OBJECTIVE To investigate the effects and potential mechanism of Yiqi wenyang huwei decoction （YQWY） in improving airway inflammation and remodeling in rats with bronchial asthma （BA） based on the Toll-like receptor 4 （TLR4）/myeloid differentiation primary response protein 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway. METHODS Male SD rats were randomly divided into the normal group， the model group， the dexamethasone group （positive control， 0.5 mg/kg）， and YQWY low-， medium- and high-dose groups （5， 10， 20 g/kg， calculated by the crude drug）， with 8 rats in each group. Except for the normal group， rats in all other groups were sensitized twice with ovalbumin combined with aerosol challenge to establish a BA model. From day 14 to day 34 of the experiment， the rats in each group were administered the corresponding drug solution or normal saline intragastrically， once a day， 1 hour before aerosol challenge. At 24 hours after the final aerosol challenge， asthma symptom scores were assessed， serum levels of immunoglobulin E （IgE） were measured， and the levels of inflammatory cytokines （interleukin-4， interleukin-5， interleukin-13 and tumor necrosis factor-α） and the numbers of inflammatory cells （white blood cell， eosinophil， neutrophil， lymphocyte， monocyte and basophil） in bronchoalveolar lavage fluid were determined. Pathological changes in lung tissue were observed. The mRNA expressions of TLR4， MyD88 and NF-κB， as well as the protein expressions of TLR4， MyD88， NF-κB p65 and phosphorylated NF-κB p65 in lung tissue， were detected. RESULTS Compared with the model group， the pathological changes， such as inflammatory cell infiltration， abnormal deposition of collagen fibers， and goblet cell hyperplasia in the lung tissue of rats in each drug group， were alleviated to varying degrees. The asthma symptom scores （except for the YQWY low-dose group）， the levels of IgE and inflammatory cytokines （except for interleukin-5 in the YQWY medium-dose group）， the number of inflammatory cells （except for monocyte and basophil in the YQWY low-dose group）， the mRNA expression of TLR4， MyD88 and NF-κB， as well as the protein expressions of TLR4， MyD88， NF-κB p65 and phosphorylated NF-κB p65 （except for MyD88 and NF-κB p65 proteins in the YQWY low-dose group as detected by Western blo t） were all significantly reduced or down-regulated （ P ＜0.05 or P ＜0.01）. CONCLUSIONS YQWY can alleviate asthma-like manifestations in BA rats and improve their airway inflammation and remodeling； these effects may be related to the formula’s inhibition of the abnormal activation of the TLR4/MyD88/NF-κB signaling pathway.

Objective: To analyze the risk factors of recurrence after transurethral resection of bladder tumor (TURBT) in patients with non-muscle-invasive bladder cancer (NMIBC)，and establish a risk prediction model，so as to optimize the clinical detection and management of NMIBC. Methods: A total of 174 patients with initial diagnosis of NMIBC who underwent TURBT in the First Affiliated Hospital of Xinjiang Medical University during Jan.2020 and Oct.2022 were followed up for 24 months，and were then divided into the recurrence group (n=74) and non-recurrence group (n=100).After univariate analysis and multivariate logistic regression，risk factors of recurrence were identified，a nomogram was established，and the calibration curve was plotted，which was verified with receiver operator characteristic (ROC) curve. Results: The 2-year recurrence rate was 42.53%.Logistic regression showed high body mass index (BMI)，poor differentiation，multiple tumors，and tumor diameter greater than 3 cm were risk factors of recurrence (P<0.05，OR≥1)，while immediate postoperative intravesical instillation was a protective factor (P<0.05).The C-index of the nomogram was 0.893 (95%CI:0.851-0.938)，the area of ROC curve (AUC) was 0.894 (95%CI：0.847-0.941)，the sensitivity was 82.4%，and the specificity was 83.0%. Conclusion: The prediction model based on BMI，tumor stage，grade，number，diameter，and immediate postoperative intravesical instillation fits well and can provide reference for predicting the risk of tumor recurrence.

In cases where a tracheal injury exceeds half the length of the adult trachea or one-third of the length of the child trachea, it becomes difficult to perform end-to-end anastomosis after tracheal resection due to excessive tension at the anastomosis site. In such cases, tracheal replacement therapy is required. Advances in tissue engineering technology have led to the development of tissue engineering tracheal substitutes, which have promising applications. Hydrogels, which are highly hydrated and possess a good three-dimensional network structure, biocompatibility, low immunogenicity, biodegradability, and modifiability, have had wide applications in the field of tissue engineering. This article provides a review of the characteristics, advantages, disadvantages, and effects of various hydrogels commonly used in tissue engineering trachea in recent years. Additionally, the article discusses and offers prospects for the future application of hydrogels in the field of tissue engineering trachea.

