Antioxidant effect of dimethyl fumarate in pentylenetetrazole-kindled epilepsy mice and is activated by nuclear factor erythroid 2-related factor 2 pathway.

This study was designed to examine the anti-oxidative stress effect of dimethyl fumarate (DMF) on pentylenetetrazole (PTZ)-induced epileptic mice, and to evaluate the correlation of its mechanism with the nuclear factor E2-related factor 2 (Nrf2)-mediated signaling pathway. The experimental mice were separated into three groups: control, model, and DMF groups. Mice in the model group were administered PTZ to establish an epilepsy model, mice in the DMF group were administered DMF concurrently when modeling, and mice in the control group were administered a 0.9% NaCl solution. The latency, severity, and frequency of epileptic seizures in mice after each treatment were recorded, and the modelling success rate was computed at the conclusion of the experiment. The mice were euthanized, their levels of malondialdehyde (MDA), reactive oxygen species (ROS), superoxide dismutase (SOD), 8-hydroxy-deoxyguanosine (8-OHdG), and Nrf2 were measured, and the electron microscope was used to examine the mitochondrial damage of brain tissue. The latency of epileptic seizures was longer in the DMF group compared to the model group (P<0.05). The levels of MDA and ROS in the DMF group were lower than those in the model group (P<0.0001), and the activity of SOD in the DMF group was higher than that in the model group (P<0.0001); however, the levels of MDA and ROS were elevated and the activity of SOD was lower in both groups relative to the control group. The levels of 8-OHdG were lower in the DMF group than the model group (P<0.0001), however, the levels were higher in both groups compared to the control group. Mitochondrial abnormalities were more prevalent in the model group than in the DMF group, and more prevalent in both groups compared to the control group. The DMF group contained more Nrf2 content than the model group (P<0.0001), and both groups contained more Nrf2 than the control group. We concluded that the mechanism by which DMF reduced the level of oxidative stress in epileptic mice might involve the Nrf2-mediated signaling pathway.

Burden and trend of dietary risk-related colorectal cancer in China and its provinces: findings from the Global Burden of Disease Study 2019.

OBJECTIVES: The objective of this experiment was to evaluate the spatial pattern and temporal trend of colorectal cancer (CRC) burden attributed to dietary risk factors in China from 1990 to 2019 using data from the Global Burden of Diseases, Injuries, and Risk Factors study (GBD) 2019. METHODS: Numbers and age-standardised rates of deaths, disability-adjusted life years (DALYs) and corresponding average annual percentage change (AAPC) were determined. The joinpoint regression analysis was used to assess the temporal trends of CRC deaths and DALYs from 1990 to 2019. RESULTS: In China, the number of diet-attributable CRC deaths and DALYs in 2019 were 90.41 (95% uncertainty interval: 65.69, 114.67) and 2234.06 (1609.96, 2831.24) per-1000 population, marking 2.05% and 1.68% annual increases since 1990, respectively. The region with the highest increase in age-standardised rates (ASRs) of diet-related CRC deaths and DALYs was in Taiwan with an AAPC of 2.00% (1.51, 2.48), whereas the highest decline in ASRs of CRC deaths and DALYs was observed in Hong Kong with an AAPC of -0.63% (-0.90, -0.35) (all P < 0.05). Nationally, men suffered higher CRC deaths and DALY burdens attributable to dietary risks than did women. Regarding the specific diet group, diets low in calcium, milk, and whole grains contributed to CRC deaths and DALYs the most. CONCLUSIONS: Diet is an important contributor to increasing CRC burden in China. Necessary measures should be taken to kerb the growing burden attributed to dietary factors, particularly in males and in regions with middle Socio-demographic Index or lower.

Drought priming-induced stress memory improves subsequent drought or heat tolerance via activation of γ-aminobutyric acid-regulated pathways in creeping bentgrass.

