Complexity of avian evolution revealed by family-level genomes.

Despite tremendous efforts in the past decades, relationships among main avian lineages remain heavily debated without a clear resolution. Discrepancies have been attributed to diversity of species sampled, phylogenetic method and the choice of genomic regions1-3. Here we address these issues by analysing the genomes of 363 bird species4 (218 taxonomic families, 92% of total). Using intergenic regions and coalescent methods, we present a well-supported tree but also a marked degree of discordance. The tree confirms that Neoaves experienced rapid radiation at or near the Cretaceous-Palaeogene boundary. Sufficient loci rather than extensive taxon sampling were more effective in resolving difficult nodes. Remaining recalcitrant nodes involve species that are a challenge to model due to either extreme DNA composition, variable substitution rates, incomplete lineage sorting or complex evolutionary events such as ancient hybridization. Assessment of the effects of different genomic partitions showed high heterogeneity across the genome. We discovered sharp increases in effective population size, substitution rates and relative brain size following the Cretaceous-Palaeogene extinction event, supporting the hypothesis that emerging ecological opportunities catalysed the diversification of modern birds. The resulting phylogenetic estimate offers fresh insights into the rapid radiation of modern birds and provides a taxon-rich backbone tree for future comparative studies.

Induced Aggregation, Solvent Regulation, and Supracluster Assembly of Aluminum Oxo Clusters.

ConspectusRecent years have witnessed the development of cluster materials as they are atomically precise molecules with uniform size and solution-processability, which are unattainable with traditional nanoparticles or framework materials. The motivation for studying Al(III) chemistry is not only to understand the aggregation process of aluminum in the environment but also to develop novel low-cost materials given its natural abundance. However, the Al-related clusters are underdeveloped compared to the coinage metals, lanthanides, and transition metals. The challenge in isolating crystalline compounds is the lack of an effective method to realize the controllable hydrolysis of Al(III) ions. Compared with the traditional hydrolysis of inorganic Al(III) salts in highly alkaline solutions and hydrolysis of aluminum trialkyl compounds conducted carefully in an inert operating environment, we herein developed an effective way to control the hydrolysis of aluminum isopropanol through an alcoxalation reaction. By solvothermal/low melting point solid melting synthesis and using "ligand aggregation, solvent regulation, and supracluster assembly" strategies, our laboratory has established an organic-inorganic hybrid system of aluminum oxo clusters (AlOCs). The employment of organic ligands promotes the aggregation and slows the hydrolysis of Al(III) ions, which in turn improves the crystallization process. The regulation of the structure types can be achieved through the selection of ligands and the supporting solvents. Compared with the traditional condensed polyoxoaluminates, we successfully isolated a broad range of porous AlOCs, including aluminum molecular rings and Archimedes aluminum oxo cages. By studying ring expansion, structural transformation, and intermolecular supramolecular assembly, we demonstrate unique and unprecedented structural controllability and assembly behavior in cluster science. The advancement of this universal synthetic method is to realize materials customization through modularly oriented supracluster assembly. In this Account, we will provide a clear-cut definition and terminology of "ligand aggregation, solvent regulation, and supracluster assembly". Then we will discuss the discovery in this area by using a strategy, such as aluminum molecular ring, ring size expansion, ring supracluster assembly, etc. Furthermore, given the internal and external pore structures, as well as the solubility and modifiability of the AlOCs, we will demonstrate their potential applications in both the solid and liquid phases, such as iodine capture, the optical limiting responses, and dopant in polymer dielectrics. The strategy herein can be applied to extensive cluster science and promote the research of main group element chemistry. The new synthetic method, fascinating clusters, and unprecedented assembly behaviors we have discovered will advance Al(III) chemistry and will also lay the foundation for functional applications.

Hyperfractionation compared with standard fractionation in intensity-modulated radiotherapy for patients with locally advanced recurrent nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial.

