Background Manganese is an essential trace element for the human body and maintains normal development of many organs including the brain. However, long-term exposure to a high manganese environment or excessive manganese intake will lead to manganese poisoning and result in neurological diseases, and currently no effective treatment plan is available. Objective To develop an animal model for subchronic manganese exposure and assess the impact of Dendrobium nobile Lindl. alkaloids (DNLA) on manganese associated behavioral and hippocampal effects in rats. Methods Fifty male SPF SD rats were randomly allocated into a control group (0.9% normal saline by intraperitoneal injection), two experimental groups [7.5 mg·kg⁻¹ (low) or 15 mg·kg⁻¹ (high) of MnCl₂·4H₂O by intraperitoneal injection], and two DNLA antagonistic groups [15 mg·kg⁻¹ MnCl₂·4H₂O by intraperitoneal injection then either 20 mg·kg⁻¹ (low) or 40 mg·kg⁻¹ (high) DNLA by oral administration]. All groups of rats were adminaistered 5 d per wek, once a day, for consecutive 13 weeks. Following modeling, neurobehavioral assessments were conducted using open field, Morris water maze, and Y maze. Inductively coupled plasma mass spectrometry (ICP-MS) was utilized to measure manganese levels in the blood and brain tissues of the rats, and hematoxylin-eosin (HE) staining was employed to examine neuronal morphological changes in the hippocampal tissues of the rats. Results The neurobehavioral tests revealed that the manganese-exposed rats exhibited decreased total movement distance, prolonged central zone dwelling time, and reduced motor activity in the open field test, indicating tendencies toward depression and anxiety (P<0.05). In the Y-maze test, the mean exploration distance in the novel arm, the number of entries into the novel arm, and the time spent in the novel arm of the managanses-exposed rats were all reduced, while the latency period increased, suggesting impaired spatial exploration and learning-memory functions (P<0.05). In the Morris water maze navigation test, the escape latency was significantly longer in the manganese-exposed rats compared to the control group, and the number of platform crossings decreased in the spatial probe test, indicating a significant decline in spatial learning and memory (P<0.05). The ICP-MS analysis showed elevated manganese concentrations in the blood and hippocampus of the exposed rats (P<0.05), and the histopathological observation revealed hippocampal damage. Following the DNLA intervention, the manganese-exposed rats showed increased total movement distance and reduced central zone dwelling time in the open field test (P<0.05). In the Y-maze test, the mean exploration distance in the novel arm, the number of entries into the novel arm, and the time spent in the novel arm increased, while the latency period decreased, suggesting alleviation of anxiety and improved exploratory behavior (P<0.05). In the Morris water maze test, the escape latency gradually shortened, and both the number of platform crossings and the percentage of time spent in the target quadrant increased, indicating improved spatial learning and memory (P<0.05). Additionally, the manganese levels in the blood and hippocampus decreased (P<0.05), and the hippocampal pathological changes were partially restored. Conclusion DNLA demonstrates the ability to counteract multiple neurotoxic effects following the elevation of manganese levels in the blood and hippocampal tissues of rats induced by subchronic manganese exposure. Specifically, DNLA is shown to ameliorate the behavioral alterations observed in rats after manganese exposure, and mitigate the hippocampal damage in manganese-exposed rats.

