ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

OBJECTIVE: To explore effectiveness of musculoskeletal ultrasound combined with Wide-Awake technique in extensor indicis proprius tendon (EIP) transfer for repairing extensor pollicis longus tendon (EPL) rupture. METHODS: A clinical data of 20 patients with EPL spontaneous rupture, who were admitted between January 2019 and June 2024 and met the selective criteria, was retrospectively analyzed. During EIP transfer surgery, the musculoskeletal ultrasound-guided incision marking combined with Wide-Awake technique was used in combination group (n=10) and the tourniquet-assisted surgery under brachial plexus block anesthesia in the control group. There was no significant difference in the baseline data between groups (P>0.05), including gender, age, affected side, cause and location of tendon rupture, and time from injury to hospitalization. The accuracy of preoperative musculoskeletal ultrasound in predicting the actual tendon rupture site was evaluated in the combination group. The operation time, intraoperative blood loss, visual analogue scale (VAS) scores during operation and at 6 hours after operation, total incision length, and postoperative complications were recorded. Surgical outcomes were assessed at 12 months after operation using the specific EIP-EPL evaluation method (SEEM), which included measurements of thumb elevation loss, thumb flexion loss, index finger dorsiflexion loss, and total score. RESULTS: In the combination group, the incision position marked by preoperative musculoskeletal ultrasound positioning was consistent with the actual tendon rupture position. Compared with the control group, the operation time and total incision length in the combination group were significantly shorter and the VAS score at 6 hours after operation was significantly higher (P<0.05). There was no significant difference in intraoperative blood loss or intraoperative VAS score between groups (P>0.05). All incisions in both groups healed by first intention. Two patients in the control group developed swelling and blisters in the tourniquet area, which subsided spontaneously without special treatment. All patients were followed up 12-14 months, with an average of 12.5 months. The thumb dorsiflexion function of all patients recovered to varying degrees. At last follow-up, the thumb elevation loss in combination group was significantly lower than that in control group, and the total score was significantly higher (P<0.05); there was no significant difference in thumb flexion loss or index finger dorsiflexion loss between groups (P>0.05). CONCLUSION Musculoskeletal ultrasound can accurately locate the site of tendon rupture, assist the Wide-Awake technique in implementing precise anesthesia, and adjust tendon tension while reducing tissue trauma, with satisfactory effectiveness.
Humans ; Male ; Tendon Injuries/diagnostic imaging* ; Tendon Transfer/methods* ; Female ; Retrospective Studies ; Adult ; Middle Aged ; Ultrasonography/methods* ; Rupture/surgery* ; Treatment Outcome ; Operative Time ; Tendons/surgery* ; Young Adult

OBJECTIVE: To explore the mechanism of colon dialysis with Yishen Decoction (YS) in improving the autophagy disorder of intestinal epithelial cells in chronic renal failure (CRF) in vivo and in vitro. METHODS: Thirty male SD rats were randomly divided into normal, CRF, and colonic dialysis with YS groups by a random number table method (n=10). The CRF model was established by orally gavage of adenine 200 mg/(kg•d) for 4 weeks. CRF rats in the YS group were treated with colonic dialysis using YS 20 g/(kg•d) for 14 consecutive days. The serum creatinine (SCr) and urea nitrogen (BUN) levels were detected by enzyme-linked immunosorbent assay. Pathological changes of kidney and colon tissues were observed by hematoxylin and eosin staining. Autophagosome changes in colonic epithelial cells was observed with electron microscopy. In vitro experiments, human colon cancer epithelial cells (T84) were cultured and divided into normal, urea model (74U), YS colon dialysis, autophagy activator rapamycin (Ra), autophagy inhibitor 3-methyladenine (3-MA), and SIRT1 activator resveratrol (Re) groups. RT-PCR and Western blot were used to detect the mRNA and protein expressions of zonula occludens-1 (ZO-1), Claudin-1, silent information regulator sirtuin 1 (SIRT1), LC3, and Beclin-1 both in vitro and in vivo. RESULTS: Colonic dialysis with YS decreased SCr and BUN levels in CRF rats (P<0.05), and alleviated the pathological changes of renal and colon tissues. Expressions of SIRT1, ZO-1, Claudin-1, Beclin-1, and LC3II/I were increased in the YS group compared with the CRF group in vivo (P<0.05). In in vitro study, compared with normal group, the expressions of SIRT1, ZO-1, and Claudin-1 were decreased, and expressions of Beclin-1, and LC3II/I were increased in the 74U group (P<0.05). Compared with the 74U group, expressions of SIRT1, ZO-1, and Claudin-1 were increased, whereas Beclin-1, and LC3II/I were decreased in the YS group (P<0.05). The treatment of 3-MA and rapamycin regulated autophagy and the expression of SIRT1. SIRT1 activator intervention up-regulated autophagy as well as the expressions of ZO-1 and Claudin-1 compared with the 74U group (P<0.05). CONCLUSION Colonic dialysis with YS could improve autophagy disorder and repair CRF intestinal mucosal barrier injury by regulating SIRT1 expression in intestinal epithelial cells.
Animals ; Sirtuin 1/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Autophagy/drug effects* ; Male ; Intestinal Mucosa/drug effects* ; Rats, Sprague-Dawley ; Epithelial Cells/metabolism* ; Colon/drug effects* ; Humans ; Kidney Failure, Chronic/drug therapy* ; Signal Transduction/drug effects* ; Renal Dialysis ; Rats ; Kidney/drug effects*

