Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorders (PTLD) are one of the most severe complications after hematopoietic stem cell transplantation (HSCT). This study includes 31 cases of aplastic anemia (AA) patients who developed PTLD after haploidentical transplantation, summarizing their clinical characteristics and categorizing them into either rituximab monotherapy group or combination therapy group based on whether their condition improved by 1 log after a single dose of rituximab. The incidence of PTLD after HSCT in children with AA was 10.16%, and the incidence of PTLD in patients with age >10 years was significantly increased ( χ2=11.336, P=0.010). Of the 31 patients, 27 were clinically diagnosed and 4 were pathologically confirmed. Finally, 15 patients were classified into the rituximab treatment group and 15 patients into the combination treatment groups. Finally three patients died, and the 2-year overall survival rate was (89.7±5.6) %. Standard pre-treatment protocols and EBV reactivation are risk factors affecting the prognosis of PTLD. There was no statistically significant difference in the impact of the two treatment schemes on prognosis.

Objective:To investigate the efficacy and safety of venetoclax combined with the decitabine, cytarabine, and homoharringtonine (HHT) regimen and donor lymphocyte infusion (DLI) for the preventive and salvage therapy of pediatric acute myeloid leukemia (AML) /myelodysplastic syndrome (MDS) after allogeneic hematopoietic stem cell transplantation (HSCT) .Methods:A total of 29 relapsed pediatric/minimal residual disease-positive AML after HSCT were recruited at the Peking University Institute of Hematology from January 1, 2021, to June 1, 2023. They were treated with the above combination regimen and administered with DLI after 24-48 hours at the end of chemotherapy, and the treatment response and adverse reactions were regularly assessed.Results:The overall response rate (ORR) was 75.8%, CR rate was 88.9% (8/9) in the hematologic relapse group, and MRD negativity rate was 61.1% (11/18) in the MRD-positive group. The incidence of agranulocytosis, anemia, and thrombocytopenia with a classification above grade 3 were 100%, 82.7%, and 100%, respectively. The median time of the granulocyte deficiency period was 15 days. Acute graft-versus-host diseases (aGVHD) with a classification of grades Ⅲ-Ⅳ occurred in 11.1% of the patients after DLI, while moderate or severe cGVHD occurred in 7.4% of the patients. The single risk factor for ORR was MNC counts of less than 10×10 8/kg, and the relapse occurred within 100 days. At a median follow-up of 406 days, the 1-year OS was 65%, and the 1-year OS was 57% in the group with no reaction ( P=0.164) compared with 71% in the group who had an overall reaction. Conclusion:The combined regimen based on the DAC, VEN, and modified HA regimen showed a high response rate in the salvage therapy for pediatric AML after the relapse of HSCT. However, bridging to transplantation should be performed immediately after remission to result in a long survival rate.

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

Febrile infection-related epilepsy syndrome(FIRES)is a lethal encephalopathy with refractory status epilepticus as the main manifestation,and the selection of effective antiepileptic drugs(AEDs)is the focus and difficulty of treatment.This review summarises the mechanism of action,drug administration and adverse effects of different anti-inflammatory immunotherapies in the treatment of this disease,and finds that early initiation of ketogenic diet(KD)is one of the most effective treatments at present,and further studies are needed to clarify the adverse effects of the drugs and the effects of the combination of different drugs.

