3D printing technology, with a layer-by-layer construction method, enables the fabrication of intricately shaped and customizable bolus. In contrast to traditional preparation methods, 3D printing technology addresses challenges such as poor bolus fit and cumbersome production processes, offering a novel approach to efficient and personalized bolus fabrication. This article discusses the research progress of 3D printing technology in radiotherapy bolus from aspects such as the preparation process, clinical application, and research advancements, combined with the actual printing experience of Department of Radiation Oncology in Chongqing University Cancer Hospital.
Printing, Three-Dimensional ; Humans ; Radiotherapy/methods*

Objective To analyze the virus subtypes, molecular evolutional and molecular transmission network features of the first confirmed mpox case in Huai’an City, Jiangsu Province, so as to provide insights into understanding of the transmission and evolution dynamics of mpox virus and formulation of the mpox control strategy in the city. Methods Genomic DNA was extracted from swabs of the first confirmed mpox case’s skin lesions in Huai’an City, and the amplicon sequencing library was constructed using the hypersensitive mpox virus whole-genome capture kit. High-throughput sequencing was performed using the GridION X5 nanopore sequencer on the Nanopore sequencing platform, and single nucleotide polymorphism (SNP) analysis of mpox virus genome sequences was performed following sequence assembly. In addition, phylogenetic analysis, genetic genealogy and molecular traceability analysis were performed. Results The virus whole genome sequence of the first confirmed mpox case was successfully obtained by high-throughput sequencing, with a full length of 197 182 bp, and was named hMpxV/China/JS-HA01/2023, which belonged to the clade IIb (West African clade) lineage B.1.3. Compared with the mpox virus reference sequence MPXV-M5312_HM12_Rivers-001 (GenBank accession number: NC_063383), the genome sequence of the Huai’an virus isolate carried 86 SNPs, including 40 SNPs in the coding region as non-synonymous mutations and 73 SNPs as nucleotide mutations caused by APOBEC3 (APOBEC3). Of the 97 mpox virus gene sequences, 79 sequences were included in the molecular network (81.44%), and the threshold of the genetic distance accessed to the network was 0.35/10⁵. There were two large molecular transmission clusters and one scattered cluster in the molecular transmission network of the mpox virus, andthehMpxV/China/JS-HA01/2023 sequence was located in the large cluster. The 97 gene sequences formed 92 haplotypes, including three shared haplotypes Hap_4, Hap_6 and Hap_38, and an exclusive haplotype Hap_1 of hMpxV/China/JS-HA01/2023 generated from mutation of the exclusive haplotype Hap_43, while the exclusive haplotype Hap_43 was generated from mutation of the shared haplotype Hap_38. Conclusions The whole genome sequence of the mpox virus isolated from the first confirmed mpox case in Huai’an City has been successfully obtained, and the molecular evolutionary and molecular transmission network characteristics of the virus have been preliminarily understood.

(+)-Borneol, the main component of "Natural Borneol" in the Chinese Pharmacopoeia, is a high-end spice and precious medicine. Plant extraction cannot meet the increasing demand for (+)-borneol, while microbial biosynthesis offers a sustainable supply route. However, its production was extremely low compared with other monoterpenes, even with extensively optimizing the mevalonate pathway. We found that the key challenge is the complex and unusual dephosphorylation reaction of bornyl diphosphate (BPP), which suffers the side-reaction and the competition from the cellular dephosphorylation process, especially lipid metabolism, thus limiting (+)-borneol synthesis. Here, we systematically optimized the dephosphorylation process by identifying, characterizing phosphatases, and balancing cellular dephosphorylation metabolism. For the first time, we identified two endogenous phosphatases and seven heterologous phosphatases, which significantly increased (+)-borneol production by up to 152%. By engineering BPP dephosphorylation and optimizing the MVA pathway, the production of (+)-borneol was increased by 33.8-fold, which enabled the production of 753 mg/L under fed-batch fermentation in shake flasks, so far the highest reported in the literature. This study showed that rewiring dephosphorylation metabolism was essential for high-level production of (+)-borneol in Saccharomyces cerevisiae, and balancing cellular dephosphorylation is also helpful for efficient biosynthesis of other terpenoids since all whose biosynthesis involves the dephosphorylation procedure.