Objective:To investigate the dynamic trend of platelet（PLT）count and mean platelet volume（MPV）in children with severe community-acquired pneumonia（SCAP）in PICU and their correlation with prognosis.Methods:A retrospective study was conducted in 215 SCAP children who were admitted to the PICU of Beijing Children's Hospital Affiliated to Capital Medical University from January 2016 to December 2019.According to the disease outcome，the patients were divided into improvement group ( n=184) and unrecovered group ( n=31).The changes of PLT count and MPV at admission，on the 2nd，3rd，and 7th days of hospitalization and before discharge were observed，and the relationship between changes in PLT parameters and poor prognosis was analyzed. Meanwhile，the correlation between thrombocytopenia on admission and on the 7th day of hospitalization and prognosis was further explored. Results:The PLT count of improvement group at admission，on the 2nd，3rd，and 7th days of hospitalization and at discharge[(328±159, 329±137, 362±159, 439±168, 510±171)×10 9/L] were significantly higher than those of unrecovered group [(210±142, 207±152, 267±143, 260±162, 343±159)×10 9/L]（ P＜0.05）.Although the MPV of improvement group [(10.9±1.9)fL] on admission was significantly lower than that of the unrecovered group[(12.7±2.5) fL]（ P＜0.05），there was no significant difference in MPV between two groups on the 2nd，3rd，7th days of hospitalization and discharge（ P＞0.05）.In addition，compared with the admission，children in improvement group had significantly higher PLT count on the 7th day of hospitalization and before discharge（ P＜0.05），but there was no significant change in unrecovered group（ P＞0.05）.Compared with SCAP patients with thrombocytopenia at admission (PLT＜100×10 9/L)( n=22),those with thrombocytopenia on 7th day of hospitalization had a significant higher rate of non recovery( P＜0.05). Conclusion:The occurrence of thrombocytopenia on admission and after 7 days of hospitalization in children with SCAP is associated with poor prognosis.No significant increase or decrease in PLT count after 7 days of hospitalization is often indicative of poor prognosis.Dynamic monitoring of PLT parameter changes may help to better judge the prognosis of severe pneumonia.

Osteoporotic fractures represent the most severe complications of osteoporosis,characterized by insidious onset,high mortality and disability rates,and a steadily increasing incidence,imposing a significant socioeconomic burden.Western medicine has advantages in diagnosis and surgical interventions,while traditional Chinese medicine excels in holistic manage-ment and the restoration of bodily equilibrium.The integration of both traditional Chinese medicine(TCM)and western medicine emerges as an effective therapeutic strategy for osteoporotic fractures.In order to propagate the concept of integrated diagnosis and treatment,foster the advancement of integrated medical techniques for osteoporotic fractures,and establish standardized and nor-mative protocols for disease prevention,diagnosis,and treatment,a consensus expert group,led by Geriatric Branch of Chinese Geriatrics Society,the Young Osteoporosis Group of Orthopedics Branch of Chinese Medical Association,Osteoporosis Group of Orthopedics Branch of Chinese Physician Association,and Osteoporosis Professional Committee of the Shanghai Society of Inte-grated Traditional Chinese and Western Medicine,was established.This group engaged in deliberations and formulated the"Ex-pert Consensus on Integrated Traditional Chinese and Western Medicine Diagnosis and Treatment of Osteoporotic Fractures"elu-cidating the concept of integrated medicine and offering recommendations in the domains of prevention,diagnosis,and treatment,with the aspiration of ameliorating the prognosis of osteoporotic fractures and enhancing the quality of life for these patients.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

