Objective To analyze the layout and shielding effectiveness of medical accelerator vaults, and to provide a reference for the layout, shielding design, and optimization of protection of medical accelerator vaults. Methods Four medical accelerator radiotherapy vaults were selected. The layouts of these vaults were compared with the layout requirements in the radiation therapy protection standards. For each vault, the dose rates at four points of interest outside the shielding were calculated, including the primary shielding area, secondary shielding area, maze outer wall, and lateral shielding area. These values were then compared with the actual measurements obtained using a dose rate meter. Results All four vaults were located on the ground floor of the building and included a maze, with the auxiliary rooms all placed outside the treatment rooms. However, one vault was not located at one end of the building, and in another vault, the control room was exposed to direct irradiation of the useful beam. The calculated dose rates outside the primary shielding area ranged from 0.04 μSv/h to 0.62 μSv/h, while the measured values ranged from 0.10 μSv/h to 0.66 μSv/h, with the measured values being higher than the calculated ones. The calculated dose rates outside the secondary shielding area ranged from 0.0005 μSv/h to 0.12 μSv/h, those outside the maze outer wall ranged from 0.06 μSv/h to 0.18 μSv/h, and those outside the lateral shielding area ranged from 0.009 μSv/h to 0.15 μSv/h; the measured values were all below the detection limit. Conclusion Inadequate layouts were observed in some of the accelerator vaults. The calculated and measured dose rates at points of interest outside the vaults were both significantly lower than the shielding protection requirements in standards, indicating that the shielding designs were overly conservative. Construction units should follow the principle of optimization of radiation protection to design the layout and shielding reasonably and pay attention to the underestimation of dose rates outside the primary shielding caused by the tenth value layer.

Objective: To analyze the adverse treatment outcome status and spatio temporal characteristics of pulmonary tuberculosis cases among students in Qinghai Province, providing a reference basis for pulmonary tuberculosis prevention and control in schools. Methods: The data of student pulmonary tuberculosis cases during 2013-2023 in Qinghai Province were obtained through the "National Tuberculosis Management Information System", and the treatment outcome was retrospectively analyzed. The Joinpoint model was applied to analyze the adverse outcome rate trend. Global and local spatial autocorrelation analysis, and spatiotemporal scan cluster analysis were conducted on the adverse outcome rate of pulmonary tuberculosis among students in Qinghai Province. Results: During 2013-2023, 488 cases of adverse outcomes were reported among 6 155 students with pulmonary tuberculosis in Qinghai Province, with an adverse outcome rate of 7.93%. The reporting adverse outcome rate of pulmonary tuberculosis among students showed a downward trend from 2013 to 2023 (APC=-16.20, t =-3.89, P <0.05). The results of spatial autocorrelation showed that the adverse outcome rate of pulmonary tuberculosis was Moran s I >0 among students in Qinghai Province. Among them, there was a spatially positive correlation in the adverse outcome rate of pulmonary tuberculosis among students in 2020, 2021 and 2022(all Z >1.96, all P <0.05). The results of clustering and outlier analysis in local spatial autocorrelation showed that the areas with high high aggregation were mainly concentrated in Yushu Prefecture(Zhiduo County, Zaduo County, Nangqian County, Yushu City), Huangnan Prefecture (Zeku County, Henan County) and Hainan Prefecture (Tongde County). The low low concentration areas were distributed in Haidong City, Xining City, Haibei Prefecture (Gangcha County, Qilian County), Haixi Prefecture (Tianjun County, Ulan County), Hainan Prefecture (Gonghe County, Guide County) and Huangnan Prefecture (Tongren City, Jianzha County). The spatio temporal scanning showed that a total of two possible aggregation areas had been detected. Among them, the first level aggregation area composed of 10 counties and districts in Yushu Prefecture and Guoluo Prefecture of Qinghai Province, and the cluster radius was 658.09 km, the RR was 10.58 , and the LLR was 305.91; the second level aggregation area was composed of 16 counties and districts in Hainan Prefecture, Haixi Prefecture, Huangnan Prefecture and Guoluo Prefecture, and the cluster radius was 407.02 km, the RR was 9.83, and the LLR was 152.48 (both P <0.05). Conclusions The reporting rates of adverse treatment outcome of pulmonary tuberculosis cases among students in Qinghai Province remain relatively high and unevenly distribute throughout the province. Supervision should be strengthened to improve cases compliance,and to reduce student pulmonary tuberculosis adverse treatment outcomes incidence.

