ObjectiveTo investigate the performance of fibrosis-4 （FIB-4） versus aspartate aminotransferase-to-platelet ratio index （APRI） in predicting advanced liver fibrosis and disease progression in patients with chronic HBV infection. MethodsA total of 497 patients with chronic HBV infection who underwent liver biopsy in The First Affiliated Hospital of Guangxi Medical University from February 2013 to December 2022 were enrolled， among whom 404 were enrolled in a retrospective study and 75 were enrolled in a prospective study. Related indicators were collected， including demographic features （sex and age）， biochemical indices （alanine aminotransferase ［ALT］ and aspartate aminotransferase ［AST］）， and platelet count， and FIB-4 and APRI were calculated. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups； the chi-square test was used for comparison of categorical data between groups. The area under the ROC curve （AUC） was used to assess the ability of APRI and FIB-4 in evaluating liver fibrosis degree and disease progression in patients with chronic HBV infection. ResultsIn the retrospective analysis， compared with the FIB-4<2.67 group， the FIB-4≥2.67 group had a significantly higher proportion of the patients who were diagnosed with liver cirrhosis or hepatocellular carcinoma （66.19% vs 47.54%， χ²=12.75， P<0.001）. The medians of FIB-4 and APRI increased significantly with liver fibrosis degree from F0 to F4 （H=42.5 and 35.9， both P<0.001）. As for the fibrosis stage of F0-F4， the median of FIB-4 was significantly higher than that of APRI in the patients with the same fibrosis stage （H=59.71， P<0.001）. FIB-4 and APRI had a similar AUC for predicting stage F3 fibrosis （0.67 vs 0.65， Z=0.71， P=0.480）， while FIB-4 had a higher AUC for predicting stage F4 fibrosis than APRI （0.72 vs 0.64， Z=10.50， P<0.001）. In the prospective study cohort， FIB-4 and APRI showed an increasing trend over time in predicting disease progression （chronic hepatitis B to liver cirrhosis）， with an AUC of 0.718 （95% confidence interval ［CI］： 0.476‍ ‍—‍ ‍0.760） and 0.555 （95%CI： 0.408‍ ‍—‍ ‍0.703）， respectively， and FIB-4 had a significantly higher accuracy than APRI in predicting disease progression （χ²=12.44， P<0.001）. ConclusionFIB-4 and APRI can be used to evaluate advanced liver fibrosis （F3 and F4） and predict disease progression， and FIB-4 is superior to APRI in certain aspects.

Objective:To analyze the gene mutation type and clinical phenotype of patients with PRRT2 mutation, and explore their relations with prognosis. Methods:A total of 18 patients with PRRT2 gene mutation (1 patient with novel mutation in PRRT2 gene, and 17 probands in 17 families with PRRT2 gene mutation) were enrolled in Department of Neurology, First Affiliated Hospital of Air Force Medical University from January 2018 to July 2023. Serum of the patients was collected for whole exon sequencing, and mutation sites and types of PRRT2 gene were analyzed. SWISS-MODEL website was used to predict the changes in protein structure caused by PRRT2 gene mutation. The relations of gene mutation type and clinical phenotype with prognosis of these patients were analyzed. Results:(1) All 18 patients with PRRT2 gene mutation were heterozygous mutation, including 12 frameshift mutations, 5 missense mutations, and 1 integer mutation. The clinical phenotype included benign familial infantile epilepsy (BFIE) in 5 patients, epilepsy in 6 patients, exercise-induced paroxysmal kinesigenic dyskinesia (PKD) in 5 patients, and infantile convulsion and choreoathetosis (ICCA) in 2 patients. A total of 8 mutation sites were found in 18 patients with PRRT2 gene mutation, of which 3 mutation sites have been reported, and 5 mutation sites have not been reported, including c.647(exon2)C>A, c.647(exon2)C>G, c.170(exon2)delC, c.981(exon3)C>G, and lossl(EXON: 2)(all). (2) Eighteen patients mainly accepted oxcarbazepine, levetiracetam, and sodium valproate in combination or monotherapy. Among them, 5 BFIE patients, 2 ICCA patients and 3 epilepsy patients were seizure-free after treatment. PKD patients did not respond well to oxcarbazepine. (3) Three frameshift mutations (mutation sites: c.649 [exon2]_c.650 [exon2] insC, c.640 [exon2]_c.641 [exon2] insC, and c.170 [exon2] delC) led to premature termination of protein translation, resulting in significant changes in protein structure. Four missense mutations (mutation sites: c.640[exo2]G>C, c.647[exon2]C>A, c.647[exon2]C>G, and c.981[exon3]C>G) had little effect on protein structure changes. No relation was found between changes of protein structure caused by different mutation types and prognosis. Conclusion:PRRT2 gene mutation patients with clinical phenotypes of BFIE and ICCA have good prognosis, but the mutation type is not related with the prognosis of patients.