Recurrent drought can induce stress memory in plants to induce tolerance to subsequent stress, such as high temperature or drought. Drought priming (DP) is an effective approach to improve tolerance to various stresses; however, the potential mechanism of DP-induced stress memory has not been fully resoved. We examined DP-regulated subsequent drought tolerance or thermotolerance associated with changes in physiological responses, GABA and NO metabolism, heat shock factor (HSF) and dehydrin (DHN) pathways in perennial creeping bentgrass. Plants can recover after two cycle of DP, and DP-treated plants had significantly higher tolerance to subsequent drought or heat stress, with higher leaf RWC, Chl content, photochemical efficiency, and cell membrane stability. DP significantly alleviated oxidative damage through enhancing total antioxidant capacity in response to subsequent drought or heat stress. Endogenous GABA was significantly increased by DP through activating glutamic acid decarboxylase activity and inhibiting GABA transaminase activity. DP also enhanced accumulation of NO, depending on NOS activity, under subsequent drought or heat stress. Transcript levels of multiple transcription factors, heat shock proteins, and DHNs in the HSF and DHN pathways were up-regulated by DP under drought or heat stress, but there were differences between DP-regulated heat tolerance and drought tolerance in these pathways. The findings indicate that under recurrent moderate drought, DP improves subsequent tolerance to drought or heat stress in relation to GABA-regulated pathways, providing new insight into understanding of the role of stress memory in plant adaptation to complex environmental stresses.

[A real-world study on the features of postpartum hepatitis flares in pregnant women with chronic HBV infection].

Objective: To analyze the clinical features of postpartum hepatitis flares in pregnant women with hepatitis B virus (HBV) infection. Methods: A retrospective study was conducted. Patients who met the enrollment criteria were included. Liver function and HBV virology tests were collected from pregnant women with chronic HBV infection at delivery, 6, 24, 36, and 48 weeks after delivery through the hospital information and test system. Additionally, antiviral therapy types and drug withdrawal times were collected. Statistical analysis was performed on all the resulting data. Results: A total of 533 pregnant women who met the inclusion criteria were included, with all patients aged (29.5±3.7) years old. A total of 408 cases received antiviral drugs during pregnancy to interrupt mother-to-child transmission. There was no significant difference in the levels of alanine aminotransferase (ALT, z = -1.981, P = 0.048), aspartate aminotransferase (AST, z = -3.956, P < 0.001), HBV load (z = -15.292, P < 0.001), and HBeAg (z = -4.77, P < 0.001) at delivery in patients who received medication and those who did not. All patients ALT, AST, total bilirubin, direct bilirubin, and albumin showed an upward trend within six weeks after delivery. A total of 231 cases developed hepatitis within 48 weeks after delivery. Among them, 173 cases first showed ALT abnormalities within six weeks postpartum. Conclusion: Hepatitis flare incidence peaked six weeks after delivery or six weeks after drug withdrawal in pregnant women with chronic HBV infection.

[Disease burden of acute viral hepatitis in Guangdong Province, 1990-2019].

Objective: To examine the burden and trends of acute viral hepatitis in Guangdong Province from 1990 to 2019, and provide reference evidences for hepatitis prevention and control in the province. Methods: Data on acute viral hepatitis (hepatitis A, B, C, and E) in Guangdong from 1990 to 2019 were extracted from the Global Burden of Disease Study 2019 database. The incidence, prevalence, mortality, and disability-adjusted life years (DALY) data were analyzed by age and gender, and the estimated annual percentage change (EAPC) was calculated to describe the changing trends in disease burden. Results: From 1999 to 2019, the standardized incidence, prevalence, mortality, and DALY of acute viral hepatitis in Guangdong were higher than the national averages. In 2019, 51.43% (2 245 087/4 365 221) of acute viral hepatitis cases in Guangdong Province were mainly attributed to hepatitis B, and 77.18% (106/138) of deaths were due to acute hepatitis B. In different age groups, except for acute hepatitis B, which was more common in adults, the incidence rates of other types of viral hepatitis such as hepatitis A, B, and E showed an overall decreasing trend with age. The mortality rates of different types of acute viral hepatitis, except for the <5 age group, increased with age. The overall incidence and mortality rates of acute viral hepatitis were higher in men than in women. Conclusions: The overall burden of acute viral hepatitis in Guangdong declined in 2019, but remained higher than the national level. Further efforts are needed to strengthen hepatitis prevention and screening in different population in Guangdong Province, especially in children and the elderly.

[Ophthalmic surgical robot-assisted retinal puncture and injection for submacular hemorrhage caused by polypoid choroidal vasculopathy: a case report].

A 65-year-old man presented with decreased visual acuity in the left eye for 1 month. The diagnosis of hemorrhagic retinal detachment (submacular hemorrhage), which was caused by idiopathic polypoid choroidal vasculopathy, was confirmed by the ultra-wide-angle fundus examination, optical coherence tomography, and B-ultrasound. A vitrectomy combined with an ophthalmic surgical robot-assisted retinal puncture and injection was performed. The recombinant tissue plasminogen activator was injected accurately by the ophthalmic surgical robot between the retinal nerve epithelium and retinal pigment epithelium through a micro-injection needle. During the 2-month follow-up, the subretinal hemorrhage was significantly regressive, the visual acuity of the left eye was improved from hand movement to 0.1, and no other complications were observed.

