AIM:To investigate the inhibitory effect of mogroside V(MV)on ferroptosis of human neuroblas-toma SH-SY5Y cells induced by RAS-selective lethal 3(RSL3),and to explore its possible mechanism.METHODS:To establish a model of ferroptosis,the SH-SY5Y cell was induced by RSL3.The cell viability and cellular morphology were determined by MTT assay and inverted microscopy,respectively.The intracellular ferrous ion content was measured by ferrous ion fluorescence probe FerrOrange.Mitochondrial membrane potential(MMP)was detected by mitochondrial red fluorescent probe MitoTracker Red CMXRos.The intracellular and mitochondrial reactive oxygen species(ROS)were de-tected by superoxide anion fluorescent probe dihydroethidium and mitochondrial superoxide red fluorescent probe MitoSOX Red,respectively.The cellular glutathione(GSH)and malondialdehyde(MDA)levels were tested by microplate assay.The protein levels of acyl-coenzyme A synthetase long-chain family member 4(ACSL4),cyclooxygenase-2(COX-2),glu-tathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11)were detected by Western blot.Molecu-lar docking techniques were employed to predict the targeting relations between MV and ACSL4/COX-2/GPX4/SLC7A11.RESULTS:Compared with control group,the SH-SY5Y cell viability,the MMP and the GSH level in RSL3 group were significantly reduced(P<0.01),while the intracellular ferrous ion level,the intracellular and mitochondrial ROS levels and the MDA level were significantly increased(P<0.05 or P<0.01).The protein levels of ACSL4 and COX-2 in RSL3 group were significantly increased,while the protein levels of GPX4 and SLC7A11 were significantly decreased(P<0.01),indicating the establishment of cell ferroptosis model.Compared with RSL3 group,the viability of SH-SY5Y cells,the MMP,the GSH level,and the GPX4 and SLC7A11 protein levels in RSL3+MV groups were significantly in-creased(P<0.05 or P<0.01),while the intracellular ferrous ion level,the intracellular and mitochondrial ROS levels,the MDA level,and the ACSL4 and COX-2 protein levels were significantly decreased(P<0.05 or P<0.01).The binding sites between MV and ferroptosis core proteins(ACSL4,COX-2,GPX4 and SLC7A11)were found by molecular docking.CONCLUSION:Treatment with MV alleviates RSL3-induced ferroptosis of SH-SY5Y cells,and the underlying mecha-nism may be associated with the activation of SLC7A11/GPX4 and the inhibition of ACSL4/COX-2.

