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*

(+)-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.

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.

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 hep-atoprotective 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.

Objective To construct a prognostic model of lung adenocarcinoma(LUAD)based on m5C modification-related genes and to explore its clinical value.Methods Based on the LUAD data in TCGA,GSE30219,GSE31210,and GSE50081 cohorts,prognosis-related m5C modification-related genes were screened,and the prognostic model was constructed by using univariate Cox,Lasso,and multivariate Cox regression analyses.Kaplan-Meier curve,ROC curve,and Cox regression were used to observe the robustness and prognostic performance of the model.The correlation between the prognostic model and clinico-pathologic features was further explored.Results A prognostic model consisting of eight m5C modifi-cation-related genes,including CDK1,CDKN1A,NOP2,RRM2,TCL6,TLR8,TRDMT1,and YTHDF2,was constructed.Risk score was an independent risk factor for the prognosis of patients with LUAD,and it is combined with age,T stage,and N stage to constitute a nomogram which can accurately predict the prognosis of patients.The infiltration of macrophages and CD4+/CD8+T cells was significantly reduced in high-risk patients.The risk score in LUAD tissues was significantly higher than that in normal tissues and was positively correlated with T stage and N stage.The risk score of smoking and EGFR wild-type patients was higher than that of non-smoking and EGFR-mutant patients.Conclusion The prognostic model constructed based on m5C modification-related genes has shown good accuracy and stability in predicting the prognosis of patients with LUAD,and it is closely related to clinical features,driver gene mutations,and immune infiltration,which can provide a potential basis for the treatment and prognostic assessment of LUAD.

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.

Objective To observe the value of machine learning(ML)models based on ultrasound radiomics for preoperatively distinguishing atypical parathyroid tumor(APT)/parathyroid carcinoma(PC)and parathyroid adenoma(PA).Methods Totally 330 primary hyperparathyroidism patients who underwent surgical treatments were retrospectively enrolled and categorized into APT/PC group(n=78)and PA group(n=252)according to surgical pathology and clinical follow-up results,also divided into training set(n=231)and test set(n=99)at the ratio of 7∶3.Based on preoperative ultrasound,545 radiomics features were extracted,and recursive feature elimination(RFE),Kruskal-Wallis or analysis of variance methods were used to screen the features,respectively.Support vector machine(SVM),linear discriminant analysis(LDA),least absolute shrinkage and selection operator logistic regression(LRLASSO),also random forest(RF)and decision tree(DT)algorithms were adopted to construct ML models for differentiating APT/PC and PA,respectively.Then the models were trained in training set,their performance were verified in test set,and a 5-fold cross-validation was adopted to screen out the better combinations.Results Compared with Kruskal-Wallis and analysis of variance methods,the distinguishing efficacy of SVM,LDA,LRLASSO,RF and DT models constructed based on features screened out using RFE method in training set(area under the curve[AUC]=0.870,0.878,0.850,0.847,1.000)and test set(AUC=0.856,0.842,0.827,0.847 and 0.704)were all relatively higher.In test set,the AUC of SVM,LDA,LRLASSO and RF models constructed based on the features screened out using RFE method(included 25,23,17 and 23 features)were all higher than that of DT model(8 features)(all P＜0.001).No significant difference of AUC was found between SVM,LRLASSO or RF models and LDA model(all P＞0.05).The AUC of SVM and RF models were higher than that of LRLASSO model(both P＜0.05),while of SVM and RF models were not significantly different(P＞0.05),indicating that SVM,LDA and RF models were better ones.Conclusion SVM,LDA,LRLASSO,RF and DT models based on ultrasound radiomics could effectively distinguish APT/PC and PA preoperatively,among which SVM,LDA and RF models had better diagnostic efficacy.

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.