Role and molecular mechanism of NOD2 in chronic non-communicable diseases.

Nucleotide-binding oligomerization domain containing 2 (NOD2), located in the cell cytoplasm, is a pattern recognition receptor belonging to the innate immune receptor family. It mediates the innate immune response by identifying conserved sequences in bacterial peptide glycans and plays an essential role in maintaining immune system homeostasis. Gene mutations of NOD2 lead to the development of autoimmune diseases such as Crohn's disease and Blau syndrome. Recently, NOD2 has been shown to be associated with the pathogenesis of diabetes, cardiac-cerebral diseases, and cancers. However, the function of NOD2 in these non-communicable diseases (CNCDs) is not well summarized in reviews. Our report mainly discusses the primary function and molecular mechanism of NOD2 as well as its potential clinical significance in CNCDs.

The effects of manual therapy in pain and safety of patients with knee osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: Manual therapy (MT) is frequently used in combination with management of osteoarthritis of the knee, but there is no consensus on the exact efficacy of this treatment strategy. The purpose of this systematic review and meta-analysis was to evaluate the pain relief and safety of MT for treatment of knee osteoarthritis (KOA). METHODS: Randomized controlled trials evaluating MT in patients with KOA in major English and Chinese journals were searched in the following databases: Wanfang, China Science and Technology Journal Database (VIP database), China National Knowledge Infrastructure (CNKI), PubMed, Embase, Web of Science, and the Cochrane Library databases through June 2023. The methodological quality and quality of evidence of the included studies were assessed using Cochrane's risk-of-bias 2 (ROB 2) tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool. Data analysis was performed using Stata version 15.0 software. After use of Galbraith plots to exclude studies that could lead to heterogeneity, random effects models were used to analyze the remaining data and test the consistency of the findings. We used meta-regression to assess the effect of treatment period, patient age, and sex ratio on outcomes. Funnel plots and Egger's test were used to evaluate publication bias. Sensitivity analyses were used to determine the reliability of the results. RESULTS: A total of 25 studies, with 2376 participants, were included in this review. The overall methodological quality of the included studies was limited. Our findings suggest that MT has a positive impact on pain relief outcomes in KOA patients. The meta-analysis showed that MT was superior to usual care (SMD = 2.04, 95% CI 0.94, 3.14, I 2 = 96.3%; low evidence quality) and exercise (SMD = 1.56, 95% CI 0.41, 2.71, I 2 = 96.3%; low evidence quality) for reducing pain. In terms of improvement in visual analogue scale (VAS) scores, MT treatment beyond 4 weeks (SMD = 1.56, 95% CI 0.41, 2.71, I 2 = 96.3%) may be superior to treatments less than or equal to 4 weeks (SMD = 1.24, 95% CI 0.56, 1.95, I 2 = 94.7%). No serious adverse events associated with MT were reported. CONCLUSIONS: MT may be effective at reducing pain in patients with KOA and may be more effective after a 4-week treatment period. Compared with usual care and exercise therapy, MT may be superior at reducing KOA pain in the short term (9 weeks), but its long-term efficacy requires careful consideration of evidence-based outcomes. MT appears to be safe for KOA patients, though clinicians should inform patients of the potential risk of MT-related adverse events.

Efficacy and safety of traditional Chinese manual therapy (Tuina) in patients with non-specific chronic low back pain: a study protocol for a randomised controlled trial.

