Objective:To analyze the clinical phenotypes and TSC1/TSC2 gene variations in 52 children with tuberous sclerosis complex. Methods:The clinical data of 59 children with tuberous sclerosis complex hospitalized in Linyi People′s Hospital between January 2017 and October 2022 were collected. The analysis of TSC1 and TSC2 gene variations on main family members was performed, and then bioinformatics analysis followed. The positive children were divided into TSC1 gene group and TSC2 gene group, and the difference of clinical characteristics between the two groups was analyzed. Results:Among 59 children, 52 cases were detected TSC1/ TSC2 gene variations (17 cases in the TSC1 gene group and 35 cases in the TSC2 gene group). Of the 52 children, 28 (53.8%) were male, 24 were female (46.2%); 17 (32.7%) were familial cases (10 with TSC1 gene variations and 7 with TSC2 gene variations), 35 (67.3%) were sporadic cases; 46 (88.5%) had hypomelanotic macules, 13 (25.0%) had facial angiofibromas, 5 (9.6%) had shagreen patches, 49 (94.2%) had subependymal nodules/calcifications, 47 (90.4%) had cortical nodules, 2 (3.8%) had subependymal giant cell astrocytomas, 39 (75.0%) had intellectual/developmental disabilities, 49 (94.2%) had epileptic seizures, 8 (15.4%) had cardiac rhabdomyomas, 9 (17.3%) had renal angiomyolipomas, and 4 (7.7%) had retinal hamartomas. Of the 52 children, 49 variations were detected, including 4 large fragment deletion/duplication variations, and 45 point variations; 41 pathogenic variations, 7 likely pathogenic variations, and 1 variation of uncertain significance. In this study, 16 point mutations and 1 large fragment duplication mutation which had not been reported at home and abroad, and 3 high-frequency mutation sites (p.Arg692 *, p.Arg228 *, and p.Arg1200Try) were found. There was a statistically significant difference in the proportion of familial cases [10/17 vs 7/35(20%), χ2=7.838, P=0.005], median onset age of epilepsy [38.0(0.5-134.0) months vs 8.0(0.1-63.0) months, Z=3.506 , P<0.001] and the incidence of developmental retardation/intellectual impairment [8/17 vs 31/35(88.6%), χadj2=8.423, P=0.004] between the TSC1 gene and TSC2 gene groups. Conclusions:Tuberous sclerosis compiex has widespread phenotypes, can affect every body system, especially the skin and nervous system. The pathogenic gene is TSC1/ TSC2. The TSC1 gene group has more familial cases. The TSC2 gene group has an earlier onset age of epilepsy and a higher incidence of developmental retardation/intellectual impairment. In this study, 16 novel point mutations, 1 novel large fragment duplication mutation, and 3 hotspot mutations were identified, expanding the gene variation spectrum of tuberous sclerosis complex.

