Objective To investigate the effect of progesterone receptor membrane component 1(PGRMC1)mediated autophagy on the sensitivity of liver cancer cells to 125I particles irradiation.Methods Hepatoma cell lines Huh7 and LM3 were exposed to different doses(0,2,4,6 and 8 Gy)of 125I particles,and cell autophagy was observed by transmission electron microscopy(TEM).Then,autophagy inhibitor chloroquine(CQ),agonist rapamycin(Rapa),and PGRMC1 inhibitor AG-205 were used respectively to verify that PGRMC1-mediated autophagy plays a key role in the sensitivity of hepatocellular carcinoma cells to 125I particle irradiation.Cell proliferation,colony formation and apoptosis were detected by CCK-8 assay,clonal formation test and flow cytometry,respectively.The expression levels of PGRMC1,microtubule-associated protein light chain 3-Ⅰ(LC3-Ⅰ),LC3-Ⅱ and p62 were detected by Western blotting.Results Different doses of 125I particles irradiation significantly decreased the proliferation and clonogenesis of Huh7 and LM3 cells(P＜0.05),and increased the apoptotic cells(P＜0.01),in a dose-dependent manner.Compared with the 0 Gy group,the ratio of LC3-Ⅱ/LC3-Ⅰ in Huh7 and LM3 cells was obviously increased,and the expression of p62 was significantly down-regulated in the 6 Gy group.The proliferation capacity and clonal formation ability of Huh7 and LM3 cells were decreased significantly,and their apoptotic cells were increased notably in the 6 Gy+CQ group than the 6 Gy group,while the above results were on the contrary in the 6 Gy+Rapa group.The 6 Gy+AG205 group had notably decreased LC3-Ⅱ/LC3-Ⅰ ratio in the Huh7 and LM3 cells,up-regulated p62 expression,reduced cell proliferation capacity and clone formation ability,and enhanced cell apoptosis when compared with the 6 Gy group,and the above results of the 6 Gy+PGRMC1 group were opposite.Conclusion Increment of PGRMC1 induced by 125I irradiation can promote autophagy,increase the proliferation and clonogenesis,and reduce the apoptosis in hepatocellular carcinoma cells.

Objective:To evaluate the efficacy and safety of Xiao′er Huangjin Zhike Granules in the treatment of cough caused by acute bronchitis in children, which is defined in TCM terms as a syndrome of phlegm-heat obstructing the lung.Methods:This was a block-randomized, double-blind, placebo-controlled, multicenter clinical trial.From January 2022 to September 2023, 359 children aged 3 to 7 years old diagnosed as acute bronchitis (lung-obstructing phlegm-heat syndrome) were enrolled from 21 participating hospitals and randomly assigned to the experimental group and placebo group in a 3︰1 ratio, and respectively treated with Xiao′er Huangjin Zhike Granules and its matching placebo.Cough resolution/general resolution rate after 7 days of treatment was used as the primary efficacy outcome for both groups.Results:(1)On the seventh day of treatment, the rate of cough disappearance/basically disappearance in the experimental group and placebo group were 73.95% and 57.61% retrospectively, which had statistically significance ( P=0.001).(2)After 7 days of treatment, the median duration of cough disappearance/basic disappearance were 5 days and 6 days in the two groups , with a statistically significant difference ( P=0.006).The area under the curve of cough symptom severity time was 7.20 ± 3.79 in the experimental group and 8.20±4.42 in the placebo group.The difference between the two groups was statistically significant ( P=0.039).(3) After 7 days of treatment, the difference between TCM syndrome score and baseline was -16.0 (-20.0, -15.0) points in the experimental group and -15.0 (-18.0, -12.0) points in the placebo group, with significant difference between the two groups ( P=0.004).In the experimental group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 49.04%, 28.35%, 16.48% and 6.13% severally; and in the placebo group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 38.04%, 26.09%, 29.35%, and 6.52% separately, which had statistically significant ( P=0.014).(4) There was no significant difference in the incidence of adverse events or adverse reactions during the trial between both groups.Moreover, while adverse reactions in the form of vomiting and diarrhea were occasionally reported, no serious drug-related adverse event or adverse reaction was reported.(5)The tested drug provided good treatment compliance, showing no statistically significant difference from the placebo in terms of compliance rate. Conclusions:Based on the above findings, it can be concluded that Xiao′er Huangjin Zhike Granules provides good safety, efficacy, and treatment compliance in the treatment of cough caused by acute bronchitis, and lung-obstructing phlegm-heat syndrome, in children.