Accurately assessing and positioning the current development status of disciplines can help hospitals formulate targeted disciplinary development strategies and achieve disciplinary development goals. In 2022, a large tertiary public hospital established a discipline-demand-oriented " pyramid" hierarchical discipline evaluation system based on Maslow′s need-hierarchy theory. The discipline evaluation system set six levels of evaluation indicators from low to high, including medical quality and safety, department operation, sub specialty construction, scientific and educational achievements, platform construction, and talent cultivation(including 6 primary indicators, 21 secondary indicators, and 44 tertiary indicators). By applying the evaluation system and providing feedback on the evaluation results in the form of " disciplinary diagnostic reports" and " disciplinary evaluation conferences, " the hospital′s discipline construction had been improved at six levels. From 2022 to 2023, the hospital added five national clinical key specialties; The number of sub major construction disciplines increased from 18 in 2021 to 61 in 2023, and patient satisfaction increased from 94.64% to 96.25%. This evaluation system could objectively reflect the level of discipline development, lead the high-quality development of disciplines, and provide references for other public hospitals to promote discipline development.

Objective:To investigate the clinicopathological features, differential diagnosis, treatment and prognosis of undifferentiated embryonal sarcoma of the liver (UESL).Methods:Five UESL cases operated on at Hunan Provincial People's Hospital from 2014 to 2021 were retrospectively analyzed. H&E and immunohistochemical staining were done for pathological observation.Results:The 5 UESL patients(two boys,three girls) were 0.5 to 15 years old, all underwent radical surgical resection. In 3 cases tumors located in right liver, 1 in left liver, 1 in both lobes. Radiographically and visually, the tumor is a large cystic solid mass, microscopically composed of myxoid stroma and undifferentiated stromal cells, with pleomorphic tumor giant cells and characteristic eosinophilic bodies. All 5 patients are now alive after surgical resection: 1 patient achieved disease-free survival of more than 91 months after surgery alone. Two patients had recurrence after surgery and received surgical resection plus chemotherapy or chemotherapy alone. They achieved survival of more than 35 and 16 months, respectively. Two patients were treated with chemotherapy or chemotherapy plus radiotherapy after surgery and survived more than 49 and 31 months without recurrence, respectively.Conclusions:UESL is a rare and highly malignant mesenchymal tumor with characteristic pathologic morphology. Radical resection is the key to the treatment for UESL, and chemotherapy and radiotherapy should be carried out after surgery.

Objective:To report the clinical phenotype and mutation site of a patient with grey matter heterotopia caused by a de novo heterozygous missense mutation in the TUBB2B gene, and to expand the phenotypic and mutational spectrum of TUBB2B mutations. Methods:One patient with TUBB2B mutation who presented to the Department of Neurology, the First Affiliated Hospital of Air Force Medical University in July 2017 was collected and analyzed for clinical features and mutation site, and a review of previous studies was performed. Results:The male patient started at the age of 18 and presented mainly with seizures, poor left-handed fine motor skills and poor spatial imagination. Magnetic resonance imaging showed nodular grey matter heterotopia in the right cerebral hemisphere, right frontoparietal-temporal localized cerebral gyrus, and cerebral sulcus shallow flat.The whole exon gene test suggested a heterozygous missense mutation in the TUBB2B gene: c.776 C>T (p.Pro259Leu), which was wild-type in both of his parents. The mutation site was located between the tubulin and tubulin-c structural domains and did not affect the function of the essential structural domain. After treatment with magnesium valproate in combination with levetiracetam, the patient′s seizure symptoms were significantly controlled and he has been seizure-free for 3 years now. Conclusions:The TUBB2B gene c.776 C>T (p.Pro259Leu) heterozygous missense mutation is a novel missense mutation causing grey matter heterotopia. The patient had a good prognosis, and the combination of two antiepileptic drugs resulted in complete seizure control.