ObjectiveTo determine the optimal dose of Dachengqi Decoction （大承气汤， DCQD） for the treatment of acute intestinal obstruction （AIO） through a randomized， double-blind， dosage parallel controlled， multi-center clinical trial， and to providee evidence support for the reasonable dosage of DCQD in clinical practice. MethodsBased on the commonly used clinical dose of DCQD， three different groups were set up， including low-dose group which used Dahuang （Radix et Rhizoma Rhei） 12 g， Houpo （Cortex Magnoliae Officinalis） 9 g， Zhishi （Fructus Aurantii Immaturus） 9 g， and Mangxiao （Natrii Sulfas） 4.5 g， medium-dose group using Dahuang 36 g， Houpo 27 g， Zhishi 27 g， Mangxiao 13.5 g， and high-dose group using Dahuang 60 g， Houp0 45 g， Zhishi 45 g and Mangxiao 22.5 g. Initially， 149 AIO patients with Yangming （阳明） bowel excess syndrome were randomly assigned to three groups using a stratified randomization method， and both the patients and the doctors were blinded. In addition to conventional western medicine treatment， each group was given 12 bags of granules made from the raw herbs of DCQD at different doses， taken orally or injected through a gastric catheter once every 6 hours， 3 bags each time， for 3 consecutive days. After treatment， the indicators of the three groups of patients with primary AIO and non-primary AIO were evaluated respectively， and the full analysis set （FAS） and per-protocol set （PPS） were used for analysis. The primary outcomes were the time to recover voluntary bowel movements and voluntary flatulence. The secondary outcomes were the ideal rate of spontaneous defecation and the ideal rate of spontaneous flatus. The occurrence of adverse events during the study was recorded and analyzed using the safety analysis set （SS）. ResultsA total of 91 patients with primary AIO and 58 patients with non-primary AIO were included in the FAS and SS analysis， while 80 primary AIO patients and 56 non-primary AIO patients were included in the PPS analysis. Both FAS and PPS analysis showed significant differences in the time to recover voluntary bowel movements and voluntary flatulence among primary AIO patients in different dose groups of DCQD （P＜0.01）， and the high- and medium-dose groups assumed less time than the low-dose group （P＜0.05）. There was no statistically significant difference in the ideal rate of spontaneous defecation and spontaneous flatus among the three groups （P＞0.05）. And consistent results were seen in the non-primary AIO patients among the three groups. Five adverse events occurred in primary AIO patients （3 in the low-dose group， 1 in the medium-dose group， and 1 in the high-dose group）， mainly manifested as abdominal distension and abdominal pain， and there was no statistically significant difference in the incidence of adverse events （P＞0.05）. No adverse events occurred in patients with non-primary AIO. ConclusionDCQD， as an effective treatment for patients with AIO， is commonly used at a medium dose for patients with primary AIO and at a high dose for patients with non-primary AIO. The therapeutic advantage is mainly reflected in the shorter time to recover spontaneous defecation and spontaneous flatulence and the improvement of intestinal function.

Objective To compare the dosimetric characteristics of thyroid between intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) in patients with left-sided breast cancer after modified radical mastectomy. Methods Thirty patients with left-sided breast cancer who underwent adjuvant radiotherapy after modified radical mastectomy at the Huangpu Branch of the Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, from December 2021 to May 2023, were selected as the study subjects, and IMRT and VMAT were used with a target prescription dose of 50 Gy/25 times. The target dose parameters of the two plans, including the mean dose (D_mean) and the dose-volume limit for organs at risk (V_x, x represents dose), were compared. Results The conformity index of VMAT was higher than that of IMRT (P＜0.001). Compared with VMAT, IMRT plan significantly reduced the V₅、V₁₀、D_mean of heart, the V₅ of right lung and the D_mean of right breast, while it significantly increased the V₂₀ of left lung (P＜0.001). There was no statistically significant difference in V₅ and V₁₀ of the left thyroid between IMRT and VMAT. However, the V₂₀, V₃₀, V₄₀, and D_mean of left and whole thyroid, and the V₁₀ and D_mean of right thyroid were significantly lower in IMRT than those in VMAT (P＜0.001). Conclusions Both IMRT and VMAT plans can meet the clinical dosimetric requirements, among which IMRT has lower thyroid exposure dose and is more suitable for patients with high cardiac requirements.

Objective:To investigate the rates of low disease activity and clinical remission in patients with systemic lupus erythematosus(SLE)in a real-world setting,and to analyze the related factors of low disease activity and clinical remission.Methods:One thousand patients with SLE were enrolled from 11 teaching hospitals.Demographic,clinical and laboratory data,as well as treatment regimes were collec-ted by self-completed questionnaire.The rates of low disease activity and remission were calculated based on the lupus low disease activity state(LLDAS)and definitions of remission in SLE(DORIS).Charac-teristics of patients with LLDAS and DORIS were analyzed.Multivariate Logistic regression analysis was used to evaluate the related factors of LLDAS and DORIS remission.Results:20.7％of patients met the criteria of LLDAS,while 10.4％of patients achieved remission defined by DORIS.Patients who met LLDAS or DORIS remission had significantly higher proportion of patients with high income and longer disease duration,compared with non-remission group.Moreover,the rates of anemia,creatinine eleva-tion,increased erythrocyte sedimentation rate(ESR)and hypoalbuminemia was significantly lower in the LLDAS or DORIS group than in the non-remission group.Patients who received hydroxychloroquine for more than 12 months or immunosuppressant therapy for no less than 6 months earned higher rates of LLDAS and DORIS remission.The results of Logistic regression analysis showed that increased ESR,positive anti-dsDNA antibodies,low level of complement(C3 and C4),proteinuria,low household in-come were negatively related with LLDAS and DORIS remission.However,hydroxychloroquine usage for longer than 12 months were positively related with LLDAS and DORIS remission.Conclusion:LLDAS and DORIS remission of SLE patients remain to be improved.Treatment-to-target strategy and standar-dized application of hydroxychloroquine and immunosuppressants in SLE are recommended.

