A growing body of research points out that gut microbiota plays a key role in tumor immunotherapy. By optimizing the composition of intestinal microbiota, it is possible to effectively improve immunotherapy resistance and enhance its therapeutic effect. This article comprehensively analyzes the mechanism of intestinal microbiota influencing tumor immunotherapy resistance, expounds the current strategies for targeted regulation of intestinal microbiota, such as traditional Chinese medicine and plant components, fecal microbiota transplantation, probiotics, prebiotics and dietary therapy, and explores the potential mechanisms of these strategies to improve patients' resistance to tumor immunotherapy. At the same time, the article also briefly discusses the prospects and challenges of targeting intestinal microbiota to improve tumor immunotherapy resistance, which provides a reference for related research to help the strategy research of reversing tumor immunotherapy resistance.

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 analyze the nonlinear relationship between hypothermic machine perfusion (HMP) parameters and delayed graft function (DGF) and optimize the construction of a predictive model for DGF. Methods The data of 923 recipients who underwent kidney transplantation from deceased donors were retrospectively analyzed. According to the occurrence of DGF, the recipients were divided into DGF group (n=823) and non-DGF group (n=100). Donor data, HMP parameters and recipient data were analyzed for both groups. The nonlinear relationship between HMP parameters and the occurrence of DGF was explored based on restricted cubic splines (RCS). Over-sampling, under-sampling and balanced sampling were used to address the imbalance in the proportion of DGF to construct logistic regression predictive models. The area under the curve (AUC) of each model was compared in the validation set, and a nomogram model was constructed. Results Donor BMI, cold ischemia time of the donor kidney, and HMP parameters (initial and final pressures, resistance, and perfusion time) were significantly different between the DGF and non-DGF groups (all P<0.05). The RCS analysis revealed a threshold-like nonlinear relationship between HMP parameters and the risk of DGF. Among the models constructed using different sampling methods, the balanced sampling model had the highest AUC. Using this model, a nomogram was constructed to stratify recipients based on risk scores. Recipients in the high-risk group had higher serum creatinine levels at 1, 6, and 12 months after kidney transplantation compared to those in the low-risk group (all P<0.05). Conclusions There is a nonlinear relationship between HMP parameters and the risk of DGF, and the threshold is helpful for organ quality assessment and monitoring of graft function after transplantation. The predictive model for DGF constructed on the base of balanced sampling algorithms helps perioperative decision-making and postoperative graft function monitoring of kidney transplantation.

Objective: To analyze the longitudinal relationship between cumulative multiple risks and depressive emotions in primary and secondary school students, and to examine the mediating role of executive function in the association, so as to provide scientific evidence for preventing and alleviating depressive emotions in adolescents. Methods: Using convenience sampling, 946 students from Shandong and Hunan provinces were tracked for one year (December 2023 to December 2024) regarding their exposure to multiple risks, executive function, and depressive emotion. Pearson correlation analysis was employed to examine variable relationships, while mediation modeling with Bootstrap testing (5 000 iterations) was conducted to verify the mediating effect. Results: At baseline, the prevalence of survival risks was relatively low, with 37.98% of primary school students and 30.87% of middle school students reporting no exposure to such risks. In contrast, developmental risks and harmful risks showed substantially higher prevalence, with 63.20% of primary school students and 69.63% of middle school students experiencing two or more risk factors in developmental risks, and 44.81% of primary school students and 71.60% of middle school students experiencing two or more harmful risks. After controlling for gender, age, baseline executive function and depressive emotions:higher cumulative developmental risks ( β=0.06, P <0.01) and hazardous risks ( β=0.08, P <0.01) predicted elevated depressive emotion, while survival risks showed no significant prediction ( β=0.03, P >0.05). Executive function significantly mediated the effects of both developmental risks ( Effect=0.02, 95%CI =0.01-0.04) and hazardous risks ( Effect=0.02, 95%CI =0.01-0.04) on depressive emotion (both P <0.05). Conclusions Increased exposure to developmental and hazardous risks predicts poorer executive function, which subsequently exacerbates depressive emotions in students.

During the operation of warm needling, the needle may be tilted and bent to a large degree, which will cause high temperature of moxibustion on the skin surface around, and even burns in patients. To solve this problem, the team developed a balance fixator for acupuncture needle that can be used at acupoints in various parts of the body, such as on the abdomen, waist, limbs and face. The device is composed of 3 parts, including three (or more)-bifurcated sleeve, cushion pad, and circular fixed base-plate, forming an integrated structure. The three (or more)-bifurcated sleeve increases the contact area with the filiform needle body, which can quickly and easily reduce the curvature of the needle body and fix the filiform needle. According to the different locations of acupoints in clinical practice, the cushion pad is designed as three types, i.e. rectangle, large circle, and small circle. It can not only balance needle body, but also prevent skin burns to a certain extent. This device is simple to manufacture, lightweight in material, and environmental friendly; and is applicable to a simple and safe operation in clinical practice.
Humans ; Acupuncture Therapy/methods* ; Acupuncture Points ; Needles ; Equipment Design

