BACKGROUND:Autophagy,as a key regulatory mechanism of cell development,plays an important role in different stages of embryonic development.The mechanism of how autophagy regulates embryonic development through histone modifications is currently unclear.OBJECTIVE:To investigate the effect of autophagy on trimethylation of lysine 4 on histone H3(H3K4me3)modification in embryos and its effect on embryonic development.METHODS:Mouse fertilized eggs were divided into control and autophagy inhibitor-treated groups(chloroquine phosphate-treated group and 3-methyladenine-treated group),and cultured in vitro to different periods of time,and were then classified as early 2-cell embryos,middle 2-cell embryos,late 2-cell embryos,4-cell embryos,8-cell embryos,morula stage,and blastocyst stage.Levels of reactive oxygen species,autophagy marker proteins LC3B and P62,DNA loss marker γH2AX,and H3K4me3 were analyzed by immunofluorescence assay in late 2-cell embryos of each group.Changes in H3K4me3 modification in late 2-cell embryos of each group were detected by CUT&Tag.RESULTS AND CONCLUSION:(1)Autophagy inhibition caused embryo development arrest.(2)There was no significant difference in reactive oxygen species and γH2AX between the autophagy inhibitor-treated groups and control group.(3)H3K4me3 levels were significantly elevated in the autophagy inhibitor-treated group compared with the control group.(4)CUT&Tag results showed a significantly increased H3K4me3 peaks on the proximal promoter region of the genes after autophagy inhibition and an increase of H3K4me3-specific modification genes.These findings suggest that autophagy may affect embryonic development by regulating the level of H3K4me3 modification.

BACKGROUND:Autophagy,as a key regulatory mechanism of cell development,plays an important role in different stages of embryonic development.The mechanism of how autophagy regulates embryonic development through histone modifications is currently unclear.OBJECTIVE:To investigate the effect of autophagy on trimethylation of lysine 4 on histone H3(H3K4me3)modification in embryos and its effect on embryonic development.METHODS:Mouse fertilized eggs were divided into control and autophagy inhibitor-treated groups(chloroquine phosphate-treated group and 3-methyladenine-treated group),and cultured in vitro to different periods of time,and were then classified as early 2-cell embryos,middle 2-cell embryos,late 2-cell embryos,4-cell embryos,8-cell embryos,morula stage,and blastocyst stage.Levels of reactive oxygen species,autophagy marker proteins LC3B and P62,DNA loss marker γH2AX,and H3K4me3 were analyzed by immunofluorescence assay in late 2-cell embryos of each group.Changes in H3K4me3 modification in late 2-cell embryos of each group were detected by CUT&Tag.RESULTS AND CONCLUSION:(1)Autophagy inhibition caused embryo development arrest.(2)There was no significant difference in reactive oxygen species and γH2AX between the autophagy inhibitor-treated groups and control group.(3)H3K4me3 levels were significantly elevated in the autophagy inhibitor-treated group compared with the control group.(4)CUT&Tag results showed a significantly increased H3K4me3 peaks on the proximal promoter region of the genes after autophagy inhibition and an increase of H3K4me3-specific modification genes.These findings suggest that autophagy may affect embryonic development by regulating the level of H3K4me3 modification.

Objective To analyze the coding quality of multiple primary malignant tumors in a tertiary hospital,identify existing problems,and improve the accuracy of coding for multiple primary malignant tumors.Methods We collected 393 medi-cal records from a tertiary hospital from June 1,2021,to June 30,2023,with ICD-10 code C97 for the discharge diagnosis.By carefully reading the medical records,we analyzed the reasons for coding errors in multiple primary malignant tumors with code C97.Results Among the 393 medical records,there were 34 cases with coding errors in C97,including 11 cases where meta-static malignant tumors were erroneously coded as multiple primary malignant tumors,9 cases where malignant tumors of the same organ system with non-adjacent sites and the same histological type were erroneously coded as multiple primary malignant tumors,7 cases where distant metastasis or local invasion was erroneously coded as multiple primary malignant tumors,4 cases where be-nign tumors were mistakenly coded as malignant tumors,and 3 cases where suspected malignant tumors were coded as confirmed cases.Conclusion To improve the quality and efficiency of C97 coding,coders need to have a clear understanding of the defini-tion of multiple primary malignant tumors,read the medical records carefully and completely,determine the location and histolog-ical type of the tumors accurately,and strengthen communication with clinical physicians.

Coding malignant tumors in multiple sites within the digestive system involves some coding rules.When more than two malignant tumors present various pathologic types,they should be included in the code of C97,which indicates multiple primary malignancies,and should be categorized into a specific code under the category of C97 upon corresponding treatment pur-poses.For those malignant tumors in the digestive system presenting with the same pathological results but unidentified primary sites,which are diagnosed as more than two types of tumors and recorded on the first page of a medical record,they are coded ac-cording to their specific locations.The coding principles are as followed:① If a malignant tumor spans two or more adjacent sites with an unidentified primary origin,it should be classified as a cross-site malignant tumor and coded based on the tumor's ana-tomical location.② If more than two malignant tumors are located in the separate parts of the same location,they should be co-ded with".9"as a subheading of the three-digit category specific to the right location.③If more than two malignant tumors are not adjacent to each other in the digestive system,they should be classified to the code of C26.9.In the process of coding,cod-ers should review case data thoroughly,enhance the accumulation of clinical knowledge,and strengthen communications with doc-tors,thereby enhancing coding precision.