Season-dependent physiological behavior of Miscanthus x giganteus growing on heavy-metal contaminated areas in relation to soil properties.

Miscanthus x giganteus is often considered as a suitable plant species for phytomanagement of heavy metal polluted sites. Nevertheless, its physiological behavior in response to the level of metal toxicity throughout the growing season remains poorly documented. Miscanthus x giganteus was cultivated on three sites in Belgium (BSJ: non-polluted control; CAR: slightly contaminated; VM strongly polluted by Cd, Pb, Cu, Zn, Ni and As). The presence of Miscanthus improved soil biological parameters assessed by measurement of enzyme activity and basal soil respiration on the three considered sites, although to a lower level on VM site. Heavy metal accumulation in the shoot was already recorded in spring. It displayed a contrasting distribution in the summer leaves since heavy metals and As metalloid accumulated mainly in the older leaves of CAR plants while showing a uniform distribution among leaves of different ages in VM plants. Comparatively to plants growing on BSJ, net photosynthesis decreased in plants growing on CAR and VM sites. The recorded decrease was mainly related to stomatal factors in CAR plants (decrease in stomatal conductance and in Ci) but to non-stomatal factors such as decrease in carboxylation efficiency and non-photochemical quenching in VM plants. Stomata remained open in VM plants which presented lower instantaneous and intrinsic water use efficiencies than CAR and BSJ plants. High proportions of heavy metals accumulated in CAR plants were bound to the cell wall fraction while the soluble and organelle-rich fractions were proportionally higher in VM plants, leading to a decrease in cell viability and cell membrane damages. It is concluded that not only the intensity but also the nature of physiological responses in Miscanthus x giganteus may drastically differ depending on the pollution level.

Effect of PI3K/AKT/HIF-1α signaling pathway on oxidative stress and apoptosis in nucleus pulposus cells.

OBJECTIVE: The aim of the study was to explore the expression of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT)/hypoxia-induced factor-1 alpha (HIF-1α) signaling pathway and the apoptosis of nucleus pulposus cells (NPCs) under different oxygen concentrations to clarify the biological characteristics of NPCs and the molecular mechanism of intervertebral disc degeneration (IVDD). MATERIALS AND METHODS: Normal and degenerated human NPCs were collected. Leibovitz's medium with 100 µmol/L CoCl2 was used to establish a hypoxic culture environment, and 100 µmol/L H2O2 was used to establish an oxidative stress culture environment. Third-generation NPCs were divided into 6 groups: normal NPCs + hypoxia, normal NPCs + normoxia, normal NPCs + oxidative stress, degenerated NPCs + hypoxia, degenerated NPCs + normoxia, and degenerated NPCs + oxidative stress. Normal NPCs + hypoxia was used as the experimental control group. Cell viability and proliferation were detected by using the Cell Counting Kit-8 (CCK-8) method. Cell apoptosis rate was assessed by flow cytometry, and expression levels of PI3K, AKT, and HIF-1α were determined by Real-Time-Polymerase Chain Reaction (RT-PCR) and Western blotting. RESULTS: The cell proliferation rate of both normal and degenerated NPCs decreased with increasing oxygen concentration. Conversely, the apoptosis rate increased as the oxygen concentration increased (p<0.05). Compared with the control group, whether the cells degenerated had a very significant impact on the apoptosis rate (p<0.001), and oxygen concentration also had a highly significant impact on both the cell proliferation rate and apoptosis rate (both p<0.001). The interaction between cell degeneration and oxygen concentration significantly affected both cell proliferation and apoptosis rates (p<0.05). Considering the expression levels of PI3K, AKT, and HIF-1α, normal NPCs had the highest levels under low oxygen concentrations, followed by oxidative stress and normoxia. In degenerated NPCs, the expression levels also decrease as the oxygen concentration increases. CONCLUSIONS: The PI3K/Akt/HIF-1α signaling pathway plays a significant role in inhibiting oxidative stress, antagonizing NPC apoptosis, and consequently delaying IVDD.

[Cardiovascular diseases burden attributed to low physical activity in China, 1990-2019].

