ITT and PP analyses showed noninferiority of MBCT-A compared with CBT-A for response rate [ITT rate difference = 7.25% (95% CI: -8.16, 22.65); PP rate difference = 5.85% (95% CI: - 7.83, 19.53)]. The anxiety remission rate, overall illness severity and mindfulness were significantly different between the two groups at 8 weeks. There were no significant differences between the two groups at the 3-month follow-up. No severe adverse events were identified. CONCLUSIONS: Our data indicate that MBCT-A was noninferior to CBT-A in reducing anxiety symptoms in GAD patients. Both interventions appeared to be effective for long-term benefits. TRIAL REGISTRATION: Registered at chictr.org.cn (registration number: ChiCTR1800019150 , registration date: 27/10/2018).

Organic photoredox catalytic amino-heteroarylation of unactivated olefins to access distal amino ketones.

Here we describe a metal-free amino-heteroarylation of unactivated olefins via organic photoredox catalysis, providing a concise and efficient approach for the rapid synthesis of various δ (ß, ε)-amino ketones under mild conditions. This protocol demonstrates that the new photocatalyst Cz-NI developed by our group has an excellent photoredox catalytic performance. Finally, a series of mechanistic experiments and DFT calculations indicate that this transformation undergoes a photoredox catalytic sequential radical addition/functional group migration process.

Characterization of the molecular properties and allergenicity (IgE-binding capacity) of ß-lactoglobulin by heat treatment using asymmetric-flow field-flow fractionation and ultra-performance liquid chromatography quadrupole time of flight mass chromatography.

In this study, the heat product (90 °C, 10 min) of ß-lactoglobulin (ß-LG) was analyzed by asymmetric-flow field-flow fractionation (AF4) to observe the effect of heat treatment. The changes in molar mass (M) and molar size induced by heat treatment were characterized by AF4, and changes in molar shape were observed by transmission electron microscopy (TEM). The results showed that ß-LG dissociated and aggregated into four fractions with different M values, sizes, and shapes after heat treatment. The vast aggregations with the highest allergenicity (IgE-binding capacity) might enhance the allergenicity of ß-LG. However, the number of characterized epitope peptides was decreased due to heat treatment. The above results provide some references for related studies of ß-LG and its allergenicity. Further separation and characterization of the high-allergenicity fractions and peptides will help to eliminate allergens in dairy products and reduce the occurrence of allergic reactions.

Characterization and pathogenicity of a naturally reassortant and recombinant infectious bursal disease virus in China.

Infectious bursal disease virus (IBDV), an Avibirnavirus, is the pathogen of infectious bursal disease, which is a severely immunosuppressive disease in 3-15-week-old chickens. Different phenotypes of IBDV, including classical, variant, very virulent (vv) and attenuated IBDV, have been reported in many chicken-rearing countries worldwide. Here, we isolated and identified a naturally reassortant and recombinant IBDV (designated GXB02) from 20-day-old chickens with clinicopathological changes of infectious bursal disease (IBD) in Guangxi Province, China. Whole genomic sequencing showed that the strain GXB02 simultaneously has both reassortant and recombinant characteristics with segments A and B being derived from recombinant intermediate vaccine strain and classic strains of IBDV. Segment A of strain GXB02 was incorporated into the skeleton of an intermediate IBDV vaccine strain (W2512), where the breakpoints of two recombinant events located at nucleotide positions 1468 and 1648 were replaced by reassortant vvIBDV (PK2) and vvIBDV (D6948) of segment A, respectively. We used this GXB02 strain to inoculate 21-day-old specific-pathogen-free chickens to evaluate its pathogenicity. Strain GXB02 has clinicopathologic characteristics of IBD with severe bursal lesions, as evidenced by necrosis, depletion of lymphocytes, and follicle atrophy, indicating that reassortment with classical strains in segment B or/and recombination with very virulent strains increased pathogenicity of the strain GXB02 in chickens. These findings provide important insights into the genetic exchange between classic and attenuated strains of IBDV with two recombinant events occurring at the intermediate derivative segment A with vvIBDV strains, thereby increasing the difficulty of prevention and control of IBD due to novel reassortant-recombinant strains.

Acupuncture Reduced the Risk for Insomnia in Stroke Patients: A Propensity-Score Matched Cohort Study.