Daochisan is a pediatric famous classical formula in traditional Chinese medicine（TCM） specializing in clearing the heart， disinhibiting water and enriching Yin， which has been inherited and developed by medical experts of successive generations. The formula can be traced back to Xiaoer Yaozheng Zhijue written by QIAN Yi from Song dynasty， and most of the later-developed Daochisan（Daochitang） is based on this formula with additions and subtractions. So as to promote the literature excavation of this formula， this paper conducts a thorough textual research and analysis of the composition， processing， preparation methods， clinical applications of Daochisan based on a systematic collation of relevant ancient and modern literature in the method of bibliometrics. A total of 127 pieces of data involving 86 antient TCM books were collected. Statistical analysis showed that the drug origin of Daochisan is basically clear， we suggest that Rehmanniae Radix is the root tuber of Rehmannia glutinosa of Scrophulariaceae， Akebiae Caulis is the dry stem of Akebia quinata of Lardizabalaceae， Glycyrrhizae Radix et Rhizoma is the dry root and stem of Glycyrrhiza uralensis of legume， bamboo leaf is the dry leaves of Phyllostachys nigra var. henonis of gramineous plants. Four herbs are recommended to use its raw products. The key information of the dosage and decocting method is supposed to be "4.13 g each of raw Rehmanniae Radix， raw Glycyrrhizae Radix et Rhizoma， Akebiae Caulis， adding 300 mL of water， and then adding 4.13 g of bamboo leaf， decocting together to 150 mL， taking warmly after meal". Daochisan has the effect of clearing the heart and enriching Yin， disinhibiting water and relieving stranguria， and is widely used in treating symptoms such as heart vexed hotness， hydrodipsia and reddish complexion. Modern studies have showed that Daochisan are frequently used in treating oral ulcer， herpetic stomatitis， urinary tract infection， herpes zoster and other diseases. The above research results can provide scientific reference for the future development and research of Daochisan.

This paper discussed the historic evolution of Juanbitang and similar decoctions， clarified the historic development of Yangshi Juanbitang and Chengshi Juanbitang， and probed into the key information of the meaning， original plants， processing methods， and modern dosage and usage of Chengshi Juanbitang. A total of 267 pieces of relevant information were collected from ancient traditional Chinese medicine （TCM） books， among which 53 pieces of effective data were included in this study. The results showed that both Chenshi Juanbitang and Yangshi Juanbitang were originated from Duhuo Jishengtang recoded in the Important Prescriptions Worth a Thousand Gold for Emergency （Bei Ji Qian Jin Yao Fang）. According to the standard of "1 qian roughly equals 3.73 g" in the measurement system of the Qing Dynasty， we suggest Chenshi Juanbitang is composed of 3.73 g Notopterygii Rhizoma et Radix， 3.73 g Angelicae Pubescentis Radix， 3.73 g Gentianae Macrophyllae Radix， 11.19 g Angelicae Sinensis Radix， 11.19 g Mori Ramulus， 2.61 g Chuanxiong Rhizoma， 1.87 g Cinnamomi Cortex， 1.87 g stir-fried Glycyrrhizae Radix et Rhizoma， 7.46 g Piperis Kadsurae Caulis， 2.98 g Olibanum， and 2.98 g Aucklandiae Radix， which should be decocted with 600 mL water to reach a volume of 300 mL. The decoction should be taken 3 times a day before meals. Juanbitang， a classical formula specialized for treating impediment diseases， has the effects of dispelling wind， removing dryness， and alleviating impediment to relieve pain. It can be used for treating vexing pain in body， spasm of nape and back， and heaviness in waists and legs. Modern studies have shown that Juanbitang can be used for treating rheumatoid arthritis， knee osteoarthritis， and periarthritis of shoulder. The above results served as a reference for the future development of Juanbitang.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

