Objective To determine the prognostic biomarkers and new therapeutic targets of the lung adenocarcinoma (LUAD), based on which to establish a prediction model for the survival of LUAD patients. Methods An integrative analysis was conducted on gene expression and clinicopathologic data of LUAD, which were obtained from the UCSC database. Subsequently, various methods, including screening of differentially expressed genes (DEGs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Set Enrichment Analysis (GSEA), were employed to analyze the data. Cox regression and least absolute shrinkage and selection operator (LASSO) regression were used to establish an assessment model. Based on this model, we constructed a nomogram to predict the probable survival of LUAD patients at different time points (1-year, 2-year, 3-year, 5-year, and 10-year). Finally, we evaluated the predictive ability of our model using Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves. The validation group further verified the prognostic value of the model. Results The different-grade pathological subtypes' DEGs were mainly enriched in biological processes such as metabolism of xenobiotics by cytochrome P450, natural killer cell-mediated cytotoxicity, antigen processing and presentation, and regulation of enzyme activity, which were closely related to tumor development. Through Cox regression and LASSO regression, we constructed a reliable prediction model consisting of a five-gene panel (MELTF, MAGEA1, FGF19, DKK4, C14ORF105). The model demonstrated excellent specificity and sensitivity in ROC curves, with an area under the curve (AUC) of 0.675. The time-dependent ROC analysis revealed AUC values of 0.893, 0.713, and 0.632 for 1-year, 3-year, and 5-year survival, respectively. The advantage of the model was also verified in the validation group. Additionally, we developed a nomogram that accurately predicted survival, as demonstrated by calibration curves and C-index. Conclusion We have developed a prognostic prediction model for LUAD consisting of five genes. This novel approach offers clinical practitioners a personalized tool for making informed decisions regarding the prognosis of their patients.

Objective Reliability and validity of the Chinese version of disability attitude scales(DAS-CN)toward disabled persons were created and tested to provide an assessment instrument for measuring the attitude of medical staff toward disabled persons in China.Methods Authorised by the author of DAS in August 2020,based on BRISLIN translation model,the English version of DAS was translated into Chinese followed by back translation,cultural debugging and then put it into pre-experiment in September 2020.The reliability and validity of the finalised DAS-CN were further tested in a survey with 400 randomly selected medical staff in rehabilitation from 8 general hospitals in Jinzhou,Panjin,Yingkou and Fushun in Liaoning Province,China by using the convenience sampling method in March 2021.Results A total of 357 surveyees completed the survey.The localised DSA-CN was composed of 4 dimensions with a total of 20 items,including 4 items in clinical knowledge and skills,4 in clinical responsibility,8 in clinical behaviour and 4 in emotional response.The Cronbach α coefficient of the scales was 0.943,with the split-half reliability and test-retest reliability at 0.824 and 0.899,respectively.The Cronbach α coefficient of each dimension was 0.843～0.944,and the split half reliability was 0.854～0.904.The test-retest reliability ranged from 0.701 to 0.913.The KMO value of exploratory factor analysis was 0.921.The Bartrett spherical test value was 5534.981(P<0.01).The total explanatory rate of variation was 73.050%.Conclusion The Chinese version of Disability Attitude Scales(DSA-CN)has good reliability and validity.Therefore,DSA-CN can be used as an instrument in investigation of the current status about the attitudes towards the disabled persons among the medical staff in China.