Objective To discuss the effect of PI3K-AKT signaling pathway regulated by microRNA-155(miRNA-155)targeted protein tyrosine phosphatase non-receptor type 21(PTPN21)on the proliferation,migration and invasion of hepatocellular carcinoma(HCC)cells.Methods Lentivirus transfection was used to silence the expression of miRNA-155 in human Huh7 HCC cells,and real-time fluorescent quantitative polymerase chain reaction(RT-qPCR)was used to detect the silencing effect of miR-155.After obtaining stable cell lines,the cell lines were randomly divided into Blank group(normal Huh7 cells),shNC group(Huh7 cells+empty miR-155 vector),sh-miR-155(Huh7 cells+miR-155 silencing),sh-miR-155+Recilisib group(Huh7 cells+miR-155 silencing+PI3K-AKT agonist),shNC+Recilisib group(Huh7 cells+empty miR-155 vector+PI3K-AKT agonist).Dual luciferase assay was used to determine whether PTPN21 was the downstream of miR-155.The cell proliferation ability of cells in each group was detected by MTT assay.The apoptosis level of each group was tested by flow cytometry.The invasion and migration ability of cells was assessed by Transwell assay.Western blot analysis was used to observe the differences in protein expression of PTPN21,PI3K,P-PI3K,AKT,P-AKT,and apoptosis-related proteins including BAX,BCL-2 and caspase-3 in all groups.Results The expression level of miR-155 in sh-miR-155 group was lower than that in Blank group and shNC group(P＜0.000 1),and the difference in miR-155 expression level between Blank group and shNC group was not statistically significant(P＞0.05).MTT results showed that A values of Huh7 cells at 2,3,4 and 5 day in sh-miR-155 group were lower than those in Blank group and shNC group(P＜0.000 1),while these differences between Blank group and shNC group were not statistically significant(P＞0.05).In sh-miR-155 group the A values at 2,3,4 and 5 day were lower than those in sh-miR-155+Recilisib group and shNC+Recilisib group(P=0.0052 and P＜0.0001,respectively),while the A values at 2,3,4 and 5 day in sh-miR-155+Recilisib were lower than those in shNC+Recilisib group(P＜0.000 1).There was no significant differences in cell migration and number of invasion cells between the Blank group and shNC group(P＞0.05).After activation of PI3K-AKT signaling pathway,the migration and invasion capacity of HCC cells in the shNC+Recilisib group were significantly enhanced when compared with the Blank group(P＜0.000 1).In contrast,the number of migrated and invaded Huh7 cells after miR-155 silencing was significantly lower than that in the Blank group and shNC group(P＜0.000 1)and this phenomenon became reversed by PI3K agonist.Compared with the sh-miR-155 group,in the sh-miR-155+Recilisib group the migration and invasion ability of HCC cells was enhanced(P=0.000 2).Lentiviral transfection of Huh7 human HCC cells to silence miR-155 and downregulate miR-155 inhibiting PTPN21 regulation of the PI3K-AKT signaling pathway,thus inhibiting the invasion,migration and proliferation ability of HCC cells and promoting the apoptosis of HCC cells.Conclusion miR-155 inhibits the migration,invasion and proliferation of HCC cells through targeting PTPN21 regulation of PI3K-AKT signaling pathway.The miR-155 may be a potential therapeutic target for HCC in the future.(J Intervent Radiol,2024,32:44-51)

