Objective: To investigate the clinical characteristics, the types of unexpected antibodies, and their impacts on immunological risks among patients with different frequencies of cross-matching incompatibility, so as to propose corresponding solutions. Methods: Data of cross-matching incompatibility samples from 92 medical institutions during 2022 to 2024 were collected and divided into three groups based on the frequency of cross-matching. Statistical analysis was performed on disease types, distribution of hematologic diseases, alloantibody detection rates, and proportions of alloantibody types. Results: The 858 patients were divided into three groups based on the frequency of blood cross-matching incompatibility: ≥5 times (8.28%, 71/858), 2 to 4 times (28.21%, 242/858); 1 time (63.52%, 545/858). There was a clustered distribution of disease types in the ≥5 cross-matchings group, with 71.83% (51/71) of patients having tumors or hematologic and hematopoietic diseases. In contrast, the disease types in the 2 to 4 cross-matchings and 1 cross-matching groups were more diverse. An analysis of 249 patients with hematologic diseases found that multiple myeloma was the most common disease in all three groups, accounting for 31.43% (11/35), 35.37% (29/82), and 37.88% (50/132) respectively. In the ≥5 cross-matchings group, myelodysplastic syndrome (14.29%, 5/35) and thalassemia (14.29%, 5/35) were the second most common diseases. In contrast, in the 2 to 4 cross-matchings group and 1 cross-matching group, autoimmune hemolytic anemia was the second most common disease, with prevalence rates of 20.73% (17/82) and 24.24% (32/132), respectively. Alloantibodies were detected in 54.66% of the patients, with antibodies against Rh blood group being most frequent (>50%) in all three groups. The detection rates of alloantibodies/alloantibodies with coexisting autoantibodies decreased across groups: the ≥5 cross-matchings group (70.42%, 50/71) > the 2 to 4 cross-matchings group (54.96%, 133/242) > the 1 cross-matching group (52.48%, 286/545). Conclusion: The risk of alloantibody production increases in patients with multiple cross-matching incompatibilities, especially in those with tumors or hematologic diseases. For handling of cross-matching incompatibility cases, it is recommended to optimize the cross-matching process, implement individualized transfusion plans, and enhance the technical capabilities of clinical transfusion departments and blood group reference laboratories to ensure the safety and effectiveness of transfusions.

BACKGROUND: Neoadjuvant chemoradiotherapy followed by radical surgery has been a common practice for patients with locally advanced rectal cancer, but the response rate varies among patients. This study aimed to develop a ResNet-Vision Transformer based magnetic resonance imaging (MRI)-endoscopy fusion model to precisely predict treatment response and provide personalized treatment. METHODS: In this multicenter study, 366 eligible patients who had undergone neoadjuvant chemoradiotherapy followed by radical surgery at eight Chinese tertiary hospitals between January 2017 and June 2024 were recruited, with 2928 pretreatment colonic endoscopic images and 366 pelvic MRI images. An MRI-endoscopy fusion model was constructed based on the ResNet backbone and Transformer network using pretreatment MRI and endoscopic images. Treatment response was defined as good response or non-good response based on the tumor regression grade. The Delong test and the Hanley-McNeil test were utilized to compare prediction performance among different models and different subgroups, respectively. The predictive performance of the MRI-endoscopy fusion model was comprehensively validated in the test sets and was further compared to that of the single-modal MRI model and single-modal endoscopy model. RESULTS: The MRI-endoscopy fusion model demonstrated favorable prediction performance. In the internal validation set, the area under the curve (AUC) and accuracy were 0.852 (95% confidence interval [CI]: 0.744-0.940) and 0.737 (95% CI: 0.712-0.844), respectively. Moreover, the AUC and accuracy reached 0.769 (95% CI: 0.678-0.861) and 0.729 (95% CI: 0.628-0.821), respectively, in the external test set. In addition, the MRI-endoscopy fusion model outperformed the single-modal MRI model (AUC: 0.692 [95% CI: 0.609-0.783], accuracy: 0.659 [95% CI: 0.565-0.775]) and the single-modal endoscopy model (AUC: 0.720 [95% CI: 0.617-0.823], accuracy: 0.713 [95% CI: 0.612-0.809]) in the external test set. CONCLUSION The MRI-endoscopy fusion model based on ResNet-Vision Transformer achieved favorable performance in predicting treatment response to neoadjuvant chemoradiotherapy and holds tremendous potential for enabling personalized treatment regimens for locally advanced rectal cancer patients.
Humans ; Rectal Neoplasms/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Middle Aged ; Neoadjuvant Therapy/methods* ; Aged ; Adult ; Chemoradiotherapy/methods* ; Endoscopy/methods* ; Treatment Outcome