Objective:To investigate the surgical situations and perioperative outcome of pancreaticoduodenectomy in Jiangsu Province and the influencing factors for postoperative 90-day mortality.Methods:The retrospective case-control study was conducted. The clinicopathological data of 2 886 patients who underwent pancreaticoduodenectomy in 21 large tertiary hospitals of Jiangsu Quality Control Center for Pancreatic Diseases, including The First Affiliated Hospital of Nanjing Medical University, from March 2021 to December 2022 were collected. There were 1 732 males and 1 154 females, aged 65(57,71)years. Under the framework of the Jiangsu Provincial Pancreatic Disease Quality Control Project, the Jiangsu Quality Control Center for Pancreatic Diseases adopted a multi-center registration research method to establish a provincial electronic database for pancrea-ticoduodenectomy. Observation indicators: (1) clinical characteristics; (2) intraoperative and post-operative conditions; (3) influencing factors for 90-day mortality after pancreaticoduodenectomy. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(IQR), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers or constituent ratio, and comparison between groups was conducted using the chi-square test, continuity correction chi-square test and Fisher exact probability. Maximal Youden index method was used to determine the cutoff value of continuous variables. Univariate analysis was performed using the corresponding statistical methods based on data types. Multivariate analysis was performed using the Logistic multiple regression model. Results:(1) Clinical characteristics. Of the 2 886 patients who underwent pancreaticoduodenectomy, there were 1 175 and 1 711 cases in 2021 and 2022, respectively. Of the 21 hospitals, 8 hospitals had an average annual surgical volume of <36 cases for pancreaticoduodenectomy, 10 hospitals had an average annual surgical volume of 36-119 cases, and 3 hospitals had an average annual surgical volume of ≥120 cases. There were 2 584 cases performed pancreaticoduodenectomy in thirteen hospitals with an average annual surgical volume of ≥36 cases, accounting for 89.536%(2 584/2 886)of the total cases. There were 1 357 cases performed pancrea-ticoduodenectomy in three hospitals with an average annual surgical volume of ≥120 cases, accounting for 47.020%(1 357/2 886) of the total cases. (2) Intraoperative and postoperative conditions. Of the 2 886 patients, the surgical approach was open surgery in 2 397 cases, minimally invasive surgery in 488 cases, and it is unknown in 1 case. The pylorus was preserved in 871 cases, not preserved in 1 952 cases, and it is unknown in 63 cases. Combined organ resection was performed in 305 cases (including vascular resection in 209 cases), not combined organ resection in 2 579 cases, and it is unknown in 2 cases. The operation time of 2 885 patients was 290(115)minutes, the volume of intra-operative blood loss of 2 882 patients was 240(250)mL, and the intraoperative blood transfusion rate of 2 880 patients was 27.153%(782/2 880). Of the 2 886 patients, the invasive treatment rate was 11.342%(327/2 883), the unplanned Intensive Care Unit (ICU) treatment rate was 3.087%(89/2 883), the reoperation rate was 1.590%(45/2 830), the duration of postoperative hospital stay was 17(11)days, the hospitalization mortality rate was 0.798%(23/2 882), and the failure rate of rescue data in 2 083 cases with severe complications was 6.529%(19/291). There were 2 477 patients receiving postoperative 90-day follow-up, with the 90-day mortality of 2.705%(67/2477). The total incidence rate of complication in 2 886 patients was 58.997%(1 423/2 412). The incidence rate of severe complication was 13.970%(291/2 083). The comprehensive complication index was 8.7(22.6) in 2 078 patients. (3) Influencing factors for 90-day mortality after pancreaticoduodenectomy. Results of multivariate analysis showed that age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment were independent risk factors for 90-day mortality after pancreaticoduodenectomy ( odds ratio=2.403, 2.609, 16.141, 95% confidence interval as 1.281-4.510, 1.298-5.244, 7.119-36.596, P<0.05). Average annual surgical volume ≥36 cases in the hospital was an independent protective factor for 90-day mortality after pancreaticoduodenectomy ( odds ratio=0.368, 95% confidence interval as 0.168-0.808, P<0.05). Conclusions:Pancreaticoduodenectomy in Jiangsu Province is highly con-centrated in some hospitals, with a high incidence of postoperative complications, and the risk of postoperative 90-day mortality is significant higher than that of hospitallization mortality. Age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment are independent risk factors for 90-day motality after pancreaticoduodenectomy, and average annual surgical volume ≥36 cases in the hospital is an independent protective factor.

Objective:To analyze the clinical characteristics and risk factors of ischemic stroke in young adults.Methods:A retrospective analysis was conducted on 80 ischemic stroke patients (age ≤45 years) admitted to Beijing Tiantan Hospital from March 2019 to October 2019 as the young stroke group, and 117 ischemic stroke patients (age >45 years) hospitalized during the same period as the middle-aged and elderly stroke group. The blood test indexes of the two groups were compared, and the risk factors related to stroke, including smoking history, drinking history, hypertension, hyperlipidemia and diabetes history, were compared and analyzed. Two sets of independent sample t-test, Mann-Whitney U-test or χ2 test were used to compare the above indicators of patients in the two groups. Results:The activated partial prothrombin time, protein S, uric acid, homocysteine and D-dimer levels in middle-aged and elderly stroke group were (29.73±3.40) s, (105.58±27.23) %, (297.29±85.99) μmol/L, (17.58±14.45) μmol/L and (2.75±3.08) mg/L, respectively. Compared with the middle-aged and elderly stroke group, the young stroke group had higher activated partial thrombin time (31.51±6.75) s, protein S (115.20±26.97) %, uric acid (326.82±93.51) μmol/L, homocysteine (22.63±16.98) μmol/L and lower D dimer level of (1.19±2.88) mg/L compared with the elder group, the difference between the two groups was statistically significant ( t values were 2.17, 2.01, 2.20, 2.14 and 2.13, respectively, P values were 0.032, 0.046, 0.029, 0.039 and 0.034, respectively). The positive rate of lupus anticoagulant in young stroke group was 12.5% (4/32), which was higher than 1.8% (1/57) in middle-aged and elderly stroke group, and there was significant difference between the two groups (χ 2=4.46, P=0.035). The proportions of smoking and drinking in young stroke group were 63.8% (51/80) and 62.5% (50/80), respectively, which were higher than 49.6% (58/117) and 47.9% (56/117) in middle-aged and elderly stroke group, and there was significant difference between the two groups (χ 2 values were 3.86 and 4.09; P values were 0.04 and 0.04). The proportion of hypertension and diabetes in young stroke group was 48.8% (39/80) and 17.5%(14/80), respectively, which were lower than 63.2%(74/117) and 30.8%(36/117) in middle-aged and elderly stroke group, and there was significant difference between the two groups (χ 2 values were 4.08 and 4.56; P values were 0.043 and 0.033). According to the levels of uric acid and homocysteine, young stroke was divided into different subgroups and compared.The creatinine level of high uric acid group (≥416 μmol/L) was (90.08±28.46) mmol/L, which was higher than that of normal uric acid group (<416 μmol/L) of (63.37±22.2) mmol/L. There was significant difference between the two groups ( t value was 2.23, P value was 0.046). The levels of fibrinogen and creatinine in high homocysteine group (≥15 μmol/L) were (3.27±1.09) g/L and (72.13±28.69) mmol/L, respectively which were significantly higher than those in normal homocysteine group (<15 μmol/L) of (2.78±0.67) g/L and (58.92±12.08) mmol/L, There was significant difference between the two groups (the t values were 2.32 and 2.51; P values were 0.023 and 0.014). Conclusions:Compared with middle-aged and elderly stroke, young ischemic stroke has higher levels of prothrombin time, protein S, uric acid and homocysteine, lower levels of D dimer and higher positive rate of lupus anticoagulant. At the same time, the proportion of smoking and drinking was higher in young stroke group, but the proportion of hypertension and diabetes was relatively lower.

