Intersecting evidence: Bibliometric analysis and clinical trials illuminate immunotherapy in KRAS-mutation cancer: A review.

KRAS mutations play a critical role in the development and progression of several cancers, including non-small cell lung cancer and pancreatic cancer. Despite advancements in targeted therapies, the management of KRAS-mutant tumors remains challenging. This study leverages bibliometric analysis and a comprehensive review of clinical trials to identify emerging immunotherapies and potential treatments for KRAS-related cancers. Using the Web of Science Core Collection and Citespace, we analyzed publications from January 2008 to March 2023 alongside 52 clinical trials from ClinicalTrials.gov and WHO's registry, concentrating on immune checkpoint blockades (ICBs) and novel therapies. Our study highlights an increased focus on the tumor immune microenvironment and precision therapy. Clinical trials reveal the effectiveness of ICBs and the promising potential of T-cell receptor T-cell therapy and vaccines in treating KRAS-mutant cancers. ICBs, particularly in combination therapies, stand out in managing KRAS-mutant tumors. Identifying the tumor microenvironment and gene co-mutation profiles as key research areas, our findings advocate for multidisciplinary approaches to advance personalized cancer treatment. Future research should integrate genetic, immunological, and computational studies to unveil new therapeutic targets and refine treatment strategies for KRAS-mutant cancers.

The global burden, trends and cross-country inequalities of female breast and gynaecologic cancers: A population based study.

OBJECTIVE: To analyse the global burden, trends and cross-country inequalities of female breast and gynaecologic cancers (FeBGCs). DESIGN: Population-Based Study. SETTING: Data sourced from the Global Burden of Disease Study 2019. POPULATION: Individuals diagnosed with FeBGCs. METHODS: Age-standardised mortality rates (ASMRs), age-standardised Disability-Adjusted Life Years (DALYs) rates (ASDRs) and their 95% uncertainty interval (UI) described the burden. Estimated annual percentage changes (EAPCs) and their confidence interval (CI) of age-standardised rates (ASRs) illustrated trends. Social inequalities were quantified using the Slope Index of Inequality (SII) and Concentration Index. MAIN OUTCOME MEASURES: The main outcome measures were the burden of FeBGCs and the trends in its inequalities over time. RESULTS: In 2019, the ASDRs per 100 000 females were as follows: breast cancer: 473.83 (95% UI: 437.30-510.51), cervical cancer: 210.64 (95% UI: 177.67-234.85), ovarian cancer: 124.68 (95% UI: 109.13-138.67) and uterine cancer: 210.64 (95% UI: 177.67-234.85). The trends per year from 1990 to 2019 were expressed as EAPCs of ASDRs and these: for Breast cancer: -0.51 (95% CI: -0.57 to -0.45); Cervical cancer: -0.95 (95% CI: -0.99 to -0.89); Ovarian cancer: -0.08 (95% CI: -0.12 to -0.04); and Uterine cancer: -0.84 (95% CI: -0.93 to -0.75). In the Social Inequalities Analysis (1990-2019) the SII changed from 689.26 to 607.08 for Breast, from -226.66 to -239.92 for cervical, from 222.45 to 228.83 for ovarian and from 74.61 to 103.58 for uterine cancer. The concentration index values ranged from 0.2 to 0.4. CONCLUSIONS: The burden of FeBGCs worldwide showed a downward trend from 1990 to 2019. Countries or regions with higher Socio-demographic Index (SDI) bear a higher DALYs burden of breast, ovarian and uterine cancers, while those with lower SDI bear a heavier burden of cervical cancer. These inequalities increased over time.

Immunotherapy for small cell lung cancer: the current state and future trajectories.