OBJECTIVE: Hepatic fibrosis has been widely considered as a conjoint consequence of almost all chronic liver diseases. Chuanxiong Rhizoma (Chuanxiong in Chinese, CX) is a traditional Chinese herbal product to prevent cerebrovascular, gynecologic and hepatic diseases. Our previous study found that CX extracts significantly reduced collagen contraction force of hepatic stellate cells (HSCs). Here, this study aimed to compare the protection of different CX extracts on bile duct ligation (BDL)-induced liver fibrosis and investigate plausible underlying mechanisms. METHODS: The active compounds of CX extracts were identified by high performance liquid chromatography (HPLC). Network pharmacology was used to determine potential targets of CX against hepatic fibrosis. Bile duct hyperplasia and liver fibrosis were evaluated by serologic testing and histopathological evaluation. The expression of targets of interest was determined by quantitative real-time PCR (qPCR) and Western blot. RESULTS: Different CX extracts were identified by tetramethylpyrazine, ferulic acid and senkyunolide A. Based on the network pharmacological analysis, 42 overlap targets were obtained via merging the candidates targets of CX and liver fibrosis. Different aqueous, alkaloid and phthalide extracts of CX (CX_AE, CX_AL and CX_PHL) significantly inhibited diffuse severe bile duct hyperplasia and thus suppressed hepatic fibrosis by decreasing CCCTC binding factor (CTCF)-c-MYC-long non-coding RNA H19 (H19) pathway in the BDL-induced mouse model. Meanwhile, CX extracts, especially CX_AL and CX_PHL also suppressed CTCF-c-MYC-H19 pathway and inhibited ductular reaction in cholangiocytes stimulated with taurocholate acid (TCA), lithocholic acid (LCA) and transforming growth factor beta (TGF-β), as illustrated by decreased bile duct proliferation markers. CONCLUSION Our data supported that different CX extracts, especially CX_AL and CX_PHL significantly alleviated hepatic fibrosis and bile duct hyperplasia via inhibiting CTCF-c-MYC-H19 pathway, providing novel insights into the anti-fibrotic mechanism of CX.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

ObjectiveTo explore the molecular mechanism implicated in the treatment of primary myelofibrosis （PMF） using Chinese medicinal herbs （CMH） by bioinformatics and molecular dynamics. MethodsData mining was performed to find the high-frequency CMH in treating PMF between the year of 1985 and 2024 by searching CNKI， Chinese Science and Technology Journal Database （CCD）， and China Academic Journal Database （CSPD）. TCMSP， SwissTargetPrediction and related reports were used to collect the main active ingredients of high-frequency CMH and their targets. The PMF datasets GSE44426 and GSE124281 were downloaded from GEO database， and R software was used for data normalization and differentially expressed genes （DEGs） screening. Key module hub genes were obtained by weighted gene co-expression network analysis （WGCNA） analysis. The common intersection genes of active ingredient targets， DEGs and key module hub genes of CMH were selected， and the target network was generated using Cytoscape 3.9.2 software. The core target network was generated by topological analysis， while key pathways were selected by GO and KEGG pathway enrichment analysis， and protein interaction relationships were obtained from the String database， so as to construct drug-ingredient-target network and protein interaction network （PPI） relationship diagrams. Discovery Studio 2020 software was used to perform molecular docking， and the GROMACS program was used to perform molecular dynamics simulation. ResultsA total of 21 prescriptions were collected involving 121 herbs. There were 9 herbs with a frequency ≥10 times， which were Danshen （Radix et Rhizoma Salviae Miltiorrhizae）， Huangqi （Radix Astragali）， Baizhu （Rhizoma Atractylodis Macrocephalae）， Danggui （Radix Angelicae Sinensis）， Dangshen （Radix Codonopsis）， Gancao （Radix et Rhizoma Glycyrrhizae）， Baishao （Radix Paeoniae Alba）， Fuling （Poria） and Shudihuang （Radix Rehmanniae Praeparata） from high- to low-frequency. A total of 98 active ingredients and 1125 potential targets were obtained from 9 high-frequency CMH. GSE44426 and GSE124281 data sets screened out 24 gene samples， including 14 of the healthy control group and 10 of the PMF group， and identified 319 DEGs between the two groups， including 122 up-regulated genes and 197 down-regulated genes. WGCNA screened out 24 co-expression module genes and found that the five modules closely related to the onset of PMF were MEpink， MEdarkred， MEblack， MEgrey， and MEturquoise， involving 7112 key module hub genes. The GO and KEGG enrichment analyses indicated that lipids and the atherosclerosis pathways were mainly involved in the mechanism of above high-frequency CMH in treating PMF， which included six hub protein targets： HSP90AA1， HSP90AB1， SRC， MAPK1， IL1B and IL10. From the drug-ingredient-target network， seven active ingredients of CMH targeting at these six hub targets were found， including verbascoside， verbascos isoflavone， kaempferol， luteolin， naringenin， quercetin and pachymic acid. The molecular docking and molecular dynamics analyses showed that the key CMH were Shudihuang， Huangqi， Baishao， Danshen， Gancao and Fuling， and among the seven active ingredients， calycosin had the highest binding affinity with HSP90AB1. ConclusionThe main CMH for the treatment of PMF may be Shudihuang， Huangqi， Baishao， Danshen， Gancao and Fuling， and the active ingredients include verbascoside， verbascos isoflavones， kaempferol， luteolin， naringenin， quercetin and pachymic acid. The relevant targets are HSP90AA1， HSP90AB1， SRC， MAPK1， IL-10， and IL-1β， and the most critical pathways are lipid and atherosclerosis pathways.