INTRODUCTION: Non-pharmacological interventions play a crucial role in the management of non-specific chronic low back pain (NSCLBP). One prime example is Tuina, a traditional Chinese manual therapy that incorporates pressing, kneading and rubbing techniques to alleviate physical discomfort and enhance overall well-being. It serves as a widely used technique in China and other East Asian countries. However, the effectiveness and safety of Tuina for managing NSCLBP have not been substantiated through rigorous clinical research. We sought to carry out a randomised controlled trial with an open-label design, blinded assessors and parallel arms to assess the effectiveness and safety of Tuina as a treatment for NSCLBP. The trial aims to provide high-quality evidence regarding the efficacy and safety of Tuina in improving outcomes for patients with NSCLBP. METHODS AND ANALYSIS: A total of 150 patients aged 18-60 years with NSCLBP will be recruited. Participants will be randomly assigned to one of the two groups. Both groups will receive standard health education. In addition, the treatment group will receive Tuina therapy, while the control group will participate in core stability exercises. Each group will undergo a total of 18 interventions over 6 weeks, with the interventions administered three times per week. The primary outcome measure is the patient's pain intensity, assessed using the Numerical Rating Scale, at week 6 following randomisation. Secondary outcomes encompass disability (measured by the Roland-Morris Disability Questionnaire), quality of life (assessed using the EuroQoL-5 dimensions questionnaire), adverse emotions (evaluated with the Pain Catastrophizing Scale, Tampa Scale of Kinesiophobia and Depression Anxiety Stress Scale), biomechanical outcomes, socioeconomic indicators (medication use, healthcare utilisation and absenteeism), patient satisfaction, treatment adherence and other relevant factors.The statistical analysis will follow the intention-to-treat principle. Two-way repeated measures analysis of variance will be used to compare the clinical data across different time points within both groups. ETHICS AND DISSEMINATION: The study protocol has received approval from the Ethics Committee of Shuguang Hospital, Shanghai University of Traditional Chinese Medicine (2023-1366-133-01). All study participants will be required to give written informed consent. The findings of the study will be submitted to a peer-reviewed journal for publication and presented at scientific conferences. Additionally, the participants will receive copies of the results. TRIAL REGISTRATION NUMBER: ChiCTR2300076257.

Impact of Chinese herbal medicine on sarcopenia in enhancing muscle mass, strength, and function: A systematic review and meta-analysis of randomized controlled trials.

Sarcopenia has become important to the public health with the increase in the aging population in society. However, the therapeutic effects of conventional approaches, including pharmacotherapy, exercise, and nutritional intervention, are far from satisfactory. Chinese herbal medicine is a new treatment format with interesting possibilities in sarcopenia has been widely practiced. The study aims to explore the effectiveness of Chinese herbal medicine in sarcopenia. We comprehensively searched the following electronic databases: Medline, EMBASE, APA PsycInfo, Cochrane Library, Web of Science, PubMed, and Chinese database from the establishment of the database to December 2022 (no language restrictions). Randomized controlled clinical studies on the use of Chinese herbal medicine in sarcopenia were selected in compliance with PRISMA guidelines. Review Manager and Stata were used for statistical analysis and the mean difference and standardized mean difference were adopted. Of 277 identified studies, 17 were eligible and included in our analysis (N = 1440 participants). The results showed that Chinese herbal medicine can improve total efficiency (RR = 1.29, 95% CI [1.21, 1.36], p < 0.00001) in sarcopenia and enhance muscle mass (SMD = 1.02, 95% CI [0.55, 1.50], p < 0.0001), and muscle strength measured by grip strength (SMD = 0.66, 95% CI [0.36, 0.96], p < 0.0001), measured by 60°/s knee extension peak TQ (MD = 5.63, 95% CI [-0.30, 11.57], p = 0.06) and muscle function measured by 6-meter walking speed (SMD = 1.34, 95% CI [0.60, 2.08], p = 0.0004), measured by the short physical performance battery of 1.50%, 95% CI (1.05, 1.95), measured by the EuroQoL 5-dimension of (SMD = 0.27, 95% CI [-0.10, 0.65], p = 0.16), suggesting that Chinese herbal medicine alone or combined with conventional treatment has ameliorating effect on sarcopenia. Chinese herbal medicine is a potential therapeutic strategy in sarcopenia. The funnel plot and Egger's test indicated publication bias. To confirm our conclusions, further high-quality studies should be conducted.

Bilayer LDPC Codes Combined with Perturbed Decoding for MLC NAND Flash Memory.

This paper presents a coding scheme based on bilayer low-density parity-check (LDPC) codes for multi-level cell (MLC) NAND flash memory. The main feature of the proposed scheme is that it exploits the asymmetric properties of an MLC flash channel and stores the extra parity-check bits in the lower page, which are activated only after the decoding failure of the upper page. To further improve the performance of the error correction, a perturbation process based on the genetic algorithm (GA) is incorporated into the decoding process of the proposed coding scheme, which can convert uncorrectable read sequences into error-correctable regions of the corresponding decoding space by introducing GA-trained noises. The perturbation decoding process is particularly efficient at low program-and-erase (P/E) cycle regions. The simulation results suggest that the proposed bilayer LDPC coding scheme can extend the lifetime of MLC NAND flash memory up to 10,000 P/E cycles. The proposed scheme can achieve a better balance between performance and complexity than traditional single LDPC coding schemes. All of these findings indicate that the proposed coding scheme is suitable for practical purposes in MLC NAND flash memory.