Small cell lung cancer (SCLC) constitutes approximately 10% to 15% of all lung cancer diagnoses and represents a pressing global public health challenge due to its high mortality rates. The efficacy of conventional treatments for SCLC is suboptimal, characterized by limited anti-tumoral effects and frequent relapses. In this context, emerging research has pivoted towards immunotherapy combined with chemotherapy, a rapidly advancing field that has shown promise in ameliorating the clinical outcomes of SCLC patients. Through originally developed for non-small cell lung cancer (NSCLC), these therapies have extended new treatment avenues for SCLC. Currently, a nexus of emerging hot-spot treatments has demonstrated significant therapeutic efficacy. Based on the amalgamation of chemotherapy and immunotherapy, and the development of new immunotherapy agents, the treatment of SCLC has seen the hoping future. Progress has been achieved in enhancing the tumor immune microenvironment through the concomitant use of chemotherapy, immunotherapy, and tyrosine kinase inhibitors (TKI), as evinced by emerging clinical trial data. Moreover, a tripartite approach involving immunotherapy, targeted therapy, and chemotherapy appears auspicious for future clinical applications. Overcoming resistance to post-immunotherapy regimens remains an urgent area of exploration. Finally, bispecific antibodies, adoptive cell transfer (ACT), oncolytic virus, monotherapy, including Delta-like ligand 3 (DLL3) and T cell immunoreceptor with Ig and ITIM domains (TIGIT), as well as precision medicine, may present a prospective route towards achieving curative outcomes in SCLC. This review aims to synthesize extant literature and highlight future directions in SCLC treatment, acknowledging the persistent challenges in the field. Furthermore, the continual development of novel therapeutic agents and technologies renders the future of SCLC treatment increasingly optimistic.

In vitro culture of muscle cells derived from myofascial trigger points.

OBJECTIVE: To examine for the in vitro existence of contractile nodules on the taut band of muscle fibers where myofascial trigger points (MTrPs) are located (using cell culture). METHODS: Sixteen male Sprague-Dawley rats (7 weeks old) were randomly divided into experimental and control groups. A blunt striking injury and eccentric exercise were applied to the gastrocnemius muscle of rats in the experimental group once a week for 8 weeks to establish an MTrP model. Subsequently, the rats were reared normally and rested for 4 weeks. After modeling, the skeletal muscles at the MTrPs (and non-MTrPs at the same anatomical position) were extracted from the two groups of rats for in vitro cell culture experiments of single muscle fibers. Potential contractile nodules in the MTrP group were exposed to different concentrations of acetylcholinesterase, whereas non-MTrP cells were exposed to acetylcholine. The morphological changes of muscle cells in each group were observed. RESULTS: By culturing MTrP cells in vitro, large contractile nodules remained in single MTrP muscle fibers, whereas some contractile nodules were twisted and deformed. After the addition of different acetylcholinesterase concentrations, no obvious morphological changes were observed in the contractile nodules in the MTrP group. After the non-MTrP cells were exposed to different acetylcholine concentrations, no significant morphological changes were observed in the single muscle fibers. CONCLUSION: MTrP cells can continue to maintain contractile morphology in vitro, but whether the recovery of such contractile nodules is related to acetylcholine remains uncertain.

Clinical observations in treatment of lower extremity varicose veins with trigger points acupuncture.

OBJECTIVES: To observe the effect of the acupuncture of myofascial trigger points (MTrPs) in the treatment of lower extremity varicose veins (LEVVs). METHODS: Overall, 260 patients with LEVVs participated in this study. LEVVs were selected based on diagnostic criteria of Clinical, Etiology, Anatomy, and Pathophysiology levels 2-5 and classified into six types on the basis of their anatomical positions. The MTrPs in the lower extremities were localized in accordance with the classification of LEVVs and treated by MTrPs acupuncture combined with self-massage and self-stretching. The interval between each treatment was 2 weeks to 1 month, depending on needling pain tolerance of each patient. An in-house evaluation was used to estimate the proportion of varicose veins in the lower limbs and their accompanying symptoms. The treatment effect was evaluated before each treatment and at 1-year follow-up. RESULTS: The mean evaluation score of LEVVs before the treatment course was 3.66 ± 1.19. After the course, this reduced to 1.18 ± 0.97, with the following response rates: 85% for excellent and good and 15% for medium. After 1-year follow-up, the mean evaluation score of all patients was 1.11 ± 0.92, with the following response rates: 87% for excellent and good, and 13% for medium. CONCLUSIONS: In some patients, MTrP acupuncture could cure LEVVs and its accompanying symptoms. These LEVVs are probably caused by fascia tension as a pre-pathology induced by the MTrPs.

Phylogenomic analyses of Camellia support reticulate evolution among major clades.