BACKGROUND: Bile acids (BAs) facilitate the progression of gastric intestinal metaplasia (GIM). Long non-coding RNAs (lncRNAs) dysregulation was observed along with the initiation of gastric cancer. However, how lncRNAs function in GIM remains unclear. This study aimed to explore the role and mechanism of lncRNA PVT1 in GIM, and provide a potential therapeutic target for GIM treatment. METHODS: We employed RNA sequencing (RNA-seq) to screen dysregulated lncRNAs in gastric epithelial cells after BA treatment. Bioinformatics analysis was conducted to reveal the regulatory mechanism. PVT1 expression was detected in 21 paired biopsies obtained under endoscopy. Overexpressed and knockdown cell models were established to explore gene functions in GIM. Molecular interactions were validated by dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (Ch-IP). The levels of relative molecular expression were detected in GIM tissues. RESULTS: We confirmed that lncRNA PVT1 was upregulated in BA-induced GIM model. PVT1 promoted the expression of intestinal markers such as CDX2 , KLF4 , and HNF4α . Bioinformatics analysis revealed that miR-34b-5p was a putative target of PVT1 . miR-34b-5p mimics increased CDX2 , KLF4 , and HNF4α levels. Restoration of miR-34b-5p decreased the pro-metaplastic effect of PVT1 . The interactions between PVT1 , miR-34b-5p, and the downstream target HNF4α were validated. Moreover, HNF4α could transcriptionally activated PVT1 , sustaining the GIM phenotype. Finally, the activation of the PVT1 /miR-34b-5p/ HNF4α loop was detected in GIM tissues. CONCLUSIONS BAs facilitate GIM partially via a PVT1/miR-34b-5p/HNF4α positive feedback loop. PVT1 may become a novel target for blocking the continuous development of GIM and preventing the initiation of gastric cancer in patients with bile reflux.
Humans ; RNA, Long Noncoding/metabolism* ; MicroRNAs/metabolism* ; Hepatocyte Nuclear Factor 4/genetics* ; Bile Acids and Salts ; Kruppel-Like Factor 4 ; Metaplasia/metabolism*

Objective To selectively purify antibodies with high specificity for the C subunit of tetanus toxin(TT) from traditional tetanus antitoxins(TATs).Methods In this study, NHS-activated Sepharose 4 FF resin was used in combination with the TT TeNT-Hc-C869A subunit as a ligand to develop an immunoaffinity chromatography method. The stability and durability of the resin were tested by storing it under different conditions(at 4, 25 and 37 ℃ for 3, 10 and 30 d) and monitoring its reusability. The changes in the potency of the purified fractions by immunoaffinity chromatography were evaluated both in vitro and in vivo.Results Storage at 4 and 25 ℃ for up to 30 d did not significantly affect column performance. F(ab') 2 was purified by immunoaffinity column for five times continuously, and the loading capacity, elution efficiency and purity of eluted antibody were consistent each time, with the protein purity greater than 95%. After five times of continuous alkaline washing and the following purification, the purity of the protein was above 95%. The specific activities of purified equine plasma, enzymatically digested equine tetanus immunoglobulin(TIG) F(ab')2 and human TIG increased by5, 5 and 30 times respectively. And in the mouse neutralization assay, the specific activity of F(ab')2 increased significantly after purification, reaching 243 902 IU/g.Conclusion The developed immunoaffinity chromatography column shows broad applicability, and the chromatography matrix used is simple, cost-effective, and easy to replicate, making it suitable for largescale industrial applications, greatly enhancing safety, and reducing the risk of common clinical allergic reactions.

Objective:To analyze the clinical characteristics and outcomes of patients with invasive fungal sinusitis (invasive fungal rhinosinusitis, IFR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and explored the risk factors for IFR after allo-HSCT.Methods:Nineteen patients with IFR after allo-HSCT at Peking University People’s Hospital from January 2012 to December 2021 were selected as the study group, and 95 patients without IFR after allo-HSCT during this period were randomly selected as the control group (1:5 ratio) .Results:Nineteen patients, including 10 males and 9 females, had IFR after allo-HSCT. The median age was 36 (10–59) years. The median IFR onset time was 68 (9–880) days after allo-HSCT. There were seven patients with acute myeloid leukemia, five with acute lymphoblastic leukemia, two with myelodysplastic syndrome, two with chronic myeloid leukemia, one with acute mixed-cell leukemia, one with multiple myeloma, and one with T-lymphoblastic lymph node tumor. There were 13 confirmed cases and 6 clinically diagnosed cases. The responsible fungus was Mucor in two cases, Rhizopus in four, Aspergillus in four, and Candida in three. Five patients received combined treatment comprising amphotericin B and posaconazole, one patient received combined treatment comprising voriconazole and posaconazole, nine patients received voriconazole, and four patients received amphotericin B. In addition to antifungal treatment, 10 patients underwent surgery. After antifungal treatment and surgery, 15 patients achieved a response, including 13 patients with a complete response and 2 patients with a partial response. Multivariate analysis revealed that neutropenia before transplantation ( P=0.021) , hemorrhagic cystitis after transplantation ( P=0.012) , delayed platelet engraftment ( P=0.008) , and lower transplant mononuclear cell count ( P=0.012) were independent risk factors for IFR after allo-HSCT. The 5-year overall survival rates in the IFR and control groups after transplantation were 29.00%±0.12% and 91.00%±0.03%, respectively ( P<0.01) . Conclusion:Although IFR is rare, it is associated with poor outcomes in patients undergoing allo-HSCT. The combination of antifungal treatment and surgery might be effective.