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disease characterized by abnormal deposition of lipid in hepatocytes. If not intervened in time, NAFLD may develop into liver fibrosis or liver cancer, and ultimately threatening life. NAFLD has complicated etiology and pathogenesis, and there are no effective therapeutic means and specific drugs. Currently, insulin sensitizers, lipid-lowering agents and hepatoprotective agents are often used for clinical intervention, but these drugs have obvious side effects, and their effectiveness and safety need to be further confirmed. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a central role in maintaining energy homeostasis. Activated AMPK can enhance lipid degradation, alleviate insulin resistance (IR), suppress oxidative stress and inflammatory response, and regulate autophagy, thereby alleviating NAFLD. Natural herbal medicines have received extensive attention recently because of their regulatory effects on AMPK and low side effects. In this article, we reviewed the biologically active natural herbal medicines (such as natural herbal medicine formulas, extracts, polysaccharides, and monomers) that reported in recent years to treat NAFLD via regulating AMPK, which can serve as a foundation for subsequent development of candidate drugs for NAFLD.

The efficacy of preoperative neoadjuvant chemoradiotherapy(nCRT)in locally advanced rectal cancer(LARC)is predicted using radiomic features of the target areas in radiotherapy for rectal cancer and an interpretable machine learning model.The clinical data are collected from 290 LARC patients who are divided into effective and ineffective groups based on tumor regression grade.The extracted radiomic features and clinicopathological data are used to develop prediction models.The optimal model is determined based on AUC performance evaluation,and the explanatory analysis is conducted using nomogram and decision curve.A total of 223 patients are included in the study,with 48 in the effective group.There are 156 patients in the training set(34 in the effective group)and 67 patients in the validation set(14 in the effective group).The nomogram model shows the best performance,with AUC of 0.858 in the training set and 0.844 in internal test set,and decision curve analysis demonstrated its superior net clinical benefit across most threshold ranges than other models.Combining radiomics and clinical variables,the nomogram can effectively predict nCRT outcomes and support clinical decision-making.