Camellia (Theaceae) is a morphologically highly diverse genus of flowering plants and includes many famous species with high economic value, and the phylogeny of this genus is not fully resolved. We used 95 transcriptomes from 87 Camellia species and identified 1481 low-copy genes to conduct a detailed analysis of the phylogeny of this genus according to various data-screening criteria. The results show that, very different from the two existing classification systems of Camellia, 87 species are grouped into 8 main clades and two independent species, and that all 8 clades except Clade 8 were strongly supported by almost all the coalescent or concatenated trees using different gene subsets. However, the relationships among these clades were weakly supported and different from analyses using different gene subsets; furthermore, they do not agree with the phylogeny from chloroplast genomes of Camellia. Additional analyses support reticulate evolution (probably resulting from introgression or hybridization) among some major Camellia lineages, providing explanation for extensive gene tree conflicts. Furthermore, we inferred that together with the formation of East Asian subtropical evergreen broad-leaved forests, Camellia underwent a radiative divergence of major clades at 23 âˆ¼ 19 Ma in the late Miocene then had a subsequent species burst at 10 âˆ¼ 5 Ma. Principal component and cluster analyses provides new insights into morphological changes underlying the evolution of Camellia and a reference to further clarify subgenus and sections of this genus. The comprehensive study here including a nuclear phylogeny and other analyses reveal the rapid evolutionary history of Camellia.

Dry needling on latent and active myofascial trigger points versus oral diclofenac in patients with knee osteoarthritis: a randomized controlled trial.

BACKGROUND: Latent and active myofascial trigger points (MTrPs) in knee-associated muscles may play a key role in pain management among patients with knee osteoarthritis (KOA). The aim of this study was to investigate the effect of dry needling treatment on pain intensity, disability, and range of motion (ROM) in patients with KOA. METHODS: This randomized, single-blinded, clinical trial was carried out for 6 weeks of treatment and 6-month follow-up. A total of 98 patients met the entry criteria and were randomly assigned to the dry needling latent and active myofascial trigger point (MTrPs) with the stretching group or the oral diclofenacwith the stretching group. Numeric Pain Rating Scale (NPRS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and ROM were statistically analyzed before and after treatment and at the 6-month follow-up. RESULTS: A total of 42 patients in the dry needling group (DNG) and 35 patients in the diclofenac group (DG), respectively, completed the study, and there was no significant difference in the general data between the two groups. After treatments, both the groups showed a good effect in knee pain, function, and ROM, However, the DNG showed a significantly better result than the DG. Especially in the results of the 6-month follow-up, the DNG showed much better results than the DG. CONCLUSIONS: Dry needling on latent and active MTrPs combined with stretching and oral diclofenac combined with stretching can effectively relieve pain, improve function, and restore knee ROM affected by KOA. However, the effects of dry needling and stretching are better and longer lasting than those of oral diclofenac and stretching for at least 6 months. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registry ( www.chictr.org.cn ) in 17/11/2017 with the following code: ChiCTR-INR-17013432.

Effects of dry needling intervention on lower limb dysfunction after stroke: study protocol for a randomised controlled trial.

INTRODUCTION: Lower limb dysfunction is among the common sequelae of patients who had a poststroke and often results in the reduction of the quality of life. This study aims to assess the short and interim-term efficacy of dry needling (DN) intervention on lower extremity function, balance and gait in lower limb dysfunction after stroke. METHODS AND ANALYSIS: This protocol entails an assessor and statistician-blinded, single-centre study with a randomised controlled trial. Forty-four patients who had a poststroke will be randomly allocated (1:1) to either the conventional treatment group (n=22) or the DN group (n=22). The conventional treatment group will receive conventional rehabilitation treatment once a day for 40 min each time. The treatment will be performed five times a week for 2 weeks. In the DN group, participants will be treated with DN on the basis of the conventional treatment. The intervention will be performed thrice a week for 2 weeks. The primary outcome that determines the efficacy of lower limb dysfunction will be the change in the Fugl-Meyer Assessment of Lower Extremity scale. The secondary indicators include the range of motion of knee and ankle joints, limits of stability, modified Clinical Test of Sensory Interaction on Balance, Timed Up and Go test, Modified Ashworth Scale and Barthel Index. Results will be evaluated at baseline, at 24 hours after intervention, at 2 weeks after intervention and at 3-month follow-up. Data will be released after the completion of the study. Adverse events will be reported. ETHICS AND DISSEMINATION: The experiment was approved by the Ethical Committee of Shanghai Tong Ren Hospital in October 2021 (approval number: 202105702). The results of this study will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2000040754.

