It is very limited that the benefit of perioperative chemotherapy in early non-small cell lung cancer (NSCLC), and the 5-year survival rate is only 5% higher than surgery. Antibodies that block programmed cell death protein 1/programmed death-ligand 1 significantly improve the survival of advanced NSCLC. The value of immunotherapy in early NSCLC is also being explored. This paper firstly summarized and analyzed the progress of immunotherapy in the perioperative period of NSCLC. Secondly, the safety and feasibility of surgical resection after neoadjuvant immunotherapy were discussed. Finally, the clinical value of different therapeutic efficacy prediction indicators was summarized, in order to clarify the current status of immunotherapy in the perioperative period, so as to improve the clinical benefits of early NSCLC patients.

Objective: To explore the key factors affecting the selection and effectiveness of bladder management modalities in patients with spinal cord injury，so as to provide reference for the optimization of individualized bladder management strategies. Methods: The clinical and follow-up data of 78 patients with spinal cord injury treated in our hospital during Jan.1,2013 and Dec.31,2022 were retrospectively analyzed.The distribution of bladder management modalities among different grades of injuries was analyzed. Bowker symmetry test was used to evaluate the difference between bladder management modalities at discharge and at the end of follow-up. Multiple linear regression was used to explore the influencing factors of bladder management effects. Plotting Kaplan-Meier survival curves were adopted to calculate the median time of changes in bladder management. Results: At discharge，there were 9 cases of self-catheterization，19 cases of intermittent catheterization，22 cases of reflexive voiding，26 cases of long-term catheterization，and 2 cases using urinary collector.At the end of follow-up，there were 15 cases of self-catheterization，8 cases of intermittent catheterization，34 cases of reflexive voiding，14 cases of long-term catheterization，and 7 cases using urinary collector.There was a significant difference between the modalities of bladder management at discharge and at the end of follow-up (χ =21.43，P=0.018).Multiple linear regression showed a significant decrease of 8.60 in the total neurogenic bladder symptom score (NBSS) for grade D injuries compared with grade A injuries (P=0.026). The median time to bladder management change was 7.93 months (95%CI:5.44-9.44), with approximately 50% of patients experiencing a change in bladder management within 8 months after discharge. Conclusion: The modalities of bladder management changed significantly after discharge.The grade of injury was a key factor affecting the effectiveness of bladder management.Higher grade was associated with worse effectiveness of bladder management.

Objective: Previous observational studies have confirmed the correlation between gut microbiota and bladder cancer，but the causal relationship is still unclear.This study aimed to explore the causal relationship between them with Mendelian randomization. Methods: Genetic variation summary data of 211 gut microbiota and bladder cancer genome-wide association studies (GWAS) were obtained from the MiBioGen Consortium and Finngen database.Single nucleotide polymorphisms (SNPs) closely related to these studies were screened as instrumental variables.The causal relationship between gut microbiota and bladder cancer were analyzed with inverse variance weighting (IVW)，MR-Egger，weighted median，maximum likelihood，robust adjustment feature score and MR-PRESSO，with IVW as the primary analysis method.Additionally，sensitivity analysis was used to test the heterogeneity (Cochran Q) and horizontal pleiotropy (MR-Egger intercept term and global test from MR-PRESSO estimator) to ensure the robustness of the results. Results: The IVW results indicated that Lachnospiraceae UCG004 (OR：1.42)，Desulfovibrionales (Order) (OR：1.48)，Eubacterium ruminantium group (OR：1.33)，Olsenella (OR：1.24)，Ruminococcaceae UCG002 (OR：1.39)，Ruminococcaceae UCG005 (OR：1.42) and Ruminococcaceae UCG013 (OR：1.64) significantly increased the risk of bladder cancer.Conversely，Bacteroidetes (Phylum) (OR：0.61)，Eubacterium brachy group (OR：0.80)，Ruminococcaceae UCG004 (OR：0.73)，Rikenellaceae (Family) (OR：0.67)，Lachnospiraceae ND3007 group (OR：0.47), Adlercreutzia (OR：0.73) and an unknow genus (OR：0.75) were associated with a reduced risk of bladder cancer.Sensitivity analyses did not reveal any heterogeneity or horizontal pleiotropy. Conclusion: This study reveals the causal role of 14 gut microbiota in the pathogenesis of bladder cancer，among which Lachnospiraceae UCG004，Desulfovibrionales (Order)，Eubacterium ruminantium group，Olsenella，Ruminococcaceae UCG002，Ruminococcaceae UCG005 and Ruminococcaceae UCG013 are risk factors for bladder cancer，while Bacteroidetes (Phylum)，Eubacterium brachy group，Ruminococcaceae UCG004，Rikenellaceae (Family)，Lachnospiraceae ND3007 group，Adlercreutzia and an unknown genus are the protective factors.