Correlated optical convolutional neural network with "quantum speedup".

Compared with electrical neural networks, optical neural networks (ONNs) have the potentials to break the limit of the bandwidth and reduce the consumption of energy, and therefore draw much attention in recent years. By far, several types of ONNs have been implemented. However, the current ONNs cannot realize the acceleration as powerful as that indicated by the models like quantum neural networks. How to construct and realize an ONN with the quantum speedup is a huge challenge. Here, we propose theoretically and demonstrate experimentally a new type of optical convolutional neural network by introducing the optical correlation. It is called the correlated optical convolutional neural network (COCNN). We show that the COCNN can exhibit "quantum speedup" in the training process. The character is verified from the two aspects. One is the direct illustration of the faster convergence by comparing the loss function curves of the COCNN with that of the traditional convolutional neural network (CNN). Such a result is compatible with the training performance of the recently proposed quantum convolutional neural network (QCNN). The other is the demonstration of the COCNN's capability to perform the QCNN phase recognition circuit, validating the connection between the COCNN and the QCNN. Furthermore, we take the COCNN analog to the 3-qubit QCNN phase recognition circuit as an example and perform an experiment to show the soundness and the feasibility of it. The results perfectly match the theoretical calculations. Our proposal opens up a new avenue for realizing the ONNs with the quantum speedup, which will benefit the information processing in the era of big data.

Serum Aldo-Keto Reductase Family 1 Member B10 (AKR1B10) as a Potential Biomarker for Diagnosis of Hepatocellular Carcinoma.

Objective: To evaluate the diagnostic performance of aldo-keto reductase family 1 member B10 (AKR1B10) in a Beijing cohort with hepatocellular carcinoma (HCC). Methods: This study included 521 subjects who visited Peking Union Medical College Hospital from June 2017 to May 2023, including 109 cases of HCC, 165 cases of healthy controls, 106 cases of benign liver diseases, and 141 cases of other cancers. Serum AKR1B10 levels were measured and compared across various groups. Diagnostic performances of serum AKR1B10 and other tumor markers were assessed using receiver operator characteristic (ROC) curves. In addition, a subset of HCC patients who underwent surgical resection were recruited for clinical follow-up study. Results: We found that serum AKR1B10 expression was higher in patients with HCC relative to other control groups. The association between serum AKR1B10 and clinical features of HCC was not observed. Serum AKR1B10 showed a high diagnostic performance for HCC, and when combined with AFP, the diagnostic effectiveness was significantly improved. Specifically, serum AKR1B10 showed superior diagnostic effectiveness for AFP-negative HCC. The clinical follow-up study indicated a gradual decrease in serum AKR1B10 after surgery. Conclusion: Our study demonstrated that serum AKR1B10 is a promising biomarker for HCC, and when used in combination with AFP can significantly improve the detection rate of HCC.

Breast surgery for patients with de novo metastatic breast cancer: A meta-analysis of randomized controlled trials.