ObjectiveTemporal heterogeneity in lung cancer presents as fluctuations in the biological characteristics, genomic mutations, proliferation rates, and chemotherapeutic responses of tumor cells over time, posing a significant barrier to effective treatment. The complexity of this temporal variance, coupled with the spatial diversity of lung cancer, presents formidable challenges for research. This article will pave the way for new avenues in lung cancer research, aiding in a deeper understanding of the temporal heterogeneity of lung cancer, thereby enhancing the cure rate for lung cancer. MethodsRaman spectroscopy emerges as a powerful tool for real-time surveillance of biomolecular composition changes in lung cancer at the cellular scale, thus shedding light on the disease’s temporal heterogeneity. In our investigation, we harnessed Raman spectroscopic microscopy alongside multivariate statistical analysis to scrutinize the biomolecular alterations in human lung epithelial cells across various timeframes after benzo(a)pyrene exposure. ResultsOur findings indicated a temporal reduction in nucleic acids, lipids, proteins, and carotenoids, coinciding with a rise in glucose concentration. These patterns suggest that benzo(a)pyrene induces structural damage to the genetic material, accelerates lipid peroxidation, disrupts protein metabolism, curtails carotenoid production, and alters glucose metabolic pathways. Employing Raman spectroscopy enabled us to monitor the biomolecular dynamics within lung cancer cells in a real-time, non-invasive, and non-destructive manner, facilitating the elucidation of pivotal molecular features. ConclusionThis research enhances the comprehension of lung cancer progression and supports the development of personalized therapeutic approaches, which may improve the clinical outcomes for patients.

Glycosylation is one of the most important reactions in living organisms as it results in the formation of glycoconjugates with diverse biological functions. Sugar nucleotides are structurally composed of sugar and nucleoside diphosphate or monophosphate, which are widespread within a variety of biological cells. As glycosyl donors for the transglycosyl reactions catalyzed by Leloir-type glycosyltransferases, sugar nucleotides are essential for the synthesis of glycans and glycoconjugates. However, high costs and limited availability of nucleotide sugars prevent applications of biocatalytic cascades on an industrial scale. Therefore, attentions on synthetic strategies of sugar nucleotides have been increasing to achieve their wide applications in various fields. The 9 common sugar nucleotides in mammals have been fully studied with large-scale synthesis through chemical, enzymatic (chemo-enzymatic) and cell factory strategies. In addition to common sugar nucleotides, many rare sugar nucleotides are present in plants and bacteria. Although unnatural sugar nucleotides cannot be synthesized in organisms, they have great potential in research as substrates for glycosyltransferases in carbohydrate synthesis, as enzyme inhibitors in biochemical studies, and as components of glycoconjugate biosynthesis. Therefore, increasing attention has been paid to explore the efficient synthesis of unnatural sugar nucleotides. Currently, strategies for chemical synthesis of sugar nucleotides have been greatly improved, such as the use of effective catalysts for forming pyrophosphate bonds and the development of entirely new synthesis protocols. Multiple sugar nucleotides, especially unnatural sugar nucleotides, are synthesized chemically. However, chemical synthesis requires tedious protection and deprotection steps, resulting in complex steps, high cost and low yield. In contrast, enzymatic (chemo-enzymatic) and cell factory methods have significant advantages such as high yield, easy operation and easy process scale-up in the preparation of sugar nucleotides. Hence, they are prominent strategies for sugar nucleotide preparation. Herein, the biosynthesis and application of sugar nucleotides are reviewed, mainly focusing on the 9 sugar nucleotides common in mammals. The early strategies for enzymatic synthesis of sugar nucleotides generally used de novo synthesis pathway. With the discoveries of enzymes involved in salvage pathway of sugar nucleotide synthesis and the development of one-pot multienzyme (OPME) method, the synthesis of sugar nucleotides was greatly simplified. Cell factory method employs the microbial living cells as a “processing plant” by engineering their metabolic pathways through genetic engineering technology. The cell factory method has high yield, and has been applied for efficient synthesis of several sugar nucleotides. Moreover, the strategy of gram-scale synthesis of multiple rare sugar nucleotides by cascade reactions from common sugar nucleotides using sugar nucleotides synthases cloned from different sources was illustrated. In recent years, the synthesis cost of sugar nucleotides has been further reduced through various ways, such as regeneration of nucleotides, regeneration of organic cofactors, and application of immobilized enzyme technology. Furthermore, through the continuous improvement of sugar nucleotide purification process, the use of high concentration of multi-enzyme cascade and rapid non-chromatographic purification process, the synthesis of multiple sugar nucleotides and their derivatives from monosaccharides was achieved, which gradually broke the limitations of the existing strategy. With the efficient synthesis of sugar nucleotides, their applications in various fields have been increasingly explored, including the synthesis of glycans and glycoconjugates, biochemical characterization of glycosyltransferases and bioorthogonal labeling strategies, which are of great significance to the research of biochemistry, glycobiology and the development of related pharmaceutical products.