Objective: To analyze the burden of cardiovascular disease (CVD) attributed to low physical activity (LPA) and its changing trends in China from 1990 to 2019. Methods: On the basis of the province results of the Study of Global Burden of Disease 2019 in China, we described the distribution of CVD death and disability-adjusted life year (DALY) attributed to LPA by sex, age and province. Joinpoint 4.9.1.0 was used to calculate the average annual percentage change. Results: In 2019, the number of CVD deaths and DALY attributed to LPA in people aged ≥25 years were 0.127 million and 1.863 million person-years in China, respectively, The age-standardized mortality rate (ASMR) and standardized DALY rate of CVD attributed to LPA were slightly higher in men than in women, and much higher in ischemic heart disease patients than in ischemic stroke patients. The ASMR (8.85/100 000) and the standardized DALY rate (112.34/100 000) of CVD attributed to LPA in China in 2019 showed no obvious change compared with 1990, while decreased in the last decade. The largest increases in the mortality rate and DALY rate were observed in people aged ≥75 years from 1990 to 2019 (26.89%, 15.61%), but the mortality rate and DALY rate in people aged 60-74 years showed a decreasing trend. The mortality rate and DALY rate in men aged 25- 44 years showed the largest increases (37.50%, 35.49%), while women aged ≥75 years had the largest increases (31.00%, 18.02%). In 2019, the highest ASMR and standardized DALY rate of CVD attributed to LPA were found in Jilin, Inner Mongolia and Hebei. The largest increases were found in Qinghai (182.41%, 154.70%), Gansu (181.29%, 152.77%), and Chongqing (132.01%, 102.79%) and the largest decreases were found in Beijing (59.11%, 62.09%), Macau (41.89%, 39.37%) and Guangdong (36.93%, 40.72%) from 1990 to 2019. Conclusion: The disease burden of CVD attributed to LPA in China was quite high and showed gender, age and area specific differences.

[Growth rate of adult obesity prevalence in China and target population for prevention and control from 2013 to 2018].

Objective: To investigate the annual growth rate of obesity prevalence of residents aged 18 and above in China and prevention keypoints for target populations from 2013 to 2018. Methods: This was a cross-sectional study. Subjects from China Chronic Disease and Risk Factor Surveillance project in 2013 and 2018 were included. The prevalence of obesity and growth rate in 31 provinces (autonomous regions and municipalities) in China were collected through survey questionnaires and on-site measurements. Other demographic data such as the proportion of obesity control measures, diet, exercise and drug use was also analyzed. Obesity among adults was defined as body mass index≥28.0 kg/m². Results: A total of 174 736 residents, aged (51.5±14.2) years, which included 74 704 (42.8%) males were recruited in 2013, and 179 125 residents, aged (55.1±13.8) years, which included 79 337 (44.3%) males were included in 2018. The average annual increase rate of adult obesity prevalence in China from 2013 to 2018 was 3.2% (uncertainty interval (UI) 2.7%-3.6%), and the average increase rate of obesity prevalence among men (5.2% (UI 4.6%-5.9%)) was higher than that of women (0.9% (UI 0.5%-1.3%)). For subgroups analysis, the average increase rate of obesity prevalence among residents aged 18 to 29 (7.4% (UI 6.9%-7.9%)), education level beyond college degree (6.3% (UI 5.5%-7.1%)), and unmarried population (11.2% (UI 10.2%-12.1%)) were higher than that of other subgroups between 2013 and 2018. The residents in Hainan province showed the highest average annual growth rate of obesity. With the exception of Shanxi, Hunan, Gansu and Ningxia province, the annual growth rate of obesity prevalence among adults increased in all other provinces (autonomous regions and municipalities) from 2013 to 2018. For the obese population, the proportion of people who took weight control measures increased from 22.6% in 2013 to 32.7% in 2018. Conclusions: The prevalence of obesity growth characteristics in subpopulations and regions in China are obviously different. Accordingly the focus points of obesity prevention and control in different regions should have their own emphasis.

Association of the triglyceride-glucose index variability with blood pressure and hypertension: a cohort study.

