Objective: To investigate the hematological characteristics of the rare McLeod phenotype associated with X-linked chronic granulomatous disease, KEL and XK gene analysis, identification of unexpected antibodies, serological characteristics of high-frequency antigen antibodies, and transfusion strategies. Methods: Serological methods were employed to determine the ABO, Rh, and other blood group system antigen phenotypes of the child, along with screening and identification of unexpected antibodies. The titers of high-frequency antigen antibodies were measured using tube antihuman globulin and microcolumn gel card techniques. Kell blood group typing was performed using serological and genotyping methods, while XK gene sequencing was conducted via next-generation sequencing. Peripheral blood smears from the child's mother were examined for erythrocyte morphology. Results: The child's serological results were as follows: blood group O, ccDEE, MM, Le(a-b+), JK(a+b+), Fy(a+b-), and Kell phenotype K-k+, Kp(a-b+). Plasma analysis revealed alloantibodies anti-C、e, as well as a high-frequency antigen antibody anti-KL, with titers of 512 (tube method) and 2 048 (microcolumn gel method). Genotyping results showed KEL genotype K-k+, Kp(a-b+), Js(a-b+), while XK gene NGS identified a hemizygous deletion of exons 1-3 (XK N. 01), consistent with XK: -1 or Kx-(McLeod). The mother's peripheral blood smear exhibited prominent acanthocytes. Conclusion: The hematological features of this rare McLeod phenotype with X-CGD include weakened Kell antigen expression and a complete exon deletion in the XK gene. Early clinical attention should be given to the symptoms and laboratory diagnosis of X-linked chronic granulomatous disease in pediatric patients. XK genotyping for McLeod phenotype should be prioritized to guide cautious transfusion strategies, preventing life-threatening complications due to incompatible blood products.

Metastasis is the leading cause of death from cutaneous melanoma. Identifying metastasis-related targets and developing corresponding therapeutic strategies are major areas of focus. While functional genomics strategies provide powerful tools for target discovery, investigations at the protein level can directly decode the bioactive epitopes on functional proteins. Aptamers present a promising avenue as they can explore membrane proteomes and have the potential to interfere with cell function. Herein, we developed a target and epitope discovery platform, termed functional aptamer evolution-enabled target identification (FAETI), by integrating affinity aptamer acquisition with phenotype screening and target protein identification. Utilizing the aptamer XH3C, which was screened for its migration-inhibitory function, we identified the Chondroitin Sulfate Proteoglycan 4 (CSPG4), as a potential target involved in melanoma migration. Further evidence demonstrated that XH3C induces cytoskeletal rearrangement by blocking the interaction between the bioactive epitope of CSPG4 and integrin α4. Taken together, our study demonstrates the robustness of aptamer-based molecular tools for target and epitope discovery. Additionally, XH3C is an affinity and functional molecule that selectively binds to a unique epitope on CSPG4, enabling the development of innovative therapeutic strategies.

Objective:To summarize the clinical characteristics of patients with epilepsy caused by focal cortical dysplasia (FCD), and identify the influencing factors for postoperative seizure controls.Methods:Fifty-seven patients with epilepsy caused by FCD admitted to Department of Neurosurgery, Third Affiliated Hospital of Zhengzhou University from July 2019 to November 2023 were chosen; standard preoperative evaluation, surgery, postoperative management and follow-up were performed. A retrospective study of clinical data, imaging and video electroencephalogram (VEEG) data, surgical approaches, pathological findings, and follow-up data was performed; influencing factors for postoperative seizure controls were analyzed.Results:In these 57 patients with epilepsy caused by FCD, 29 were males (50.88%) and 28 were females (49.12%). Onset age was 30.00 (8.00, 74.50) months, and surgery age was 95.00 (50.00, 138.50) months. Focal to bilateral tonic-clonic seizures (42/57; 73.68%) and epileptic spasms (13/57; 22.81%) were common seizure types. Cranial MRI was positive in 34 patients (59.65%), mainly manifested as abnormal cortical gyri/sulci morphology (17/57; 29.82%). In 43 patients accepted PET-CT, hypometabolic sites were detected in 40 (93.02%), and complete agreement between PET/MRI fusion results and actual lesion sites was noted in 40 (93.02%). FCD type I was noted in 16 patients (28.07%), type II in 39 (68.42%), and type III in 2 (3.51%). By December 2023, 44 (77.19%) had Engel grading I, 4 (7.02%) had grading II, 4 (7.02%) had grading III, and 5 (8.77%) had grading IV. Children with good prognosis (Engel grading I+II) and those with poor prognosis (Engel grading III+IV) showed significant differences in terms of time from first seizure to surgery, positive/negative MRI, and regularity of postoperative ASMs ( P<0.05). Conclusions:Focal to bilateral tonic-clonic seizure is the most common seizure type in patients with epilepsy caused by FCD, and abnormal cortical gyri/sulci morphology is the most common MRI manifestation; PET/MRI fusion imaging is superior to PET-CT or MRI in identifying epileptogenic foci. Poor seizure control can be noted in patients with long onset time to surgery, with negative cranial MRI results, or with irregular postoperative ASMs.

