Objective To observe the effects of Huoxue Digui Decoction on iron accumulation and ferroptosis in renal podocytes of diabetic nephropathy(DN)mice.Methods Totally 50 C57BL/6J mice were randomly divided into normal group(6 mice)and modeling group(44 mice).The DN model was established by streptozotocin injection.Mice conforming to DN model were randomly divided into model group(8 mice),and sulforaphane group,Huoxue Digui Decoction low-,medium-and high-dosage groups(6 mice for each group).The sulforaphane group was injected with sulforaphane intraperitoneally,while Huoxue Digui Decoction low-,medium-and high-dosage groups were orally administered with corresponding solution for 12 consecutive weeks.The fasting blood glucose,blood urea nitrogen,serum creatinine,24 h urinary albumin were detected,HE staining was used to observe the morphology of renal tissue,PAS staining was used to observe glycogen deposition in renal tissue,Masson staining was used to observe fibrosis in renal tissue;transmission electron microscopy was used to observe the ultrastructure of renal tissue,immunohistochemistry was used to detect the expressions of Podocin and Nephrin in renal tissue,Western blot was used to detect the protein expressions of glutathione peroxidase 4(GPX4),ACSL4,nuclear factor E2 related factor 2(Nrf2)and ferroportin 1(FPN1)in renal tissue,Prussian blue staining was used to observe the deposition of ferric ion in renal tissue.Results Compared with the normal group,the fasting blood glucose,blood urea nitrogen,serum creatinine and 24 h urinary albumin in model group significantly increased(P<0.01),with renal tissue capillary atrophy,increased glycogen deposition,and worsening fibrosis,the expressions of Podocin and Nephrin in renal tissue were down-regulated,while the expressions of GPX4,Nrf2 and FPN1 protein were significantly decreased(P<0.01),the expression of ACSL4 protein significantly increased(P<0.01),and the deposition of ferric ion in renal tissue increased.Compared with the model group,the fasting blood glucose,blood urea nitrogen,serum creatinine and 24 h urinary albumin in sulforaphane group and Huoxue Digui Decoction groups were reduced to different degrees(P<0.05,P<0.01),renal tissue pathological damage was reduced to varying degrees,glycogen deposition was reduced,and fibrosis was alleviated,the expressions of Podocin and Nephrin in renal tissue were up-regulated,while the expressions of GPX4,Nrf2 and FPN1 protein significantly increased(P<0.01),the expression of ACSL4 protein significantly decreased(P<0.05,P<0.01),and the deposition of ferric ion in renal tissue was reduced.Conclusion Huoxue Digui Decoction can alleviate renal pathological injury,reduce blood glucose and delay the progression of DN mice.The mechanism may be related to regulating the expressions of Nrf2 and FPN1,inhibiting iron accumulation and ferroptosis in renal podocytes of DN mice.

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.

Human parvovirus B19 (HPVB19) belongs to Parvoviridae, a genus of erythrovirus, and has been associated with various human diseases, and HPVB19 infection is one of the most important causes of refractory anemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study retrospectively analyzed 24 patients with HSCT combined with HPVB19 infection to collate and summarize the clinical presentation, treatment, and regression of patients with combined HPVB19 infection after allo-HSCT and provide experience in the management of HPVB19 infection after allo-HSCT. The median age of the patients with HPVB19 infection was 25 years, and the median time of infection occurrence was +107 days after transplantation, and 22 (91.7% ) had anemia with a median hemoglobin (HGB) level of 77.5 (46-149) g/L, and 13 (54.2% ) had new-onset anemia or persistent decline in HGB. The median length of hospital stay was 19 days. Among patients with new-onset anemia or persistent decline in HGB, the mean increase in HGB after treatment with intravenous immunoglobulin and/or antiviral therapy was 15.69 g/L, and treatment was effective in 10 (76.92% ) patients. HPVB19 infection should be alerted to the development of refractory anemia after HSCT; despite the lack of specific treatment, the overall prognosis of HPVB19-infected patients is good.

