Ferroptosis is a way of cell death with lipid peroxides as the core.Cells can reduce ferroptosis sensitivity by relying on glutathione peroxidase 4(GPX4)/glutathione(GSH)antioxidant systems.Triple-negative breast cancer(TNBC)cells are more dependent on the intracellular antioxidant mechanism than normal cells,thus induction of ferroptosis based on the GPX4/GSH system has shown bright anti-TNBC prospects.This paper reviews the recent research on TNBC treatment with ferroptosis in the background of GPX4/GSH,in order to provide references for the clinical treatment of TNBC.

Objective:To summarize the clinical phenotype and genetic characteristics of children with neurodegeneration caused by UBTF gene mutations in childhood. Methods:The clinical and genetic data of 3 children with neurodegeneration in childhood diagnosed in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University from February 2020 to January 2023 were retrospectively analyzed. All the 3 probands were found having UBTF gene mutations through the whole exome gene sequencing, and the first generation Sanger sequencing method was used to verify the UBTF gene in their family members. The variation characteristics of the UBTF gene were analyzed, and the treatment and follow-up results of the 3 children were summarized. Results:Among the 3 children with childhood onset neurodegeneration, 2 were male and 1 female, aged 9 months, 4 years and 6 months after birth, respectively. The clinical phenotypes mainly included motor retardation, speech and mental retardation, and dystonia. Among them, case 1 and case 2 had seizures, case 1 had dysphagia, feeding problems, no weight gain and ataxia. Brain MRI plain scan showed that case 1 and case 2 had different degrees of cerebral atrophy, case 1 had hypoplasia of corpus callosum, ventricle expansion and softening focus, and case 3 showed non-specific widening of the subarachnoid space. There were no abnormalities in the chromosome copy number variation and mitochondrial ring gene testing in the 3 children; the whole exon gene testing suggested the de novo missense variant in the UBTF gene [NM_014233.4: c.1414(exon14) G>A (p.Gly472Ser), c.1392(exon14)G>T(p.Lys464Asn)] and the maternal nonsense variant [NM_014233.4:c.520C>T(p.Arg174 *)], which were unreported site variants. In terms of treatment, the 3 children received comprehensive rehabilitation function training, and achieved a certain degree of language and intelligence improvement. Seizure control was effectively managed in case 1 with a single antiepileptic drug. Epileptic seizures were effectively treated and controlled in case 2 using more than 4 types of antiepileptic drugs. Conclusions:Neurodegenerative changes caused by UBTF gene mutations in childhood are relatively rare, and some cases may be accompanied with brain atrophy. De novo missense variation and maternal nonsense variation of the UBTF gene are the genetic etiology of the 3 probands.

Objective:To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis.Methods:Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups.Results:Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old ( OR=0.54,95% CI 0.30-0.93), tumor lysis syndrome before chemotherapy ( OR=0.48,95% CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy ( OR=0.55,95% CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions:The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.

The growth, differentiation and proliferation of adipose cells run through the whole life process. Dysregulation of lipid metabolism in adipose cells affects adipose tissue immunity and systemic energy metabolism. Increasingly available data suggest that lipid metabolism is involved in regulating the occurrence and development of various diseases, such as hyperlipidemia, nonalcoholic fatty liver disease, diabetes and cancer, which pose a major threat to human and animal health. Hypoxia inducible factor (HIF) is a major transcription factor mediating oxygen receptors in tissues and organs. HIF can induce disease by regulating lipid synthesis, fatty acid metabolism and lipid droplet formation. However, due to the difference of hypoxia degree, time and mode of action, there is no conclusive conclusion whether it has harmful or beneficial effects on the development of adipocytes and lipid metabolism. This article summarizes the regulation of hypoxia stress mediated transcription regulators and regulation of adipocyte development and lipid metabolism, aiming to reveal the potential mechanism of hypoxia induced changes in adipocyte metabolism pathways.
Animals ; Humans ; Lipid Metabolism ; Adipocytes/metabolism* ; Adipose Tissue/metabolism* ; Hypoxia/metabolism* ; Transcription Factors/metabolism*

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread worldwide and threatened human's health. With the passing of time, the epidemiology of coronavirus disease 2019 evolves and the knowledge of SARS-CoV-2 infection accumu-lates. To further improve the scientific and standardized diagnosis and treatment of maternal SARS-CoV-2 infection in China, the Chinese Society of Perinatal Medicine of Chinese Medical Association commissioned leading experts to develop the Recommendations for the Diagnosis and Treatment of Maternal SARS-CoV-2 Infection under the guidance of the Maternal and Child Health Department of the National Health Commission. This recommendations includes the epidemiology, diagnosis, management, maternal care, medication treatment, care of birth and newborns, and psychological support associated with maternal SARS-CoV-2 infection. It is hoped that the recommendations will effectively help the clinical management of maternal SARS-CoV-2 infection.

