L-phosphinothricin (L-PPT) is an efficient broad-spectrum herbicide. To realize the multi-enzyme catalytic preparation of L-PPT, we constructed an engineered strain Escherichia coli YM-1 for efficient expression of D-amino acid transaminase, which could catalyze the generation of the intermediate 2-oxo-4-[(hydroxymethylphosphonyl)] butyric acid (PPO) from D-phosphinothricin (D-PPT). In addition, E. coli pLS was constructed to co-express glutamate dehydrogenase and glucose dehydrogenase, which not only catalyzed the generation of L-PPT from PPO but also regenerated the coenzyme nicotinamide adenine dinucleotide phosphate (NADPH). A fed-batch fermentation process was then established for E. coli YM-1 and pLS, and the apparent activities of D-amino acid transaminase and glutamate dehydrogenase were increased by 22.68% and 100.82%, respectively, compared with those in shake flasks. The process parameters were optimized for the catalytic preparation of L-PPT by whole-cell cascade of E. coli YM-1 and pLS with D, L-PPT as the substrate. After reaction for 8 h, 91.36% conversion of D-PPT was achieved, and the enantiomeric excess of L-PPT reached 90.22%. The findings underpin the industrial production of L-PPT.
Escherichia coli/enzymology* ; Aminobutyrates/metabolism* ; Glutamate Dehydrogenase/biosynthesis* ; Glucose 1-Dehydrogenase/biosynthesis* ; Herbicides/metabolism* ; Multienzyme Complexes/metabolism* ; Transaminases/metabolism* ; Phosphinic Acids/metabolism*

Surgery-based multidisciplinary comprehensive treatment is the preferred treatment strategy for local advanced esophageal cancer. Neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy have been recommended by the Chinese Society of Clinical Oncology (CSCO) guideline. With the advent of immunotherapy, neoadjuvant immunotherapy combined with chemotherapy has received much attention, and the first phase Ⅲ study has also confirmed that neoadjuvant immunotherapy combined chemotherapy is a promising treatment option. This article will review the recent advances and hot spots of neoadjuvant immunotherapy combined with chemotherapy.

BACKGROUND: The burden of esophageal cancer varies across different regions of the world. The aim of this study is to analyze the current burden of esophageal cancer in 185 countries in 2022 and to project the trends up to the year 2050. METHODS: We extracted data on primary esophageal cancer cases and deaths from the GLOBOCAN 2022 database, which includes data from 185 countries. Age-standardized incidence rates (ASIR) and mortality rates (ASMR) per 100,000 person-years were calculated by stratifying by Human Development Index (HDI) levels and regions. Considering changes in population size and age structure, we assumed that the risks of incidence and mortality remain constant at the levels of 2022 to forecast the number of new cases and deaths from esophageal cancer globally by 2050. RESULTS: In 2022, an estimated 511,054 people were diagnosed with esophageal cancer globally, and 445,391 died from the disease. The global ASIR and ASMR for esophageal cancer were 5.00 and 4.30 per 100,000, respectively. The highest rates were observed in East Africa (7.60 for incidence, 7.20 for mortality per 100,000), East Asia (7.60 for incidence, 5.90 for mortality per 100,000), Southern Africa (6.30 for incidence, 5.90 for mortality per 100,000), and South Central Asia (5.80 for incidence, 5.50 for mortality per 100,000). Among the 185 countries worldwide, esophageal cancer was among the top five causes of cancer incidence in 18 countries and among the top five causes of cancer mortality in 25 countries. In 2022, China had 224,012 new cases and 187,467 deaths from esophageal cancer, accounting for approximately 43.8% and 42.1% of the global total, respectively, which is higher than the proportion of China's population to the global population (17.9%). ASIR was 8.30 per 100,000, and ASMR was 6.70 per 100,000. The highest burden of esophageal cancer was in high HDI countries, with new cases and deaths accounting for 51.3% and 50.0% of the global total, respectively. The ASIR and ASMR were highest in the high HDI group (6.10 and 5.10 per 100,000, respectively), also exceeding the global averages. There was a trend of decreasing mortality to incidence ratio with increasing HDI, but no correlation was observed between HDI and ASIR or ASMR. In all regions worldwide, the incidence and mortality rates were higher in males than in females (with a male-to-female ASR ratio ranging from 1.10 to 28.7). Compared to 2022, it is projected that by 2050, the number of new esophageal cancer cases will increase by approximately 80.5%, and deaths will increase by 85.4% due to population growth and aging. CONCLUSIONS The burden of esophageal cancer remains heavy. Adopting a healthy lifestyle, including reducing tobacco and alcohol intake, avoiding moldy foods, and increasing intake of fresh fruits and vegetables, can help reduce the risk of stomach and esophageal cancer. In addition, the development and implementation of evidence-based and effective public health policies are critical to reducing the global disease burden of esophageal cancer.
Esophageal Neoplasms/mortality* ; Humans ; Male ; Incidence ; Female ; Middle Aged ; Global Health ; Aged ; Adult