Objective:To compare the maternal and fetal outcomes of women with cervical insufficiency (CI) undergoing McDonald cerclage (MC) and laparoscopic cervicoisthmic cerclage (LCC), so as to provide evidence for the selection of cerclage methods.Methods:A retrospective trial was carried out in the First Affiliated Hospital of Sun Yat-sen University from January 2010 to December 2020. A total of 221 women who underwent the prophylactic cerclage were divided into MC group ( n=54), LCC with MC history group ( n=28) and LCC without MC history group ( n=129) by the mode of operation and whether the pregnant women who underwent LCC had MC history. General clinical data, pregnancy complications and pregnancy outcomes were compared between the three groups. Results:(1) General clinical data: the proportion of women accepted cervical cerclage during pregnancy in MC group, LCC with MC history group and LCC without MC history group were 100.0% (54/54), 7.1% (2/28) and 27.1% (35/129), respectively ( P<0.001). The indications of the three groups showed statistical significance ( P=0.003), and the main indication was the history of abortion in the second and third trimester [75.9% (41/54) vs 89.3% (25/28) vs 84.5% (109/129)]. (2) Pregnancy complications: the incidence of abnormal fetal position [7.8% (4/51) vs 17.4% (4/23) vs 19.8% (24/121)], placenta accrete [5.9% (3/51) vs 13.0% (3/23) vs 11.6% (14/121)], uterine rupture [0 vs 4.3% (1/23) vs 5.8% (7/121)] in the MC group were all lower than those in LCC with MC history and LCC without MC history groups. However, there were no statistical significances (all P>0.05). Intrauterine inflammation or chorioamnionitis [15.7% (8/51) vs 0 vs 0.8% (1/121)] and premature rupture of membrane [23.5% (12/51) vs 4.3% (1/23) vs 0] were both significantly higher in MC group than those in LCC with MC history and LCC without MC history groups (all P<0.001). (3) Pregnancy outcomes: the cesarean section rate was significantly lower in MC group (41.2%, 21/51) than that in LCC with MC history group (100.0%, 23/23) and LCC without MC history group (100.0%, 121/121; P<0.001). MC group was associated with lower expenditure than LCC with MC history and LCC without MC history groups (12 169 vs 26 438 vs 27 783 yuan, P<0.001). The success rates of live birth cerclage did not differ significantly in MC (94.4%, 51/54), LCC with MC history (82.1%, 23/28) and LCC without MC history (93.8%, 121/129) groups ( χ2=5.649, P=0.059). There was no significant difference in neonatal intensive care unit occupancy, neonatal birth weight and neonatal asphyxia between the three groups (all P>0.05). Conclusions:Both LCC and MC are the treatment choice for women with CI, which may get similar liver birth. However, MC has the advantages of low cesarean section rate, economical and easy operation. Therefore, MC is recommended as the first choice for CI patients, and LCC is for women with failed MC.

Objective:To investigate the genomic manifestation and pathogenesis of osteosarcoma with different relapse pattens, which were respectively initially presented with bone metastasis or pulmonary metastasis.Methods:From May 1, 2021 to October 1, 2021, 38 fresh tumor specimens and some paraffin-embedded specimens of high-grade osteosarcoma were collected in Peking University People's Hospital, including 29 males and 9 females, aged 19.6±2.2 years (range, 6-61 years). Among the 38 cases, 12 cases had initial bone metastasis (group A) and 26 cases had initial lung metastasis (group B), of which 15 cases (40%, 15/38) had paired specimens of primary and metastatic lesions. Based on Illumina NovaSeq 6000, we analyzed whole-exome sequencing (WES) as well as transcriptome for osteosarcoma with paired samples in different relapse patterns. During all their treatment courses, we also collected their paired samples to reveal these tumors' evolution. We sought to redefine disease subclassifications for osteosarcoma based on genetic alterations and correlate these genetic profiles with clinical treatment courses to elucidate potential evolving cladograms.Results:We found that osteosarcoma in group A mainly carried single-nucleotide variations (83%, 10/12), displaying higher tumor mutation burden [4.9 (2.8, 12.0) & 2.4 (1.4, 4.5), P=0.010] and neoantigen load [743.0 (316.5, 1,034.5) & 128.5 (49.0, 200.5), P=0.003], while those in group B mainly exhibit structural variants (58%, 15/26). The mutation spectrum showed that there was a significant difference in age-related gene imprinting 1 between the bone metastasis group and the lung metastasis group ( P=0.005). Samples were randomly selected from group A (3 patients) to investigate immunologic landscape by multiplex immunohistochemistry, from which we noticed tertiary lymphatic structure from one patient from group A. High conservation of reported genetic sequencing over time was found in their evolving cladograms. Conclusion:Osteosarcoma with mainly single-nucleotide variations other than structural variants might exhibit biological behavior predisposing toward bone metastases with older in age as well as better immunogenicity in tumor microenvironment.

