Metabolic associated fatty liver disease has become the most important chronic liver disease in China.Its mechanism is not completely clear.Professor Sheng Guoguang examines the symptoms and seek the cause,treats the disease by stages from the perspective of"earth-obstructing and wood-stagnation,phlegm and blood stasis",summarizes the core pathogenesis of each stage,and prescribes drugs for the pathogenesis.In the early stage,the disease is mainly caused by earth-obstructing and wood-stagnation and phlegm and blood stasis and the corresponding treatment method should be activating spleen to eliminate depression,relieving phlegm and promoting blood circulation,with common use of modified Sizhu Decoction combined with Erchen Decoction.In the middle stage,phlegm and blood stasis transform into heat are the main pathogenesis,and the appropriate treatment is clearing liver and purging fire,and relieving phlegm and promoting blood circulation,with common use of modified Xiaochaihu Decoction combined with Erchen Decoction.In the late stage,weakness of the internal organs is the main pathogenesis,and it is appropriate to nourish liver and fortify the spleen,tonifying the kidney and consolidate the root,supplementing with reducing phlegm and activating blood circulation,with common use of modified Yiguan Decoction combined with Liujunzi Decoction in modification,which has achieved confirmed clinical efficacy.

Objective To explore the biological basis of different diseases with the same syndrome for pulmonary related comorbidities(pulmonary hypertension,obstructive sleep apnea syndrome,chronic obstructive pulmonary disease,lung cancer)in idiopathic pulmonary fibrosis(IPF)through genomic bioinformatics analysis.Methods GSE110147,GSE113439,GSE135917,GSE106986 and GSE118370 datasets were downloaded as research subjects.The differential genes between each disease group and the control group were screened.Cytoscape 3.10.0 software was used for topology analysis to screen core genes.OmicShare was used to perform GO and KEGG pathway enrichment analyses on core genes.Results A total of 23 core genes related to IPF was obtained.GO enrichment analysis showed that core genes were mainly enriched in biological processes such as cellular process,metabolic process,biological regulation/biological process,developmental process,localization,response to stimulus,immune system process and signaling;in cellular components such as cellular anatomical entity and protein-containing complex;in molecular functions such as binding,catalytic activity,structural molecule activity,molecular adaptor activity,molecular function regulator and transcription regulator activity.KEGG pathway enrichment analysis showed that core genes were mainly enriched in ribosome biogenesis in eukaryotes,AGE-RAGE signaling pathway in diabetic complications,Th17 cell differentiation,JAK-STAT signaling pathway,RNA polymerase,neutrophil extracellular trap formation.Conclusion Using genomic bioinformatics analysis to explore the core genes and signaling pathways of pulmonary related comorbidities in IPF can reveal the mechanism of different diseases with the same syndrome for pulmonary related comorbidities in IPF to a certain extent.

Objective:To construct a composite evaluation index of fourth-level surgical, for references for horizontal comparison of fourth-level surgical between clinical departments of hospital and hospital performance appraisal.Methods:The data were extracted from the medical record information system and disease diagnosis related group information system of a tertiary public hospital, including the number of surgical patients, the number of fourth-level surgical patients, the case mix index (CMI), and the average length of hospital stay for 23 surgical departments from 2019 to 2023. Based on disease diagnosis related groups, the average length of hospital stay for patients undergoing fourth-level surgery was standardized to obtain the time cost index; Multiply the CMI and time cost index by the fourth-level surgical ratio to obtain the quality coefficient. This coefficient was used to weight the number of fourth-level surgeries to establish the contribution degree of fourth-level surgeries, which was used for the comprehensive evaluation of fourth-level surgery quality and quantity for each surgical department.Results:A total of 329 177 surgical patients were included in this study, including 139 704 patients with fourth-level surgery. From 2019 to 2023, the top 3 departments in terms of the proportion of fourth-level surgery were department J, B and A, and the proportion of fourth-level surgery in departments with high surgical difficulty, such as C and I, ranked 8th and 16th. The top 3 departments with the contribution degree of fourth-level surgery were department A, B and C, I rosed to the 9th, and J felled to the 11th.Conclusions:The fourth-level surgery contribution degree combined the four factors of surgical composition, difficulty, cost and quantity, which could objectively evaluate fourth-level surgeries in different departments.