BACKGROUND: Reirradiation in standard fractionation for locally advanced recurrent nasopharyngeal carcinoma after a previous course of high-dose radiotherapy is often associated with substantial late toxicity, negating its overall benefit. We therefore aimed to investigate the efficacy and safety of hyperfractionation compared with standard fractionation in intensity-modulated radiotherapy. METHODS: This multicentre, randomised, open-label, phase 3 trial was done in three centres in Guangzhou, China. Eligible patients were aged 18-65 years with histopathologically confirmed undifferentiated or differentiated, non-keratinising, advanced locally recurrent nasopharyngeal carcinoma. Participants were randomly assigned (1:1) to either receive hyperfractionation (65 Gy in 54 fractions, given twice daily with an interfractional time interval of at least 6 h) or standard fractionation (60 Gy in 27 fractions, given once a day). Intensity-modulated radiotherapy was used in both groups. A computer program generated the assignment sequence and randomisation was stratified by treatment centre, recurrent tumour stage (T2-T3 vs T4), and recurrent nodal stage (N0 vs N1-N2), determined at the time of randomisation. The two primary endpoints were the incidence of severe late complications defined as the incidence of grade 3 or worse late radiation-induced complications occurring 3 months after the completion of radiotherapy until the latest follow-up in the safety population, and overall survival defined as the time interval from randomisation to death due to any cause in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02456506. FINDINGS: Between July 10, 2015, and Dec 23, 2019, 178 patients were screened for eligibility, 144 of whom were enrolled and randomly assigned to hyperfractionation or standard fractionation (n=72 in each group). 35 (24%) participants were women and 109 (76%) were men. After a median follow-up of 45·0 months (IQR 37·3-53·3), there was a significantly lower incidence of grade 3 or worse late radiation-induced toxicity in the hyperfractionation group (23 [34%] of 68 patients) versus the standard fractionation group (39 [57%] of 68 patients; between-group difference -23% [95% CI -39 to -7]; p=0·023). Patients in the hyperfractionation group had better 3-year overall survival than those in the standard fractionation group (74·6% [95% CI 64·4 to 84·8] vs 55·0% [43·4 to 66·6]; hazard ratio for death 0·54 [95% CI 0·33 to 0·88]; p=0·014). There were fewer grade 5 late complications in the hyperfractionation group (five [7%] nasal haemorrhage) than in the standard fractionation group (16 [24%], including two [3%] nasopharyngeal necrosis, 11 [16%] nasal haemorrhage, and three [4%] temporal lobe necrosis). INTERPRETATION: Hyperfractionated intensity-modulated radiotherapy could significantly decrease the rate of severe late complications and improve overall survival among patients with locally advanced recurrent nasopharyngeal carcinoma. Our findings suggest that hyperfractionated intensity-modulated radiotherapy could be used as the standard of care for these patients. FUNDING: Key-Area Research and Development of Guangdong Province, the National Natural Science Foundation of China, the Special Support Program for High-level Talents in Sun Yat-sen University Cancer Center, the Guangzhou Science and Technology Plan Project, and the National Ten Thousand Talents Program Science and Technology Innovation Leading Talents, Sun Yat-Sen University Clinical Research 5010 Program.

Outcomes of patients in nasopharyngeal adenoid cystic carcinoma in the IMRT era: a single-center experience.

OBJECTIVE: Nasopharyngeal adenoid cystic carcinoma (NACC) is a rare malignancy with special biological features. Controversies exist regarding the treatment approach and prognostic factors in the IMRT era. This study aimed to evaluate the long-term outcomes and management approaches in NACC. METHODS: Fifty patients with NACC at our institution between 2010 and 2020 were reviewed. Sixteen patients received primary radiotherapy (RT), and 34 patients underwent primary surgery. RESULTS: Between January 2010 and October 2020, a total of 50 patients with pathologically proven NACC were included in our analysis. The median follow-up time was 58.5 months (range: 6.0-151.0 months). The 5-year overall survival rate (OS) and progression-free survival rate (PFS) were 83.9% and 67.5%, respectively. The 5-year OS rates of patients whose primary treatment was surgery and RT were 90.0% and 67.3%, respectively (log-rank P = 0.028). The 5-year PFS rates of patients whose primary treatment was surgery or RT were 80.8% and 40.7%, respectively (log-rank P = 0.024). Multivariate analyses showed that nerve invasion and the pattern of primary treatment were independent factors associated with PFS. CONCLUSIONS: Due to the relative insensitivity to radiation, primary surgery seemed to provide a better chance of disease control and improved survival in NACC. Meanwhile, postoperative radiotherapy should be performed for advanced stage or residual tumours. Cranial nerve invasion and treatment pattern might be important factors affecting the prognosis of patients with NACC.

Blood Lipid Metabolic Profiles and Causal Links to Site-Specific Cancer Risks: A Mendelian Randomization Study.