Objective:To investigate the temporal expression of Growth Differentiation Factor-15 (GDF15) in the serum of patients with Acute Coronary Syndrome (ACS) and explore the clinical significance of GDF15 in protecting cardiomyocytes in ACS.Methods:A retrospective study was conducted on 289 ACS patients admitted to the emergency departments from February to October 2023. Data on gender, age, troponin T (TnT), creatine kinase isoenzyme (CK-MB), GDF15, and B-type natriuretic peptide (BNP) within 30 minutes of admission were recorded. Differences in these indicators among different groups were compared. Receiver Operating Characteristic (ROC) curves were plotted to evaluate the diagnostic value of GDF15, TnT, and BNP for ACS. Among the patients, 15 exhibited a temporal expression pattern of GDF15, and their blood samples were re-measured using a GDF15 fluorescent quantitative immunochromatographic assay kit. Fifteen patients without temporal expression were randomly selected as controls, and their samples were also re-measured to exclude detection errors. Fifteen patients with temporal expression were included in the temporal expression group, and 15 without temporal expression were included in the non-temporal expression group. Laboratory indicators such as fasting blood glucose, glycated hemoglobin, triglycerides, creatinine, and uric acid were compared between the groups. Additionally, patient age, gender, body mass index (BMI), coronary angiography results, echocardiography, Gensini score, left ventricular ejection fraction (LVEF), and GRACE risk score were recorded to assess their correlation with GDF15 temporal expression. Statistical analysis was performed using SPSS 27 software, with continuous data expressed as mean ± standard deviation (Mean ± SD) and compared using t-tests and χ2 tests. Results:The overall trend in ACS patients showed a higher proportion of males than females (73.36% vs. 26.64%). The oldest group was the Unstable Angina (UA) group, with a mean age of (63.98 ± 15.19) years, while the youngest group was the non-ACS chest pain group, with a mean age of (54.29 ± 16.39) years. A higher proportion of patients in the UA, ST-segment elevation myocardial infarction (STEMI), and non-ST-segment elevation myocardial infarction (NSTEMI) groups had a history of smoking. The combination of GDF15 and TnT showed high diagnostic value for ACS, with an area under the ROC curve (AUC) of 0.843, consistent with previous studies. Among all ACS patients, 15 exhibited a temporal expression pattern of GDF15, where GDF15 levels peaked at 4 hours, gradually decreased, and peaked again at 24 hours. Patients in the temporal expression group had higher LVEF and left ventricular end-systolic diameter compared to the non-temporal expression group. The Gensini score was lower in the temporal expression group, and the GRACE risk score was significantly lower in the temporal expression group (00.7±14.72) compared to the non-temporal expression group (116.1±23.46), with a statistically significant difference ( P = 0.0115). There were no significant differences in general characteristics (age, gender, BMI) or clinical biochemical indicators (fasting blood glucose, glycated hemoglobin, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, creatinine, uric acid) between the temporal and non-temporal expression groups ( P > 0.05). Conclusions:GDF15 demonstrates significant diagnostic and prognostic predictive value in ACS. Patients with temporally dynamic expression of serum GDF15 exhibit milder myocardial injury and a lower probability of mortality. These findings provide novel therapeutic targets and research directions for further exploring the role of GDF15 in ACS management.

Objective To retrieve the anticoagulation management related evidences in postoperative patients with heart valve operation to provide an evidence-based basis for medical professionals conducting the antithrombotic therapy in postoperative patients with heart valve operation.Methods The related evidences of anticoagulation management after heart valve surgery were retrieved from major databases and websites at home and abroad based on the"6S"evidence resource pyramid modeling system.The retrieval time was from January 1,2017 to February 29,2024.Two researchers trained by evidence-based care evaluated the quality of the literatures and extracted the relevant evidences meeting the criteria by combining with clinical situation.Results A total of 12 literatures were included,including 5 guidelines,4 clinical practices and 3 expert consen-sus.Thirty pieces of best evidences were summarized in eight aspects:contraindications,postoperative an-tithrombotic regimens,warfarin use method,vitamin K use precautions,daily life precautions,anticoagulation complications,long term perioperative anticoagulation bridging and complicating pregnancy.Conclusion The evidences summarized in this study could provide a reference for standardizing anticoagulation management in postoperative pa-tients with heart valve operation and for clinical healthcare workers in order to standardize the anticoagulation therapy after heart valve replacement and reduce the occurrence of anticoagulation-related complications.