Drug optimization, which improves drug potency/specificity by structure‒activity relationship (SAR) and drug-like properties, is rigorously performed to select drug candidates for clinical trials. However, the current drug optimization may overlook the structure‒tissue exposure/selectivity-relationship (STR) in disease-targeted tissues vs. normal tissues, which may mislead the drug candidate selection and impact the balance of clinical efficacy/toxicity. In this study, we investigated the STR in correlation with observed clinical efficacy/toxicity using seven selective estrogen receptor modulators (SERMs) that have similar structures, same molecular target, and similar/different pharmacokinetics. The results showed that drug's plasma exposure was not correlated with drug's exposures in the target tissues (tumor, fat pad, bone, uterus), while tissue exposure/selectivity of SERMs was correlated with clinical efficacy/safety. Slight structure modifications of four SERMs did not change drug's plasma exposure but altered drug's tissue exposure/selectivity. Seven SERMs with high protein binding showed higher accumulation in tumors compared to surrounding normal tissues, which is likely due to tumor EPR effect of protein-bound drugs. These suggest that STR alters drug's tissue exposure/selectivity in disease-targeted tissues vs. normal tissues impacting clinical efficacy/toxicity. Drug optimization needs to balance the SAR and STR in selecting drug candidate for clinical trial to improve success of clinical drug development.

Objective:To analyze the prevalence of malnutrition among human immunodeficiency virus-exposed uninfected (HEU) children and to identify the associated factors in Hunan Province.Methods:All children born to human immunodeficiency virus (HIV)-infected mothers retrieved from Information System of Prevention of Mother-to-Child Transmission of human immunodeficiency virus Management (IPMTCT) in Hunan Province between July 2013 and June 2019 were included. Information including maternal demographic characteristic, maternal comorbidities/complications, anti-retroviral therapy during pregnancy, anti-retroviral prophylaxis for children, birth weight, and disease during follow-up was collected. The length and weight of children at one, three, six, nine, 12 and 18 months of follow-up time points were detected, and the prevalences of stunting, underweight, wasting and malnutrition among HEU children were evaluated. The generalized estimating equation was used to fit the logistic regression model to analyze the associated factors for malnutrition.Results:A total of 656 HEU children were finally included. The prevalences of stunting, underweight, wasting, and malnutrition among HEU children were highest at one month of age, which were 11.9%(78/656), 9.1%(60/656), 7.0%(45/656) and 21.0%(138/656), respectively. Maternal comorbidities/complications (adjusted odds ratio (a OR)=2.30, 95% confidence interval ( CI) 1.48 to 3.58), mono/dual anti-retroviral therapy during pregnancy (a OR=2.38, 95% CI 1.54 to 3.68), birth weight <2 500 g (a OR=2.66, 95% CI 1.69 to 4.21) and disease during follow-up (a OR=1.73, 95% CI 1.10 to 2.70) were the risk factors for malnutrition among HEU children (all P<0.050). Both taking zidovudine (a OR=0.60, 95% CI 0.38 to 0.94) and nevirapine (a OR=0.31, 95% CI 0.18 to 0.52) for anti-retroviral prophylaxis were the protective factors for malnutrition among HEU children (both P<0.050). Conclusions:The prevalence of malnutrition among HEU children is high. The prevalence of malnutrition is affected by maternal comorbidities/complications, anti-retroviral therapy during pregnancy, and birth weight, diseases during follow-up and anti-retroviral prophylaxis for children.

Objective:To investigate the effect of placenta previa attached to cesarean scar for adverse pregnant outcomes in patients with or without placenta accreta spectrum disorders (PAS).Methods:The clinical information of patients with cesarean section history and placenta previa during the perioperative period at Peking University First Hospital from January 1st, 2015 to December 31st, 2020 were collected retrospectively. There were 53 cases without PAS and 172 cases with PAS, 153 cases with abnormally invasive placenta (containing placenta increta and placenta percreta) and 72 cases without PAS or with placenta accreta. The pregnant outcomes including rate of postpartum hemorrhage, transfusion, hysterectomy between the above groups were compared. Multivariate analysis was performed to study the factors significantly associated with PAS.Results:Pregnant women with PAS were at higher risk of adverse pregnant outcomes than those without PAS. Patients with PAS had higher incidences of hysterectomy [12.2% (21/172) vs 0(0/53); P=0.005], postpartum hemorrhage [60.5% (104/172) vs 5.7% (3/53); P<0.01] and blood transfusion [66.9% (115/172) vs 7.5% (4/53); P<0.01]. In the subgroup analysis stratified by the type of PAS, patients with abnormally invasive placenta were at higher risk of hysterectomy [13.7% (21/153) vs 0 (0/72); P<0.01], postpartum hemorrhage [66.7% (102/153) vs 6.9% (5/72); χ2 =70.873, P<0.01] and blood transfusion [74.5% (114/153) vs 6.9% (5/72); χ2 =90.869, P<0.01]. After multiple logistic regression, the type of creta had the positive relation with postpartum hemorrhage ( OR=27.622, 95% CI:9.873~77.280; P<0.01) and blood transfusion ( OR=36.912, 95% CI:13.239~102.922; P<0.01). There were no significant correlations between adverse pregnant outcomes and the type of placenta previa or the times of cesarean section (all P>0.01). Conclusions:Placenta previa attached to cesarean scar without PAS or with placenta accreta could not act as the factor of predicting adverse pregnant outcomes in clinic. Placenta previa attached to cesarean scar with placenta increta or placenta percreta could increase the risk of adverse pregnant outcomes.