Objective:To investigate the effects of vagus nerve stimulation on postoperative cognitive dysfunction and the role of hippocampal insulin growth factor 1 signaling pathway in aged mice.Methods:Seventy-five clean-grade C57 mice of both sexes, aged 21-23 months, weighing 28-34 g, were divided into 5 groups ( n=15 each) using a random number table method: sham operation group (group S), operation group (group O), operation + vagus nerve stimulation group (group O+ V), operation + IGF-1 siRNA group (group O+ I) and operation + vagus nerve stimulation + IGF-1 siRNA group (group O+ V+ I). Group O underwent exploratory laparotomy.Group O+ V received a 30-min electrical stimulation of the vagus nerve (intensity 0.5 mA, frequency 20 Hz, time 30 s, 6 times, interval 5 min) after the end of exploratory laparotomy.Group O+ I underwent exploratory laparotomy and inhaled IGF-1 siRNA solution 10 μl intranasally at 24 h before surgery and 24 and 48 h after surgery.Group O+ V+ I underwent electrical vagus nerve stimulation after exploratory laparotomy and inhaled IGF-1 siRNA solution 10 μl intranasally at 24 h before surgery and 24 and 48 h after surgery.Morris water maze tests were performed on 14-18 days after operation.On day 7 after operation, the mice were sacrificed and the hippocampus was obtained for determination of the expression of Bax, ionized calcium-binding adapter molecule 1 (Iba-1), insulin-like growth factor 1 (IGF-1), insulin-like growth factor 1 receptor (IGF1R), phosphorylated IGF1R (p-IGF1R), interleukin-1beta (IL-1β) and activated caspase-3 by Western blot. Results:Compared with group S, the escape latency was significantly prolonged on days 16-18 after operation, the frequency of crossing the platform was reduced, the time spent in the target quadrant was shortened, the expression of IGF-1 and p-IGF1R was down-regulated, and the expression of Iba-1, IL-1β, activated caspase-3 and Bax was up-regulated in group O ( P<0.05). Compared with group O, the escape latency was significantly shortened on days 16-18 after operation, the frequency of crossing the platform was increased, the time spent in the target quadrant was prolonged, the expression of IGF-1 and p-IGF1R was up-regulated, and the expression of Iba-1, IL-1β, activated caspase-3 and Bax was down-regulated in group O+ V ( P<0.05), and no significant change was found in the parameters mentioned above in group O+ I ( P>0.05). Compared with group O+ V, the escape latency was significantly prolonged on days 16-18 after operation, the frequency of crossing the platform was reduced, the time spent in the target quadrant was shortened, the expression of IGF-1 and p-IGF1R was down-regulated, and the expression of Iba-1, IL-1β, activated caspase-3 and Bax was up-regulated in group O+ V+ I ( P<0.05). There was no significant difference in the expression of IGF1R among the four groups ( P>0.05). Conclusions:Vagus nerve stimulation can reduce postoperative cognitive dysfunction, and the mechanism is related to activation of IGF-1 signaling pathway and reduction of hippocampal neuroinflammation and neuronal apoptosis in aged mice.

Amyotrophic lateral sclerosis (ALS) is a relentless, progressive, and presently incurable neurodegenerative disease. Its drug development has been hampered by the lack of effective biomarkers for early diagnosis, progression and prognosis. Recently, significant progress has been made for the identification of body fluid biomarkers for ALS, which conferred both theoretical and practical feasibility for the early diagnosis and progression monitoring. Meanwhile, it also facilitated identification of genes and/or pathways for the pathogenesis of ALS. This review summarized biomarkers identified from cerebrospinal fluid, blood and urine of ALS patients and their clinical implications.
Amyotrophic Lateral Sclerosis/genetics* ; Biomarkers ; Humans ; Neurodegenerative Diseases ; Prognosis

Objective:To understand the social support, social network, and sexual behavior characteristics of foreigners living in Guangzhou, analyze factors relating to aspects of online social interactions and sexual behaviors of foreigners in Guangzhou, and provide references for targeted HIV intervention services for foreigners.Methods:A cross-sectional survey (both online and offline), among those who met the inclusion criteria was conducted between November 2019 and January 2020. Data were collected on demographics, social support, online social interactions, sexual behaviors, and so on. Statistics were compiled to analyze the factors that may influence casual sexual behaviors.Results:A total of 434 participants were included in the study (241 offline and 193 online). The majority of the participants were male 68.4% (297/434), age (31.0±8.8) years old, African 79.0% (343/434), business people 46.5% (202/434), students 48.2% (209/434), who have business partners and family members in China were 59.4% (258/434) and 28.1% (122/434) separately. They also had the following features: less than 10 close friends 57.1% (248/434); spend 1-3 hours on social applications per day 43.3% (188/434), had casual sexual behaviors in the last 3 months 15.2% (55/363). Multiple logistic regression model analysis showed that compared with those who used social applications for less than 1 hour per day, participants who used social applications for more than 6 hours per day were more likely to have casual sexual behaviors in the last 3 months ( OR=3.63, 95% CI: 1.31-10.08). Conclusions:Participants who used social applications for a longer period every day were more likely to have casual sexual behaviors among foreigners in Guangzhou. Good use of social applications for health promotion and education of HIV can increase the health awareness of foreigners in China.