OBJECTIVE: To investigate the accuracy and safety of pedicle screw placement using 3D-printed auxiliary guides in scoliosis correction surgery for adolescents. METHODS: A retrospective analysis was conducted on the clinical data of 51 patients who underwent posterior scoliosis correction surgery from January 2020 to March 2023. Among them, there were 35 cases of adolescent idiopathic scoliosis and 16 cases of congenital scoliosis. The patients were divided into two groups based on the auxiliary tool used:the 3D-printed auxiliary guide screw placement group (3D printing group) and the free-hand screw placement group (free-hand group, without auxiliary tools). The 3D printing group included 32 patients (12 males and 20 females) with an average age of (12.59±2.60) years;the free-hand group included 19 patients (7 males and 12 females) with an average age of (14.58±3.53) years. The two groups were compared in terms of screw placement accuracy and safety, spinal correction rate, intraoperative blood loss, number of intraoperative fluoroscopies, operation time, hospital stay, and preoperative and last follow-up scores of the Scoliosis Research Society-22 (SRS-22) questionnaire. RESULTS: A total of 707 pedicle screws were placed in the two groups, with 441 screws in the 3D printing group and 266 screws in the free-hand group. All patients in both groups successfully completed the surgery. There was a statistically significant difference in operation time between the two groups (P<0.05). The screw placement accuracy rate of the 3D printing group was 95.46% (421/441), among which the Grade A placement rate was 89.34% (394/441);the screw placement accuracy rate of the free-hand group was 86.47% (230/266), with a Grade A placement rate of 73.31% (195/266). There were statistically significant differences in the accuracy of Grade A, B, and C screw placements between the two groups (P<0.05), while no statistically significant differences were observed in intraoperative blood loss, number of fluoroscopies, correction rate, or hospital stay (P>0.05). In the SRS-22 questionnaire scores, the scores of functional status and activity ability, self-image, mental status, and pain of patients in each group at the last follow-up were significantly improved compared with those before surgery (P<0.05), but there were no statistically significant differences in all scores between the two groups (P>0.05). CONCLUSION In scoliosis correction surgery, compared with traditional free-hand screw placement, the use of 3D-printed auxiliary guides for screw placement significantly improves the accuracy and safety of screw placement and shortens the operation time.
Humans ; Male ; Scoliosis/surgery* ; Female ; Adolescent ; Printing, Three-Dimensional ; Retrospective Studies ; Pedicle Screws ; Child

OBJECTIVE: To identify the gene mutation types of 4 suspected β-thalassemia patients in Yunnan Province, and to analyze the genotypes and hematological phenotypes. METHODS: Whole genome sequencing was performed on the samples of 4 suspected β-thalassemia patients from the Dai ethnic group in a thalassemia endemic area of Yunnan Province, whose hematological phenotypes were not consistent with the results of common thalassemia gene mutations. The mutations of β-globin gene clusters were confirmed by polymerase chain reaction (PCR) and Sanger DNA sequencing technology. RESULTS: The 3.5 kb deletion in β-globin gene cluster (NC_000011.10: g. 5224302-5227791del3490bp) was detected in 4 patients' samples, of which 1 case was also detected with HbE mutation and 1 case with CD17 mutation. These 2 patients displayed moderate anemia phenotype, while the two patients with only the 3.5 kb deletion presented with other mild anemia phenotype. CONCLUSION Heterozygous carriers with rare 3.5 kb deletion of the β-globin gene cluster may develop mild anemia, compound mutations of the 3.5 kb deletion with other mutations may led to intermediate thalasemia with moderate to sever anemia. In areas with a high incidence of thalassemia, suspected patients should undergo genetic testing to avoid missing or misdiagnosing rare mutations.
Humans ; beta-Globins/genetics* ; Multigene Family ; beta-Thalassemia/genetics* ; Mutation ; Genotype ; Sequence Deletion ; Phenotype ; Male ; Female

Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, we demonstrated that a GsMTx4-based 17-residue peptide, which we call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.

The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson's disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K⁺ channels, or Ca²⁺-activated K⁺ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.
Animals ; Histamine/metabolism* ; Male ; Oxidopamine/toxicity* ; Rats ; Ventral Thalamic Nuclei/physiopathology* ; Rats, Sprague-Dawley ; Disease Models, Animal ; Parkinson Disease/metabolism* ; Neurons/physiology* ; Humans ; Optogenetics