Observational and Mendelian randomization (MR) studies have established links between dyslipidemia and select cancer susceptibilities. However, there is a lack of comprehensive exploration of causal relationships spanning diverse cancer types. Here, we conducted a two-sample MR analysis to elucidate the causative connections between 9 blood lipid metabolic profiles (namely, adiponectin, leptin, lipoprotein A, apolipoprotein A1, apolipoprotein B, cholesterol, triglycerides, LDL-cholesterol, and HDL-cholesterol) and 21 site-specific cancer risks. Our findings reveal genetically predicted adiponectin levels to be associated with a reduced ovarian cancer risk, while genetically determined leptin increases bladder cancer risk but decreases prostate cancer risk. Lipoprotein A elevates risk of prostate cancer while diminishing risk of endometrial cancer, while apolipoprotein A1 heightens risks of breast and cervical cancers. Furthermore, elevated levels of cholesterol are positively correlated with kidney cancer, and triglycerides demonstrate a positive association with non-melanoma skin cancer but a negative association with breast cancer. Protective effects of genetically predicted LDL-cholesterol on endometrial cancer and adverse effects of HDL-cholesterol on breast cancer are also observed. Our study conclusively establishes that blood lipid metabolic profiles exert causal effects on cancer susceptibility, providing more robust evidence for cancer prevention and prompting contemplation regarding the future health of the human populace.

High Enhancement in Proton Conductivity by Incorporating Sulfonic Acids into a Zirconium-Based Metal-Organic Framework via "Click" Reaction.

Taking a robust zirconium-based metal-organic framework, UiO-66, as a prototype, functional postmodification via the versatile Cu(I)-catalyzed azide-alkyne "click" reaction was carried out, and sulfonic acid groups were successfully grafted into its skeleton. Characterizations revealed that the MOF network was still well maintained after being treated by "clicked" modification. Investigations by electrochemical impedance spectroscopy measurements revealed that its proton conductivity increases exponentially up to 8.8 × 10-3 S cm-1 at 80 °C and 98% RH, while those of the UiO-66 and UiO-66-NH2 are only 6.3 × 10-6 and 3.5 × 10-6 S cm-1, respectively, at the same condition. Additionally, the continuous test shows it possesses long-life reusability. Such a remarkable enhancement on the proton conductivities and high performance in long-life reusability of the resultant MOF demonstrated that the "click" reaction is a facile reaction in postmodification of robust porous materials toward targeted applications, with which highly promising candidates of proton-conductive electrolytes for applying in proton-exchange-membrane (PEM) fuel cell can be achieved.

CD44-mediated monocyte transmigration across Cryptococcus neoformans-infected brain microvascular endothelial cells is enhanced by HIV-1 gp41-I90 ectodomain.

BACKGROUND: Cryptococcus neoformans (Cn) is an important opportunistic pathogen in the immunocompromised people, including AIDS patients, which leads to fatal cryptococcal meningitis with high mortality rate. Previous researches have shown that HIV-1 gp41-I90 ectodomain can enhance Cn adhesion to and invasion of brain microvascular endothelial cell (BMEC), which constitutes the blood brain barrier (BBB). However, little is known about the role of HIV-1 gp41-I90 in the monocyte transmigration across Cn-infected BBB. In the present study, we provide evidence that HIV-1 gp41-I90 and Cn synergistically enhance monocytes transmigration across the BBB in vitro and in vivo. The underlying mechanisms for this phenomenon require further study. METHODS: In this study, the enhancing role of HIV-1 gp41-I90 in monocyte transmigration across Cn-infected BBB was demonstrated by performed transmigration assays in vitro and in vivo. RESULTS: Our results showed that the transmigration rate of monocytes are positively associated with Cn and/or HIV-1 gp41-I90, the co-exposure (HIV-1 gp41-I90 + Cn) group showed a higher THP-1 transmigration rate (P < 0.01). Using CD44 knock-down HBMEC or CD44 inhibitor Bikunin in the assay, the facilitation of transmigration rates of monocyte enhanced by HIV-1 gp41-I90 was significantly suppressed. Western blotting analysis and biotin/avidin enzyme-linked immunosorbent assays (BA-ELISAs) showed that Cn and HIV-1 gp41-I90 could increase the expression of CD44 and ICAM-1 on the HBMEC. Moreover, Cn and/or HIV-1 gp41-I90 could also induce CD44 redistribution to the membrane lipid rafts. By establishing the mouse cryptococcal meningitis model, we found that HIV-1 gp41-I90 and Cn could synergistically enhance the monocytes transmigration, increase the BBB permeability and injury in vivo. CONCLUSIONS: Collectively, our findings suggested that HIV-1 gp41-I90 ectodomain can enhance the transmigration of THP-1 through Cn-infected BBB, which may be mediated by CD44. This novel study enlightens the future prospects to elaborate the inflammatory responses induced by HIV-1 gp41-I90 ectodomain and to effectively eliminate the opportunistic infections in AIDS patients.