ObjectiveTo observe the clinical efficacy of modified Yigongsan combined with multi-enzyme tablets and bifidobacterium triple live powder on infantile anorexia with spleen-stomach Qi deficiency syndrome. MethodA total of 112 infantile patients anorexia with spleen-stomach Qi deficiency syndrome treated at Hebei Provincial Hospital of Traditional Chinese Medicine from January 2022 to June 2023 were enrolled and divided into a control group and an observation group， with 56 cases in each group， according to a random number table. Children in the control group were treated with multi-enzyme tablets and Bifidobacterium triple live powder， while those in the observation group were treated with modified Yigongsan in addition to the treatment in the control group. During the study， one case dropped out in the control group and two cases dropped out in the observation group. The clinical efficacy of the two groups of children was compared， including changes in traditional Chinese medicine （TCM） syndrome scores （main symptoms， secondary symptoms， tongue， and pulse）， time to restore normal food intake， and increase in body weight. Changes in calcium， iron， zinc levels， hemoglobin， and albumin levels before and after treatment， as well as changes in gastrointestinal hormones such as gastrin and motilin， vasoactive intestinal peptide， somatostatin， neuropeptide Y， orexin， and leptin， were observed. The occurrence of adverse reactions in the two groups of children during the study was also recorded. ResultThe total effective rate of children in the control group after treatment was 85.19% （46/54）， while that in the observation group was 98.15% （53/54） （χ² =5.939， P<0.05）. Compared with the control group， the time for food intake to return to normal in the observation group was shorter， and the increase in body weight was greater （P<0.05）. Compared with the results before treatment， the TCM syndrome scores （main symptoms， secondary symptoms， tongue， and pulse） in both groups of children significantly decreased， while the levels of calcium， iron， zinc， hemoglobin， albumin， gastrin， motilin， neuropeptide Y， and orexin increased， and the levels of vasoactive intestinal peptide， somatostatin， and leptin decreased （P< 0.01）. Compared with the control group after treatment， the improvement in the above indicators in the observation group was more significant （P<0.01）. The incidence of adverse reactions in the two groups of children during the treatment period was similar， and the difference was not statistically significant. ConclusionModified Yigongsan combined with multi-enzyme tablets and Bifidobacterium triple live powder is highly effective in treating infantile anorexia （spleen-stomach Qi deficiency syndrome）. After treatment， symptoms of the children were improved，appetite and food intake increased， gastrointestinal function was improved， body weight increased， and adverse reactions were few， indicating that the treatment was safe and reliable.

Background::A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA) has previously shown its preliminary efficacy in ST elevation myocardial infarction (STEMI) patients. This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase (rt-PA) in Chinese patients with STEMI.Methods::In this multicenter, randomized, open-label, non-inferiority trial, patients with acute STEMI were randomly assigned (1:1) to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min. The primary endpoint was recanalization defined by thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3. The secondary endpoint was clinically justified recanalization. Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events (MACCEs) and safety endpoints.Results::From July 2016 to September 2019, 767 eligible patients were randomly assigned to receive rhTNK-tPA ( n = 384) or rt-PA ( n = 383). Among them, 369 patients had coronary angiography data on TIMI flow, and 711 patients had data on clinically justified recanalization. Both used a –15% difference as the non-inferiority efficacy margin. In comparison to rt-PA, both the proportion of patients with TIMI grade 2 or 3 flow (78.3% [148/189] vs. 81.7% [147/180]; differences: –3.4%; 95% confidence interval [CI]: –11.5%, 4.8%) and clinically justified recanalization (85.4% [305/357] vs. 85.9% [304/354]; difference: –0.5%; 95% CI: –5.6%, 4.7%) in the rhTNK-tPA group were non-inferior. The occurrence of 30-day MACCEs (10.2% [39/384] vs. 11.0% [42/383]; hazard ratio: 0.96; 95% CI: 0.61, 1.50) did not differ significantly between groups. No safety outcomes significantly differed between groups. Conclusion::rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery, a validated surrogate of clinical outcomes, among Chinese patients with acute STEMI.Trial registration::www.ClinicalTrials.gov (No. NCT02835534).

Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).