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Objective To investigate the effects and molecular mechanisms of inhibition of the Ras homolog gene(Rho)/Rho-associated coiled-coil forming protein kinase(ROCK)pathway on the proliferation and migration of airway smooth muscle cells involving myocardin(MYOCD).Methods Human airway smooth muscle cells were infected with the adenoviral vector Ad-ZsGreen-shRNA-hROCK1 in vitro.The cells were randomly divided into four groups:ROCK1 gene silencing control(shNC)group,shNC+arachidonic acid(AA,Rho/ROCK pathway activator)group,ROCK1 gene silencing(shROCK1)group,and shROCK1+AA group(n=3 each).Quantitative real-time polymerase chain reaction and Western blot were used to detect the expression levels of ROCK1 and MYOCD mRNA and protein.ELISA was employed to measure the levels of globular actin and filamentous actin,while immunofluorescent staining and scratch assays were utilized to assess cell proliferation and migration.Results Compared to the shNC+AA group,the shROCK1+AA group exhibited decreased levels of ROCK1 and MYOCD mRNA and protein expression,reduced expression levels of globular actin and filamentous actin,and diminished cell proliferation and migration capabilities(P<0.05).Conclusions Inhibition of the Rho/ROCK pathway suppresses the proliferation and migration of airway smooth muscle cells,which may be associated with the downregulation of MYOCD.

Objective:To explore the clinical features and prognosis of patients with primary central nervous system lymphoma(PCNSL).Methods:A retrospective analysis was performed on the relationship between clinical features,treatment regimen and prognosis in 46 newly diagnosed patients with primary central nervous system lymphoma who were diagnosed and treated in The Second Hospital of Lanzhou University from January 2015 to September 2022.Fisher's exact probability method was used to analyze the differences in clinical data of different subgroups.Kaplan-Meier survival curve was used to analyze the overall survival rate and progression-free survival rate of patients with different treatments,and the factors influencing survival were analyzed.Results:Among 46 patients with PCNSL,which pathological type were diffuse large B-cell lymphoma(DLBCL).There were 26(56.5％)cases of male and 20(43.5％)of female,with a median age of 54(17-71)years.In Hans subtypes,14 cases(30.4％)of GCB subtype,32 cases(69.6％)of non-GCB subtype.32 cases(69.6％)of Ki-67 ≥80％.Among 36 patients who completed at least 2 cycles of treatment with follow-up data,the efficacy evaluation was as follows:overall response rate(ORR)was 63.9％,complete response(CR)rate was 47.2％,17 cases of CR,6 cases of PR.The 1-year progression-free survival rate and 1-year overall survival rate was 73.6％and 84.9％,respectively.The 2-year progression-free survival rate and 2-year overall survival rate was 52.2％and 68.9％,respectively.The ORR and CR rate of 17 patients treated with RMT regimen was 76.5％and 52.9％(9 cases CR and 4 cases PR),respectively.Univariate analysis of 3 groups of patients treated with RMT regimen,RM-BTKi regimen,and RM-TT regimen as first-line treament showed that deep brain infiltration was associated with adverse PFS(P=0.032),and treatment regimen was associated with adverse OS in PCNSL patients(P=0.025).Conclusion:Different treatment modalities were independent prognosis predictors for OS,the deep brain infiltration of PCNSL is a poor predictive factor for PFS.Patients with relapse/refractory(R/R)PCNSL have a longer overall survival time because to the novel medication BTKi.They have strong toleration and therapeutic potential as a first-line therapy for high-risk patients.

Objective:To investigate gene mutation characteristics of primary central nervous system lymphoma(PCNSL)through whole exome sequencing(WES)to 18 patients with PCNSL.Methods:Tumor tissues from 18 patients with diffuse large B-cell lymphoma who were diagnosed with PCNSL in Department of Hematology,Lanzhou University Second Hospital from September 2018 to December 2020 and had normal immune function,no history of HIV or immunosuppressant therapy were collected.High-throughput-based WES was performed on the tumor tissues,with an average sequencing depth of＞100 x.After data processing and bioinformatics analysis of sequencing results,the mutation maps and mutation characteristics of 18 PCNSL patients were obtained.Results:Obvious somatic mutations were detected in all 18 patients.The median number of somatic mutations was 321.Missense mutations were most prominent(accounting for about 90％),and the mutation type was dominated by C＞T(50.2％),reflecting the age-related mutation pattern.Among the top 15 frequently mutated genes,PSD3,DUSP5,MAGEB16,TELO2,FMO2,TRMT13,AOC1,PIGZ,SVEP1,IP6K3,and TIAM1 were the driver genes.The enrichment results of driver gene pathways showed that RTK-RAS,Wnt,NOTCH,Hippo and Cell-Cycle pathways were significantly enriched.The tumor mutation burden was between 3.558 48/Mb and 8.780 89/Mb,and the average was 4.953 32/Mb,which was significantly higher than other cancer research cohorts in the TCGA database.Conclusions:PCNSL occurs somatic missense mutations frequently,mainly point mutations,and the mutation type is mainly C＞T.The driver genes are mainly involved in RTK-RAS,Wnt,NOTCH and Hippo pathways,indicating that the above pathways may be related to the pathogenesis of PCNSL.PCNSL has a significantly high tumor mutation burden,which may explain the efficacy of PD-1 inhibitors in PCNSL.