BACKGROUND: Several studies have indicated that the triglyceride-glucose index (TyG) index is associated with hypertension; however, evidence on the association of change in the TyG index with blood pressure and hypertension is limited. AIMS: To assess the association of the TyG index with blood pressure and hypertension. DESIGN: A cohort study. METHODS: We included 17 977 individuals with a mean age of 60.5 years from the Dongfeng-Tongji cohort. The TyG index was calculated as ln [fasting triglyceride (mg/dl)×fasting glucose (mg/dl)/2]. Hypertension was defined as blood pressure ≥140/90 mmHg, self-reported current use of antihypertensive medication or self-reported physician diagnosis of hypertension. RESULTS: In the longitudinal analyses, we found a linear dose-response relationship between changes in the TyG index and change in blood pressure. Each one-unit change in the TyG index was associated with a 1.93 (1.23-2.63) mmHg increase in systolic blood pressure (SBP) and a 1.78 (1.42-2.16) mmHg increase in diastolic blood pressure (DBP). During a median follow-up of 9.37 years, a total of 3594 individuals were newly diagnosed with hypertension. We also found a linear dose-response relationship between the TyG index and the incidence of hypertension. The hazard ratio (HR) of hypertension for each one-unit increase in the TyG index was 1.21 (1.13-1.29). In addition, the best cut-off point of TyG for predicting hypertension was 8.4797, with sensitivity, and specificity of 57.85% and 55.40%, respectively. CONCLUSIONS: The TyG index had a positive dose-response relationship with blood pressure and could be used to predict the risk of hypertension.

Acupuncture and its ability to restore and maintain immune homeostasis.

Immune homeostasis is a steady immune state that not only protects the host from pathogens but also prevents the emergence of pathological self-reactive immune cells. The disruption of immune homeostasis leads to the development of various diseases, such as cancer and autoimmune diseases. An emerging paradigm for the treatment of these diseases with dysfunctional immune systems is the restoration and maintenance of immune homeostasis. However, currently available drugs exert a unidirectional influence on immunity whereby they either augment or inhibit it. This strategy is associated with the drawback of potential adverse effects arising from uncontrolled activation or suppression of the immune system. Fortunately, evidence suggests that acupuncture can bidirectionally regulate the immune system to maintain immune homeostasis. In cases of immunosuppressive diseases (e.g. cancer), acupuncture has an enhancing effect on immunity. Conversely, in autoimmune diseases (e.g. rheumatoid arthritis), acupuncture has been observed to have an immunosuppressive effect, which helps restore normal immune tolerance. However, there is no publication systematically summarizing the bidirectional regulatory effects of acupuncture on the immune system in the literature. Here, our review provides a comprehensive overview of the various mechanisms through which acupuncture modulates the immune system in a bidirectional manner. These mechanisms include the augmentation of NK and CD8+ T cell function, as well as the restoration of Th1/Th2, Th17/Treg and M1/M2 balance. Thus, we propose the concept that acupuncture has the potential to alleviate illnesses through the facilitation of immune normalization. Moreover, we further highlight the therapeutic potential of acupuncture.

The application of quantitative perfusion analysis of golden-angle radial sparse parallel MRI and R2∗ value for predicting pathological prognostic factors in rectal cancer.

AIM: To investigate the diagnostic value of golden-angle radial sparse parallel magnetic resonance imaging (MRI) (GRASP) and R2∗ in predicting the prognostic factors of resectable rectal cancer. MATERIALS AND METHODS: A total of 108 patients with rectal adenocarcinoma were included in this retrospective study. The volume transfer constant (Ktrans), rate constant (Kep), plasma volume fraction (Ve), and R2∗ were obtained. Univariate and multivariate logistic regression were conducted. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of the imaging parameters. RESULTS: The Ktrans was found to be significantly higher in rectal cancers with positive lymph node metastasis (LNM), higher tumour grade, positive lymphovascular invasion (LVI), and higher ki-67 (all p<0.05). The Kep was also significantly higher in the LNM-positive group (p<0.001), while the R2∗ was higher in rectal cancers with LNM-positive, higher tumour grade, LVI-positive, and higher ki-67 (all p<0.05). Combining the Ktrans and R2∗ provided the highest area under the ROC curve (AUC) for LNM-positive and higher ki-67 tumours differentiation (0.790 and 0.823, respectively). DISCUSSION: Combining quantitative parameters of the Ktrans and R2∗ could be used to non-invasively predict pathological prognostic factors preoperatively.

[Analysis and prediction of burden of viral hepatitis C-associated diseases in China from 1990 to 2044].