Objective:To establish a rat model of neurogenic bladder and analyze the changes in kidney morphology and function and the expression of proteins in AngiotensinⅡ(AngⅡ)/transforming growth factor β1 (TGF-β1)/Smads pathway.Methods:Sprague-Dawley rats were randomly divided into experimental group (spinal nerve amputation, n=36) and control group (sham operation, n=12). At 6, 12, and 24 weeks, the bladder compliance was measured by cystometry, the kidney morphology was detected by B-ultrasound, blood urea nitrogen (BUN) and serum creatinine (Scr) in blood samples were examined, the kidney pathological changes were detected by Masson and HE staining, the distribution of AngⅡ/TGF-β1/Smads pathway proteins was analyzed by immunohistochemisty, and the protein expressions in kidney were detected by Western blotting. Results:Urodynamics showed that the basic bladder pressure in experimental group was higher than that in control group. B-ultrasound showed that compared with the control group, the diameter of the renal pelvis of the rats with nerve dissection gradually increased ( P<0.05), and the hydronephrosis was gradually obvious. Compared with the control group, the BUN and Scr in experimental group gradually increased (both P<0.01). Masson and HE staining showed that compared with the control group, the collagen expression and renal tubulointerstitial scores in experimental group were gradually increased (both P<0.01). Immunohistochemisty showed that compared with the control group, in experimental group the expression of angiotensinⅡ receptor type 1 (AT1), TGF-β receptor 1(TGF-βR1), phosphorylated Smad2 gradually increased (all P<0.01), the pathway inhibitor Smad6 gradually decreased ( P<0.01), and the distribution of each protein in kidney was consistent. Western blotting showed a corresponding expression trend with immunohistochemisty. Conclusions:In neurogenic bladder caused by bilateral spinal nerve amputation, due to bladder dysfunction, increased bladder pressure induces hydronephrosis, destruction of the nephron structure, activation of AngⅡ/TGF-β1/Smads pathway, and renal fibrosis. This method is effective and has clinical similarities, laying a foundation for exploring neurogenic bladder treatment.

ObjectiveTo review the efficacy and safety in secondary prevention of ischemic stroke with cilostazol or aspirin.Methodswe searched Cochrane Library(the 4th issue, 2009 ), PubMed(1980.1～2009.11), EMBASE(1980.1～2009.11), CBM(1978.1～2009.11), CNKI(1979.1～2009.11) and some other databases, then collected all of the studies describing the outcomes in curing the ischemic stroke after taking cilostazol or aspirin. According to the strict inclusion and exclusion criteria, two reviewers independently selected trials, extracted datas, made cross-checking and methodological quality assessment of the homogeneity studies by using the Cochrane systematic review methods, then made Meta analysis using RevMan 5.0 software.ResultsThis systematic review study included two randomized controlled trials and a cross-over trial, which contained a total of 838 participants. The evidence quality of one of the randomized controlled trials was high, however, the evidence quality of another randomized controlled trial and the cross-over trial was poor. Meta analysis results suggested that the effectiveness of cilostazol and aspirin in the secondary prevention of ischemic stroke performed no significantly statistical difference: primary endpoint(30 d［RR=3.00, 95%CI(0.31,28.70)］; 90 d［RR=1.67, 95%CI(0.40,6.92)］; 180 d［RR=1.25, 95%CI(0.50, 3.13)］; 360 d［RR=0.65, 95%CI(0.33, 1.29)］; 540 d［RR=0.80,95%CI(0.54, 1.18)］); combined endpoint(30 d［RR=4.00, 95%CI(0.45,35.61)］; 90 d ［RR=1.75,95%CI(0.52,5.93)］; 180 d［RR=1.00, 95%CI(0.48, 2.07)］; 360 d ［RR=0.77, 95%CI(0.45, 1.29)］; 540 d［RR=0.66,95%CI(0.40,1.09)］); the recurrence of ischemic stroke: cilostazol group: RR=0.64, 95%CI(0.31,1.30)，aspirin group: RR=0.21, 95%CI(0.04,1.06); PDMP［RR=1.00, 95%CI(0.39, 2.58)］. But in terms of the probability of intracranial hemorrhage (［RR=7.14, 95%CI(0.7,58.33)］) and other safety standards, taking cilostazol performed lower than taking aspirin.ConclusionThe side effects of cilostazol and aspirin in the treatment for ischemic stroke were similar to each other, but in terms of the probability of dizziness, headache, tachycardia and palpitation, taking cilostazol performed higher than taking aspirin, however, taking cilostazol performed lower in the probability of intracranial hemorrhage and other organ hemorrhage than taking aspirin. Since this study included a small amount of studies, in which the evidence quality of one of the randomized controlled trials and the cross-over study was poor, therefore, it would be necessary to make a further validation with lots of high-quality clinical trials.