Phylogenomic analyses unraveled the evolution of viral tolerance in bats.

Bats host a range of viruses, exhibiting a coevolution process with many virus genera and a special capacity for viral tolerance. Foley et al.1 performed phylogenomic analyses for 60 bat species, finding that swarming behavior might facilitate cross-species introgression and the spread of anti-virus immunity gene loci across species.

The impact of ageing mechanisms on musculoskeletal system diseases in the elderly.

Ageing is an inevitable process that affects various tissues and organs of the human body, leading to a series of physiological and pathological changes. Mechanisms such as telomere depletion, stem cell depletion, macrophage dysfunction, and cellular senescence gradually manifest in the body, significantly increasing the incidence of diseases in elderly individuals. These mechanisms interact with each other, profoundly impacting the quality of life of older adults. As the ageing population continues to grow, the burden on the public health system is expected to intensify. Globally, the prevalence of musculoskeletal system diseases in elderly individuals is increasing, resulting in reduced limb mobility and prolonged suffering. This review aims to elucidate the mechanisms of ageing and their interplay while exploring their impact on diseases such as osteoarthritis, osteoporosis, and sarcopenia. By delving into the mechanisms of ageing, further research can be conducted to prevent and mitigate its effects, with the ultimate goal of alleviating the suffering of elderly patients in the future.

A novel endoscopic nasopharyngectomy by low-temperature plasma radiofrequency ablation in localized recurrent nasopharyngeal carcinoma.

OBJECTIVE: Endoscopic nasopharyngectomy (ENPG) with en bloc resection has been well accepted in resectable localized recurrent nasopharyngeal carcinoma (rNPC), but it is a difficult technique to master for most otorhinolaryngology head and neck surgeons. Ablation surgery is a new and simplified method to remove tumors. We designed a novel method using low-temperature plasma radiofrequency ablation (LPRA) and evaluated the survival benefit. METHODS: A total of 56 localized rNPC patients were explained in detail and retrospectively analyzed. The surgery method was ablated from the resection margin to the center of the tumor. The postmetastatic overall survival (OS), local relapse-free survival (LRFS) rate, progression-free survival (PFS) and distant metastasis-free survival (DMFS) were analyzed using the Kaplan-Meier method and compared by the log-rank test. RESULTS: All surgeries were successfully performed without any severe postoperative complications or deaths. The median operation time of ablation and harvested NSFF respectively were 29 min (range, 15-100 min) and 101 min (range, 30-180 min). The average number of hospital days postoperation was 3 days (range, 2-5 days). All cases (100.0%) had radical ablation with negative resection margins. The nasopharyngeal defects were completely re-epithelialized in 54 (96.4%) patients. As of the data cutoff (September 3, 2023), the median follow-up time was 44.3 months (range, 17.1-52.7 months, 95% CI: 40.4-48.2). The 3-year OS, LRFS, PFS and DMFS of the entire cohort were 92.9% (95% CI: 0.862-0.996), 89.3% (95% CI: 0.813-0.973), 87.5% (95% CI: 0.789-0.961), and 92.9% (95% CI: 0.862-0.996), respectively. Cycles of radiotherapy were independent risk factors for OS (p = 0.003; HR, 32.041; 95% CI: 3.365-305.064), LRFS (p = 0.002; HR, 10.762; 95% CI: 2.440-47.459), PFS (p = 0.004; HR, 7.457; 95% CI: 1.925-28.877), and DMFS (p = 0.002; HR, 34.776; 95% CI: 3.806-317.799). CONCLUSION: Radical endoscopic nasopharyngectomy by using low-temperature plasma radiofrequency ablation is a novel, safe and simplified method to master and disseminate for treating resectable rNPC. However, further data and longer follow-up time are needed to prove its efficacy.

Circulating DNA genome-wide fragmentation in early detection and disease monitoring of hepatocellular carcinoma.