OBJECTIVE: To explore the clinical and genetic characteristics of a child featuring developmental delay. METHODS: The child was subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing. RESULTS: Whole genome sequencing revealed that the child has carried compound heterozygous variants c.2607-1G>C and c.899 + 2dupT of the RAB3GAP1 gene, which were respectively derived from her mother and father. CONCLUSION A rare case of Warburg micro syndrome type 1 was diagnosed. The phenotype of the child was consistent with the literature, in addition with dysplasia of palatine arch, prominent high palatal arch and tooth dysplasia. Above finding has provided a basis for genetic counseling and prenatal diagnosis for the family.
Abnormalities, Multiple/genetics* ; Adult ; Cataract/genetics* ; Child ; Cornea/abnormalities* ; Female ; Humans ; Hypogonadism/genetics* ; Intellectual Disability/genetics* ; Male ; Microcephaly/genetics* ; Mutation ; Optic Atrophy/genetics* ; Whole Exome Sequencing ; rab3 GTP-Binding Proteins/genetics*

In order to enhance the comprehensive ability,scientific research consciousness and scientific research skills of laboratory medicine students,the clinical laboratory center of Beijing Children's Hospital carried out the exploration for strengthening the scientific research ability of laboratory medicine students in the implementation of scientific research projects.Depending on the platform of National Center for Children's Health,the clinical laboratory center of Beijing Children's Hospital used patient resources and top research facilities to provide comprehensive trainings for students who volunteered to take part in this project with the goal of offering more opportunities for further study and employment to them.Teachers can impart the ideas,thoughts and skills of scientific research to the students through the training,which can help them to improve their core competitiveness by combining the theoretical knowledge and practical work,developing the innovative thinking and improving the ability in scientific research innovation and practice.