Objectives:To determine the effect of glucose-6-phosphate-dehydrogenase (G6PD) deficiency on patients’ complications and prognosis following allogeneic stem cell hematopoietic transplantation (allo-HSCT) .Methods:7 patients with G6PD deficiency (study group) who underwent allo-HSCT at Peking University People's Hospital from March 2015 to January 2021 were selected as the study group, and thirty-five patients who underwent allo-HSCT during the same period but did not have G6PD deficiency were randomly selected as the control group in a 1∶5 ratio. Gender, age, underlying diseases, and donors were balanced between the two groups. Collect clinical data from two patient groups and perform a retrospective nested case-control study.Results:The study group consisted of six male patients and one female patient, with a median age of 37 (range, 2-45) years old. The underlying hematologic diseases included acute myeloid leukemia ( n=3), acute lymphocytic leukemia ( n=2), and severe aplastic anemia ( n=2). All 7 G6PD deficiency patients achieved engraftment of neutrophils within 28 days of allo-HSCT, while the engraftment rate of neutrophils was 94.5% in the control group. The median days of platelet engraftment were 21 (6–64) d and 14 (7–70) d ( P=0.113). The incidence rates of secondary poor graft function in the study group and control group were 42.9% (3/7) and 8.6% (3/35), respectively ( P=0.036). The CMV infection rates were 71.4% (5/7) and 31.4% (11/35), respectively ( P=0.049). The incidence rates of hemorrhagic cystitis were 57.1% (4/7) and 8.6% (3/35), respectively ( P=0.005), while the bacterial infection rates were 100% (7/7) and 77.1% (27/35), respectively ( P=0.070). The infection rates of EBV were 14.3% (1/7) and 14.3% (5/35), respectively ( P=1.000), while the incidence of fungal infection was 14.3% (1/7) and 25.7% (9/35), respectively ( P=0.497). The rates of post-transplant lymphoproliferative disease (PTLD) were 0% and 5.7%, respectively ( P=0.387) . Conclusions:The findings of this study indicate that blood disease patients with G6PD deficiency can tolerate conventional allo-HSCT pretreatment regimens, and granulocytes and platelets can be implanted successfully. However, after transplantation, patients should exercise caution to avoid viral infection, complications of hemorrhagic cystitis, and secondary poor graft function.

Objective:To summarize the clinical features associated with respiratory syncytial virus (RSV) infection in patients following the hematopoietic stem cell transplant (HSCT) and exploring the risk factors for death.Methods:Patients who had RSV infection after undergoing HSCT from October 2023 to January 2024 in the hematology department of Peking University People’s Hospital were enrolled in the study. The clinical characteristics of the participating patients were summarized. The clinical characteristics of the surviving and the dying patients were compared, and the risk factors of death were analyzed by binary logistic regression.Results:Among the 43 RSV-positive HSCT patients, 20 (46.5%) were hypoxemic, six (14.0%) were admitted to the ICU for further treatment, four (9.3%) required tracheal intubation assisted ventilation, and seven patients (16.3%) died. A comparison of the clinical features of the surviving patients and the deceased patients demonstrated that the deceased patients had a lower PLT when infected with RSV [74.5 (8.0-348.0) ×10 9/L vs 15.0 (10.0-62.0) ×10 9/L, P=0.003], a higher incidence of simultaneous bacterial infections (85.7% vs 41.7%, P=0.046), and a higher rate of hematological recurrence (71.4% vs 13.9%, P=0.004). Hematological recurrence ( OR=15.500, 95% CI 2.336-102.848, P=0.005), influenza A viral infection ( OR=14.000, 95% CI 1.064-184.182, P=0.045), and low PLT at the time of RSV infection ( OR=0.945, 95% CI 0.894-0.999, P=0.048) were the factors associated with death following HSCT. Conclusion:Patients infected with RSV after undergoing HSCT have a poor prognosis, and active prevention and treatment of RSV in the autumn and winter requires urgent attention.