Objective To explore association between childhood trauma,resilience and non-suicidal self-injury in adolescents.Methods One hundred and fifty-eight first-episode adolescent patients with mood disorders were selected and divided into NSSI group(n=94)and non-NSSI group(n=64)based on presence or absence of NSSI.The Hamilton depression scale(HAMD),Hamilton anxiety scale(HAMA),childhood trauma questionnaire(CTQ-SF)and Connor-Davidson resilience scale(CD-RISC)were used to evaluate the depression and anxiety symptoms,childhood trauma and resilience.Results There were more cases of younger age(16.17±1.67 vs.16.73±1.37),lower education level(30.9% vs.15.6% ),left behind experience(48.9% vs.29.7% ),school bullying(46.8% vs.25.0% ),suicide ideation(85.1% vs.37.5% )and history of attempted suicide(29.8% vs.6.3% )in the group with NSSI compared to those without NSSI.The HAMD score(27.99±5.94 vs.24.19±5.19),HAMA score(18.02±5.94 vs.15.45±4.99),CTQ total score(48.43±15.40 vs.41.97±9.75),emotional abuse score(12.77±6.06 vs.10.19±4.06),and emotional neglect score(11.40±5.34 vs.9.14±3.55)were higher in the group with NSSI,and the differences between the two groups were significant(P<0.05).The total scores of psychological resilience(39.83±10.27 vs.28.66±12.75),resilience(19.59±4.92 vs.12.28±6.47),strength(12.03±3.98 vs.9.99±4.67),and optimism(8.98±2.97 vs.6.47±3.73)in the group without NSSI were higher than those in the group with NSSI(P<0.05).Logistic regression analysis showed that left behind experience(OR=4.494,95% CI:1.192-16.940),school bullying(OR=5.983,95% CI:1.329-26.945),suicidal ideation(OR=13.225,95% CI:2.908-60.146),history of attempted suicide(OR=16.769,95% CI:1.845-152.379),HAMD(OR=1.264,95% CI:1.046-1.626),emotional abuse(OR=1.327,95% CI:1.093-1.612),and resilience(OR=0.468,95% CI:0.266-0.823)were significantly associated with adolescent mood disorders with NSSI(P<0.05).Conclusion Left behind experience,campus bullying,suicidal ideation and attempted suicide,emotional abuse,degree of depression,and psychological resilience may be associated with NSSI behavior in adolescents with mood disorders.

Objective To compare the effects of ginsenosides Rg1 and Rb1 on depression-and anxiety-like behaviors in chronic unpredictable stress-induced rats.Methods Seventy male SPF grade SD rats were tested for sugar and water preference after 5 days of adaptation and divided into seven groups according to their preference index:a control group,model group,fluoxetine hydrochloride group,ginsenoside Rg1 24 mg/kg group,ginsenoside Rg1 48 mg/kg group,ginsenoside Rb1 33 mg/kg group,and ginsenoside Rb1 67 mg/kg group.All rats,except for the control group,were subjected randomly to one or two different stimulating factors every day for a total of 35 days.On the 36th day,behavioral experiments including sugar and water preference,open field,novel environment feeding inhibition,elevated cross maze,and forced swimming experiments were conducted to investigate the anti-depression and anti-anxiety effects of the treatments.Serum and hippocampal levels of interleukin(IL)-1β,IL-6,tumor necrosis factor(TNF)-α and serum corticosterone were measured by enzyme-linked immunosorbent assay.Results Compared with the model group,ginsenoside Rg1 and Rb1 significantly increased sucrose consumption in the sucrose preference test and decreased immobility in the forced swimming test.Ginsenoside Rg1(48 mg/kg)significantly reduced the latency to eat in the novelty-suppressed feeding test,and ginsenoside Rg1(24 and 48 mg/kg)significantly increased the percentage of open arm entries and time in the elevated cross maze test.Serum corticosterone levels were significantly decreased in the ginsenoside Rg1 and Rb1 groups,serum IL-1β and IL-6 levels were significantly decreased in the ginsenoside Rg1(48 mg/kg)group,serum TNF-α and IL-6 levels were significantly decreased in the ginsenoside Rb1(33 mg/kg)group,and IL-1β,IL-6,and TNF-α levels in the hippocampus were significantly decreased in the ginsenoside Rg1(48 mg/kg)and Rb1(67 mg/kg)groups.Conclusions Both ginsenosides can regulate the hypothalamic-pituitary-adrenal axis and inhibit neuroinflammation,improving depression-and anxiety-like behaviors in rats induced by chronic unpredictable stress.Ginsenoside Rg1 has a significantly better anti-anxiety effect than Rb1.