Type 2 diabetes (T2D) is often accompanied with an induction of retinaldehyde dehydrogenase 1 (RALDH1 or ALDH1A1) expression and a consequent decrease in hepatic retinaldehyde (Rald) levels. However, the role of hepatic Rald deficiency in T2D progression remains unclear. In this study, we demonstrated that reversing T2D-mediated hepatic Rald deficiency by Rald or citral treatments, or liver-specific Raldh1 silencing substantially lowered fasting glycemia levels, inhibited hepatic glucogenesis, and downregulated phosphoenolpyruvate carboxykinase 1 (PCK1) and glucose-6-phosphatase (G6PC) expression in diabetic db/db mice. Fasting glycemia and Pck1/G6pc mRNA expression levels were strongly negatively correlated with hepatic Rald levels, indicating the involvement of hepatic Rald depletion in T2D deterioration. A similar result that liver-specific Raldh1 silencing improved glucose metabolism was also observed in high-fat diet-fed mice. In primary human hepatocytes and oleic acid-treated HepG2 cells, Rald or Rald + RALDH1 silencing resulted in decreased glucose production and downregulated PCK1/G6PC mRNA and protein expression. Mechanistically, Rald downregulated direct repeat 1-mediated PCK1 and G6PC expression by antagonizing retinoid X receptor α, as confirmed by luciferase reporter assays and molecular docking. These results highlight the link between hepatic Rald deficiency, glucose dyshomeostasis, and the progression of T2D, whilst also suggesting RALDH1 as a potential therapeutic target for T2D.

OBJECTIVE: To explore the clinical phenotype and genetic variant in a child with Verheij syndrome (VRJS). METHODS: A child who had presented at the Soochow University Affiliated Children's Hospital and Wujiang District Children's Hospital in July 2022 for "elevated scapula since early childhood" was selected as the study subject. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child had manifested elevated scapulae, torticollis, neck asymmetry, facial dysmorphism, dispersed café-au-lait spots, limited mobility of upper limbs and shoulder joints, and intellectual disability. Sequencing revealed that he has harbored a de novo heterozygous c.405dupT (p.Ile136Tyrfs*4) variant of the PUF60 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), this variant was classified as pathogenic (PVS1+PS2_moderate+PM2_supporting). Combined his clinical features and result of genetic testing, the child was diagnosed with VRJS due to variant of the PUF60 gene. CONCLUSION The clinical manifestations of VRJS include facial dysmorphism, intellectual disability, elevated scapulae, vertebral fusion, other skeletal malformations, without significant abnormalities of the heart, kidney, and eyes, which need to be distinguished from Klippel-Feil syndrome. Above finding has expended the mutation spectrum of the PUF60 gene and provided a reference for delineation of the genotype-phenotype correlation of the VRJS.
Child ; Child, Preschool ; Humans ; Male ; Cafe-au-Lait Spots ; Computational Biology ; Genetic Testing ; Genomics ; Intellectual Disability/genetics* ; Mutation

Lenvatinib mesylate is an oral receptor tyrosine kinase inhibitor against targets of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor α, stem cell growth factor receptor, and rearranged during transfection, et al. Lenvatinib has been approved by the National Medical Products Administration of China on September 4,2018, for the first-line treatment of patients with unresectable hepatocellular carcinoma who have not received systematic treatment before. Up to February 2023, Lenvatinib has been listed in China for more than 4 years, accumulating a series of post-marketing clinical research evidences. Based on the clinical practice before and after the launch of lenvatinib and referring to the clinical experience of other anti-angiogenesis inhibitors, domestic multidisciplinary experts and scholars adopt the Delphi method to formulate the Chinese Expert Guidance on Overall Application of Lenvatinib in Hepatocellular Carcinoma after repeated discussions and revisions, in order to provide reference for reasonable and effective clinical application of lenvatinib for clinicians.

Lenvatinib mesylate is an oral receptor tyrosine kinase inhibitor against targets of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor α, stem cell growth factor receptor, and rearranged during transfection, et al. Lenvatinib has been approved by the National Medical Products Administration of China on September 4, 2018, for the first-line treatment of patients with unresectable hepatocellular carcinoma who have not received systematic treatment before. Up to February 2023, Lenvatinib has been listed in China for more than 4 years, accumulating a series of post-marketing clinical research evidences. Based on the clinical practice before and after the launch of lenvatinib and referring to the clinical experience of other anti-angiogenesis inhibitors, domestic multidisciplinary experts and scholars adopt the Delphi method to formulate the Chinese Expert Guidance on Overall Application of Lenvatinib in Hepatocellular Carcinoma after repeated discussions and revisions, in order to provide reference for reasonable and effective clinical application of lenvatinib for clinicians.