Background: Post-stroke insomnia (PSI) affects the quality of life for stroke patients, reduces the likelihood of successful rehabilitation, and produces additional complications following stroke. Previous reports have provided some information regarding PSI risk factors, but little is known concerning protective factors for PSI. This study analyzed the relationship between acupuncture and insomnia in stroke patients and explored the use of acupuncture as a preventive treatment. Methods: Patients diagnosed with stroke from 2010 to 2019 were identified in the case database of the First Affiliated Hospital of Guangzhou University of Chinese These patients followed until 2020, and numerous factors were examined, including gender, age, stroke type, stroke location, and baseline comorbidities. A 1:1 propensity score was used to match an equal number of patients receiving acupuncture with stroke patients who did not receive acupuncture (N = 1,680 for each group). The purpose of the study was to compare the incidence of insomnia in these two stroke cohorts. We used the Cox regression model and Kaplan-Meier method to estimate the risk of insomnia as the outcome event. Results: Compared with the non-acupuncture cohort in general, stroke patients who received acupuncture treatment exhibited a lower risk of insomnia after adjusting for age, gender, stroke type, stroke location, and comorbidities (adjusted hazard ratio HR = 0.27, 95% confidential interval = 0.23 to 0.32). Acupuncture also reduced the risk of PSI for both genders. The respective risks were HR = 0.28 (adjusted) for males and HR = 0.26 (adjusted) for females. Acupuncture also lowered the risk for PSI for different age groups. The risks were HR = 0.22 (adjusted) for individuals 18 to 39 years of age, HR = 0.31 (adjusted) for individuals 40 to 59 years of age, HR = 0.28 (adjusted) for those 60 to 79 years of age, and HR = 0.18 (adjusted) for individuals 80 years of age and older. Concerning the stroke type, regardless of whether the stroke was ischemic, hemorrhagic, or a combination of the two stroke types, patients who received acupuncture exhibited lower risk (adjusted HR = 0.28, 0.17, and 0.49, respectively). Concerning stroke location, except for the cerebral hemispheres (adjusted HR = 1.10, 95% confidential interval = 0.12 to 1.01), the risk of PSI after receiving acupuncture was lower for the frontal lobe (adjusted HR = 0.42), the basal ganglia (adjusted HR = 0.22), the radiation crown (adjusted HR = 0.42), the diencephalon (adjusted HR = 0.20), or multiple partial strokes (adjusted HR = 0.26), the risk of PSI after receiving acupuncture was lower. For all baseline complications, acupuncture reduced the risk of insomnia. The cumulative incidence of insomnia in the acupuncture cohort was significantly lower than the non-acupuncture cohort (log-rank test, P = 0.000). Limitations: First, our research only included patients from a single center. Second, we did not classify the post-stroke insomnia severity. Second, the information was extracted manually. Overall, the sample size was small, and we needed to increase the sample size to strengthen the conclusions. Conclusion: Acupuncture treatment reduced the risk of insomnia in stroke patients. Future research be conducted with increased sample sizes and further elaboration on the specific acupuncture protocols that were used.

Totally Implantable Venous Access Port Systems: Implant Depth-based Complications in Breast Cancer Therapy - A Comparative Study.

BACKGROUND: Totally implantable venous access port system (TIVAPS) is widely used in breast cancer therapy; TIVAPS has several associated complications depending on the depth of implantation in breast cancer (BC) patients during continuous infusional chemotherapy regimens. The purpose of this study is to find out the optimal depth of TIVAPS implantation to reduce the incidence of complications during infusional chemotherapy. METHODS: This study reviewed the depth of TIVAPS implantation in the internal jugular vein in 1282 breast cancer patients over a ten-year period (2009-2019), and associated complications. We segregated the patients as 5 groups: 'Group A (depth < 4 mm), Group B (depth of 4-8 mm), Group C (depth of 8-12 mm), and Group D (depth of 12-16 mm), and Group E (depth of > 16 mm)'. Consequently, the 'internal complications' such as infection, venous thrombotic syndrome, catheter folding & migration, extravasation, whereas the 'external complications' viz., inflammation, local hematoma, local cutaneous reactions, and port exteriorization were significantly analyzed during TIVAPS implantation at different depths in BC patients. RESULTS: Overall incidence of 'internal complications' such as infections (8.6%, 2/23 cases), venous thrombotic syndrome (7.69%, 1/13 cases), catheter folding & migration (8.3%, 1/12 cases), and extravasation (8.3%, 1/12 cases) was comparatively lesser in Group C (8-12 mm) (p<0.01) than the Group A, Group B, Group D, and Group E respectively. Mainly, the external complications such as inflammation in Group C (8-12 mm) (pp< 0.01) was lesser (6.8%, 3/44 cases) than Group A, Group B, Group D, Group E. On the similar note, the local hematoma, and local cutaneous reaction, and port exteriorization were observed as '5% (1/20 cases), 4.2% (2/47 cases), and (3.2%, 1/31 cases)' in Group C patients (p<0.01), which were comparatively lesser than the other groups. CONCLUSION: Subcutaneous implantation of TIVAPS at a depth of 8-12 mm could be preferred due to the lowest incidence of internal and external complications compared to the incidence of these complications in other groups; this depth could be referred to as the safe and convenient implantation depth for the effective delivery of chemotherapy regimen in BC patients without difficulty in transcutaneous access to the port.

The G-Protein-Coupled Estrogen Receptor (GPER) Regulates Trimethylation of Histone H3 at Lysine 4 and Represses Migration and Proliferation of Ovarian Cancer Cells In Vitro.

Histone H3 lysine 4 trimethylation (H3K4me3) is one of the most recognized epigenetic regulators of transcriptional activity representing, an epigenetic modification of Histone H3. Previous reports have suggested that the broad H3K4me3 domain can be considered as an epigenetic signature for tumor-suppressor genes in human cells. G-protein-coupled estrogen receptor (GPER), a new membrane-bound estrogen receptor, acts as an inhibitor on cell growth via epigenetic regulation in breast and ovarian cancer cells. This study was conducted to evaluate the relationship of GPER and H3K4me3 in ovarian cancer tissue samples as well as in two different cell lines (Caov3 and Caov4). Silencing of GPER by a specific siRNA and two selective regulators with agonistic (G1) and antagonistic (G15) activity were applied for consecutive in vitro studies to investigate their impacts on tumor cell growth and the changes in phosphorylated ERK1/2 (p-ERK1/2) and H3K4me3. We found a positive correlation between GPER and H3K4me3 expression in ovarian cancer patients. Patients overexpressing GPER as well as H3K4me3 had significantly improved overall survival. Increased H3K4me3 and p-ERK1/2 levels and attenuated cell proliferation and migration were observed in Caov3 and Caov4 cells via activation of GPER by G1. Conversely, antagonizing GPER activity by G15 resulted in opposite effects in the Caov4 cell line. In conclusion, interaction of GPER and H3K4me3 appears to be of prognostic significance for ovarian cancer patients. The results of the in vitro analyses confirm the biological rationale for their interplay and identify GPER agonists, such as G1, as a potential therapeutic approach for future investigations.