Objective To investigate the effects of banding width on hemodynamic characteristics of pulmonary artery (PA) by constructing pulmonary artery banding (PAB) models with different widths. Methods Based on clinical practice, with the same banding position and degree, computer-aided design (CAD) was utilized to reconstruct three-dimensional PAB models with different banding widths (2, 3, 4, 5 mm). Hemodynamic characteristics of the models with different banding widths, including pressure, streamlines, energy loss, energy efficiency and blood flow distribution ratio, were compared and analyzed through computational fluid dynamics (CFD). Results The pressure of PA decreased significantly, while the change of banding width had no significant effects on the pressure drop level at banding position. With the increase of banding width, the energy loss decreased, and the energy efficiency showed an upward trend. The blood flow of the left PA raised, and the ratio of blood flow distribution between the left PA and right PA increased, with the maximum reaching up to 2.28 : 1. Conclusions The increase of banding width can reduce the energy loss of PA and improve the energy efficiency of blood flow, but it will lead to the imbalance of blood flow distributions between the left and right lungs. Both the balance of blood flow distribution and the energy loss should be considered in choice for banding width of PAB. The virtual design of PAB surgery based on CAD and CFD will assist individualized banding width selection in future.

Objective:To investigate the clinical features of patients with Langerhans cell histiocytosis (LCH), and analyze the association between BRAF V600E mutation status and clinical features. Methods:A retrospective analysis was carried out for the clinical data of 60 patients with LCH at the Department of Pediatric Oncology, Sun Yat-sen Memorial Hospital between April 2013 and December 2019.Among them, 39 patients undertook BRAF V600E mutation testing, which in paraffin-embedded tissue samples were detected by quantitative real-time PCR (qRT-PCR), and in peripheral blood and/or bone marrow were tested by high-throughput sequencing, for analyzing the correlation between BRAF V600E mutation and clinical characteristics of LCH. Results:(1)Clinical characteristics: the age of 60 LCH patients was (4.08±0.45) years, with 43 male cases and 17 female cases.Patients at young age (≤2 years) and with risk organ (RO+ ) and central nervous system (CNS) risk lesions involvement were concentrated in the multisystem involvement (MS) group ( P<0.05). (2)Therapeutic response after induction therapy: the response to induction therapy was achieved in 28 of 60 treated patients (41.7%) and 32 (53.3%) did not.After excluding stratification factors of treatment regimen, MS ( OR=6.855, 95% CI: 2.077-22.622, P=0.002) and the age≤2 years ( OR=4.944; 95% CI: 1.601-15.275; P=0.005) were risk factors in poor chemotherapy response.RO+ ( OR=8.250, 95% CI: 1.617-42.090, P=0.005) was a significant risk factor for a poor chemotherapy response in JLSG-02 treatment group.Differently, RO+ had no dramatic effect on chemotherapy response in CCHG-LCH-2019 treatment group.(3) BRAF V600E mutation: 39 patients were determined BRAF V600E status, with the positive rate of BRAF V600E mutation in paraffin-embedded tissue samples reaching 70.3%(26 cases). BRAF V600E mutation was not associated with early treatment response, age, sex, MS and RO+ ( P>0.05). However, the positive rate of BRAF V600E in children with MS and CNS risk lesions was higher than the controls, with 76.0% (19 cases) vs.57.1% (8 cases) and 74.1% (20 cases) vs.58.3% (7 cases), respectively.Totally, 3 of 8 cases were positive in bone marrow, with 2 cases of MS, and 1 case of multiple bone invasions, and 1 of 5 cases was positive in peripheral blood, with liver and spleen being involved. Conclusions:LCH patients with age≤2 years, MS and RO+ exhibited a poor response to initial treatment, required for more aggressive treatment strategy.Lesion with activating BRAF V600E mutations suggests that LCH is a clonal disorder.There may be great variability between BRAF V600E mutations and MS as well as CNS risk lesions.In the mutation dataset, part of patients had positive BRAF V600E mutations in bone marrow/peripheral blood.This might suggest a different pathogenesis in such patients, has a certain clinical sense in some aspect.

Objective:To study the risk of malnutrition and related factors of cancer patients in community of Shanghai.Methods:From October 2018 to January 2019, four communities, Pengpu New Village Street, Pengpu Town, Jiangning Road Street, and Caojiadu Street, from 14 communities in Jing ′an District, Shanghai City, were selected by using a random cluster sampling method based on the Shanghai Cancer Registration and reporting system. All cases of malignant tumors and benign tumors of the central nervous system were included. A total of 4 396 questionnaires were distributed. After the exclusion of 9 invalid questionnaires, 3 310 valid questionnaires were included with a rate of 99.73%. A self-designed questionnaire was used to collect data including basic demographic characteristics, history of malignant, physical and psychological pain, nutritional demands and cognitive status. Malnutrition Universal Screening Tools (MUST) was used to analyze the nutritional risk of cancer patients in the community. Multivariate logistic regression model was applied to analyze potential factors.Results:Among the 3 310 cancer patients who completed the survey, the average age of study participants was (64.05±13.02), and 1 467 cases (44.32%) were males. The incidence rate of nutritional risk was 12.84% (425/3 310). The result of logistic regression analysis showed that compared with male, other cancer patients and no physical pain, the risk factors of the occurrence of nutritional included: female ( OR=1.53,95% CI:1.23-1.92), head and neck malignant tumors ( OR=1.42,95% CI:1.07-1.90), bronchus/lung malignant tumors ( OR=1.93,95% CI:1.43-2.61), liver, biliary/pancreatic malignant tumors ( OR=2.11,95% CI:1.21-3.65) and upper gastrointestinal malignant tumors ( OR=6.04,95% CI:4.31-8.46), patients with physical pain ( OR=1.39,95% CI:1.02-1.89). Conclusion:Nutritional risk of cancer patients is higher in community of Shanghai. Gender, location of tumors and physical pain are associated with the occurrence of nutritional risk.