OBJECTIVE: To measure the burden of hepatitis C-associated diseases in China from 1990 to 2019, and to predict its changes from 2020 to 2044, so as to provide insights into formulation of the targeted hepatitis C control strategy. METHODS: The total burden due to hepatitis C-associated diseases in China from 1990 to 2019 were extracted from the Global Burden of Disease 2019 (GBD 2019) data resources, and the trends in age-standardized prevalence, incidence, mortality and disability-adjusted life years (DALYs) rate of hepatitis C-associated acute hepatitis C (AHC), chronic liver diseases (CLD) and liver cancer in China from 1990 to 2019 were evaluated in China from 1990 to 2019 using estimated annual percentage change (EAPC). In addition, the changes in the burden of hepatitis C-associated diseases were predicted in China from 2020 to 2044 using a Bayesian model. RESULTS: The prevalence, incidence, mortality and DALY rate of hepatitis C-associated diseases all appeared an overall tendency towards a decline in China from 1990 to 2019 (EAPC = -2.64%, -2.24%, -3.81% and -3.90%, respectively); however, there was a minor rise in the incidence and prevalence of hepatitis C-associated diseases from 2015 to 2019. The overall prevalence of hepatitis C-associated diseases reduced from 2 152.7/105 in 1990 to 1 254.1/105 in 2019 in China, with a reduction of 41.7%. The overall incidence reduced from 87.9/105 in 1990 to 55.0/105 in 2019 in China, with a reduction of 37.4%, and the highest incidence was seen for AHC, followed by CLD and liver cancer. The overall mortality and DALY rate of hepatitis C-associated diseases was 4.0/105 and 100.8/105 in China from 1990 to 2019, with CLD showing the largest contributions to the gross mortality and DALY. The mortality and DALY rate of hepatitis C-associated diseases were 5.5/105 and 142.4/105 among men in China in 2019, which were both much higher than among women (2.8/105 and 60.3/105, respectively), and the overall prevalence (1 604.9/105), mortality (30.2/105) and DALYs (437.1/105) of hepatitis C-associated diseases were all highest among patients at ages of 70 years and older, and the highest incidence was seen among patients at ages of 0 to 9 years (167.3/105). The incidence of hepatitis C-associated diseases was predicted to rise in China from 2020 to 2044; however, the DALY rate was projected to appear a tendency towards a decline. CONCLUSIONS: Although the burden of hepatitis C-associated diseases showed a tendency towards a decline in China from 1990 to 2019, the burden remained high, and was predicted to slightly rise from 2020 to 2044. High attention should be paid to screening of hepatitis C among infants and treatment among adults.

[HIF-1α activation induces cholesterol homeostasis dysfunction to accelerate progression of diabetic nephropathy in rats].

OBJECTIVE: To investigate the effect of hypoxia inducible factor-1α (HIF-1α) activation on cholesterol homeostasis dysfunction in diabetic nephropathy (DN). METHODS: Rat models of type 1 diabetes established by intraperitoneal STZ injection were treated with intraperitoneal injection of Lificiguat (YC-1, a HIF-1α inhibitor). Human proximal tubular cell line HK-2 was incubated with cobalt chloride (CoCl2, 100 µmol/L) in the presence or absence of 30 mmol/L glucose for 24 h. Renal injury of the rats was assessed by measuring 24-h urinary total protein level and PAS staining of the renal tubules. Cholesterol deposition in rat kidneys and HK-2 cells were observed using a quantitative assay of total cholesterol and Filipin staining, and HIF-1α protein expression was detected using Western blotting, immunohistochemistry or immunofluorescence assay; the expressions of cholesterol metabolism-related proteins HMGCR, LDLr, CXCL16 and profibrogenic factors including TGF-ß1 and CTGF were also analyzed. RESULTS: The diabetic rats showed significantly increased 24-h urinary protein level (P<0.001), obvious renal tubular injury, and increased renal cholesterol content (P<0.05) with significantly increased HIF-1α expression in the renal tubular (P<0.01). YC-1 treatment significantly ameliorated tubulointerstitial injury in the diabetic rats as shown by decreased 24-h urinary total protein (P<0.05) and reduced damage area of the tubules, and effectively decreased renal cholesterol levels and renal expression of HIF-1α (P<0.05). In HK-2 cells, CoCl2 stimulation in the presence of high glucose effectively activated HIF-1α expression (P<0.0001), aggravated cholesterol accumulation (P<0.05), and increased the expressions of HMGCR, LDLr, CXCL16, TGF-ß1, and CTGF (P<0.05 or 0.01). Consistent with the in vitro study, YC-1 treatment also significantly decreased the expressions of cholesterol metabolism-related proteins and the profibrogenic factors in the renal tubules of the diabetic rats. CONCLUSION: HIF-1α activation induces cholesterol homeostasis dysregulation possibly by upregulating the de novo synthesis and uptake of cholesterol, thereby aggravating tubulointerstitial injury in DN.