The role of breast surgery in the treatment of patients with de novo metastatic breast cancer(dnMBC) remains controversial, with conflicting trial results. We did a meta-analysis to comprehensively investigate and assess whether breast surgery is associated with survival and quality of life outcomes in patients with dnMBC.We systematically searched PubMed, Embase, Google Scholar, Scopus, and Web of Science, from database inception to March 30, 2022, for randomized controlled trials(RCTs) that compared breast surgery or locoregional therapy with non-surgical treatment based on systemic therapy for managing dnMBC.We also reviewed abstracts and presentations from major conference proceedings. We excluded non-randomised trials and considered only papers published in English. The primary outcomes were overall survival(OS),locoregional progression-free survival(LPFS), distant progression-free survival(DPFS), and quality of life(QoL). The quality of RCTs was appraised with the Cochrane Collaboration risk of bias tool. Random-effects model or fixed effects model were used to calculate the effect sizes of included RCTs.Quality of evidence was assessed with GRADE criteria. Data analysis was performed with STATA 17.0. A total of 1018 women from seven randomized clinical trials were included in the analysis. Pooled analyses revealed that compared with systemic therapy, breast surgery was not associated with beneficial outcomes in OS(hazard ratio [HR],0.87; 95%CI,0.68 to 1.11; I2 = 53.08 %; p = 0.265),DPFS(HR,1.20; 95%CI,0.94 to 1.54; I2 = 86.45 %; p = 0.136), or QoL-global health status (standardized mean difference[SMD],0.08; 95%CI,-0.15 to 0.32; I2 = 79.45 %; p = 0.478) and QoL-mental-physical functionality(SMD,-0.19; 95%CI,-0.50 to 0.13; I2 = 0.00 %; p = 0.255), but was associated with a benefit in LPFS(HR,0.27; 95%CI,0.19 to 0.38; I2 = 84.16 %; p < 0.001). These findings were consistent in subgroup analyses of the timing of surgery, site and number of metastases and tumor molecular subtype. The evidence grade was moderate because of the substantial heterogeneity among studies. Based on the RCTs evidence, we found that breast surgery may benefit locoregional control but does not prolong OS and improve QoL in patients with dnMBC. The Prospero registration number: CRD42020206460.

Structure-based improvement of the binding affinity and recognition specificity of peptide competitors to target pediatric IL-5R/IL-5 interaction by gluing halogen bonds at their complex interface.

Human interleukin-5 (IL-5) cytokine mediates the development of eosinophils and is involved in a variety of immune inflammatory responses that play a major role in the pathogenesis of childhood asthma, leukemia, and other pediatric allergic diseases. The immunomodulatory cytokine functions by binding to its cognate cell surface receptor IL-5R in a sheet-by-sheet manner, which can be conformationally mimicked and competitively disrupted by a double-stranded cyclic AF18748 peptide. In this study, we systematically examined the co-crystallized complex structure of human IL-5R with AF18748 peptide and rationally designed a halogen bond to glue at the protein-peptide complex interface by substituting the indole moiety of AF18748 Trp13 residue with a halogen atom (X = F, Cl, Br, or I). High-level theoretical calculations imparted presence of the halogen bond between the oxygen atom (O) of IL-5R Glu58 backbone and the halogen atom (X) of AF18748 Trp13 side chain. Experimental assays confirmed that the halogen bond can promote peptide binding moderately or considerably. More importantly, the halogen bond not only enhances peptide affinity to IL-5R, but also improves peptide selectivity for its cognate IL-5R over other noncognate IL-R proteins. As might be expected, the affinity and selectivity conferred by halogen bond increase consistently in the order: H < F < Cl < Br < I. Structural modeling revealed that the halogen bond plus its vicinal π-cation-π stacking co-define a ringed noncovalent system at the complex interface, which involves a synergistic effect to effectively improve the peptide binding potency and recognition specificity.

Congenital dyserythropoietic anemia type II in a newborn with a novel compound heterozygous mutation in the SEC23B: a case report and review of the literature.

Congenital dyserythropoietic anemia type II (CDA II) refers to a group of extremely rare heterozygous disorders characterized by ineffective erythropoiesis and morphological abnormalities of erythrocytes and bone marrow erythroblasts. Six types of CDA with differing heterogenous genetic mutations have been identified to date. Due to the genetic and clinical heterogeneity of CDA, accurate diagnosis can be very challenging, especially with the clinical overlap observed between CDA and other dyserythropoietic diseases. A 1-month-old infant girl, born to a non-consanguineous family, presented with severe normocytic anemia that required transfusions every 2 to 3 weeks since birth, as well as jaundice. Whole exome sequencing revealed a novel compound heterozygosity in the SEC23B gene, thus establishing the diagnosis of CDA II. Analysis by multiple bioinformatics tools predicted that the mutant proteins were deleterious. Here, we report a novel variation in SEC23B that extends the mutation spectrum of SEC23B in the diagnosis of CDA II.