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 observe the clinical and symptomatic improvement three months after uterine artery embolization(UAE),and to analyze the value of apparent diffusion coefficient(ADC)in MR diffusion weighted imaging(DWI)in assessing the response of fibroids volume after UAE.Methods A total of 40 patients with uterine fibroids were included.The volume changes of fibroids,clinical and symptomatic improvement before and after treatment were recorded,and the efficacy of UAE was comprehensively analyzed.All patients underwent MR DWI before UAE and were evaluated at three months postoperatively by outpatient MR follow-up,with fibroids vol-ume and ADC quantitative measurements were performed to compare the changes in ADC values of fibroids preoperatively and post-operatively at each b value.Pearson correlation analysis was performed to analyze the correlation between baseline ADC values and postoperative fibroids volume reduction.Regression analysis was performed to assess the relationship between ADC and fibroids volume reduction after UAE.And the receiver operating characteristic(ROC)curve were plotted to analyze the predictive value of ADC values for evaluating fibroids volume reduction of more than 30％after UAE.Results The patients'clinical symptoms was improved in the three months after surgery,the volume of fibroids was significantly reduced,and the life quality was improved,the difference was sta-tistically significant(P＜0.05).There was no significant effect on ovarian function,hormone levels did not change significantly com-pared to before surgery,with no statistical significance(P＞0.05).When b=50,1 000 s/mm2,the changes in ADC values before and after uterine fibroids treatment were not significant,with no statistical significance(P＞0.05).However,the changes in ADC values before and after uterine fibroids treatment were significant when b=800 s/mm2 and the difference was statistically significant(P＜0.05).Under the condition of b=800 s/mm2,Pearson correlation analysis showed ADC value had a positive correlation with postoperative uterine fibroids volume reduction rate(r=0.45,P＜0.05),and the area under the curve(AUC)for ADC value to predict the reduction rate of uterine fibroids volume by more than 30％after UAE was 0.787.The cut-off value was 1.143 × 10-3 mm2/s,with sensitivity and specificity of 0.793 and 0.818,respectively.Conclusion UAE is more effective in treating uterine fibroids.The baseline ADC value of uterine fibroids correlated significantly with the volume reduction after UAE.The ADC value can be used to assess the volume response after UAE.

Objective:The primary goal of this study is to explore the safety and effectiveness of a new modified eversion carotid endarterectomy (MECEA).Methods:This is a retrospective case series study. One hundred patients were consecutively treated with MECEA by the same operator at Department of Vascular Surgery,Peking Union Medical College Hospital from January 2019 to December 2023. There were 77 males and 23 females. The age was (66.0±8.6)years (range: 39 to 85 years). Twenty-four (24.0%) patients were symptomatic with the degree of carotid stenosis over 50%,76 patients (76.0%) were asymptomatic with the degree of stenosis over 70%. All these patients meet the indication of carotid endarterectomy. The main difference between MECEA and traditional eversion carotid endarterectomy was the anterior,lateral,and posterior walls of the internal carotid artery were incised obliquely from the origin of the internal carotid artery toward the common carotid artery,leaving the wall of internal carotid artery intact at the bifurcation. The surgical process,cardiovascular and cerebrovascular complications and other surgical complications were recorded. The incidences of complications,restenosis of intraoperative target lesions and re-intervention were collected during follow-up.Results:All procedures were performed successfully under general anesthesia. The total operation time was (36.5±10.1)minutes (range: 22 to 65 minutes),and carotid clamping time was (15.0±6.3)minutes (range: 7 to 31 minutes). One patient (1.0%) occurred postoperative cerebrovascular accident,1 patient (1.0%) developed cerebral hyperperfusion syndrome (CHS),and another 1 patient (1.0%) suffered myocardial infarction. All these patients were recovered after medical treatment within a week. The follow-up time( M(IQR)) was 24 (28) months (range: 6 to 62 months). Two patients (2.0%) were reported to have hemodynamically significant restenosis within 2 years,with one patient requiring intervention. No patient suffered from ipsilateral ischemic stroke. Conclusions:MECEA is a safe and effective surgical method of treating carotid artery stenosis. This method can reduce carotid clamping time and lowers the risk of ischemic stroke. Meantime,it preserves the integrity of the adventitia at the bifurcation of carotid artery,reduces the chance of restenosis. Moreover,it might be helpful to prevent postoperative CHS due to reducing damage to the carotid body and carotid sinus nerve.