[Diagnosis status and genetic characteristics analysis of Fanconi anemia in China].

Objective: To analyze the clinical and molecular diagnostic status of Fanconi anemia (FA) in China. Methods: The General situation, clinical manifestations and chromosome breakage test and genetic test results of 107 pediatric FA cases registered in the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) and the Chinese Children Blood and Marrow Transplantation Registry Group (CCBMTRG) from August 2009 to January 2022 were analyzed retrospectively. Children with FANCA gene variants were divided into mild and severe groups based on the type of variant, and Wilcoxon-test was used to compare the phenotypic differences between groups. Results: Of the 176 registered FA patients, 69 (39.2%) cases were excluded due to lack of definitive genetic diagnosis results, and the remaining 107 children from 15 hospitals were included in the study, including 70 males and 37 females. The age at transplantation treatment were 6 (4, 9) years. The enrolled children were involved in 10 pathogenic genes, including 89 cases of FANCA gene, 7 cases of FANCG gene, 3 cases of FANCB gene, 2 cases of FANCE gene and 1 case each of FANCC, FANCD1, FANCD2, FANCF, FANCJ, and FANCN gene. Compound heterozygous or homozygous of loss-of-function variants account for 69.2% (72/104). Loss-of-function variants account for 79.2% (141/178) in FANCA gene variants, and 20.8% (37/178) were large exon deletions. Fifty-five children (51.4%) had chromosome breakage test records, with a positive rate of 81.8% (45/55). There were 172 congenital malformations in 80 children.Café-au-Lait spots (16.3%, 28/172), thumb deformities (16.3%,28/172), polydactyly (13.9%, 24/172), and short stature (12.2%, 21/172) were the most common congenital malformations in Chinese children with FA. No significant difference was found in the number of congenital malformations between children with severe (50 cases) and mild FANCA variants (26 cases) (Z=-1.33, P=0.185). Conclusions: FANCA gene is the main pathogenic gene in children with FA, where the detection of its exon deletion should be strengthened clinically. There were no phenotypic differences among children with different types of FANCA variants. Chromosome break test is helpful to determine the pathogenicity of variants, but its accuracy needs to be improved.

[Assessment of risk factors for bronchopulmonary dysplasia with pulmonary hypertension and construction of a prediction nomogram model].

Objective: To explore the risk factors of pulmonary hypertension (PH) in premature infants with bronchopulmonary dysplasia (BPD), and to establish a prediction model for early PH. Methods: This was a retrospective cohort study. Data of 777 BPD preterm infants with the gestational age of <32 weeks were collected from 7 collaborative units of the Su Xinyun Neonatal Perinatal Collaboration Network platform in Jiangsu Province from January 2019 to December 2022. The subjects were randomly divided into a training cohort and a validation cohort at a ratio of 8∶2 by computer, and non-parametric test or χ2 test was used to examine the differences between the two retrospective cohorts. Univariate Logistic regression and multivariate logistic regression analyses were used in the training cohort to screen the risk factors affecting the PH associated with BPD. A nomogram model was constructed based on the severity of BPD and its risk factors,which was internally validated by the Bootstrap method. Finally, the differential, calibration and clinical applicability of the prediction model were evaluated using the training and verification queues. Results: A total of 130 among the 777 preterm infants with BPD had PH, with an incidence of 16.7%, and the gestational age was 28.7 (27.7, 30.0) weeks, including 454 males (58.4%) and 323 females (41.6%). There were 622 preterm infants in the training cohort, including 105 preterm infants in the PH group. A total of 155 patients were enrolled in the verification cohort, including 25 patients in the PH group. Multivariate Logistic regression analysis revealed that low 5 min Apgar score (OR=0.87, 95%CI 0.76-0.99), cesarean section (OR=1.97, 95%CI 1.13-3.43), small for gestational age (OR=9.30, 95%CI 4.30-20.13), hemodynamically significant patent ductus arteriosus (hsPDA) (OR=4.49, 95%CI 2.58-7.80), late-onset sepsis (LOS) (OR=3.52, 95%CI 1.94-6.38), and ventilator-associated pneumonia (VAP) (OR=8.67, 95%CI 3.98-18.91) were all independent risk factors for PH (all P<0.05). The independent risk factors and the severity of BPD were combined to construct a nomogram map model. The area under the receiver operating characteristic (ROC) curve of the nomogram model in the training cohort and the validation cohort were 0.83 (95%CI 0.79-0.88) and 0.87 (95%CI 0.79-0.95), respectively, and the calibration curve was close to the ideal diagonal. Conclusions: Risk of PH with BPD increases in preterm infants with low 5 minute Apgar score, cesarean section, small for gestational age, hamodynamically significant patent ductus arteriosus, late-onset sepsis, and ventilator-associated pneumonia. This nomogram model serves as a useful tool for predicting the risk of PH with BPD in premature infants, which may facilitate individualized early intervention.