The main lysosomal protease cathepsin D (cathD) is essential for maintaining tissue homeostasis via its degradative function, and its loss leads to ceroid accumulation in the mammalian nervous system, which results in progressive neurodegeneration. Increasing evidence implies non-proteolytic roles of cathD in regulating various biological processes such as apoptosis, cell proliferation, and migration. Along these lines, we here showed that cathD is required for modulating dendritic architecture in the nervous system independent of its traditional degradative function. Upon cathD depletion, class I and class III arborization (da) neurons in Drosophila larvae exhibited aberrant dendritic morphology, including over-branching, aberrant turning, and elongation defects. Re-introduction of wild-type cathD or its proteolytically-inactive mutant dramatically abolished these morphological defects. Moreover, cathD knockdown also led to dendritic defects in the adult mushroom bodies, suggesting that cathD-mediated processes are required in both the peripheral and central nervous systems. Taken together, our results demonstrate a critical role of cathD in shaping dendritic architecture independent of its proteolytic function.

Objective:To analyze the influencing factors of HIV testing behavior among foreigners in Guangzhou, and provide a reference for promoting HIV testing and intervention services in foreigners.Methods:A cross-sectional survey was conducted from November 2019 to January 2020 among 230 eligible foreigners selected in Guangzhou through convenient sampling method in the form of one-to-one questionnaire interview, HIV testing behaviors and related influencing factors were described and analyzed with χ2 test and multivariate logistic regression model. Results:A total of 230 foreigners were included in the study, in whom 156 were males (67.8%), 217 were from Africa (94.3%), 138 (60.0%) were with education level of university and above, 169 (73.5%) were in business, 47 (20.4%) were students, 132 (57.4%) had cumulative residence >12 months in Guangzhou and 113 (49.1%) had health examination in China in the past 6 months. In these foreigners, the rate of AIDS-related knowledge awareness was 76.0%, the proportion of condom use in the last sex was 39.6%(89/225) and 47.8%(110/230) received HIV tests in the past 3 months. Multivariate logistic regression analysis showed, the influencing factors of HIV testing behavior in the past 3 months included cumulative residence ≤12 months (compared with cumulative residence >12 months, OR=3.12, 95 %CI: 1.49-6.56), health examination in China in the past 6 months (compared to those who had not, OR=2.53, 95 %CI: 1.17-5.48), awareness of HIV testing and consulting service in Guangzhou (compared with those who had no awareness, OR=3.65, 95 %CI: 1.71-7.78). Conclusions:Some foreigners in Guangzhou had relatively low rates of HIV testing and condom use. Those who pay attention to their own health status and know well about HIV testing and consulting services are more likely to receive HIV testing, foreigners in Guangzhou should be encouraged to receive HIV testing. Their self-testing awareness should be improved.

Objective: To understand the mechanism of chemotherapy resistance in nasopharyngeal carcinoma under hypoxic conditions through the perspective of protein SUMOylation modification. Methods: Cobalt chloride (CoCl₂) was used to establish the hypoxic model of human nasopharyngeal carcinoma CNE1 cells. Then, the cell cycle was detected by flow cytometry, and the expression level of small ubiquitin-related modifier(SUMO) and cyclin-dependent kinase 6 (CDK6) proteins were detected by western blotting. MTT assay was used to determine the median lethal dose (IC₅₀) of cancer cells against cisplatin, and enzyme-linked immunosorbent assay (ELISA) was used to determine lactate dehydrogenase (LDH) level. Results: The cell cycle of CNE1 induced by hypoxia was arrested in G0/G1 phase.The results of Western blot showed that the protein expression level of CDK6 in CNE1 cells was lower than that in the control group (0.83±0.25 vs. 0.43±0.21, t=14.67, P=0.003). The protein level of conjugated SUMO1 was significantly lower than that in the control group (2.69±0.48 vs. 1.38±0.31, t=17.22, P=0.001), while the level of free SUMO1 protein was significantly higher than that in the control group (2.01±0.43 vs. 2.60±0.59, t=15.45, P=0.002).The LC50 of CNE1 cells in the control group was significantly lower than that in the hypoxic group (29.44 μg/ml vs. 97.72 μg/ml, t=12.79, P=0.001). After CNE1 cells received 50 μg/ml cisplatin for 48 h, the LDH content in the supernatant of the control group was significantly higher than that in the hypoxic group ((541.49±64.59) ng/ml vs. (234.67±41.03) ng/ml, t=11.94, P=0.007)). The apoptosis rate of CNE1 cells in the control group was significantly higher than that in the hypoxic group ((76.64±5.37)% vs. (32.84±4.77) ng/ml, t=8.49, P=0.003)). Conclusion Hypoxia can dissociate the covalent modification of CDK6 and SUMO1, inhibit cell cycle and increase the chemotherapy resistance of nasopharyngeal carcinoma.