Objective To investigate the reliability and validity of the assessment tools of Brief ICF Core Sets for Arthroplasty of Knee Osteoarthritis in Perioperative Period(ICSAKOPP). Methods From May,2022 to April,2023,320 patients undergoing knee arthroplasty were selected in Peking University Third Hospital,China-Japan Friendship Hospital,Peking University First Hospital and Chinese PLA General Hospital.Trained assessors used Brief ICSAKOPP to evaluate all enrolled patients before arthroplasty,three days(±one day)after arthroplasty,three weeks(±one week)after arthroplasty,and three months(±one month)after ar-throplasty.Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)scores were recorded at the same time.Five professionals were asked to score all the items of Brief ICSAKOPP,and the content validity index(CVI)was caculated. Results A total of 64 cases were dropped down.CVI of all the items of the Brief ICSAKOPP were above 0.8,with a av-erage CVI of the scale of 0.938.The Cronbach's α coefficient of the Brief ICSAKOPP was 0.813.There was a moderate correlation(r=0.681,P<0.001)between the overall Brief ICSAKOPP and WOMAC scores,as well as body functional dimension score(r=0.668,P<0.001)and activities and participation dimension score(r=0.657,P<0.001). Conclusion Brief ICSAKOPP is good in content validity,internal consistency reliability and criterion validity.

Objective To investigate the long-term incidence of in-stent stenosis(ISS)in patients with intracranial aneurysms receiving pipeline embolization device(PED)who showed no ISS at short-to-medium term follow-up examination.Methods The clinical data of patients,who received PED treatment at the Department of Neurointervention,First Affiliated Hospital of Zhengzhou University of China between April 2015 and June 2022,were retrospectively collected.The patients with intracranial aneurysms,who showed no ISS at the initial follow-up with DS A and completed＞12 months long-term follow-up check after treatment at the same hospital,were screened out,and their relevant clinical data and imaging materials were collected.The incidence of ISS occurring in postoperative＞12 months long-term follow-up was calculated.The ISS was defined as a＞25％lumen loss of the parent artery when compared with its lumen size measured immediately after PED implantation.Results A total of 57 patients with 61 aneurysms were enrolled in this study,and a total of 68 PEDs were implanted.Forty-one(67.21％)aneurysms were treated by PED implantation only,and 20(32.79％)aneurysms by PED plus spring coils.The median initial follow-up time was 184.0 days(119.0,212.5).At postoperative＞12 months long-term follow-up visit,DSA was employed for 35(57.38％)aneurysms,CTA was adopted for 22(36.07％)aneurysms,and 3D-SPACE sequence MR scan was performed in 4(6.56％)aneurysms.The median follow-up time was 538.0 days(407.5,678.0),and the incidence of ISS was 0％.No ISS-related neurological symptoms occurred in all patients.Conclusion In treating intracranial aneurysms with PED,the postoperative incidence of ISS is low.No ISS is found during the short-term follow-up period,and long-term follow-up results tend to indicate that no ISS events have occurred.