Objective:To investigate the clinical and genetic characteristics of KDM6B gene variation associated neurological developmental disorder in a child. Methods:Clinical data were collected from a child of KDM6B gene variation associated neurological developmental disorder admitted to Children′s Hospital Affiliated to Zhengzhou University in July 2021. His clinical manifestations and genetic variation profiles were retrospectively analyzed and literature review was conducted. Results:The patient was a one-year-six-month old male, with protruding forehead, joint laxity, distal skeletal abnormalities, and behavioral, cognitive, language, intellectual, and psychomotor development disorder. The whole-exome sequencing and Sanger sequencing confirmed that there was a de novo heterozygous frameshift variation c.1718delC(p.Pro573Hisfs *9) in exon 11 of the KDM6B gene. This variation was classified as pathogenic (PVS1+PS2+PM2_supporting) according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines, with no prior reports. By literature review, no relevant Chinese literature was retrieved, whereas 4 English literatures were found, reporting 98 patients, totally 99 patients (including this case) with nervous system development disorder due to KDM6B gene variation. The main manifestations were neurodevelopmental disorders such as speech, motor, and behavioral abnormalities, mental retardation, as well as facial deformities, hypotonia, infantile feeding difficulties/gastroesophageal reflux, joint/ligament laxity, and abnormalities of the hands and toes/palms. A total of 83 variation sites were found, including 37 frameshift variations, 18 missense variations, 21 nonsense variations, and 7 splicing variations, all of which were heterozygous variations. Conclusions:The KDM6B gene variation can lead to neurodevelopmental disorder, craniofacial developmental and skeletal abnormalities. The de novo heterozygous variation in the KDM6B gene is considered to be the genetic etiology of this child. This study extends the spectrum of KDM6B gene variant.

BACKGROUND:The study of deer antler stem cells and exosomes to promote the repair of acute skin injuries has received increasing attention in recent years,but the effect and mechanism of exosomes composite hydrogel to promote the repair of burn wounds are still unclear.OBJECTIVE:To investigate the effect of deer antler stem cell exosome composite hydrogel on the healing speed and quality of rat deep third-degree burn wound and its mechanism of action.METHODS:Deer antler stem cell exosomes and bone marrow mesenchymal stem cell exosomes were extracted and compounded with Pluronic F-127 to prepare a temperature-sensitive hydrogel.A constant temperature and pressure burn apparatus was used to prepare a rat model of deep third-degree burn.The drug was administered to four groups:deer antler stem cell exosome composite hydrogel group,bone marrow mesenchymal stem cell exosome composite hydrogel group,human epidermal growth factor gel group,and the control group.The healing of burned rats was observed and the wound healing rate was calculated.At 28 days after burn,hematoxylin-eosin staining was used to observe the generation of skin accessory structures in the healing tissues.Masson staining was used to analyze the accumulation of collagen in the healing tissues.Immunohistochemistry was used to examine the angiogenesis and nflammatory response in the healing tissues.qRT-PCR was used to examine the expression level of mRNA of the wound healing-related genes in the healing tissues.RESULTS AND CONCLUSION:(1)Deer antler stem cell exosome composite hydrogel can significantly promote the healing rate of deep burn wounds in rats,and improve the quality of wound healing by promoting the regeneration of skin collateral structures,increasing the dermal thickness and enhancing the accumulation of collagen.(2)The number of myofibroblasts in the wound healing tissues of deer antler stem cell exosome composite hydrogel group was significantly reduced,and the number of neovascularization and M2 macrophages was significantly increased.(3)The mRNA levels of transforming growth factor β3 and type Ⅲ collagen in the wound healing tissue of deer antler stem cell exosome composite hydrogel group were significantly higher than those of the blank group,and the mRNA levels of transforming growth factor β1,matrix metalloproteinase 3,and type Ⅰ collagen were significantly lower than those of the blank group,and there was no significant difference between the bone marrow-derived mesenchymal stem cell exosome composite hydrogel group and the human epidermal growth factor gel group.In conclusion,deer antler stem cell exosome composite hydrogel can promote the healing speed and the quality of healing of deep burned wounds in rats,which may be achieved by inhibiting fibroblastogenesis,promoting angiogenesis,macrophage M2 polarization,and regulating the expression of genes for collagen production/degradation.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective To analyze the impact of the interval time(IT)between prostate biopsy(PB)and radical prostatectomy(RP)on the perioperative safety and prognostic efficacy of prostate cancer patients.Methods A retrospective analysis was performed on 87 patients who underwent extraperitoneal laparoscopic RP at our hospitals during Jun.2022 to Nov.2024.The patients were divided into the IT ≤2 weeks group(n=42)and the IT ≥4 weeks group(n=45)according to the interval between PB and RP.Baseline data,perioperative indicators,postoperative inflammatory factors,postoperative pathological results,urinary continence,and complication rates were compared between the two groups.Results No statistically significant differences were observed between the two groups in baseline information,operation time,intraoperative blood loss,intraoperative transfusion rate,postoperative hospital stay,catheter removal time,inflammatory factors and complications(P＞0.05).Pathological results showed no significant differences in cancer tissue proportion,positive rate of lymph node,positive rate of surgical margins,and postoperative Gleason scores(P＞0.05).However,the IT ≤2 weeks group exhibited significantly fewer cases of perineural invasion(25 vs.36,59.52％vs.80.00％)and vascular invasion(5 vs.12,11.90％vs.26.67％)compared to the IT≥4 weeks group(P＜0.05).There were no significant differences in postoperative urinary control rate and prostate-specific antigen(PSA)level between the two groups(P＞0.05).Conclusion Radical prostatectomy performed ≤2 weeks after prostate biopsy demonstrates better safety and prognosis.