Objective To compare the prognostic differences between simple and complex segmentectomies. Methods We conducted a retrospective cohort analysis of patients with solid pulmonary nodules (≤2 cm) who underwent segmentectomy. Recurrence-free survival (RFS) and local recurrence rates were evaluated. Results We included57 patients undergoing complex segmentectomy and 53 patients undergoing simple segmentectomy. Among patients who did not receive adjuvant therapy, those in the complex group had a significantly lower five-year RFS than those in the simple group (69.86% vs. 85.97%, P=0.04). Furthermore, the local recurrence rate was significantly higher in the complex group (18.75% vs. 4.65%, P=0.003) than in the simple group. Conclusion For solid pulmonary nodules (≤2 cm), complex segmentectomy is associated with inferior local control and worse RFS than simple segmentectomy.

BACKGROUND: Gluconeogenesis is a critical metabolic pathway for maintaining glucose homeostasis, and its dysregulation can lead to glycometabolic disorders. This study aimed to identify hub biomarkers of these disorders to provide a theoretical foundation for enhancing diagnosis and treatment. METHODS: Gene expression profiles from liver tissues of three well-characterized gluconeogenesis mouse models were analyzed to identify commonly differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA), machine learning techniques, and diagnostic tests on transcriptome data from publicly available datasets of type 2 diabetes mellitus (T2DM) patients were employed to assess the clinical relevance of these DEGs. Subsequently, we identified hub biomarkers associated with gluconeogenesis-related glycometabolic disorders, investigated potential correlations with immune cell types, and validated expression using quantitative polymerase chain reaction in the mouse models. RESULTS: Only a few common DEGs were observed in gluconeogenesis-related glycometabolic disorders across different contributing factors. However, these DEGs were consistently associated with cytokine regulation and oxidative stress (OS). Enrichment analysis highlighted significant alterations in terms related to cytokines and OS. Importantly, osteomodulin ( OMD ), apolipoprotein A4 ( APOA4 ), and insulin like growth factor binding protein 6 ( IGFBP6 ) were identified with potential clinical significance in T2DM patients. These genes demonstrated robust diagnostic performance in T2DM cohorts and were positively correlated with resting dendritic cells. CONCLUSIONS Gluconeogenesis-related glycometabolic disorders exhibit considerable heterogeneity, yet changes in cytokine regulation and OS are universally present. OMD , APOA4 , and IGFBP6  may serve as hub biomarkers for gluconeogenesis-related glycometabolic disorders.
Machine Learning ; Humans ; Computational Biology/methods* ; Biomarkers/metabolism* ; Diabetes Mellitus, Type 2/genetics* ; Animals ; Mice ; Gluconeogenesis/physiology* ; Gene Expression Profiling ; Transcriptome/genetics* ; Gene Regulatory Networks/genetics* ; Clinical Relevance

Fermented traditional Chinese medicine(TCM) has a long history of medicinal use, such as Sojae Semen Praeparatum, Arisaema Cum Bile, Pinelliae Rhizoma Fermentata, red yeast rice, and Jianqu. Fermentation technology was recorded in the earliest TCM work, Shen Nong's Classic of the Materia Medica. Microorganisms are essential components of the fermentation process. However, the contamination of fermented TCM by toxigenic fungi and mycotoxins due to unstandardized fermentation processes seriously affects the quality of TCM and poses a threat to the life and health of consumers. In this paper, the characteristics, microbial composition, and mycotoxin profile of fermented TCM are systematically summarized to provide a theoretical basis for its quality and safety control.
Fermentation ; Mycotoxins/analysis* ; Drugs, Chinese Herbal/analysis* ; Fungi/classification* ; Bacteria/genetics* ; Drug Contamination ; Medicine, Chinese Traditional