[Clinical and etiological characteristics of infectious vulvovaginitis in children in Zhejiang province from 2009 to 2019].

Objective: To explore the clinical characteristics, common pathogens in children with vulvovaginitis. Methods: This was a retrospective cases study. A total of 3 268 children with vulvovaginitis were enrolled, who visited the Department of Pediatric and Adolescent Gynecology, Children's Hospital, Zhejiang University School of Medicine from January 2009 to December 2019. Patients were divided into 3 groups according to the age of <7, 7-<10 and 10-18 years. Patients were also divided in to 4 groups according to the season of first visit. The pathogen distribution characteristics of infective vulvovaginitis were compared between the groups. Their clinical data were collected and then analyzed by χ2 test. Results: The were 3 268 girls aged (6.2±2.5) years. There were 1 728 cases (52.9%) aged <7 years, 875 cases (26.8%) aged 7-<10 years, and 665 cases (20.3%) aged 10-18 years. Of these cases, 2 253 cases (68.9%) were bacterial vulvovaginitis, 715 cases (21.9%) were fungal vulvovaginitis and 300 cases (9.2%) were vulvovaginitis infected with other pathogens. Bacterial culture of vaginal secretions was performed in 2 287 cases, and 2 287 strains (70.0%) of pathogens were detected, of which the top 5 pathogens were Streptococcus pyogenes (745 strains, 32.6%), Haemophilus influenzae (717 strains, 31.4%), Escherichia coli (292 strains, 12.8%), Staphylococcus aureus (222 strains, 9.7%) and Klebsiella pneumoniae (67 strains, 2.9%). Regarding different age groups, H.influenzae was the most common in children under 7 years of age (40.3%, 509/1 263), S.pyogenes (41.9%, 356/849) was predominantly in children aged 7 to 10 years, and E.coli was predominant in children aged 10 to 18 years (26.3%, 46/175). Susceptibility results showed that S.pyogenes was susceptible to penicillin G (610/610, 100.0%), ceftriaxone (525/525, 100.0%), and vancomycin (610/610, 100.0%); the resistance rates to erythromycin and clindamycin were 91.9% (501/545)and 90.7% (495/546), respectively. For H.influenzae, 32.5% (161/496) produced ß-elactamase, and all strains were sensitive to meropenem (489/489, 100.0%) and levofloxacin (388/388, 100.0%), while 40.5% (202/499) were resistant to ampicillin. Among E.coli, all strains were sensitive to imipenem(100%, 175/175). The resistance rates of E.coli to levofloxacin and ceftriaxone were 29.1% (43/148) and 35.1% (59/168), respectively. A total of 48 strains of methicillin-resistant Staphylococcus aureus (MRSA) were isolated with a proportion of 28.3% (45/159) in 3 268 patients. The results of drug susceptibility test showed that all MRSA strains were sensitive to linezolid 100.0% (40/40), vancomycin (45/45, 100.0%), and tigecycline (36/36, 100.0%); the resistance rates of MRSA to penicillin G, erythromycin and clindamycin were 100% (45/45), 95.6% (43/45) and 88.9% (40/45), respectively. All methicillin-sensitive Staphylococcus aureus (MSSA) strains were sensitive to oxacillin (114/114, 100.0%), linezolid (94/94, 100.0%), vancomycin (114/114, 100.0%), and tigecycline (84/84, 100.0%); it's resistance rates to penicillin G, erythromycin and clindamycin were 78.1% (89/114), 59.7% (68/114) and 46.5% (53/114), respectively. The drug resistance rate of MSSA to penicillin G, erythromycin and clindamycin were lower than those of MRSA (χ²=11.71,19.74,23.95, respectively, all P<0.001). Conclusions: The age of consultation for pediatric infectious vulvovaginitis is mainly around 6 years. The most common pathogens are S.pyogenes, H.influenzae and Escherichia coli. Third generation cephalosporins can be used as the first choice of empirical anti-infection drugs. However, the results of drug susceptibility should be considered for targeted treatment.