Effects of traditional Chinese mind-body exercises for patients with chronic fatigue syndrome: A systematic review and meta-analysis.

Background: Chronic fatigue syndrome (CFS) is a global public health concern. We performed this systematic review of randomised controlled trials (RCTs) to evaluate the effects and safety of traditional Chinese mind-body exercises (TCME) for patients with CFS. Methods: We comprehensively searched MEDLINE, Embase, Web of Science, PsycINFO, Cochrane Library, CNKI, VIP databases, and Wanfang Data from inception to October 2022 for eligible RCTs of TCME for CFS management. We used Cochran's Q statistic and I2 to assess heterogeneity and conducted subgroup analyses based on different types of TCME, background therapy, and types of fatigue. We also assessed the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Results: We included 13 studies (n = 1187) with a maximal follow-up of 12 weeks. TCME included Qigong and Tai Chi. At the end of the treatment, compared with passive control, TCME probably reduces the severity of fatigue (standardised mean differences (SMD) = 0.85; 95% confidence interval (CI) = 0.64, 1.07, moderate certainty), depression (SMD = 0.53; 95% CI = 0.34, 0.72, moderate certainty), anxiety (SMD = 0.29; 95% CI = 0.11, 0.48, moderate certainty), sleep quality (SMD = 0.34; 95% CI = 0.10, 0.57, low certainty) and mental functioning (SMD = 0.90; 95% CI = 0.50, 1.29, low certainty). Compared with other active control therapies, TCME results in little to no difference in the severity of fatigue (SMD = 0.08; 95% CI = -0.18, 0.34, low certainty). For long-term outcomes, TCME may improve anxiety (SMD = 1.74; 95% CI = 0.44, 3.03, low certainty) compared to passive control. We did not identify TCME-related serious adverse events. Conclusions: In patients with CFS, TCME probably reduces post-intervention fatigue, depression, and anxiety and may improve sleep quality and mental function compared with passive control, but has limited long-term effects. These findings will help health professionals and patients with better clinical decision-making. Registration: PROSPERO: CRD42022329157.

68Ga-Labeled Fibroblast Activation Protein Inhibitor PET/CT for the Early and Late Prediction of Pathologic Response to Neoadjuvant Chemotherapy in Breast Cancer Patients: A Prospective Study.

68Ga-labeled fibroblast activation protein inhibitor (68Ga-FAPI) PET/CT has demonstrated promising clinical results, with a higher SUVmax and tumor-to-background ratio (TBR) in breast cancer (BC) patients than 18F-FDG PET/CT. Here, we aimed to evaluate the suitability of 68Ga-FAPI PET/CT for the early and late prediction of the pathologic response to neoadjuvant chemotherapy (NAC) in BC. Methods: Twenty-two consecutive patients with newly diagnosed BC and an indication for NAC were prospectively included. All patients underwent standard chemotherapy and 68Ga-FAPI PET/CT at baseline, after 2 cycles of NAC (PET2), and 1 wk before surgery (PET3). SUVmax was measured in the primary tumor region and positive regional lymph nodes. The expression of fibroblast activation protein in the primary lesion was analyzed by immunohistochemistry. Results: Seven patients (31.8%) achieved a pathologic complete response (pCR), and 15 (68.2%) had residual tumors. Thirteen patients (59.1%) showed concentric withdrawal of the primary tumor, and 9 (40.9%) showed diffuse withdrawal. Between PET2 and PET3, the ΔSUVmax of the primary tumor (R 2 = 0.822; P = 0.001) and metastatic lymph nodes (R 2 = 0.645; P = 0.002) were significantly correlated. The absolute values of SUVmax and TBR at PET2 and PET3 were lower in patients with pCR than in those without pCR (P < 0.05). Moreover, a larger ΔSUVmax at any time point was strongly associated with pCR (P < 0.05). Similar downward trends in SUVmax, TBR, and ΔSUVmax were observed in the pattern of primary tumor reduction. For predicting pCR, the optimal cutoff values for ΔSUVmax after 2 chemotherapy cycles, ΔSUVmax before surgery, TBR after 2 chemotherapy cycles, and TBR before surgery of the primary tumor were 3.4 (area under the curve [AUC], 0.890), 1.1 (AUC, 0.978), -63.8% (AUC, 0.879), -90.8% (AUC, 0.978), 7.6 (AUC, 0.848), and 1.4 (AUC, 0.971), respectively. Immunohistochemistry showed that the SUVmax and TBR of 68Ga-FAPI PET/CT were positively correlated with fibroblast activation protein expression (P < 0.001 for both). Conclusion: Assessment of early changes in 68Ga-FAPI uptake during NAC by 68Ga-FAPI PET/CT can predict pCR and primary tumor concentric withdrawal in BC patients. 68Ga-FAPI PET/CT has great potential for the early and late prediction of the pathologic response to NAC in BC.