Microcystin-leucine arginine (MC-LR), a potentially carcinogenic toxin, is produced by Cyanobacteria such as Microcystis and Ananabacteria during water bloom. Increasing evidence demonstrated that MC-LR induces male reproductive toxicity, mainly by inducing germ cell apoptosis, destroying cell cytoskeleton, interfering with DNA damage repair pathway, and damaging blood-testicular barrier (BTB), which eventually lead to male sterility. Testicular Sertoli cells are the somatic cells that directly contact with spermatogenic cells in seminiferous tubules. They not only regulate immune response to maintain testicular immune homeostasis by secreting a variety of cytokines and immunosuppressive factors, but also provide the protective effects of spermatogenic cells by forming BTB. MC-LR induces inflammation and apoptosis of Sertoli cells, and destroys the integrity of the BTB, and then causes spermatogenesis dysfunction.
Male ; Humans ; Sertoli Cells ; Leucine/pharmacology* ; Arginine/pharmacology* ; Microcystins/metabolism* ; Immunity

Pulmonary hypertension (PH) is an extremely malignant pulmonary vascular disease of unknown etiology. ADAR1 is an RNA editing enzyme that converts adenosine in RNA to inosine, thereby affecting RNA expression. However, the role of ADAR1 in PH development remains unclear. In the present study, we investigated the biological role and molecular mechanism of ADAR1 in PH pulmonary vascular remodeling. Overexpression of ADAR1 aggravated PH progression and promoted the proliferation of pulmonary artery smooth muscle cells (PASMCs). Conversely, inhibition of ADAR1 produced opposite effects. High-throughput whole transcriptome sequencing showed that ADAR1 was an important regulator of circRNAs in PH. CircCDK17 level was significantly lowered in the serum of PH patients. The effects of ADAR1 on cell cycle progression and proliferation were mediated by circCDK17. ADAR1 affects the stability of circCDK17 by mediating A-to-I modification at the A5 and A293 sites of circCDK17 to prevent it from m1A modification. We demonstrate for the first time that ADAR1 contributes to the PH development, at least partially, through m1A modification of circCDK17 and the subsequent PASMCs proliferation. Our study provides a novel therapeutic strategy for treatment of PH and the evidence for circCDK17 as a potential novel marker for the diagnosis of this disease.

Premature infants have immature gastrointestinal function and are prone to various comorbidities after birth, which have a great impact on their near and long-term prognosis.Proper nutritional support is the basis of their survival and treatment plan, of which enteral nutrition is the main tool.However, the management of enteral nutrition varies considerably between neonatal facilities worldwide, and the nutritional management of preterm infants varies between physicians.This review summarized and discussed the existing literature on enteral nutrition in preterm infants, to provide a review of the current status of enteral nutrition support in preterm infants in China and abroad and the factors that currently influence the time to achieve adequate enteral nutrition, aiming to provide a reference for improving clinical practice protocols.

There are over 6000 rare diseases in the world, affecting more than 300 million people. Early and precise diagnosis of rare diseases has always been the goal in clinical medicine. Emerging computer vision technology now greatly enhance medicine and healthcare and shows the potential in assisting the diagnosis and treatment for rare diseases. The technology can be a useful tool for extracting disease-relevant patterns from medical imaging. However, the effectiveness of its application depends on the complexity of the medical cases. In this paper, we summarize the challenges and emerging solution for the application of computer vision in diagnosis, rehabilitation as well as management of rare musculoskeletal diseases.