Objective To detect and analyze the percentages of CD4+T, CD8+T and invariant na-ture killer T ( iNKT) cells as well as iNKT subsets in different tissues and organs of non-obese diabetic (NOD)/LtJ mice before the onset and in the early and late stages of type 1 diabetes (T1D) for better under-standing the immune function in different disease stages. Methods Female NOD/LtJ mice were selected as experimental subjects. Their fasting blood glucose levels were measured by blood glucose meter. Glycosuria and blood glucose level ≥11. 1 mmol/L in two consecutive detections were used as the diagnostic criteria of T1D. These mice were divided into three groups as follows: non-onset, early stage and late stage groups. Changes in food and water intake, glucose level in the urine, body weight, mental state, fur color and urine volume were recorded. Percentages of CD4+T, CD8+T and iNKT cells and ratios of subsets in peripheral blood, thymus, spleen, liver and inguinal lymph nodes were detected by flow cytometry (FACS). Results (1) Compared with the non-onset and the early stage groups, mice in the late stage group were apathetic and had rough hair. Moreover, significantly increased water and food intake and urine output (P<0. 05) and de-creased body weight, thymus index, spleen index and the absolute lymphocyte counts of spleen, liver and thymus (P<0. 05) were observed in the late stage group. (2) Compared with the non-onset group, the early stage group showed significantly increased percentages of CD4+T cells in spleen, liver, thymus and inguinal lymph nodes (P<0. 05). Compared with the early stage group, the late stage group showed decreased per-centages of CD4+T cells in liver, thymus, inguinal lymph nodes and peripheral blood (P<0. 05). Compared with the non-onset group, the percentages of CD8+T cells in the early stage group were significantly increased in spleen and thymus, but reduced in inguinal lymph nodes (P<0. 05). Compared with the early stage group, the percentages of CD8+T cells in late stage group were significantly reduced in liver and thymus, but increased in inguinal lymph nodes (P<0. 05). (3) The percentages of iNKT cells in liver and inguinal lymph nodes of mice in the early stage group were significantly higher than those of the non-onset group (P<0. 05). The percentages of iNKT cells in peripheral blood and liver of mice in the late stage group were sig-nificantly lower than those of the early stage group (P<0. 05). No significant difference in the percentages of iNKT cells in spleen and thymus was found among the three groups (P>0. 05). (4) Compared with the non-onset group, the percentages of iNKT1 subset in thymus in the early and late stage groups were significantly increased, while the percentages of iNKT2 subset were significantly decreased (P<0. 05). No significant difference in the percentages of iNKT1 and iNKT2 subsets in spleen, liver and inguinal lymph nodes was found among the three groups (P>0. 05). (5) The percentages of iNKT2 subset in spleen, liver and ingui-nal lymph nodes were significantly lower than those of the iNKT1 subset in the three groups (P<0. 05). The percentage of iNKT2 subset in thymus was significantly higher than that of iNKT1 subset in the non-onset group (P<0. 05). (6) Compared with the non-onset and the late stage groups, the early stage group showed significantly increased levels of IFN-γ, IL-4 and IL-17A and up-regulated ratio of IFN-γ/IL-4 (P<0. 05). Compared with the non-onset and the early stage groups, the late stage group showed significantly increased IL-6 level (P<0. 05). Compared with the non-onset group, IL-10 level in the other two groups was in-creased, especially in the late stage group (P<0. 05). No significant difference in IL-2 level was found among the three groups (P>0. 05). Conclusion Increased percentages of iNKT cells and iNKT1 subset in NOD/LtJ mice with early stage of T1D might be involved in the development of T1D.

The common negative pressure drainage bottle used in the vacuum sealing drainage (VSD) cannot quantitative and automatically cut off. Excessive drainage damages the negative pressure source, causes drainage interruption, so once drainage was continuously performed, medical staff need to closely observe drainage bottle calibration. It was also important to known whether there was a large amount of fresh blood sucked out during continuous drainage because it could lose too much blood. To solve these two problems, we designed a kind of negative pressure drainage device, which volume was constant, with the function of automatic cutting off continuous drainage. It can not only prevent drainage fluid flowing back to the negative pressure source and cause drainage interruption, but also prevent massive blood loss from continued drainage after the hemorrhage. We could benefit from this device, which possess many advantages, such as simple structure, security and reliability. It is worthy promoting in the clinical work.

Objective To evaluate the effects of individual extralevator abdominalperineal excision (ELAPE) for rectal neoplasms below levator hiatus on pelvic floor by finite element analysis. Methods MIMICS 10.01, GeoMagic Studio 12 and ANSYS Workbench 14.0 were used to deal with magnetic resonance data of 27 healthy nulliparous volunteers'pelvic, and then three types of finite element models were developed:intact models, ELAPE models and individual ELAPE models. The maximum stress in non levator ani tissue under the same load were measured in three types of models, and levator ani 's maximal stresses were measured in intact model and individual ELAPE and their stress distributions under the same pressure were analyzed and compared. Results The maximal stresses of non-levator ani tissue were (1.963±0.061) MPa, (5.127±0.070) MPa and (4.703±0.110) MPa for intact model, ELAPE model and individual ELAPE model respectively. The maximal stress was lower in individual ELAPE model than that in ELAPE model, but which was higher than that of intact model (P<0.01). The high-stress zone was found at the joints with surrounding structures on both sides of intact model and ELAPE model. The high-stress zone was found in front of the joints with surrounding structures on both sides in individual ELAPE model. The maximal stresses of three types of models were found in front of both sides. In intact model levator ani 's maximal stress was (0.812 ± 0.042) MPa, which was higher than that of individual ELAPE model (0.719 ± 0.027) MPa (P<0.01). The high-stress zone of intact model was found in front of the joints on both sides. The maximal stress was showed at ventral ends on both sides. For the individual ELAPE model the high-stress zone was found at the anterior part of the levator ani muscle and the surrounding structure. The maximum stress appeared at the top end of the left and right sides. Conclusion This individual ELAPE is able to decrease the stress of non-levator ani tissue, which suggests that the risk of postoperative pelvic floor hernia is relatively reduced.