The impact of the COVID-19 pandemic on the prevalence and genotype distribution of HPV infection in Beijing, China.

Human papillomavirus (HPV) is one of the most common sexually transmitted infections nationwide. The COVID-19 pandemic has greatly influenced on the HPV prevention project. The objective of this study was to examine the influence of the pandemic on HPV prevalence and genotype distribution in Beijing, China. A total of 44 401 genital swabs were obtained from outpatients at Peking Union Medical College Hospital during two distinct periods: the prepandemic stage from January 2017 to December 2019 and the pandemic stage from January 2020 to December 2022. During the prepandemic and pandemic stages, a total of 33 531 and 10 870 swabs were respectively collected. Fifteen high-risk HPV (HR-HPV) DNA type and a combination of two low-risk (LR-HPV) types (6/11) of genital swabs were detected to compare the HPV infection rates and genotype distributions in two stages. The results showed that the pandemic period witnessed a decrease in the overall HPV infection rate from 33.43% (11 245/33 531) to 29.43% (5527/18 780) compared to the prepandemic. There were statistically significant differences in infection rates between females and males (p < 0.05). Single infection was the predominant type while multiple infection was more prevalent in males than females in both prepandemic and pandemic periods. HR-HPV infection constituted the majority of infections and cannot be disregarded. The distribution of HR-HPV genotypes exhibited little variation before and after the outbreak, but there were some differences between females and males. HPV 16, 52, 58, 56, and 66 were the most commonly detected genotypes in females, whereas HPV 16, 52, 51, 58, and 18 were frequently detected in males. Additionally, HPV 6/11 exhibited a higher prevalence in males than in females. Notably, the age group of 31-40 years old exhibited the highest prevalence of HPV and the lowest infection rate was detected among individuals aged ≤20 years (p < 0.05), which remained relatively consistent before and during the pandemic. These findings underscore the importance of monitoring the trend of HPV epidemic and offer valuable insights for the prevention, treatment, and scientific investigation of HPV in the post-COVID-19 era.

Prevalence of Ureaplasma species among patients at a tertiary hospital in China: a 10-year retrospective study from 2013 to 2022.

BACKGROUND: Ureaplasma species are common pathogens of the urogenital tract and can cause a range of diseases. Unfortunately, there is still a scarcity of large-scale and cross-sectional studies on the prevalence of Ureaplasma species in China to clarify their epidemic patterns. METHODS: This study retrospectively analyzed the data of 18667 patients who visited Peking Union Medical College Hospital for showing various symptoms of (suspected) Ureaplasma species infection during the period 2013-2022. The overall prevalence of Ureaplasma species was calculated, and subgroup analyses were conducted in view of gender, age, specimen types, and diagnosis in every year within the period studied. Furthermore, previous literature that reported on the prevalence of Ureaplasma species in various regions of China was searched and summarized. RESULTS: The overall positive rate of Ureaplasma species in this study reached 42.1% (7861/18667). Specifically, the prevalence of Ureaplasma species was significantly higher in female patients, while the highest detection rate was found in the 21-50 age group. From 2013 to 2022, there were no significant differences in positive rates of Ureaplasma species among years. However, the detection rate of Ureaplasma species was decreased in COVID-19 period (2020-2022) compared to pre-COVID-19 period (2017-2019). In view of the distribution of patients, outpatients predominated, but the detection rate was lower than inpatients. Urine was the most common specimen type, while cervical swabs had the highest detection rate of Ureaplasma species. When grouped by diagnosis, the highest positive rate of Ureaplasma species was seen in patients with adverse pregnancy outcomes and the lowest rate in patients with prostate disease. The previous literature, although heterogeneous, collectively suggested a high prevalence of Ureaplasma species in China. CONCLUSIONS: Our study has shown that Ureaplasma species have reached a significant prevalence in China and demands adequate attention.