The weight coefficients of appearance traits, extract yield of standard decoction, and total content of honokiol and magnolol were determined by analytic hierarchy process(AHP), criteria importance though intercrieria correlation(CRITIC), and AHP-CRITIC weighting method, and the comprehensive scores were calculated. The effects of ginger juice dosage, moistening time, proces-sing temperature, and processing time on the quality of Magnoliae Officinalis Cortex(MOC) were investigated, and Box-Behnken design was employed to optimize the process parameters. To reveal the processing mechanism, MOC, ginger juice-processed Magnoliae Officinalis Cortex(GMOC), and water-processed Magnoliae Officinalis Cortex(WMOC) were compared. The results showed that the weight coefficients of the appearance traits, extract yield of standard decoction, and total content of honokiol and magnolol determined by AHP-CRITIC weighting method were 0.134, 0.287, and 0.579, respectively. The optimal processing parameters of GMOC were ginger juice dosage of 8%, moistening time of 120 min, and processing at 100 ℃ for 7 min. The content of syringoside and magnolflorine in MOC decreased after processing, and the content of honokiol and magnolol followed the trend of GMOC>MOC>WMOC, which suggested that the change in clinical efficacy of MOC after processing was associated with the changes of chemical composition. The optimized processing technology is stable and feasible and provides references for the modern production and processing of MOC.
Ginger ; Magnolia/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Biphenyl Compounds/chemistry* ; Lignans/chemistry*

Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.
Humans ; Brain Neoplasms/pathology* ; Neoplasm Recurrence, Local/metabolism* ; Glioma/pathology* ; Neural Stem Cells/pathology* ; Oligodendrocyte Precursor Cells/pathology* ; Tumor Microenvironment

Objective:To explore the therapeutic characteristics of population with gout achieving treat-to-target (T2T) indicators through real-world research and evaluate their safety.Methods:A total of 3 287 patients diagnosed with gout by rheumatologists in 21 first-class tertiary hospitals in 10 provinces, municipalities, and autonomous regions in China from January 2015 to December 2021 were included in this polycentric cross-sectional study. The database included patients′ general information, disease characteristics, and clinical application of traditional Chinese and Western medicine treatment measures. SPSS and Excel software were used for data analysis. Frequency analysis, cluster analysis, and factor analysis were used to summarize the characteristics and rules of treatment measures for patients with gout who achieved the target after treatment. The occurrence of adverse events (AE) was recorded during treatment.Results:After treatment, 691 visits (7%) achieved the serum urate (SUA) target, and the most frequent use of urate-lowering therapy (ULT) was febuxostat, followed by benzbromarone. The most common treatment options were following: GroupⅠ: traditional Chinese medicine (TCM) decoction-TCM external treatment-physical exercise-proprietary Chinese medicine; GroupⅡ: ferulic acid-nonsteroidal anti-inflammatory drugs (NSAIDs); Group Ⅲ: allopurinol-sodium bicarbonate-benzbromarone; Group Ⅳ: glucocorticoid-colchicine; Group Ⅴ: febuxostat. A total of 5 898 visits (60%) chieved manifestations of joint pain VAS scores target, and the most frequently used drug to control joint symptoms was NSAIDs. The frequency of use of drugs to control joint symptoms were 2 118 times (usage rate reached 35.9%), while the frequency of ULT were 2 504 times (usage rate reached 42.5%), which was higher than the joint symptom control drug. The most common treatment options were following: Group Ⅰ: proprietary Chinese medicine-TCM decoction-TCM external treatment-physical exercise; Group Ⅱ: NSAIDs-colchicine hormones; Group Ⅲ: allopurinol, Group Ⅳ: benzbromarone; Group Ⅴ: febuxostat. A total of 59 adverse events occurred during treatment.Conclusion:The proportions of gout patients who reach target serum urate level & good control of joint symptoms are both very low, and ULT and anti-inflammatory prescription patterns are very different from international guidelines, so it is necessary to strengthen the standardized management of gout patients. At the same time, life intervention measures account for a certain proportion of the treatment plans for the T2T population, and further exploration is needed.

The application status of acupuncture and moxibustion therapy for assisted reproductive field in the United States was analyzed, and the existing problems and future development directions were discussed. According to the survey on the 456 websites of assisted reproductive clinic in the United States mentioned in the report of U.S. Centers for Disease Control and Prevention (CDC), 111 clinics among 456 assisted reproductive clinics recommend and used acupuncture and moxibustion therapy, accounting for 24.3%. Acupuncture and moxibustion therapy had obvious effect, good safety and low cost, and the assisted reproductive institutions in the United States had a high degree of application and recognition to acupuncture and moxibustion therapy. However, some problems, such as immature treatment scheme, unclear mechanism and imperfect insurance policies, still existed. In the future, the advantages of Chinese traditional acupuncture and moxibustion should combine with international modern assisted reproductive technology, and multi-center and large-sample clinical randomized controlled trials and basic experimental research on the mechanism of acupuncture and moxibustion for assisted reproduction should be carried out.
Acupuncture ; Acupuncture Therapy ; Medicine, Chinese Traditional ; Moxibustion ; Reproduction ; United States