Objective:To evaluate the effects of individual extralevator abdominoperineal excision (ELAPE) of rectal neoplasms in the low posterior wall on the pelvic floor by finite element analysis. Methods:MIMICS 10.01, Geo Magic Studio 12, and ANSYS Workbench 14.0 were used to analyze the magnetic resonance data obtained from the pelvic region of 27 healthy nulliparous volunteers. Three types of finite element models (intact model, ELAPE model, and individual ELAPE model) were developed. The maximal stress on non levator ani tissues were analyzed using the three models, while the maximal stress on levator ani tissues were analyzed using the in-tact model and the individual ELAPE model. Their stress distributions under the same pressure were analyzed and compared. Results:The maximal stress on non levator ani tissues obtained using the intact model, ELAPE model, and individual ELAPE model were (1.963± 0.061), (5.127 ± 0.070), and (3.667 ± 0.126) MPa, respectively, with P<0.01. High-stress zones were obtained at the joints with pelvic walls on both sides using the three models, while the maximal stresses were obtained at the joints with pubis on both sides. The maxi-mal stress on levator ani tissues obtained using the intact model and individual ELAPE model were (0.812 ± 0.042) MPa and (1.437 ± 0.043) MPa, respectively. Thus, the individual ELAPE model yielded higher values of maximal stress compared to the intact model. Both models generated high-stress zones at the joints with tendinous arch of levator ani tissues on both sides, and maximum stresses at the joints with pubis on both sides. Conclusion:Individual ELAPE decreases the stress on non levator ani tissues. This suggests that the risk of postoperative pelvic floor hernia is relatively reduced.

OBJECTIVETo compare the effects between moxibustion at Guanyuan (CV 4), Shenshu (BL 23), Zusanli (ST 36) and western medication on immune function in children with cerebral palsy.

METHODSA total of 230 children with cerebral palsy were randomly divided into an observation group and a control group, 115 cases in each one. Patients in the observation group were treated with warm moxibustion at Guanyuan (CV 4), Shenshu (BL 23) and Zusanli (ST 36). Patients in the control group were treated with oral administration of pidotimod 10 mL every time. The treatment was given once a day, and 30 days were considered as one session for total 90 days. The changes of T-lymphoctyte subgroups, serum immunoglobulin and development quotient were compared 30 days, 60 days and 90 days into treatment respectively; also the occurrence rate.of disease was observed during 6-month and 12-month follow-up visit.

RESULTSThe T-lymphoctyte subgroups (CD3+, CD4+, CD4+/CD8+), serum immunoglobulin (IgG, IgA) and development quotient were significantly improved 30 days, 60 days and 90 days into treatment (P < 0.01, P < 0.05). Regarding the changes of CD3+, CD4+, CD4+/CD4+, IgG, IgA and development quotient, the control group was superior to the observation group 30 days into treatment (all P < 0.05), and the control group was similar to the observation group 60 days into treatment (all P > 0.05), and the observation group was superior to the control group 90 days into treatment (all P < 0.05). There was no significant difference of CD8+ and IgM before and after treatment in two groups (all P > 0.05). The rate of adverse events was 7.0% (8/115) in the observation group, which was lower than 23.5% (27/115) in the control group (P < 0.01); during 6-month and 12-month follow-up visit, the occurrence rate of disease in the observation group was lower than that in the control group (P < 0.05).

CONCLUSIONMoxibustion at Guanyuan (CV 4), Shenshu (BL 23) and Zusanli (ST 36) can improve immune function of children with cerebral palsy, which is superior to pidotimod.

Acupuncture Points ; Cerebral Palsy ; immunology ; therapy ; Child, Preschool ; Female ; Humans ; Immunoglobulin A ; immunology ; Immunoglobulin G ; immunology ; Infant ; Male ; Moxibustion ; T-Lymphocyte Subsets ; immunology ; Treatment Outcome