Objective To investigate the clinical features and prognosis of childhood acute lymphoblastic leukemia (ALL) with CREBBP gene mutation. Methods A retrospective analysis was performed for the clinical data of 14 ALL children with CREBBP gene mutation who were admitted to Children's Hospital of the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2023. Results The ALL patients with CREBBP gene mutation accounted for 1.5％ (14/963) among all children diagnosed with ALL during the same period of time,among whom there were 4 boys (29％) and 10 girls (71％),with a median age of 4 years and 3.5 months. All children had an immunological type of B-cell ALL and concurrent mutations in other genes including NRAS,KRAS,ETV6,FLT3,PAX5,SH2B3,CDKN2A,and CDKN2B,and 4 children had karyotype abnormality. All 14 children received induction therapy with the VDLP regimen,with a complete remission (CR) rate of 79％ (11/14) after the first course of treatment. Three children experienced bone marrow recurrence alone,with a recurrence rate of 21％ (3/14),among whom 1 child achieved CR after blinatumomab therapy and 2 received bridging hematopoietic stem cell transplantation after chemotherapy for recurrence. Among the 14 children,1 died due to treatment discontinuation and 13 achieved disease-free survival. The 5-year overall survival rate was 92％±7％,and the event-free survival rate was 73％±13％. Conclusions ALL with CREBBP gene mutation is more common in girls and has a low induction remission rate and a high recurrence rate,and it is often accompanied by other types of gene mutations and abnormal karyotypes. Most children with recurrence can achieve long-term survival after immunotherapy or hematopoietic stem cell transplantation.

Objective:The primary goal of this study is to explore the safety and effectiveness of a new modified eversion carotid endarterectomy (MECEA).Methods:This is a retrospective case series study. One hundred patients were consecutively treated with MECEA by the same operator at Department of Vascular Surgery,Peking Union Medical College Hospital from January 2019 to December 2023. There were 77 males and 23 females. The age was (66.0±8.6)years (range: 39 to 85 years). Twenty-four (24.0%) patients were symptomatic with the degree of carotid stenosis over 50%,76 patients (76.0%) were asymptomatic with the degree of stenosis over 70%. All these patients meet the indication of carotid endarterectomy. The main difference between MECEA and traditional eversion carotid endarterectomy was the anterior,lateral,and posterior walls of the internal carotid artery were incised obliquely from the origin of the internal carotid artery toward the common carotid artery,leaving the wall of internal carotid artery intact at the bifurcation. The surgical process,cardiovascular and cerebrovascular complications and other surgical complications were recorded. The incidences of complications,restenosis of intraoperative target lesions and re-intervention were collected during follow-up.Results:All procedures were performed successfully under general anesthesia. The total operation time was (36.5±10.1)minutes (range: 22 to 65 minutes),and carotid clamping time was (15.0±6.3)minutes (range: 7 to 31 minutes). One patient (1.0%) occurred postoperative cerebrovascular accident,1 patient (1.0%) developed cerebral hyperperfusion syndrome (CHS),and another 1 patient (1.0%) suffered myocardial infarction. All these patients were recovered after medical treatment within a week. The follow-up time( M(IQR)) was 24 (28) months (range: 6 to 62 months). Two patients (2.0%) were reported to have hemodynamically significant restenosis within 2 years,with one patient requiring intervention. No patient suffered from ipsilateral ischemic stroke. Conclusions:MECEA is a safe and effective surgical method of treating carotid artery stenosis. This method can reduce carotid clamping time and lowers the risk of ischemic stroke. Meantime,it preserves the integrity of the adventitia at the bifurcation of carotid artery,reduces the chance of restenosis. Moreover,it might be helpful to prevent postoperative CHS due to reducing damage to the carotid body and carotid sinus nerve.