Objective:To explore the clinical features of a child with Lamb-Shaffer syndrome (LAMSHF) due to a variant of SOX5 gene. Methods:A child who was admitted to Children′s Hospital Affiliated to Zhengzhou University in July 2022 was selected as the study subject. Clinical data of the child was collected. Whole exome sequencing (WES) was carried out on peripheral blood samples from the child and his parents, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. The study has been approved by the Medical Ethics Committee of the Children′s Hospital Affiliated to Zhengzhou University (Ethics No. 2024-K-100).Results:The child, an one-year-and-seven-month-old male, has manifested delayed development in speech and language, intelligence and movement, in addition with mild facial deformities and eye signs. Whole exome sequencing revealed that he has harbored a heterozygous c. 1828_1829insGACT (p.Y610fs*1) frameshifting variant of the SOX5 gene. Sanger sequencing confirmed the variant to be de novo in origin. The variant was also unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+ PS2+ PM2_supporting). Conclusion:The c. 1828_1829insGACT (p.Y610fs*1) variant of the SOX5 gene probably underlay the pathogenesis of LAMSHF in this child. For children with delayed mental, language, intellectual, and motor development, genetic testing should be conducted to facilitate early diagnosis. Above finding has enriched the mutational spectrum of the SOX5 gene.

Objective:To explore the clinical features, genetic characteristics in a child with Miller-McKusick-Malvaux syndrome (3MS) type 1 caused by CUL7 gene variant. Methods:A child diagnosed with 3MS type 1 at the Children′s Hospital Affiliated to Zhengzhou University in February 2021 was selected as the subject of this study. Peripheral blood samples were collected from the child and her parents for genomic DNA extraction. Whole exome sequencing (WES) was performed on the child, and Sanger sequencing was used to validate the candidate variants and analyze their pathogenicity. A literature search was conducted using the keywords "3M syndrome" in the China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and PubMed databases from inception to December 2024. The clinical data of Chinese children with 3MS reported in the literature were summarized. This study was approved by the Medical Ethics Committee of the Children′s Hospital Affiliated to Zhengzhou University (Ethics No. 2024-K-020).Results:①The child was a 6-year-old and 2-month-old female with facial dysmorphism, skeletal abnormalities, and growth and developmental delay. ②WES revealed compound heterozygous variants in the CUL7 gene: c. 2686G>T (p.E896*) and c. 1200delT (p.R401Gfs66). Sanger sequencing confirmed that these two variants were inherited from the child′s father and mother, respectively. According to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants, c. 2686G>T (p.E896) was classified as a pathogenic (PVS1+ PM2_Supporting+ PM3), and c. 1200delT (p.R401Gfs*66) was classified as a likely pathogenic (PVS1+ PM2_Supporting). ③ Based on the literature search strategy, 18 relevant articles were identified, including a total of 32 Chinese cases of 3MS, of which 8 were fetuses. A total of 32 Chinese 3MS cases were included in the literature review, of which 8 were fetuses. The majority of these cases carried variants in the CUL7 gene (20/32, 62.5%) and OBSL1 gene (12/32, 37.5%). The main clinical manifestations included intrauterine or postnatal growth and developmental delay (32/32, 100.0%), triangular facies (27/32, 84.3%), and skeletal abnormalities (21/32, 65.6%). Conclusion:The compound heterozygous variants c.2686G>T (p.E896*) and c. 1200delT (p.R401Gfs*66) in the CUL7 gene are likely the genetic cause of 3MS type 1 in the child. For children presenting with facial dysmorphism, skeletal abnormalities, and intrauterine or postnatal growth and developmental delay, 3MS should be considered as a differential diagnosis.