Objective:To study the risk of malnutrition and related factors of cancer patients in community of Shanghai.Methods:From October 2018 to January 2019, four communities, Pengpu New Village Street, Pengpu Town, Jiangning Road Street, and Caojiadu Street, from 14 communities in Jing ′an District, Shanghai City, were selected by using a random cluster sampling method based on the Shanghai Cancer Registration and reporting system. All cases of malignant tumors and benign tumors of the central nervous system were included. A total of 4 396 questionnaires were distributed. After the exclusion of 9 invalid questionnaires, 3 310 valid questionnaires were included with a rate of 99.73%. A self-designed questionnaire was used to collect data including basic demographic characteristics, history of malignant, physical and psychological pain, nutritional demands and cognitive status. Malnutrition Universal Screening Tools (MUST) was used to analyze the nutritional risk of cancer patients in the community. Multivariate logistic regression model was applied to analyze potential factors.Results:Among the 3 310 cancer patients who completed the survey, the average age of study participants was (64.05±13.02), and 1 467 cases (44.32%) were males. The incidence rate of nutritional risk was 12.84% (425/3 310). The result of logistic regression analysis showed that compared with male, other cancer patients and no physical pain, the risk factors of the occurrence of nutritional included: female ( OR=1.53,95% CI:1.23-1.92), head and neck malignant tumors ( OR=1.42,95% CI:1.07-1.90), bronchus/lung malignant tumors ( OR=1.93,95% CI:1.43-2.61), liver, biliary/pancreatic malignant tumors ( OR=2.11,95% CI:1.21-3.65) and upper gastrointestinal malignant tumors ( OR=6.04,95% CI:4.31-8.46), patients with physical pain ( OR=1.39,95% CI:1.02-1.89). Conclusion:Nutritional risk of cancer patients is higher in community of Shanghai. Gender, location of tumors and physical pain are associated with the occurrence of nutritional risk.

Objective To investigate the induction and regulatory mechanism of placental trophoblast cell autophagy in women with preeclampsia (PE).Methods Twenty gravidas with severe PE who underwent cesarean section in the Department of Obstetrics and Gynecology of Changzhou Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University from August 2016 to November 2016 were enrolled in PE group.An equal number of normotensive gravidas without proteinuria who also underwent cesarean section during the same period were randomly selected as control group.Placental tissue samples were collected from all gravidas.Ultrastructure of placental trophoblast cells and changes in autophagosome formation were observed by transmission electron microscope.Expressions ofmicrotubule associated protein 1 light chain 3B (MAP1LC3B,or LC3B) and Beclin 1 in placental tissue samples were detected by quantitative real-time polymerase chain reaction (PCR) and Western blot.Activities of protein kinase B (PKB,also known as Akt)/mammalian target of rapamycin (mTOR) pathway in placental tissue samples were detected by Western blot.Two independent samples t-test or Mann-Whitney U test was used for statistical analysis.Results Sparse and disordered villi and many typical autophagosomes were observed in placental trophoblast cells from patients with severe PE.Significantly enhanced expression of LC3B at mRNA and protein levels and increased ratio of LC3-Ⅱ/LC3-Ⅰ were observed in the PE group as compared with the control group [3.37 (2.37-6.11) vs 0.62 (0.25-4.15),1.40±0.17 vs 1.00±0.13,1.57±0.25 vs 1.00±0.31,Zor t=--4.440,3.274 and 3.113,all P＜0.05].No significant difference in the expression ofBeclin 1 at mRNA or protein level in placental tissues was found between the two groups (both P＞0.05).Furthermore,Akt and mTOR phosphorylation in the PE group was significantly suppressed as compared with that in the control group (1.00±0.29 vs 0.64±0.21,1.00±0.32 vs 0.60±0.22,t=--3.672 and-2.895,both P＜0.05).However,the two groups showed no significant difference in the expression of Akt or mTOR protein (both P＞0.05).Conclusions Suppressed activity of Akt/mTOR pathway and enhanced induction of trophoblast cell autophagy are detected in placental tissues of patients with severe PE,indicating that excessive trophoblast cell autophagy,induced by decreased activity of Akt/mTOR pathway,may be the pathogenesis for PE.