Genome-wide circulating cell-free DNA (ccfDNA) fragmentation for cancer detection has been rarely evaluated using blood samples collected before cancer diagnosis. To evaluate ccfDNA fragmentation for detecting early hepatocellular carcinoma (HCC), we first modeled and tested using hospitalized HCC patients and then evaluated in a population-based study. A total of 427 samples were analyzed, including 270 samples collected prior to HCC diagnosis from a population-based study. Our model distinguished hospital HCC patients from controls excellently (area under curve 0.999). A high ccfDNA fragmentation score was highly associated with an advanced tumor stage and a shorter survival. In evaluation, the model showed increasing sensitivities in detecting HCC using 'pre-samples' collected ≥4 years (8.3%), 3-4 years (20.0%), 2-3 years (31.0%), 1-2 years (35.0%), and 0-1 year (36.4%) before diagnosis. These findings suggested ccfDNA fragmentation is sensitive in clinical HCC detection and might be helpful in screening early HCC.

Free-radical-promoted conversion of graphite oxide into chemically modified graphene.

The preparation of chemically modified graphene (CMG) generally involves the reduction of graphite oxide (GO) by using various reducing reagents. Herein, we report a free-radical-promoted synthesis of CMG, which does not require any conventional reductant. We demonstrated that the phenyl free radical can efficiently promote the conversion of GO into CMG under mild conditions and produces phenyl-functionalized CMG. This pseudo-"reduction" process is attributed to a free-radical-mediated elimination of the surface-attached oxygen-containing functionalities. This work illustrates a new strategy for preparing CMG that is alternative to the conventional means of chemical reduction. Furthermore, the phenyl-functionalized graphene shows an excellent performance as an electrode material for lithium-battery applications.

Investigation of an electrochemically switched heterocyclization reaction on gold surface.

We report an investigation of an electrochemically switched heterocyclization reaction on hydroquinone-terminated self-assembled monolayers (SAMs). This reaction involves an electrochemically modulated hydroquinone/benzoquinone transformation step in the SAMs and a subsequent heterocyclization step taking place between the electrochemically generated benzoquinone moieties in SAMs and l-cysteine in solution. The reaction process was monitored by XPS and electrochemical surface-enhanced Raman spectroscopy (EC-SERS). The surface reaction proceeds as a two-step reaction to give a benzothiazine product, which is in contrast to the much more complicated multiple step reactions in solution. This result suggests that the tight molecular packing in the SAMs does not hinder the intramolecular heterocylization reaction, but prevents the intermolecular coupling reaction from happening. This work provides insights to the control and detection of biomolecule related multistep reactions occurring at solid-liquid interface.

Effects of vestibular rehabilitation training combined with anti-vertigo drugs on vertigo and balance function in patients with vestibular neuronitis: a systematic review and meta-analysis.

Objective: To investigate the effects of vestibular rehabilitation training (VRT) combined with anti-vertigo drugs on vertigo and balance function in patients with vestibular neuronitis (VN). Data sources: PubMed, EMBASE, The Cochrane Library, Web of Science, CNKI, Wan Fang Data, VIP, and CBM were searched until July 13, 2023. Participants: Patients with vestibular neuronitis participated in the study. Results: Twenty one studies including 1,415 patients were included in this review for meta-analysis. According to the Physiotherapy Evidence Database (PEDro) quality assessment, four studies received high quality (≥seven scores) and 17 studies received moderate quality (six scores). The meta-analysis showed that VRT combined with anti-vertigo drugs significantly reduced the Dizziness Handicap Inventory (DHI) score, the Vestibular Disorders Activities of Daily Living Scale (VADL) score and the Canal Paresis (CP) score, and improved the overall efficiency and the Berg Balance Scale (BBS) score, promoting vestibular evoked myogenic potentials (VEMPs) returned to normal in VN compared to simple anti-vertigo drugs or VRT alone. Conclusion: The results of this meta-analysis demonstrate the efficacy and safety of VRT combined with anti-vertigo drugs in patients with VN. Combined therapy can alleviate vestibular dysfunction such as vertigo and vomiting in patients, improve daily activity ability and balance ability, in addition to VRT has fewer adverse reactions, so it is extremely safe. However, there are shortcomings such as lack of long-term follow-up and different frequency and duration of treatment. Therefore, future randomized controlled trials (RCTs) with larger sample sizes and longer-term observations are needed to verify the effectiveness of VRT in combination with anti-vertigo drugs for VN.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/.

Mechanistic insights into spontaneous transition from cellular alternans to ventricular fibrillation.