According to the World Health Organization (WHO) manual, sperm concentration should be measured using an improved Neubauer hemocytometer, while sperm motility should be measured by manual assessment. However, in China, thousands of laboratories do not use the improved Neubauer hemocytometer or method; instead, the Makler counting chamber is one of the most widely used chambers. To study sources of error that could impact the measurement of the apparent concentration and motility of sperm using the Makler counting chamber and to verify its accuracy for clinical application, 67 semen samples from patients attending the Department of Andrology, West China Second University Hospital, Sichuan University (Chengdu, China) between 13 September 2023 and 27 September 2023, were included. Compared with applying the cover glass immediately, delaying the application of the cover glass for 5 s, 10 s, and 30 s resulted in average increases in the sperm concentration of 30.3%, 74.1%, and 107.5%, respectively (all P < 0.0001) and in the progressive motility (PR) of 17.7%, 30.8%, and 39.6%, respectively (all P < 0.0001). However, when the semen specimens were fixed with formaldehyde, a delay in the application of the cover glass for 5 s, 10 s, and 30 s resulted in an average increase in the sperm concentration of 6.7%, 10.8%, and 14.6%, respectively, compared with immediate application of the cover glass. The accumulation of motile sperm due to delays in the application of the cover glass is a significant source of error with the Makler counting chamber and should be avoided.
Humans ; Male ; Sperm Motility/physiology* ; Sperm Count ; Semen Analysis/methods* ; Spermatozoa/physiology* ; Time Factors

OBJECTIVES: To investigate the clinicopathological characteristics and prognostic factors of pediatric Hodgkin lymphoma (HL). METHODS: A retrospective analysis was conducted on the clinical data of children with newly diagnosed HL from January 2011 to December 2023 at four hospitals: Fujian Medical University Union Hospital, Fujian Medical University Zhangzhou Hospital, First Affiliated Hospital of Xiamen University, and Fujian Children's Hospital. Patients were categorized into low-risk (R1), intermediate-risk (R2), and high-risk (R3) groups based on HL staging and pre-treatment risk factors. The patients received ABVD regimen or Chinese Pediatric HL-2013 regimen chemotherapy. Early treatment response and long-term efficacy were assessed, and prognostic factors were analyzed using the Cox proportional hazards regression model. RESULTS: The overall complete response (CR) rates after 2 and 4 cycles of chemotherapy were 42% and 68%, respectively. Compared with the ABVD regimen group, patients treated with the HL-2013 regimen in the R1 group showed significantly higher CR rates after both 2 and 4 cycles (P<0.05). However, no statistically significant differences in CR rates were observed between the two regimens in the R2 and R3 groups (P>0.05). The 5-year event-free survival (EFS) rate, overall survival rate, and freedom from treatment failure rate were 83%±4%, 97%±2%, and 88%±4%, respectively. Cox analysis indicated that the presence of a large tumor mass at diagnosis and failure to achieve CR after 4 cycles of chemotherapy were independent risk factors for lower EFS rates (P<0.05). CONCLUSIONS Pediatric HL generally has a favorable prognosis. The presence of a large tumor mass at diagnosis and failure to achieve CR after 4 cycles of chemotherapy indicate poor prognosis.
Humans ; Hodgkin Disease/pathology* ; Male ; Child ; Female ; Adolescent ; Retrospective Studies ; Child, Preschool ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Prognosis ; Proportional Hazards Models ; Survival Analysis ; Infant

OBJECTIVE: To characterize the occurrence of SRSF2 mutations in chronic myelomonocytic leukemia(CMML) patients and their correlation with other gene mutations and some clinical characteristics. METHODS: The clinical data of 43 CMML patients diagnosed in Changzhou No.2 People's Hospital and Wuxi No.2 People's Hospital were retrospectively analyzed, and gene mutations detection was performed using next-generation sequencing (NGS). RESULTS: Among the 43 CMML patients the SRSF2 mutation detection rate was 39.5%(17/43). These mutations clustered collectively at the proline 95 residue in the splicing factor SRSF2. The other genes with mutation rate greater than 15% were ASXL1 (48.8%), TET2 (41.9%), NRAS (30.2%), RUNX1 (25.6%), and SETBP1 (16.3%). Among SRSF2- mutated patients, the most common co-mutation was ASXL1, followed by TET2. The median age of SRSF2 mutant patients was significantly higher than that of the wild type (68 vs 51.5, P < 0.001), but there was not statistically significant differences in gender, peripheral leukocytes, hemoglobin, platelets, karyotype, and blast cell compared to the wild-type (all P >0.05). Notably, 4 out of the 6 SRSF2 ^mutASXL1^mut CMML patients developed leukemia transformation, and 1 out of 10 SRSF2 ^wtASXL1^wt CMML patients developed leukemia transformation, with statistically significant difference in leukemia transformation rates (66.7% vs 10%, P =0.036). CONCLUSION SRSF2 mutations have a high incidence in CMML, occurring frequently in older patients, and often coexisting with ASXL1 and TET2 mutations. Patients with CMML carrying both SRSF2^mut ASXL1^mut double mutations have a higher risk of acute leukemia transformation.
Humans ; Serine-Arginine Splicing Factors/genetics* ; Mutation ; Leukemia, Myelomonocytic, Chronic/genetics* ; Retrospective Studies ; Male ; Female ; Repressor Proteins/genetics* ; DNA-Binding Proteins/genetics* ; Dioxygenases ; Middle Aged ; Aged ; Proto-Oncogene Proteins/genetics*

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.