Objective To study the clinical and electrophysiological characteristics about ictal facial dystonia of medial temporal lobe epilepsy.Method Data was collected from patients with mesial temporal lobe epilepsy originating from unilateral temporal lobe structures through preoperative evaluation at the Functional Neurology Department of the Second People's Hospital of Shenzhen between July 1,2019 and September 1,2023.All patients did not have seizures for at least 1 year after operation.The ictal symptoms of each patient were analyzed and the patients with ictal facial dystonia were selected and the clinical and electrophysiological characteristics of ictal facial dystonia were summarized.Results Nineteen of 47 patients diagnosed as mesial temporal lobe epilepsy had ictal facial dystonia,of which the electroencephalogram starting at the right side in 11 cases and at the left side in 8 cases.Fifteen patients had the symptom in the first 1/3 period of seizure.Fifteen patients had bilateral symmetrical muscle contraction.Thirteen patients showed with negative expression,5 with neutral expression,and 1 with negative or positive expression in different seizures.None of the patient had the drop of the corners of the mouth.Five patients underwent stereotactic-electroencephalogram(SEEG),including 3 patients with bilateral implantation and 2 patients with unilateral implantation.SEEG showed that the medial temporal structure,insula and orbital lobes were all involved in the onset of ictal facial dystonia.Conclusion The medial temporal lobe epilepsy often present ictal facial dystonia in the first 1/3 period of seizure,with bilaterally symmetrically facial contraction,often accompanied by negative expression,but without drop of the corners of the mouth.The lateralization value of ictal facial dystonia is limited and this symptom involves a wide brain network structure.

Objective:To compare the postoperative recurrence rates between Thulium laser en bloc resection of bladder tumor (ERBT) and traditional transurethral resection of bladder tumor (TURBT) in treating patients with non-muscle invasive bladder cancer (NMIBC).Methods:A retrospective analysis was conducted on the clinical data of 1 439 patients with NMIBC who underwent either Thulium laser ERBT or TURBT in Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, between January 2010 and March 2024. Among them, 201 patients received Thulium laser ERBT, while 1 238 patients underwent TURBT. Propensity score matching (PSM) was employed in a 1∶1 ratio to eliminate selection bias due to non-random assignment, ensuring the comparability of clinical baseline data such as gender, age, pathological diagnosis, T stage, tumor grade, tumor size, and tumor number between the two groups. Kaplan-Meier method was used to generate recurrence-free survival curves for the matched groups, and the log-rank test was conducted to compare differences between the groups. Univariate and multivariate Cox regression analyses were performed to identify independent risk factors affecting postoperative recurrence.Results:After PSM matching, 193 patients were included in each group. There were no statistically significant differences between the two groups in terms of gender ( P=0.317), age ( P=0.207), pathological type ( P=0.756), T stage ( P=0.402), tumor grade ( P=0.965), tumor size ( P=0.821), or number of tumors ( P=0.421). The median follow-up time was 16.2(8.0, 33.9) months. Excluding patients with non-urothelial tumors such as adenocarcinoma and squamous cell carcinoma, there were 180 cases in the Thulium laser ERBT group and 184 cases in the TURBT group. Survival analysis showed that the postoperative recurrence rate of urothelial carcinoma patients in the Thulium laser ERBT group was lower than that in the TURBT group [20.0%(36/180) vs. 38.6%(71/184), P<0.001]. Stratified survival analysis indicated that in patients with tumor diameters ≤30 mm [22.3%(29/130) vs. 33.6%(45/134), P=0.017] or >30 mm [14.0%(7/50) vs. 52.0%(26/50), P=0.002], the Thulium laser ERBT group had lower postoperative recurrence rate compared to the TURBT group.Among patients with single tumor, the recurrence rate in the Thulium laser ERBT group was lower than in the TURBT group[10.5%(11/105) vs. 31.5%(35/111), P<0.001]. However, among patients with multiple tumors, there was no statistically significant difference in recurrence rates between the Thulium laser ERBT group and the TURBT group [35.7%(25/70) vs. 47.9%(34/71), P=0.061]. Univariate and multivariate Cox regression analyses indicated that Thulium laser ERBT treatment was an independent protective factor against postoperative recurrence in NMIBC patients ( HR=0.44, 95% CI 0.30-0.66, P<0.001). Patients with adenocarcinoma ( HR=5.85, 95% CI 2.07-16.51, P<0.001), squamous cell carcinoma ( HR=2.98, 95% CI 1.04-8.55, P=0.042), or other types of tumors ( HR=2.98, 95% CI 1.14-7.75, P=0.026) had higher risks of recurrence. High-grade tumor patients faced increased risks of postoperative recurrence ( HR=1.84, 95% CI 1.21-2.79, P=0.004). Additionally, tumors >30 mm had increased risks of postoperative recurrence compared to those ≤30 mm ( HR=2.00, 95% CI1.31-3.05, P=0.001). Patients with single tumor had significantly reduced risks of postoperative recurrence compared to those with multiple tumors ( HR=0.50, 95% CI 0.34-0.73, P<0.001). Conclusions:Regardless of tumor diameter (≤30 mm or >30 mm), Thulium laser ERBT significantly reduces the postoperative recurrence rate in patients with urothelial carcinoma compared to TURBT, with the advantage being more pronounced in patients with single bladder tumor. Additionally, patients with high-grade tumors, tumor diameters >30 mm, or multiple bladder tumors have higher risk of postoperative recurrence.