T-wave alternans (TWA) has been used for predicting the risk of malignant cardiac arrhythmias and sudden cardiac death (SCD) in multiple clinical settings; however, possible mechanism(s) underlying the spontaneous transition from cellular alternans reflected by TWA to arrhythmias in impaired repolarization remains unclear. The healthy guinea pig ventricular myocytes under E-4031 blocking IKr (0.1 µM, N = 12; 0.3 µM, N = 10; 1 µM, N = 10) were evaluated using whole-cell patch-clamp. The electrophysiological properties of isolated perfused guinea pig hearts under E-4031 (0.1 µM, N = 5; 0.3 µM, N = 5; 1 µM, N = 5) were evaluated using dual- optical mapping. The amplitude/threshold/restitution curves of action potential duration (APD) alternans and potential mechanism(s) underlying the spontaneous transition of cellular alternans to ventricular fibrillation (VF) were examined. There were longer APD80 and increased amplitude and threshold of APD alternans in E-4031 group compared with baseline group, which was reflected by more pronounced arrhythmogenesis at the tissue level, and were associated with steep restitution curves of the APD and the conduction velocity (CV). Conduction of AP alternans augmented tissue's functional spatiotemporal heterogeneity of regional AP/Ca alternans, as well as the AP/Ca dispersion, leading to localized uni-directional conduction block that spontaneous facilitated the formation of reentrant excitation waves without the need for additional premature stimulus. Our results provide a possible mechanism for the spontaneous transition from cardiac electrical alternans in cellular action potentials and intercellular conduction without the involvement of premature excitations, and explain the increased susceptibility to ventricular arrhythmias in impaired repolarization. In this study, we implemented voltage-clamp and dual-optical mapping approaches to investigate the underlying mechanism(s) for the arrhythmogenesis of cardiac alternans in the guinea pig heart at cellular and tissue levels. Our results demonstrated a spontaneous development of reentry from cellular alternans, arising from a combined actions of restitution properties of action potential duration, conduction velocity of excitation wave and interplay between alternants of action potential and the intracellular Ca handling. We believe this study provides new insights into underlying the mechanism, by which cellular cardiac alternans spontaneously evolves into cardiac arrhythmias.

Acupuncture combined with repeated transcranial magnetic stimulation for upper limb motor function after stroke: A systematic review and meta-analysis.

BACKGROUND: Upper limb motor dysfunction after stroke is an important factor affecting patients' motor function and daily life. Acupuncture and repetitive transcranial magnetic stimulation are effective methods for stroke rehabilitation. However, a systematic and comprehensive overview of the combined efficacy of the two is lacking. OBJECTIVE: Through a systematic review and meta-analysis of randomized controlled trials, this study aimed to assess the effectiveness of acupuncture combined with repetitive transcranial magnetic stimulation on upper extremity motor function in post-stroke patients. METHODS: The relevant randomized controlled trials on acupuncture combined with repetitive transcranial magnetic stimulation in the treatment of upper limb motor disorders after stroke were searched in PubMed, Embase, Cochrane Library, Web of Science CNKI, VIP, Wanfang, and CBM databases. After screening clinical trials that met the inclusion criteria, data extraction was conducted independently by two investigators. Meta-analysis was performed using RevMan 5.4 software. RESULTS: After the screening, 18 articles were included, with a total of 1083 subjects. The results of meta-analysis showed that combination therapy could effectively improve the patients' upper limb motor function (MD = 7.77, 95%CI [6.32, 9.22], P < 0.05), ability of daily living (MD = 8.53, 95%CI [6.28, 10.79], P < 0.05), and hemiplegic shoulder pain (MD = - 1.72, 95%CI [- 2.26, - 1.18], P < 0.05). Meanwhile, for neurophysiological indexes, combined treatment could significantly shorten the latency of motor evoked potential and central motor conduction time (MD = - 1.42, 95%CI [- 2.14, - 0.71], P < 0.05); (MD = - 0.47, 95%CI [- 0.66, - 0.29], P < 0.05), and also could increase the amplitude of motor evoked potential (SMD = 0.71, 95%CI [0.28, 1.14], P < 0.05). CONCLUSION: According to the results of the meta-analysis, we can conclude that acupuncture combined with repeated transcranial magnetic stimulation can significantly improve the upper limb motor function and daily living ability of stroke patients.