The articles involving Xiangju Capsules were retrieved, and qualitative research and quantitative research methods were combined to evaluate the evidence of the safety, effectiveness, economy, innovation, suitability, accessibility, and characteristics of traditional Chinese medicine( "6+1" dimensions) of this drug. Multi-criteria decision analysis(MCDA) model and CSC v2.0 software were used to comprehensively evaluate the clinical value of Xiangju Capsules in the treatment of rhinosinusitis and clarify the precise clinical positioning. The dimensions are graded A, B, C, or D. Multi-source safety evidence showed that the main adverse reactions were gastrointestinal reactions, rash, itching, dizziness, and headache. Based on the available studies, the risk is controllable and the safety is grade A. Meta-analysis showed that Xiangju Capsules + conventional western medicine could recover the Lund-Kennedy score, Lund-Mackay score, and CT score, relieve headache, nasal congestion, olfactory disturbance, and facial pain, with the effectiveness is grade B. The incremental cost-effectiveness ratio of Xiangju Capsules + conventional western medicine compared with conventional western medicine alone in the treatment of chronic rhinosinusitis was 263.71 yuan, about 0.82% of the per capita disposable income. The results of sensitivity analysis showed that the research results were relatively robust. Based on the assumption that the per capita disposable income in 2020 will be the threshold of patients' willingness to pay, it is more economical to use Xiangju Capsules + conventional western medicine. The drug belongs to grade A of the national medical insurance, with an average daily cost of 3.06 yuan, and the economy is grade B. This formula is modified from classic formulas and characteristic empirical formulas, be capable of improving immunity and preventing repeated attacks. It can be used for acute and chronic rhinitis-rhinosinusitis. It had a wide range of applicability, especially for the patients with head and face tenderness. Service innovation was reflected in the measures to guarantee supply, capacity, scalability, and coverage of grass-roots sales channels. The industrial innovation was improved through the management of medicinal resources, pharmaceutical industry, production technology, quality control, scientific research and development, and this formula won three national invention patents. Comprehensively, the innovation of Xiangju Capsules is grade B. According to the survey of 188 medical practitioners and 196 patients in 20 provinces, municipalities, and autonomous regions of China, the drug was characterized by easy preparation and administration, individualized medication, simple technology and management, convenient use, storage, and transport, and controllable adverse reactions, with the suitability is grade B. Xiangju Capsules showed the cost of 45.9 and 275.4 yuan for treatment of acute and chronic rhinitis-rhinosinusitis, respectively, being well affordable. It was sold in 35 000 medical institutions in China. The dosage form was suitable for transportation, storage, and grass-root application. With rich, sustainable, and available medicinal resources, the accessibility of Xiangju Capsules is grade A. This drug can be used for both acute and chronic rhinitis-rhinosinusitis, clearing heat and expelling pus, and strengthening the exterior to prevent relapse. After this drug was available on the market, over 4 000 cases were studied, with rich experience in human use accumulated, and characteristics of traditional Chinese medicine is grade B. Overall, the clinical value of Xiangju Capsules is class B. It is suggested that Xiangju Capsules should be used in accordance with the relevant policies of basic clinical drug administration to play its role.
Humans ; Rhinitis/drug therapy* ; Sinusitis/drug therapy* ; Medicine, Chinese Traditional ; Headache ; China ; Capsules