Performance appraisal of public hospitals have given a guidance for the development of public hospitals at all levels.A Class A tertiary hospital reviewed the problems in the development of the hospital at the present stage and focused on the following four aspects:①insufficient fine management;②No clear orientation of discipline development;③The bottleneck of the improvement of medical operation efficiency;④New challenges in the reform of payment mode.The tertiary hospital launched a fine management practice in May 2022,in order to solve the problems by taking the Department of Surgery as a pilot area,laying the foundation for fine management through information system construction,improving the efficiency of medical operation through management process optimization,improving the overall competitiveness of disciplines through the construction of sub-specialty and Discipline Alliance and adjusting the performance appraisal index system to play the role of performance incentives.The measures effectively improve the overall capacity and efficiency of hospital medical services and help the hospital to achieve high-quality development.

Objective:To explore the current situation of nursing human caring in hospital wards and analyze its influencing factors, so as to facilitate the development of nursing human caring practice.Methods:From July to November 2022, a total of 107 hospitals were surveyed through stratified convenience sampling method, and 4 072 ward nursing managers were recruited to finish the general information questionnaire and the ward nursing human caring status questionnaire. The general information included the region, class and type of the hospital, etc. The ward nursing human caring status questionnaire included 38 items in 5 dimensions of nursing human caring system and process, humanistic quality and training of nursing staff, humanistic environment and facilities, human caring procedures and measures, and human caring quality evaluation and improvement, with a full score of 190 points. Descriptive statistics were used to analyze the general data, independent samples t-test, ANOVA and correlation analysis were used to analyze the factors influencing the current status of nursing human caring in the ward, while multiple linear regression analysis was used to conduct a multivariate analysis. Results:The score of nursing human caring in hospital wards was 156.91±27.78. Whether the hospital had carried out nursing human caring pilot(demonstration) wards, whether the ward had previously been a hospital nursing human caring pilot(demonstration) nursing unit, the type of ward, and whether nursing managers had participated in human caring training were the influencing factors of the implication of nursing humanistic caring in wards( P<0.05). Conclusions:The practice of nursing human caring in hospital wards is at a good level, but needs to be further strengthened. Nursing managers should take systematically strategies to promote the development of nursing human caring practice.

ObjectiveTo investigate the expression and role of response gene to complement 32 （RGC32） in liver regeneration after partial hepatectomy （PH）. MethodsA total of 42 male C57BL/6 mice， aged 10 weeks， were randomly divided into control group， postoperative day 1 group （1－d group）， postoperative day 2 group （2－d group）， postoperative day 4 group （4－d group）， postoperative day 6 group （6－d group）， postoperative day 8 group （8－d group）， and postoperative day 10 group （10－d group）， with 6 mice in each group. In the control group， the complete liver of the mice was resected for weighing and photography as the normal control group （sham group）； further， the left and middle lobes of the liver were resected for weighing and photography as the surgical control group （0－day group）； the sham group and the 0－day group shared the same group of mice. After successful modeling by PH， the mice were sacrificed on days 1， 2， 4， 6， 8， and 10 after surgery， and the liver was collected to measure the change in size. HE staining and oil red O staining were used to evaluate liver histomorphological changes； serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were measured to evaluate the changes in liver function； immunohistochemical staining was used to measure the expression of proliferating cell nuclear antigen （PCNA） and Ki67 and analyze the change in cell proliferation during liver regeneration； quantitatie real－time PCR and immunohistochemical staining were uused to measure the expression and subcellular distribution of RGC32 during liver regeneration； EdU cell proliferation assay was used to analyze the effect of RGC32 overexpression or knocknout on hepatocyte proliferation in L02 cells. For continuous data， comparison between multiple groups was made by analysis of variance， and further pairwise comparisons were conducted using the LSD－t test. The independent samples t－test was used for comparison of continuous data between two groups. A Pearson correlation analysis was performed. ResultsThe liver gradually enlarged after PH， and the liver/body weight ratio rose to the peak from days 0 to 6， with significant differences between different time points （all P<0.05）， while there was no significant change in liver size from days 6 to 10. The number of liver lipid droplets significantly increased after PH surgery and gradually decreased with liver regeneration， with a significant difference between the portal vein region and the central vein region （all P<0.05）. Compared with the sham group， the 1d group had significant increases in the serum levels of ALT and AST （all P<0.05）， which gradually returned to the levels of the sham group on day 6 and day 2 after surgery， respectively （P>0.05）. Immunohistochemical staining showed that there were rapid increases in the numbers of PCNA－ and Ki67－positive liver parenchymal cells after PH surgery， with the highest numbers of 86±5 and 89±5， respectively， on day 2， which then gradually decreased； however， there were gradual increases in the numbers of PCNA－ and Ki67－positive nonparenchymal cells， with the peak numbers of 34±5 and 25±3， respectively， on day 6， which then gradually decreased. The total expression of RGC32 increased to the highest level on day 2 after PH surgery and then gradually decreased， and the changing trend of RGC32 expression in cytoplasm was consistent with that of total RGC32 expression； however， the expression of RGC32 in nucleus decreased to the lowest level on day 2 after PH surgery and then increased gradually. The correlation analysis showed that the expression of RGC32 in nucleus was negatively correlated with the proliferation of liver parenchymal cells （R²=0.308 3， P=0.016 7）， and the expression of RGC32 in cytoplasm was positively correlated with the proliferation of liver parenchymal cells （R²=0.808 6， P<0.000 1）. Cell experiments showed that compared with the control group， the EdU－positive rate was reduced by 15.6% after RGC32 overexpression （P<0.01） and was increased by 19.2% after RGC32 knockdown （P<0.01）. ConclusionLiver parenchymal cells and nonparenchymal cells show asynchronous proliferation and participate in liver regeneration together. During liver regeneration after hepatectomy， there are differences in the expression of RGC32 between nucleus and cytoplasm， and RGC32 in nucleus may inhibit hepatocyte proliferation.