OBJECTIVE: To evaluate the effectiveness of functional perforator flaps utilizing the superficial circumflex iliac artery as a vascular pedicle, as well as chimeric iliac bone flaps, in the reconstruction of composite tissue defects in the hand and foot. METHODS: A retrospective review of the clinical data from 13 patients suffering from severe hand or foot injuries, treated between May 2019 and January 2025, was conducted. The cohort comprised 8 males and 5 females, with ages ranging from 31 to 67 years (mean, 48.5 years). The injuries caused by mechanical crush incidents (n=9) and traffic accidents (n=4). The distribution of injury sites included 8 cases involving the hand and 5 cases involving the foot. Preoperatively, all patients exhibited bone defects ranging from 2.0 to 6.5 cm and soft tissue defects ranging from 10 to 210 cm². Reconstruction was performed using functional perforator flaps based on the superficial circumflex iliac artery and chimeric iliac bone flaps. The size of iliac bone flaps ranged from 2.5 cm×1.0 cm×1.0 cm to 7.0 cm×2.0 cm×1.5 cm, while the size of the soft tissue flaps ranged from 4 cm×3 cm to 15 cm×8 cm. In 1 case with a significant hand defect, a posterior interosseous artery perforator flap measuring 10.0 cm×4.5 cm was utilized as an adjunct. Likewise, an anterolateral thigh perforator flap measuring 25 cm×7 cm was combined in 1 case involving a foot defect. All donor sites were primarily closed. Postoperative flap survival was monitored, and bone healing was evaluated through imaging examination. Functional outcomes were assessed based on the location of the defects: for hand injuries, grip strength, pinch strength, and flap two-point discrimination were measured; for foot injuries, the American Orthopaedic Foot & Ankle Society (AOFAS) score, visual analogue scale (VAS) score, Maryland Foot Score, plantar pressure distribution and gait symmetry index (GSI) were evaluated. RESULTS: All flaps survived completely, with primary healing observed at both donor and recipient sites. All patients were followed up 6-18 months (mean, 12.2 months). No significant flap swelling or deformity was observed. Imaging examination showed a bone callus crossing rate of 92.3% (12/13) at 3 months after operation, and bone density recovered to more than 80% of the healthy side at 6 months. The time required for bone flap integration ranged from 2 to 6 months (mean, 3.2 months). One patient with a foot injury exhibited hypertrophic scarring at the donor site; however, no major complication, such as infection or bone nonunion, was noted. At 6 months after operation, grip strength in 8 patients involving the hand recovered to 75%-90% of the healthy side (mean, 83.2%), while pinch strength recovered to 70%-85% (mean, 80%). Flap two-point discrimination ranged from 8 to 12 mm, approaching the sensory capacity of the healthy side (5-8 mm). Among the 5 patients involving the foot, the AOFAS score at 8 months was 80.5±7.3, VAS score was 5.2±1.6. According to the Maryland Foot Score, 2 cases were rated as excellent and 3 as good. Gait analysis at 6 months after operation showed GSI above 90%, with plantar pressure distribution closely resembling that of the contralateral foot. CONCLUSION The use of functional perforator flaps based on the superficial circumflex iliac artery, combined with chimeric iliac bone flaps, provides a reliable vascular supply and effective functional restoration for the simultaneous repair of composite bone and soft tissue defects in the hand or foot. This technique represents a viable and effective reconstructive option for composite tissue defects in these anatomical regions.
Humans ; Male ; Middle Aged ; Female ; Perforator Flap/transplantation* ; Adult ; Plastic Surgery Procedures/methods* ; Hand Injuries/surgery* ; Aged ; Retrospective Studies ; Foot Injuries/surgery* ; Ilium/transplantation* ; Iliac Artery/surgery* ; Soft Tissue Injuries/surgery* ; Bone Transplantation/methods* ; Treatment Outcome

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*