Objective:To establish and evaluate a clinical and ultrasound parameters-based nomogram for the preoperative differentiating diagnosis of intrahepatic cholangiocarcinoma (ICC).Methods:A total of 723 patients undergoing hepatectomy in Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University from January 2016 to August 2022 were retrospectively screened. A total of 399 patients with hepatocellular carcinoma (HCC, 198 cases) or ICC (201 cases) were enrolled in this study, including 284 males and 115 females, aged (60.5±10.5) years. Through random sampling using computer-generated random numbers, patients were divided into training ( n=279) and validation groups ( n=120) in a ratio of 7∶3. Univariate and multivariate logistic regression were performed to identify factors differentiating ICC, and a nomogram was established using R software based on independent risk factors for ICC. The accuracy of the nomogram was evaluated by receiver operating characteristic curve and calibration curves. Decision curve analysis was performed to assess the net benefit of the model. Results:Multivariate logistic regression analysis showed that irregular shape, cholangiectasis, female, cirrhosis, carbohydrate antigen 242 >10 U/ml, carbohydrate antigen 125 >30 U/ml and alpha-fetoprotein >10 μg/L were independent differentiating factors for ICC (all P<0.05). A nomogram was constructed based on those factors. The nomogram showed a better discrimination between ICC and HCC. The area under the curve of the training group and the validation group were 0.966 and 0.956, respectively. The calibration curve showed that the prediction effect of the model is in good agreement with the actual situation. Decision curve analysis showed that the nomogram was more effective than diagnosing all patients as either HCC or ICC, which yielded a net benefit at the most reasonable threshold probabilities. Conclusion:The nomogram for the preoperative diagnosis of ICC based on clinical and ultrasound features showed a good diagnostic performance.

A 79-year male presenting with abdominal distension, diarrhea, edema and oliguria, which soon progressed to acute renal failure, was admitted in Xiamen Branch of Zhongshan Hospital. The diagnosis of atypical hemolytic uremic syndrome (aHUS) was confirmed after admission. The hematological parameters and renal function were improved after prompt hemodialysis, plasma exchange, plasma and immunoglobulin transfusion. The patient experienced multiple recurrences of aHUS within 1 year, but achieved long-term remission with regular use of eculizumab. The reported cases of aHUS were searched from Wanfang Data Knowledge Service Platform and CNKI Database from January 2000 to January 2024, and 64 non-pregnant adult aHUS cases were retrieved from literature. The analysis of 65 cases showed a male-to-female ratio was 1.2∶1 and an average age of 34.8 years ranging from 20 to 86 years. Common clinical manifestations included fever (24 cases, 36.9%), renal dysfunction (27 cases, 41.5%), and neurological symptoms (15 cases, 23.1%). Additionally, 40 cases (61.5%)had concomitant hypertension. Among the 65 patients, 36 (55.4%) received hemodialysis, 31 (47.7%) underwent plasma exchange or plasma transfusion, 29 (44.6%) were treated with glucocorticoids, and only 3 (4.6%) were treated with eculizumab. In terms of treatment outcomes, 29.2% (19 cases)of the patients achieved complete renal function recovery, 46.2% (30 cases)developed end-stage renal disease, and 4 patients died. aHUS presents with a variety of clinical manifestations involving multiple systems. Plasma exchange remains the primary treatment method at present. Early and accurate diagnosis, prompt and effective treatment can significantly improve patient prognosis.

Objective:To evaluate the characteristics of vaginal flora between normal and abnormal pregnant women throughout pregnancy.Methods:Vaginal swab specimens were collected from pregnant women in the first (<14 gestation weeks, GW), second (14~28 GW) and third trimester (>28 GW) in Anqing, Anhui Province from February 2018 to February 2020. Pregnant women were divided into normal and abnormal groups according to all clinical diagnosis. The sequences of 16S rRNA gene (V3-V4) from vaginal swabs were analyzed using QIIME2 platform. The differences in the dominance of Lactobacillus, community state type (CST) transition, Alpha diversity and Beta diversity were analyzed. Diversity data after log transition were used in the analysis of linear mixed model. Results:A total of 34 pregnant women (10 normal and 24 abnormal) with 102 samples were included for analysis. The composition of vaginal flora between two groups: the relative abundance of Lactobacillus was the highest at the genus level and Lactobacillus crispatus and Lactobacillus iners was the top two species with high relative abundance. The dominance of Lactobacillus, Alpha diversity and transition of CST were also similar. Both groups had a gradually decreased trend of Alpha diversity with GW, and the Chao1, Observed species and Faith′s PD indexes′ were different in different GW ( P<0.05). All Beta diversity metrics in normal group had descending trend, with lower value of the index of first distance which implied a higher microbiota stability, while Bray-Curtis, Weighted UniFrac distance had ascending trend in abnormal group, indicating lower stability. Jaccard distance′s first distance was statistically differed among GW and Unweighted UniFrac distance′s differed between normal and abnormal groups. Conclusions:The first distance of Unweighte UniFrac distance in abnormal pregnant women is higher than that of normal pregnant women and the vaginal flora in abnormal group has lower stability.