Objective:To investigate the value of ultrasound in the diagnosis of secondary loss of response in children with Crohn′s disease at maintenance stage treated with Infliximab.Methods:From January 2017 to December 2021, 51 children with Crohn′s disease who received Infliximab treatment and clinical response in the Beijing Children′s Hospital Affiliated to Capital Medical University were retrospectively analyzed, and whether there was secondary loss of response during the maintenance period was observed. The ultrasound examination results at the 14th week of treatment were collected to understand the correlation between ultrasound examination of intestinal wall and peri-intestinal healing and secondary loss of response.Results:A total of 15 out of 51 patients (29.4%) experienced secondary loss of response during treatment follow-up up to 54 weeks. Compared to children with continuous response, children with secondary loss of response had a thicker intestinal wall at week 14 of treatment [5.0 (3.8, 6.0)mm compared to 3.0 (2.0, 4.0)mm, P<0.001], and a higher proportion of intestinal wall stratified structure disappearance [8/15 (53.33%) compared to 3/36 (8.33%), P<0.001]. When intestinal wall thickness>3.0 mm, the sensitivity was 0.955, and the specificity was 0.483. The sensitivity and specificity of clear diagnosis of secondary loss of response in intestinal wall stratification were 0.727 and 0.825, respectively. The sensitivity and specificity of combined diagnosis for secondary loss of response were 0.933 and 0.611, respectively. Conclusions:At the 14th week of treatment with Infliximab in children with Crohn′s disease, the thickness of intestinal wall measured by ultrasound being more than 3.0 mm and the disappearance of intestinal wall statified structure provide important information for the diagnosis of secondary loss of response.

OBJECTIVE: To summarize the clinical phenotype and genotypic characteristics of 3 patients with KBG syndrome and epileptic seizure. METHODS: Clinical data of the patients were collected. Family-trio whole exon sequencing (WES) was carried out. Candidate variants were verified by Sanger sequencing. RESULTS: Patients 1 and 2 were boys, and patient 3 was an adult woman. All patients had epileptic seizures and mental deficiency. Their facial features included triangular face, low hair line, hypertelorism, large forward leaning auricles, broad nasal bridge, upturned nostrils, long philtrum, arched upper lip, and macrodontia. The two boys also had bilateral Simian creases. WES revealed that the three patients all harbored heterozygous de novo frameshift variants in exon 9 of the ANKRD11 gene including c.2948delG (p.Ser983Metfs*335), c.5397_c.5398insC (p.Glu1800Argfs*150) and c.1180_c.1184delAATAA (p.Asn394Hisfs*42). So far 291 patients with ANKRD11 gene variants or 16q24.3 microdeletions were reported, with over 75% being de novo mutations. CONCLUSION Above findings have enriched the spectrum of ANKRD11 gene mutations underlying KBG syndrome. WES is helpful for the early diagnosis of KBG, and provided reference for genetic counseling of this disease.
Abnormalities, Multiple/genetics* ; Bone Diseases, Developmental/genetics* ; Epilepsy/genetics* ; Facies ; Humans ; Intellectual Disability/genetics* ; Phenotype ; Repressor Proteins/genetics* ; Seizures/genetics* ; Tooth Abnormalities/genetics*

A survey on professional knowledge levels was conducted from April to October 2019 among 388 general practitioners (GPs) from 46 community health service centers and 30 township health centers of 6 provinces selected by stratified random sampling method. The overall knowledge test score was 31.82—84.09(56.94±9.19) points, and the pass rate was 36.3% (141/388). There were significant differences in test scores among participants with different types of work units, regions, provinces, marital status, educational background, professional titles, types of employment, length of service, and training status (all P<0.05). Multivariate regression analysis showed that educational background ( B=-2.835), professional title ( B=-8.867), and participation in professional course training ( B=2.214) were the influencing factors of knowledge level (all P<0.05). The pass rates in knowledge of prevention/health management (13.7%, 53/388) and policies and regulations (12.1%, 47/388) were low. The results show that the levels of professional knowledge among GPs working in grassroots health institutions are relatively low, and suggest that continuing education should be strengthened to improve the professional knowledge level of GPs in primary care institutions, particularly, knowledge of health policies and regulations, disease prevention and health management.