[Clinical efficacy of Longjintonglin Capsules on chronic prostatitis with damp-heat stasis syndrome Re-evaluation based on multicenter real-world study].

OBJECTIVE: To re-evaluate the clinical efficacy of Longjintonglin Capsules (LJTL) in the treatment of chronic prostatitis with damp-heat stasis syndrome. METHODS: This multicenter real-world study included 1 352 cases of chronic prostatitis with damp-heat and stagnation syndrome treated with LJTL (3 capsules once, tid, 30 minutes after meals, for 2 four-week courses) in addition to routine treatment. Before and after treatment, we analyzed the NIH-CPSI scores, the scores of Chinese medicine symptom quantitative classification and changes in individual symptom scores, and observed adverse reactions to medication. RESULTS: The total effectiveness rate of LJTL was 93.64%. Compared with the baseline, the NIH-CPSI scores were significantly decreased after treatment (ï¼»24.27 ± 6.04ï¼½ vs ï¼»8.17 ± 4.21ï¼½, P < 0.05), and so were the scores on the pain symptoms (ï¼»9.63 ± 3.65ï¼½ vs ï¼»3.02 ± 2.23ï¼½, P < 0.05), voiding symptoms (ï¼»5.65 ± 2.15ï¼½ vs ï¼»1.62 ± 1.36) and quality of life (ï¼»8.96 ± 2.32ï¼½ vs ï¼»3.16 ± 1.89ï¼½, P < 0.05). The effectiveness rate of LJTL was 95.9% on the Chinese medicine symptom frequent urination, 90.4% on painful urination, and 91.4% scanty dark urine, with a total effectiveness rate of 82.4% － 95.9%, all with statistically significant difference in comparison with the baseline (P < 0.05). CONCLUSION: Longjintonglin Capsules combined with routine treatment can significantly improve the clinical symptoms of chronic prostatitis with damp-heat stasis syndrome, especially effective on the symptoms of frequent urination, painful urination and scanty dark urine. Besides, it recommendable for its antidepressant and antianxiety effects, and the effect of improving the quality of life of the chronic prostatitis patients with damp-heat stasis.

Neutralizing Antibodies to SARS-CoV-2 Selected from a Human Antibody Library Constructed Decades Ago.

Combinatorial antibody libraries not only effectively reduce antibody discovery to a numbers game, but enable documentation of the history of antibody responses in an individual. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has prompted a wider application of this technology to meet the public health challenge of pandemic threats in the modern era. Herein, a combinatorial human antibody library constructed 20 years before the coronavirus disease 2019 (COVID-19) pandemic is used to discover three highly potent antibodies that selectively bind SARS-CoV-2 spike protein and neutralize authentic SARS-CoV-2 virus. Compared to neutralizing antibodies from COVID-19 patients with generally low somatic hypermutation (SHM), these three antibodies contain over 13-22 SHMs, many of which are involved in specific interactions in their crystal structures with SARS-CoV-2 spike receptor binding domain. The identification of these somatically mutated antibodies in a pre-pandemic library raises intriguing questions about the origin and evolution of these antibodies with respect to their reactivity with SARS-CoV-2.

Sweet-flavored peptides with biological activities from mulberry seed protein treated by multifrequency countercurrent ultrasonic technology.

To increase the reuse of food residues, multifrequency countercurrent ultrasonic treatment was used to enhance the extraction yield of defatted mulberry seed protein (DMSP), and sweet-flavored peptides from DMSP hydrolysates (DMSPHs) were obtained for the first time. Here, the DMSP yield was increased by 16.2% (p < 0.05) while the power density was halved compared with single-frequency ultrasonic treatment. According to Fick's second law, a molecular diffusion dynamics model was developed to be suitable for predicting the pretreatment conditions (R2 = 0.9785). After that, the sweet-flavored peptides were purified and the main amino acid sequences were identified, i.e., FEGGSIE, KDFPEAHSQAT, and GSQPAEGAK. Moreover, the antioxidant activities of DMSPHs prepared with tri-frequency treatment was higher than 60%. The DMSPHs retarded the growth of HepG2 cells in vitro, increased the necrotic quadrant (Q1-UL), and extended the S phase. Therefore, the sweet-flavored peptides prepared from DMSPHs using the multifrequency-ultrasonic treatment have significant biological activities.