The synchronous abnormal discharge of neurons leads to epileptic seizures.However, in addition to neurons, microglia, as the main immune cells in the brain, plays an important role in the development and maintenance of neural circuits.Microglia is involved in early epileptic seizures, which can be mediated by increasing inflammatory cytokines and chemokines.Microglia can regulate the abnormal neurogenesis after epileptic seizures, promote the death of neurons after seizures, and cause neurodegeneration.Moreover, it can also affect synaptic pruning after seizures, eliminate synapses by phagocytosis or stripping, destroy the balance between synaptic excitation and inhibition, and aggravate seizures.Microglia plays an important role in the development of epilepsy.However, whether microglia participates in the occurrence of epilepsy still needs to be further studied.

Inherited neurotransmitter disorders are a group of rare nervous system diseases frequently diagnosed in children.The disorders are caused by biosynthesis, breakdown or transport detects of neurotransmitters or cofactors essential in their biosynthesis.They can be classified as primary and secondary disorders.The clinical phenotypes of primary inherited neurotransmitter disorders include developmental delay, dyskinesia, schizophrenia, and epilepsy.Among them, epilepsy is the main clinical phenotype.Gamma-aminobutyric acid, glutamate, acetylcholine, biogenic amine and other neurotransmitters are involved in the epileptogenesis.The epilepsy related to primary inherited neurotransmitter disorders has diverse phenotypes, from mild seizures to severe early onset epileptic encephalopathy.An inherited neurotransmitter disorder should be suspected in children with epilepsy if the following features are present: (1) early onset epileptic encephalopathies associated with developmental impairment, autonomic dysfunctions or movement disorders; (2) frequent occurrence of such peculiar electroencephalogram patterns as burst suppression, hypsarrhythmia, and diffused/focal/multifocal electroencephalogram abnormalities; (3) neuroradiological signs of metabolic intoxication; (4) detection of specific cerebrospinal fluid biomarkers.Early identification, diagnosis and treatment is of great significance in reducing the incidence, lowering the mortality rate, and improving the prognosis of patients with epilepsy related to primary inherited neurotransmitter disorders.

Background & Objective: Nonsense mutations in SMC1A have been reported only in females with cluster seizures, all of whom have been described as drug-resistant epilepsy. Here, we aim to explore the use of ketogenic diet treatment. Methods: The clinical data of female patients with de novo nonsense mutations in SMC1A were collected and analyzed. The clinical data was recruited and analyzed. The peripheral blood of children and their parents was collected. The next generation sequencing was used to find suspected pathogenic mutations and all the confirmed mutations were verified by Sanger sequencing. Results: Three patients with heterozygous de novo mutations in SMC1A gene were reviewed. All patients were females, presenting with seizure onset at age between 2.5 to 11 months old. One patient had mild developmental delay. One had moderate developmental delay. Another had severe developmental retardation. None of the patients had a clinical diagnosis of Cornelia de Lange syndrome. All three patients had prominent clinical features of cluster seizures. All the nonsense mutations were predicted damaging SMC1A protein by PolyPhen-2 HVAR. All the patients were treated with multiple antiepileptic drugs but their seizures remained refractory. When initiated with ketogenic diet, they became seizure free within 3 to 4 weeks. Conclusion: SMC1A nonsense mutations can cause early onset epilepsy only in females with cluster seizures. These patients are characterized by drug-resistant epilepsy, but all our three patients have good effect on ketogenic diet add-on therapy.