Objective:To observe the therapeutic effect of vibrating the abdomen on anorexia model rats,as well as its effects on cholecystokinin octapeptide(CCK-8)and motilin(MTL)in the peripheral blood. Methods:Forty young rats were randomly divided into a normal group(n=10)and a modeling group(n=30).Rats in the normal group were fed common feed.The anorexia model was established by the etiological simulation method in the modeling group,and these rats were further randomly divided into a drug group,a vibrating abdomen group,and a model group 3 weeks after the anorexia model was induced,with 10 rats in each group.The drug group was given Jian Wei Xiao Shi Pian by intragastric administration at a dose of 0.72 g/(kg·bw)(0.72 g drug was dissolved in 10 mL purified water).The normal group and the model group were given purified water once a day in the morning.The vibrating abdomen group was treated with vibrating the abdomen once a day for 21 times.The body mass,food intake,serum CCK-8,MTL,gastrin(GAS),neurotensin(NT)levels,and the intestinal propulsion rate of rats in each group were measured. Results:Compared with the model group,the body mass,food intake,serum MTL and GAS levels,and the small intestine propulsion rate increased significantly,and the serum CCK-8 and NT levels,the gastric residual rate decreased significantly in the vibrating abdomen group and the drug group(P<0.05).There were no significant differences between the vibrating abdomen group and the drug group(P>0.05). Conclusion:Vibrating the abdomen increases the food intake and body mass of anorexia model rats,reduces the residue of gastric contents,improves the small intestine propulsion rate,and therefore has a good therapeutic effect on anorexia.The mechanism may be related to inhibiting the secretion of CCK-8 and NT in plasma and promoting the release of MTL and GAS in serum.

Objective A feasible and stable mouse model of thoracic aortic dissection(TAD)combined with acute lung injury(ALI)was established using β-aminopropionitrile monofumarate(BAPN)1 g/(kg·d)administered in drinking water.The mouse model of TAD combined with acute lung injury(ALI)was established to provide a rational animal model to study TAD combined with ALI.Methods Forty-five SPF-grade 3-week-old C57BL/6J male mice were selected and randomly allocated to a CON group(normal dietary water;15 mice)or BAPN group(administration in sterile water at 1 g/(kg·d);30 mice)for 4 weeks.During the experimental period,the general condition and modeling rate of mice were observed.TAD model mice were validated,and the BAPN group was divided into TAD and non-TAD groups by measuring the maximum diameter of the thoracic aorta and HE staining of aortic tissues.HE pathological staining,the wet/dry weight(W/D)ratio,total protein level in bronchioalveolar lavage fluid(BALF),and interleukin(IL)-1 β,IL-6,and tumor necrosis factor-α(TNF-α)in BALF)were used to validate the TAD combined ALI model in mice.Results BAPN treatment significantly delayed the increase in body mass and water intake of mice.Compared with CON and non-TAD groups,the maximum diameter of the thoracic aorta of mice in the TAD group was significantly thickened(P＜0.05).HE staining of the aorta showed significant thickening of the middle aortic layer,and the structure of the aortic wall was damaged and disordered.HE staining of lung tissues showed significant interstitial edema and inflammatory exudation accompanied by enlargement of alveolar lumen,alveolar wall epithelial exfoliation and hyaline membrane formation,and a significant increase in the pathological scores of lung injury(P＜0.05).Total protein levels and expression of IL-1β,IL-6,and TNF-α in lung tissue,W/D ratio,and BALF were also significantly increased(P＜0.05),whereas no significant difference was observed in the above indexes between the other two groups.Conclusions A mouse model of thoracic aortic dissection combined with acute lung injury can be established by BAPN administration in drinking water.

With the rapid development of information technology， research on ancient TCM books has shifted from the traditional collation and digitization into intelligent knowledge service， thereby achieving the deep integration of ancient TCM books collation and clinical needs. Based on the clinical problem and knowledge element theory， we implemented in-depth indexing and knowledge mining for 600 kinds of ancient TCM books， built a knowledge sharing service platform for ancient TCM books by integrating database， cloud platform， knowledge graph and other technologies， and carried out the thematic literature research and developed databases for four major diseases including stroke， heart failure， liver cirrhosis， and diabetes. The digital intelligence products have been applied in hundreds of hospitals for evaluation and feedback. Finally， through "digital processing plus intelligent application"， the two-way interaction between ancient TCM books and current clinical practice is realized， and the path and paradigm of ancient TCM books knowledge serving the modern prevention and control of major diseases is formed， providing reference for the innovative utilization of ancient TCM books.