Efficacy of acupuncture combined with active exercise training in improving pain and function of knee osteoarthritis individuals: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis to investigate the clinical efficacy of acupuncture combined with active exercise training in improving pain and function of knee osteoarthritis (KOA) individuals. DATA SOURCES: PubMed, EMBASE, The Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wan Fang Data, Technology Periodical Database and China Biology Medicine were searched from their inceptions to April 5, 2023. REVIEW METHODS: We analyzed trials of acupuncture combined with active exercise training for KOA. The included studies were of high quality (Jadad ≥ 4) and RCTs. Study selection, data extraction, risk of bias and quality assessment were independently performed by two reviewers. We performed systematic analyses based on different outcome measures, including total efficiency rate, visual analogue scale (VAS), the Western Ontario and Mcmaster Universities Osteoarthritis Index (WOMAC), the Lysholm Knee Scale (LKS) and range of motion (ROM). We used Review Manager 5.3 and Stata/MP 14.0 to analyze the data. And it was verified by trial sequence analysis (TSA). If I2 > 50% and p < 0.05, we performed sensitivity analysis and subgroup analysis to find the source of heterogeneity. Publication bias was studied by funnel plot and Egger's test was used to verify it. RESULTS: Full 11 high-quality studies (Jadad ≥ 4) including 774 KOA individuals were included in this review for meta-analysis. The results showed that acupuncture combined with active exercise training (combined group) was superior to the acupuncture group in improving the total effective rate [RR = 1.13, 95%CI (1.05, 1.22), I2 = 0%, P = 0.70], reducing the pain level (VAS) [MD = - 0.74, 95%CI (- 1.04, - 0.43), I2 = 68%, P < 0.05], improving knee joint function (WOMAC) [MD = - 6.97, 95%CI (- 10.74, - 3.19), I2 = 76%, P < 0.05] and improving joint range of motion (ROM) [MD = 6.25, 95%CI (2.37, 10.04), I2 = 0%, P = 0.71]. Similarly, the combined group showed significant improvements in the total effective rate [RR = 1.31, 95% CI (1.18, 1.47), I2 = 48%, P = 0.10], pain (VAS) [MD = 1.42, 95% CI (- 1.85, - 1.00), I2 = 65%, P = 0.02] and knee function (WOMAC) [MD = 7.05, 95% CI (- 11.43, - 2.66), I2 = 86%, P < 0.05] compared with the non-acupuncture group. CONCLUSION: The combined effect of all studies showed significant benefits of acupuncture combined with active exercise training in improving the total effective rate, reducing pain, promoting recovery of knee function and expanding range of motion. However, some evaluation indicators are highly subjective and need to be further confirmed by more objective and evidence-based high-quality RCTs in future. SYSTEMATIC REVIEW REGISTRATION: [PROSPERO], identifier [No. CRD42023425823].

Prognostic significance of Dickkopf-1 in head and neck squamous cell carcinoma.

BACKGROUND: Dickkopf-1 (DKK1) exhibits abnormal expression in various cancers and correlates with poor prognosis. This study investigates DKK1's prognostic relevance in head and neck squamous cell carcinoma (HNSC). METHODS: We conducted a comprehensive search across literature and sequencing databases to gather eligible studies and HNSC datasets. We calculated pooled standardized mean differences (SMD) and 95% confidence intervals (CI) for clinical characteristics, as well as hazard ratios (HR) with 95% CIs for overall survival (OS) and progression-free/disease-free survival (PFS/DFS). Sensitivity analysis gauged result stability, and Egger's test assessed publication bias. RESULTS: Pooled results indicated that HNSC patients with higher T-stage exhibited elevated DKK1 expression levels, and this elevated expression was associated with shorter OS and PFS/DFS. While sensitivity analysis identified some studies significantly affecting pooled results, most were unaffected, and no publication bias was detected. CONCLUSION: DKK1 holds promise as a potential biomarker for predicting poor prognosis in HNSC patients, but further research is needed for confirmation.

Fosaprepitant Weekly vs Every 3 Weeks for the Prevention of Concurrent Chemoradiotherapy-Induced Nausea and Vomiting: A Pilot Randomized Clinical Trial.