Eggshell crack detection based on the transient impact analysis and cross-correlation method.

To explore the transient impact process for cracked eggshell detection, an equivalent mechanical model was built based on a self-designed automatic excitation device. Through analysis of power spectrum from dynamic force signal, it was found that the impact speed affects only the impaction energy. In contrast, the material of the impact head and the weight of the excitation rod determine the energy and the cut-off frequency of the impaction. When the weight of impact tup is less than 6.62 g, the cut-off frequency of excitation impact can cover the egg's inherent frequency. Then, an optimized experiment system was designed to acquire the response acoustic signals. The cross-correlation analysis and Bayes classification methods were carried out to detect the cracked eggshell. In the conducted experiments, a crack detection level of 97% and a false rejection level of 1% were achieved. From the findings, it can be concluded that the proposed method will assist in optimizing the impact device and simplifying the classification algorithm for an online detection system.

[Essence of acupoints and meridians based on the studies of myofascial trigger points].

Based on the modern anatomy and physiology, the referred pain of myofascial trigger points of each muscle is integrated; compared with the twelve meridians as well as conception vessel and governor vessel, the similarity of their position and running course is observed. With the current research progress of myofascial trigger points and fasciology, based on the running course of referred pain of trigger points, combined with fascia mechanics, nerve and vascular, the location of acupoints and meridians, as well as the relationship between acupoints and meridians, are discussed.

The anti-tussive, anti-inflammatory effects and sub-chronic toxicological evaluation of perilla seed oil.

BACKGROUND: Perilla seed oil (PSO) is the main constituent of perilla seeds currently being used in the food industry, however it also has great clinical potential in the regulation of lung function as a nutrition supplement because of the high content of α-linolenic acid (ALA). In this study, the pharmacological activities including anti-tussive, expectorant and anti-inflammatory effect of PSO were performed. Furthermore, the 90-day sub-chronic oral toxicity with a 30 day recovery period was evaluated in Wistar rats. RESULTS: The pharmacological studies demonstrated that PSO inhibited cough frequency induced by capsaicine in mice. PSO also inhibited the leukotriene B4 (LTB4) release from the calcium ionophore A23187-induced polymorphonuclear neutrophils (PMNs) to some extent. In this sub-chronic toxicity study, mortality, clinical signs, body weight, food consumption, hematology, serum biochemistry, urinalysis, organ weight, necropsy, and histopathology were used to evaluate the toxicity of PSO. Lower body weight and various negative impacts on liver related parameters without histopathological lesion were observed in the 16 g kg-1 groups. No clinically significant changes were discovered in the 4 g kg-1 group during the test period. CONCLUSION: In summary, PSO exhibited anti-tussive and anti-inflammatory activities in vivo and in vitro. These sub-chronic toxicity studies inferred that the 'no-observed adverse effect level' (NOAEL) of PSO in Wistar rats was determined to be 4 g kg-1 . These results may provide a safety profile and a valuable reference for the use of PSO. © 2020 Society of Chemical Industry.

Postsynaptic Targeting and Mobility of Membrane Surface-Localized hASIC1a.

Acid-sensing ion channels (ASICs), the main H+ receptors in the central nervous system, sense extracellular pH fluctuations and mediate cation influx. ASIC1a, the major subunit responsible for acid-activated current, is widely expressed in brain neurons, where it plays pivotal roles in diverse functions including synaptic transmission and plasticity. However, the underlying molecular mechanisms for these functions remain mysterious. Using extracellular epitope tagging and a novel antibody recognizing the hASIC1a ectodomain, we examined the membrane targeting and dynamic trafficking of hASIC1a in cultured cortical neurons. Surface hASIC1a was distributed throughout somata and dendrites, clustered in spine heads, and co-localized with postsynaptic markers. By extracellular pHluorin tagging and fluorescence recovery after photobleaching, we detected movement of hASIC1a in synaptic spine heads. Single-particle tracking along with use of the anti-hASIC1a ectodomain antibody revealed long-distance migration and local movement of surface hASIC1a puncta on dendrites. Importantly, enhancing synaptic activity with brain-derived neurotrophic factor accelerated the trafficking and lateral mobility of hASIC1a. With this newly-developed toolbox, our data demonstrate the synaptic location and high dynamics of functionally-relevant hASIC1a on the surface of excitatory synapses, supporting its involvement in synaptic functions.