Objective To investigate the association between the variability of remnant cholesterol inflammatory index(RCII),a novel composite biomarker,and the risk of stroke,in order to provide a theoretical basis for stroke prevention.Methods A prospective cohort study was conducted on 38 659 Kailuan individuals who took annual physical examinations in 2006,2008,and 2010.These subjects were grouped based on the quartiles of RCII variability,which was represented by standard deviation(SD)and average real variability(ARV),and were followed up every 2 years,with the occurrence of stroke(including ischemic and hemorrhagic strokes),death,or the end of follow-up on December 31,2022 as the endpoints.Kaplan-Meier method was used to calculate the cumulative incidence rate of endpoint events across different groups,and log-rank test was used to compare the difference of cumulative incidence of endpoint events in each group.Multivariate Cox proportional hazards regression model was adopted to analyze the association between RCII variability and risk of stroke.Results Among the 38 659 participants,a total of 2 539 strokes occurred during a mean follow-up period of 11.22±2.26 years.After adjusting confounding factors,when the participants were grouped by the quartiles of RCII-SD,the hazard ratio(HR)for stroke was 1.034(95%CI:0.917～1.167,P=0.584),1.146(95%CI:1.018～1.290,P=0.025),and 1.209(95%CI:1.066～1.370,P=0.003),respectively in the Q2,Q3,and Q4 groups,when compared with the Q1 group(Ptrend<0.05).When they were grouped by the quartiles of RCII-ARV,the HR for stroke was 1.008(95%CI:0.894～1.136,P=0.901),1.109(95%CI:0.986～1.248,P=0.085),and 1.152(95%CI:1.018～1.303,P=0.025),respectively,in the Q2,Q3,and Q4 groups,when compared with the Q1 group.Furthermore,both sensitivity and stratified analyses yielded similar results.Conclusion RCII variability is significantly associated with stroke,and the risk of stroke is gradually increasing with increment of the variability.Countermeasures Relevant authorities can focus on reducing RCII variability as a central objective by establishing regular monitoring mechanism,strengthening lifestyle interventions,and standardizing dietary,exercise,and weight management in order to suppress the index fluctuations.The principle of stable lipid-lowering in medication and optimization of therapeutic regimens with stable efficacy should be emphasized to prevent the risk of additional vascular damage.

Objective:To investigate the correlation between cerebral blood flow (CBF) in different brain regions and gait disorder (GD) in patients with cerebral small vessel disease (CSVD).Methods:Patients with CSVD visited the Department of Neurology, the Second Affiliated Hospital of Xuzhou Medical University from November 2023 to October 2024 were included prospectively. They were divided into GD group (<0.8 m/s) and non-GD group (≥0.8 m/s) based on their step speed. CBF was measured using 3D pseudo-continuous arterial spin labeling (3D-pCASL) perfusion imaging. Gait parameters were quantitatively evaluated using a wearable gait analyzer. Multivariate logistic regression analysis was used to determine independent factors associated with GD in patients with CSVD. Partial correlation analysis was used to determine the correlation between gait parameters and CBF in different brain regions. Results:A total of 52 patients with CSVD were enrolled, including 26 males and 26 females, aged 67.00±6.84 years. Thirty-eight cases (73.1%) had mild overall burden of CSVD, and 14 cases (26.9%) had a moderate to severe overall burden of CSVD. There were 17 patients (32.7%) in the GD group and 35 (67.3%) in the non-GD group. Compared with the non-GD group, the body mass index was significantly higher, the CBF of the left occipital lobe and bilateral cerebellum decreased significantly, the step speed, step length, stride length, step frequency, swing phase, peak arm angular velocity, arm swing amplitude, maximum calf anterior/posterior swing angle, peak calf angular velocity, foot swing speed, and peak sagittal plane angular velocity in the torso decreased significantly, while the number of steps, stance phase, step length asymmetry, stride length, and step length variability increased significantly in the GD group (all P<0.05). Multivariate logistic regression analysis showed that left cerebellar CBF was an independent protective factor for GD in patients with CSVD (odds ratio 0.902, 95% confidence interval 0.827-0.982; P=0.019). For every 1 ml/(100 g.min) decreased in left cerebellar CBF, the patients with CSVD had an increased risk of developing GD by approximately 9.8%. Partial correlation analysis showed that left occipital lobe CBF was significantly positively correlated with step speed ( r=0.305, P=0.032), maximum calf back swing angle ( r=0.314, P=0.026), and peak calf angular velocity ( r=0.356, P=0.011). The left cerebellar CBF was significantly positively correlated with step speed ( r=0.295, P=0.037) and significantly negatively correlated with step length variability ( r=-0.335, P=0.017); the right cerebellar CBF was significantly positively correlated with step speed ( r=0.309, P=0.029) and significantly negatively correlated with step length variability ( r=-0.344, P=0.014). Conclusion:GD in patients with CSVD is associated with decreased CBF in the left occipital lobe and bilateral cerebellum, and decreased CBF in the left cerebellum significantly increased the risk of GD in patients with CSVD.