The effect of Tuina based on the concept of hip-knee-ankle conjugation in patients with chronic ankle instability: study protocol for a randomized controlled trial.

Background: Chronic ankle instability (CAI) is a common sports injury disease and characterized by limited mobility, perceived instability and muscle weakness, combined treatment of hip-knee-ankle is a common rehabilitation method. Tuina, as a traditional Chinese manual therapy, is usually used for CAI, but many of them only focus on the local ankle joint rather than the combination of hip and knee joint. Therefore, we have designed a randomized controlled trial (RCT) to investigate the effects of Tuina base on the concept of hip-knee-ankle conjugation on the stability and balance of lower limbs and ankle function in patients with CAI. Methods: We have designed a randomized controlled trial. A total of 72 participants with CAI will be randomly divided into functional training groups and hip-knee-ankle Tuina combined with functional training group in a 1:1 ratio. Participants in control group will receive 8 sessions of functional training (30 min per session, twice a week for 4 weeks). Participants in intervention group will receive 8 sessions of Tuina combined with functional training (twice a week for 4 weeks). The primary outcomes include the Y-Balance Test (YBT) and Cumberland Ankle Instability Tool (CAIT). The Secondary outcomes include the Foot and Ankle Ability Measure (FAAM) and ankle range of motion (ROM). The outcome assessments will be conducted before the first intervention and after the last intervention. Discussion: The aim of this study is to explore a safe and effective manipulation program and serve as reference for clinical treatment of CAI and expect to provide the necessary theoretical and practical support to our future research. Clinical Trial Registration: Chinese Clinical Trail Registry ChiCTR2300068274.

Fabrication of N-doped carbon-coated MnO/ZnMn2O4 cathode materials for high-capacity aqueous zinc-ion batteries.

Rechargeable aqueous zinc-ion batteries (ZIBs) are highly promising energy storage devices due to their advantages of high energy density, low cost, environmental friendliness, and excellent safety. Investigation of advanced cathode materials featuring high capacity is desired for their applications in high-capacity ZIBs. In this study, a porous N-doped carbon-coated manganese oxide/zinc manganate (MZM@N-C) composite was successfully prepared as an advanced cathode material for aqueous ZIBs. The MZM@N-C cathode demonstrated a superior specific capacity of 772.8 mA h g-1 at 50 mA g-1 and maintained a high specific capacity of 205 mA h g-1 after 300 cycles at a high current density of 500 mA g-1. As compared to the unmodified MnOx cathode, MZM@N-C has a higher reversible capacity and cycling stability which could be assigned to the robust one-dimensional (1D) structure and the synergistic effect of MZM@N-C, providing instructive insight into the design of high-capacity manganese-based cathodes for rechargeable aqueous ZIBs. Furthermore, a soft-pack battery was assembled using the MZM@N-C cathode, demonstrating its potential applications in various devices.

The influence of methotrexate-related transporter and metabolizing enzyme gene polymorphisms on peri-engraftment syndrome and graft-versus-host disease after haplo-hematopoietic stem cell transplantation in pediatric patients with malignant hematological diseases.

Background: Methotrexate (MTX), utilized as a graft-versus-host disease (GvHD) prophylactic agent in allogeneic hematopoietic stem cell transplantation (allo-HSCT), has been proven to effectively decrease the occurrence of the peri-engraftment syndrome (Peri-ES) and acute GvHD (aGvHD). Changes in the pharmacodynamics of MTX are closely associated with gene polymorphisms in genes encoding drug-metabolizing enzymes and transporters. Nevertheless, the current studies mainly concentrate on leukemia or autoimmune diseases, and limited studies on allo-HSCT were reported. Methods: Here, we retrospectively assessed the relationship between MTX-related transporter and metabolizing enzyme gene polymorphisms, clinical characteristics, and outcomes in 57 pediatric patients who received haploid HSCT (haplo-HSCT) with malignant tumors at a single center. Results: We discovered all gene polymorphisms were in the Hardy-Weinberg equilibrium in our cohort. We discovered a significant correlation between platelet recovery time and ABCB1 (1236C>T) (p = 0.042). Compared with patients with SLCO1B1 (1865+4846T>C) TT, patients with SLCO1B1 (1865+4846T>C) TC/CC had an increased incidence of Peri-ES (p = 0.030). Based on the multivariate Cox analysis, we discovered that SLCO1B1 (1865+4846T>C) TT genotype was an independent protective factor for Peri-ES morbidity (hazard ratio (HR) = 0.464, p = 0.031), and the dose of mononuclear cells reinfused was significantly correlated with II-IV aGvHD (HR = 2.604, p = 0.039). Conclusion: In summary, our findings prove that the host's genotypes might modify the risk of developing Peri-ES, contribute to a better understanding of the inter-individual difference in efficacy, and facilitate the development of individualized approaches to GvHD prophylaxis.