Unlike healthy, non-transformed cells, the proteostasis network of cancer cells is taxed to produce proteins involved in tumor development. Cancer cells have a higher dependency on molecular chaperones to maintain proteostasis. The chaperonin T-complex protein ring complex (TRiC) contains eight paralogous subunits (CCT1-8), and assists the folding of as many as 10% of cytosolic proteome. TRiC is essential for the progression of some cancers, but the roles of TRiC subunits in osteosarcoma remain to be explored. Here, we show that CCT4/TRiC is significantly correlated in human osteosarcoma, and plays a critical role in osteosarcoma cell survival. We identify a compound anticarin-β that can specifically bind to and inhibit CCT4. Anticarin-β shows higher selectivity in cancer cells than in normal cells. Mechanistically, anticarin-β potently impedes CCT4-mediated STAT3 maturation. Anticarin-β displays remarkable antitumor efficacy in orthotopic and patient-derived xenograft models of osteosarcoma. Collectively, our data uncover a key role of CCT4 in osteosarcoma, and propose a promising treatment strategy for osteosarcoma by disrupting CCT4 and proteostasis.

Objective:To explore the safety and efficacy of the minimally invasive treatment of unstable pelvic fractures with the blunt head technique of Kirschner wire and 3D-printed external template technique.Methods:A retrospective study was conducted of the clinical data of 21 patients with unstable pelvic fracture who had undergone minimally invasive treatment at Department of Orthopaedics, Union Hospital from May 2016 to July 2018 using 3D-printed external templates and the blunt head technique of Kirschner wire. There were 7 males and 14 females with an age of 43.6 years (from 19 to 65 years). According to the Tile classification, there were 3 cases of B1, 7 ones of B2, 6 ones of C1 and 5 ones of C2. The intraoperative fluoroscopy, operation time, postoperative fracture reduction and functional recovery of the pelvis at the last follow-up were recorded.Results:The 21 patients were followed up for an average of 16.3 months (from 12 to 24 months). A total of 33 wires were inserted in the 21 patients, including 15 S 1 ones and 18 S 2 ones. The intraoperative fluoroscopy ranged from 13 to 27 times, averaging 21.8 times. The operation time ranged from 65 to 130 min, averaging 88.6 min. The anterior subcutaneous internal fixation was used to fix the anterior ring in 9 patients. No vascular injury occurred during the operation. By the Matta criteria, the postoperative fracture reduction was assessed as excellent in 14 cases, good in 5, and fair in 2, giving an excellent to good rate of 90.5% (19/21). By the Majeed scoring system, the pelvic function at the last follow-up was assessed as excellent in 10 cases, good in 8, and fair in 3, giving an excellent to good rate of 85.7% (18/21). Lateral femoral cutaneous nerve injury occurred in 2 patients but was recovered by the 3-month follow-up. No other complications were follwed up. Conclusion:The minimally invasive treatment of unstable pelvic fractures with the blunt head technique of Kirschner wire assissted by 3D-printed external templates is safe and effective, showing advatages of reduced fluoroscopic frequency and operation time.

Objective:To study the impact on dose accuracy for the treatment planning by manually assigning accurate electron density for CT image-based tumor tissues and organs at risk.Methods:Twenty cases of retrospective postoperative cervical cancer radiotherapy plans were selected. The body electron density of the corresponding organs was derived from the ICRU 46 report and assigned in the treatment planning system (Monaco5.11, Sweden), including the bladder, rectum, intestine, kidney, spinal cord, femoral head, and ilium. The original plans were double-arc volumetric modulated arc therapy plan (360° VMAT), using Monte Carlo algorithm, the calculation grid was 0.3 cm × 0.3 cm × 0.3 cm, and the minimum subfield width was 0.6 cm. Keep the original plan fluence unchanged and recalculate the dose to generate a new plan. The two-dimensional dose distribution and dose-volume histogram (DVH) were used to compare the differences between the two plans. The difference was compared between the two group plans by using the dosimetry parameters and DVH two dimension curve.Results:For the planning of assigning bulk electron density (Plan RED), the deviation of the patient′s target dose parameters and the original plan (Plan ref) was <2%, and the average deviation of all target regions D2, D98, Dmean was < 0.7%, only 2 of the 180 data were between 2% and 3%. The average deviation of V20, V30, D1 cm 3, Dmean of the bladder, rectum, and small intestine, the original Plan ref was less than 0.6%, and 4 out of 240 data had values > 2%. Plan RED′s average hop count was 0.9% higher than Plan ref, and the total number of subfields remains unchanged. The planned dose generated by manually assigning the electron density in Plan RED was higher than that in Plan ref, but met the clinical requirements. The two-dimensional curves of the DVH diagram for targets and OARs almost completely overlapped, and there was no obvious difference in the dose distribution diagram of the same cross section. The statistical result of all parameters showed that the difference in planned dose parameters between the two groups was not statistically significant( P>0.05). Conclusions:The overall deviation of dose accuracy between Plan RED and Plan ref is <2%, which meets the clinical requirements and provides a reference for realizing MRI-only treatment planning.