Objective:To evaluate the efficacy and safety of matched sibling donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of myelofibrosis (MF).Methods:In this case series, the clinical data of 18 patients with MF who received allo-HSCT in the Department of Hematology, Peking University People′s Hospital from December 2008 to December 2023 were retrospectively studied. Kaplan-Meier survival analysis and competitive risk model were used to evaluate the probabilities of 3-year overall survival (OS), disease-free survival (DFS), cumulative incidence of relapse (CIR), and transplant related mortality (TRM). The transplant related complications were also analyzed.Results:Among the 18 patients included, there were 12 males and 6 females, with a median age of 50 (range: 28-64) years. All 18 patients achieved neutrophil engraftment, and the time of neutrophil engraftment [ M ( Q1, Q3)] was 16.0 (11.8, 18.0) days. Twelve patients achieved platelet engraftment, and the platelet engraftment time was 21.0 (16.2, 43.2) days. Six patients had grade Ⅱ to Ⅳ acute graft-versus-host disease (GVHD), and six patients had chronic GVHD. The 3-year OS rate and DFS rate after transplantation were 62.2% and 52.2%, respectively. The 3-year CIR and TRM were 29.7% and 24.6%, respectively. Four patients died during follow-up, with the main cause of death being infections. Conclusion:Matched sibling allo-HSCT is a feasible option for the treatment of MF.

Objective:To evaluate the disinfection effect of high-energy pulse ultraviolet disinfection equipment in medical institution settings.Methods:The disinfection effect was evaluated through field tests and laboratory tests. Among them, 135 high-frequency contact points were selected from nine departments in the field test. Samples were collected before and after disinfection, and the disinfection effects of 75% alcohol wipes wiping disinfection, high-energy pulse ultraviolet disinfection robot disinfection and high-energy pulse ultraviolet handheld disinfection instrument were compared. In the laboratory test, 30 infected areas of the simulated test table were exposed to vertical ultraviolet irradiation and the bacterial-killing rate before and after disinfection was calculated.Results:In the field test, the bacteria-killing rates of 75% alcohol wipes, high-energy pulse ultraviolet disinfection robot and high-energy pulse ultraviolet handheld disinfection instrument were 94.99%, 91.53% and 95.94%, respectively, and the difference was statistically significant. The disinfection effect of the high-energy pulse ultraviolet handheld disinfection instrument was better than that of the high-energy pulse ultraviolet disinfection robot ( P values <0.05). In the laboratory test, the killing log value of Staphylococcus aureus and Escherichia coli on the carrier were both greater than 3.00. In the simulated field test, the killing log value of Staphylococcus aureus on the surface samples were 4.99. Conclusion:Both the high-energy pulse ultraviolet handheld disinfection instrument and the high-energy pulse ultraviolet disinfection robot have good disinfection effects, which are similar to the disinfection effects of conventional 75% alcohol wipes.