Abnormal brain activity in lumbar disc herniation patients with chronic pain is associated with their clinical symptoms.

Introduction: Lumbar disc herniation, a chronic degenerative disease, is one of the major contributors to chronic low back pain and disability. Although many studies have been conducted in the past on brain function in chronic low back pain, most of these studies did not classify chronic low back pain (cLBP) patients according to their etiology. The lack of etiologic classification may lead to inconsistencies between findings, and the correlation between differences in brain activation and clinical symptoms in patients with cLBP was less studied in the past. Methods: In this study, 36 lumbar disc herniation patients with chronic low back pain (LDHCP) and 36 healthy controls (HCs) were included to study brain activity abnormalities in LDHCP. Visual analogue scale (VAS), oswestry disability index (ODI), self-rating anxiety scale (SAS), self-rating depression scale (SDS) were used to assess clinical symptoms. Results: The results showed that LDHCP patients exhibited abnormally increased and diminished activation of brain regions compared to HCs. Correlation analysis showed that the amplitude of low frequency fluctuations (ALFF) in the left middle frontal gyrus is negatively correlated with SAS and VAS, while the right superior temporal gyrus is positively correlated with SAS and VAS, the dorsolateral left superior frontal gyrus and the right middle frontal gyrus are negatively correlated with VAS and SAS, respectively. Conclusion: LDHCP patients have brain regions with abnormally increased and abnormally decreased activation compared to healthy controls. Furthermore, some of the abnormally activated brain regions were correlated with clinical pain or emotional symptoms.

Construction of a risk model based on N6 -methyladenosinerelated lncRNAs for predicting the prognosis of breast cancer.

N6-methyladenosine modification and lncRNAs are closely related to the prognosis and immunotherapy response of breast cancer patients. LncRNAs related to m6 A-associated genes were predicted based on coexpression analysis of the TCGA database. We established a novel 7-m6 A-associated lncRNA signature for predicting patient prognosis and validated it. The model was significantly correlated with survival time and survival status and was an independent predictor of overall survival (OS). Except for the M1 disease group, the model had good predictive value for OS in different subgroups. We constructed a prognostic model based on 7 m6 A-associated lncRNAs in breast cancer. This model could serve as an independent prognostic factor with tremendous predictive ability for breast cancer patients.

FTO-mediated epigenetic upregulation of LINC01559 confers cell resistance to docetaxel in breast carcinoma by suppressing miR-1343-3p.

This study was to explore the regulatory effect of long non-coding RNA LINC01559 on Docetaxel resistance in breast carcinoma (BCa) and its underlying mechanism. In the present study, we found that LINC01559 expression was elevated and LINC01559 overexpression facilitated docetaxel resistance in BCa cells. Moreover, it was revealed that the upregulation of LINC01559 in BCa cells was induced by FTO-mediated demethylation in an m6A-YTHDF2-dependent manner. Additionally, Dual-luciferase reporter assay confirmed the binding ability between LINC01559 and miR-1343-3p, and Pearson correlation analysis showed a negative correlation between them. Particularly, miR-1343-3p inhibition partly abolished the suppression on docetaxel resistance in BCa cells caused by LINC01559 knockdown. To sum up, FTO-mediated epigenetic upregulation of LINC01559 promoted cell resistance to Docetaxel in BCa by negatively regulating miR-1343-3p.