Objective:To explore the clinical characteristics and genetic etiology of four children with Phelan-McDermid syndrome (PMS).Methods:Four children who had visited the Affiliated Women and Children′s Hospital of Ningbo University between June 2, 2022 and May 8, 2023 were selected as the study subjects. Clinical data of the children were collected. Genomic DNA was extracted from peripheral blood samples of the children and their parents and subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing and quantitative PCR (q-PCR) analysis. This study was approved by the Medical Ethics Committee of the Affiliated Women and Children′s Hospital of Ningbo University (Ethics No. EC2020-048).Results:All children had presented with speech and language delays and intellectual disability. Children 3 and 4 also presented with autistic behaviors. WES showed that the children 1 and 2 had respectively carried a heterozygous c.731T>C (p.Leu244Pro) and a c.2782_2851del (p.Gly928ArgfsTer4) variant of the SHANK3 gene. Sanger sequencing confirmed that their parents did not carry the same variant, suggesting that they were de novo in origin. Children 3 and 4 had respectively harbored a 121 kb and 52.02 kb heterozygous deletion at chromosome 22q13.33, which had both encompassed the SHANK3 and ACR genes mapped to 22q13.33. q-PCR results showed that the deletion of SHANK3 and ACR genes were de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 731T>C and c. 2782_2851del variants were predicted to be likely pathogenic (PS2+ PM2_Supporting+ PP3) and pathogenic (PVS1+ PM2_Supporting+ PS2_Supporting), respectively. Furthermore, the 52.02 kb and 121 kb heterozygous deletions in 22q13.33 were both predicted to be pathogenic (2D+ 4C, 1.05 in score; 2D+ 4C, 1 in score). Conclusion:The four children were all diagnosed with PMS by genetic testing. Above finding has enriched the phenotypic and mutational spectrum of PMS, and provided a basis for clinical diagnosis and genetic counseling for their families.

Objective:To understand the impact of diet on glycemic control in community-managed patients with type 2 diabetes mellitus (T2DM) and provide evidence for implementing prevention strategies and measures for diabetes patients.Methods:Eight communities were randomly selected from Changshu and Wuhan in 2015, and T2DM patients managed in the community were selected to conduct questionnaire surveys, physical measurements, and blood glucose testing. Factor analysis was used to obtain dietary patterns. A binary logistic regression model was used to analyze the factors affecting glycemic control.Results:Finally, 1 818 T2DM patients were included, and the control rate of FPG was 57.59% (95% CI: 55.30%-59.86%), and the control rate of 2 h postprandial blood glucose (2 h PBG) was 24.90% (95% CI: 22.93%- 26.91%). Five dietary patterns were obtained by factor analysis: animal food pattern, fruit-aquatic products-potato patterns, vegetable-grain pattern, egg-milk-bean pattern, and oil-salt patterns. No-conditional multivariate logistic regression analysis showed that after adjusting for confounding factors, the reduced probability of FPG control was related to animal food pattern ( OR=0.71, 95% CI: 0.52-0.98) and fruit-aquatic products-potato patterns ( OR=0.71, 95% CI: 0.51-0.97). The decrease in the 2 h PBG control probability was related to fruit-aquatic products-potato patterns ( OR=0.60, 95% CI: 0.40-0.90). The increased probability of FPG and 2 h postprandial glucose control were both related to vegetable-grain pattern ( OR=1.41, 95% CI: 1.03-1.94; OR=1.68, 95% CI: 1.13-2.51) and egg-milk-bean pattern ( OR=1.75, 95% CI: 1.25-2.46; OR=1.56, 95% CI: 1.00-2.42). Compared with the Q4 group of egg-milk-bean pattern, the FPG control rate of the combination of "fruit-aquatic products-potato pattern ( Q4 group), vegetable-grain pattern ( Q2 group), egg-milk-bean pattern ( Q3 group)" was higher ( OR=6.79, 95% CI: 1.15-40.23, P=0.035). Compared with the Q4 group of vegetable-grain pattern, the combination of "fruit-aquatic products-potato pattern ( Q4 group), vegetable-grain pattern ( Q3 group), egg-milk-bean pattern ( Q2 group), oil-salt pattern ( Q2 group)" had higher control rate of 2 h PBG ( OR=12.78, 95% CI: 1.26-130.05, P=0.031). Conclusions:A proper combination of dietary patterns and dietary patterns are more conducive to the control of FPG and 2 h PBG in T2DM patients managed in the communities of Wuhan and Changshu. Patient nutrition education should be strengthened, and the food-matching ability of patients should be improved.