Importance: Unlike substantial evidence in the prevention of chemotherapy-induced nausea and vomiting (CINV), research in the prevention of nausea and vomiting caused by concurrent chemoradiotherapy (CCRT) is currently lacking. Objective: To compare the efficacy and safety of fosaprepitant weekly vs every 3 weeks for the prevention of nausea and emesis caused by CCRT among patients with nasopharyngeal carcinoma. Design, Setting, and Participants: This pilot randomized clinical trial was conducted at a single cancer center from November 24, 2020, to July 26, 2021, among patients with nasopharyngeal carcinoma who had achieved CINV control after 2 to 3 cycles of induction chemotherapy. Efficacy analyses were performed in the intention-to-treat population. Data were analyzed on November 4, 2022. Interventions: Eligible patients were randomly assigned (1:1) to receive fosaprepitant either weekly or every 3 weeks. Main Outcomes and Measures: The primary end point was the proportion of patients with sustained complete response (defined as no emesis and no rescue therapy) during CCRT. Secondary end points were sustained no emesis, no nausea, no significant nausea, mean time to first emetic episode, quality of life, and 1-year progression-free survival (PFS). Results: A total of 100 patients (mean [SD] age, 46.6 [10.9] years; 83 [83.0%] male) who had achieved CINV control after induction chemotherapy were randomly assigned to receive fosaprepitant weekly (50 patients) or every 3 weeks (50 patients). There was no significantly significant difference in cumulative risk of emesis or rescue therapy in the group that received weekly fosaprepitant compared with those who received fosaprepitant every 3 weeks (subhazard ratio, 0.66 [95% CI, 0.43-1.02]; P = .06). The proportion of patients with sustained no emesis (38% vs 14%; P = .003) or no significant nausea (92% vs 72%; P = .002) was significantly higher in the group that received fosaprepitant weekly vs those who received fosaprepitant every 3 weeks. Treatments were well tolerated. Patients in the weekly group had improved scores for multiple quality-of-life measures. There was no significant difference in survival outcomes between groups (91.8% vs 93.7%; P = .99). In the mean brainstem dose subgroups, a possible treatment interaction effect was observed in sustained complete response (mean brainstem dose ≥36 Gy: hazard ratio [HR], 0.32 [95% CI, 0.15-0.69]; mean brainstem dose <36 Gy: HR, 0.95 [95% CI, 0.55-1.63]) and sustained no emesis (mean brainstem dose ≥36 Gy: HR, 0.21 [95% CI, 0.08-0.53]; mean brainstem dose <36 Gy: HR, 0.73 [95% CI, 0.41-1.28]). Conclusions and Relevance: In this pilot randomized clinical trial, there was no statistically significant difference in the complete response primary end point, but patients receiving weekly fosaprepitant were less likely to experience emesis compared with those who received fosaprepitant every 3 weeks, especially in the subgroup with a mean brainstem dose of 36 Gy or more. Weekly fosaprepitant was well tolerated and improved quality of life of patients without compromising survival. Trial Registration: ClinicalTrials.gov Identifier: NCT04636632.

Camrelizumab Plus Apatinib in Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma: An Open-Label, Single-Arm, Phase II Study.

PURPOSE: Immune checkpoint inhibitors combined with antiangiogenic therapy reportedly have potential synergistic antitumor activity. We investigated the activity and safety of this regimen for recurrent/metastatic nasopharyngeal carcinoma (NPC). METHODS: This single-arm, Simon two-stage study enrolled patients with recurrent/metastatic NPC who were refractory to at least first-line systemic therapy and treatment-naive to immune checkpoint inhibitors. The patients received camrelizumab 200 mg once every 3 weeks and apatinib 250 mg once per day. The primary end point was the objective response rate. Key secondary end points included disease control rate, progression-free survival, duration of response, overall survival, and safety. RESULTS: Between October 14, 2020, and December 23, 2021, 58 patients were enrolled, and all were included in the efficacy and safety analysis set. The objective response rate was 65.5% (95% CI, 51.9 to 77.5), and the disease control rate was 86.2% (95% CI, 74.6 to 93.9). The median duration of response was not reached, and the median progression-free survival was 10.4 months (95% CI, 7.2 to 13.6), with a median follow-up duration of 12.4 months (range, 2.1-19.9 months). Treatment-related adverse events (TRAEs) of grade 3 or higher were reported in 34 (58.6%) patients, with the most common being hypertension (19.0%), nasopharyngeal necrosis (15.5%), headache (12.1%), AST elevation (10.3%), and creatine phosphokinase elevation (10.3%). Sixteen (27.6%) patients discontinued apatinib treatment before progression because of unbearable TRAEs, and the most common complication was nasopharyngeal necrosis (9/16; 56.3%). Recurrent nasopharyngeal lesions (odds ratio, 5.94 [95% CI, 1.45 to 24.24]) and reirradiation (odds ratio, 5.33 [95% CI, 1.15 to 24.79]) were significantly positively correlated with nasopharyngeal necrosis. CONCLUSION: Camrelizumab plus apatinib had promising antitumor activity in patients with refractory recurrent/metastatic NPC who failed first-line therapy. Moderate to severe TRAEs were experienced by 58.6%, including nasopharyngeal necrosis associated with local recurrence and a history of reirradiation.