Objective To observe the effect of ginkgobalide B (GB) on neurocyte apoptosis and protein kinase B expression in neonatal rats after hypoxic-ischemic brain damage (HIBD).Methods Ninety seven-day-old Sprague-Dawley rats were randomly divided into a sham group,an HIBD group and a GB group,each of 30.HIBD was induced in the HIBD and GB groups using the classical Rice method,while the sham group was given a sham operation.GB (10 mg/kg) was injected intraperitoneally to the rats in the GB group at 0 h and 24 h after the modeling.Then 6 rats were killed 6 h,12 h,24 h and 48 h after the modeling,and the expression of caspase-3 mRNA was detected using a real-time PCR to find the time point of maximum effectiveness.Then to further explore the role of the PI3K-AKT pathway in the anti-apoptosis effect of ginkgolide B,a a GB+LY294002 group of 6 rats,which was injected with PI3K-AKT pathway inhibitor LY294002 (1.8 mg/kg) intraperitoneally at 30 min before the modeling and with GB(10 mg/kg) at 0 h and 24 h after the modeling,was added to the experiment.Hematoxylin-eosin staining,terminal-deoxynucleotidyl transferase-mediated nick end labeling and immunohistochemical staining were then used to observe any morphological changes in the cortex,to detect neuronal apoptosis and to quantify the expression of P-AKT protein.Results The expression of caspase-3 in the HI and GB groups began to increase 6 hours after the HIBD and reached a peak after 24 hours,followed by a gradual decline.The expression of caspase-3 in the GB group was significantly lower than in the HI group throughout,while that of both of those groups was significantly higher than in the sham group.Apoptosis-positive cells and the expression of caspase-3increased had significantly in the HI,GB and GB+LY294002 groups 24 hours after the HIBD compared with the sham group,while the expression of P-AKT protein had decreased significantly.Moreover,the apoptosis-positive cells and the expression of caspase-3 of the HI and GB+LY294002 groups were significantly high-er than those of the GB group,while their expression of P-AKT protein was significantly lower after 24 hours.Conclusion Ginkgobalide B can decrease neurocyte apoptosis caused by hypoxic-ischemic brain damage,especially at 24 h after the damage.The PI3K-AKT signaling pathway plays an important role in this effect.

Objective To observe the effect of the nutrition management according to the JCI(Joint Commission on Accreditation of Healthcare Organizations)management standard for critically ill pediatric patients with mechanical ventilation.Methods A total of 330 cases with mechanical ventilation were en-rolled in the control group from Hunan Province Children's Hospital PICU between Jan.2012 and Dec.2012, and these pediatric patients were managed with the conventional nutrient management.A total of 359 pediatric patients with mechanical ventilation were admitted to the experimental group from Jan.2013 to Dec.2013 and these patients were managed with nutrient management based on JCI standards.The length of mechanical venti-lation,stay in ICU,stay in hospital were compared between two groups,and the incidence of ventilator-associ-ated pneumonia,abandonment rate and mortality were also compared between experimental group and control group.Results The length of mechanical ventilation in control group[(8.39 ±1.34)days]was longer than that of experimental group[(5.69 ±1.12)days].The length of stay in PICU for control group[(12.32 ± 1.37)days]was more than that in experimental group[(9.42 ±1.53)days].The length of stay in hospital for control group [(15.37 ±2.16 )days]was higher than that of experimental group [(12.63 ±2.29 ) days].The incidence of ventilator-associated pneumonia(9.7%)in control group was higher than that of ex-perimental group,and the giving up or mortality rate in control group(8.48%)was higher than that of exper-imental group(4.35%).And there were significant differences by statistical analysis(P ﹤0.01 ,respective-ly).Conclusion According to the nutritional management in JCI standard,the length of mechanical ventila-tion,stay in PICU and stay in hospital time,the incidence of ventilator-associated pneumonia,and the aban-doned or mortality rate were reduced for critically ill pediatric patients with mechanical ventilation.

Objective To detect ED1 gene mutations in the families with X-linked hypohidrotic ec-todermal dysplasia (XLHED). Methods Blood samples were obtained from 2 pedigrees. All 8 exons and flanking intronic boundaries of ED1 gene were amplified with polymerase chain reaction technique and then directly sequenced. Results Two mutations were found in ED1 gene. One was splicing mutation (IVS8+5 del G), the other was missense mutation (A959G). None of the mutations was found in normal individuals of two XLHED families and in 188 unrelated, population-matched control individuals. Conclusion Out of the ED1 gene mutations identified in 2 Chinese XLHED families, IVS8+5del G is a novel mutation.