Objective:To elucidate the spatial distribution patterns of the right hepatic vein by analyzing the image information obtained after CT three-dimension reconstruction of liver to provide guidance in surgical planning of anatomical hepatectomy.Methods:A retrospective analysis was performed on the clinical data of 77 subjects who underwent CT examination of the liver at the Second Affiliated Hospital of Harbin Medical University from September 2018 to October 2021. There were 42 males and 35 females, aged (50.2±12.8) years old. CT DICOM data of the patients were collected, and the two-dimensional image data were reconstructed into a three-dimensional model by using the 3D reconstruction software. The characteristics and typing were studied by analyzing the number of branches of the right hepatic vein and the spatial location of the main trunk.Results:Of 77 subjects, 645 branches of the right hepatic vein were observed in the liver CT 3D reconstruction model, including 268 (41.6%) right-sided branches, 240 (37.2%) dorsal branches, 70 (10.9%) left-sided branches, and 67 (10.3%) ventral branches. Each right hepatic vein possessed 3 (3, 4) right-sided branches, 3 (3, 4) dorsal branches, 1 (0, 1) left-sided branch, and 1 (0, 1) ventral branch. The numbers of branches in the four directions were significantly different ( H=175.89, P<0.001). Comparison showed that the number of right-sided branches was significantly more than that of the left-sided (χ 2=136.86) and ventral (χ 2=140.07), respectively. The number of dorsal branches was more than that of left-sided (χ 2=-123.36) and ventral (χ 2=126.57) branches, respectively. The differences were significant ( P<0.001). There were no significant differences between the number of ventral and left-sided branches, and between the dorsal and right-sided branches (all P>0.05). Conclusion:The right hepatic vein had fewer ventral and left-sided branches. It is relatively safe to dissect the right hepatic vein from the ventral or the left side during surgery. For resection of the central liver segments or segment VIII of the liver, it is reasonable to transect the liver along the left border of the right hepatic vein.

In the early stage of diabetes retinopathy(DR),the change in the molecular level is often earlier than chan-ges in retinal microvessels.Under the chronic high-glucose environment,oxidative stress,epigenetic changes and other mechanisms cause retinal mitochondrial DNA(mtDNA)damage,affect the transcription process of mtDNA coding genes,and damage the electronic transport chain,leading to a vicious cycle of free radicals,which accelerates the apoptosis of retinal capillary pericytes and endothelial cells,leads to retinal microcirculation dysfunction,and cause DR.This paper will review the epigenetic changes,oxidative stress,damage to replication and repair system,gene mutation and other aspects,in order to elaborate on the research progress of retinal mtDNA damage in the pathogenesis of DR.

Objective:To explore the detection and segmentation of ischemic core infarct volume of the acute stroke in diffusion weighted imaging (DWI) images using cascaded VB-Net.Methods:MRI data of 1 500 patients (2 456 lesions) with acute ischemic stroke in Henan Provincial People′s Hospital from December 2016 to December 2018 were retrospectively analyzed. Firstly, manual segmentation of ischemic core was performed on DWI images (b=1 000 s/mm 2), and then all data were divided into training set, validation set and independent test set by 8∶1∶1. Then, the cascaded VB-Net was constructed, and the core infarct was automatically detected and segmented in the test set. Interclass correlation coefficient (ICC) was used to evaluate the consistency of volume size measured by manual segmentation and cascaded VB-Net. The patients were divided into large ischemic core lesion group (ischemic core volume ≥10 ml) and small ischemic core lesion group (ischemic core volume<10 ml), and the Dice coefficient difference between the two groups was compared using Mann-Whitney U test. Results:In independent test set, cascaded model had the detection rate of 94.6% (243/257) with Dice coefficient of 0.76 (0.68, 0.84). The agreement of cacade VB-Net segmented [4.19(1.21,14.13)ml] and manual segmented ischemic core infarct volume [4.08(1.19,17.92)ml] was high (ICC=0.97, P<0.001). There was no significant difference in Dice coefficient between large and small lesion groups [0.76 (0.69, 0.85), 0.76 (0.67, 0.84), Z=-0.44, P=0.657]. Conclusions:The cascaded VB-Net model provided a tool to realize automatic detection, segmentation, and calculation of ischemic core infarct volume. It has good segmentation accuracy and high consistency with manual segmentation, which can provide an auxiliary decision-making tool for the selection of treatment plans.

Objective:To investigate the value of quantitative parameters derived from dual-layer spectral detector CT (SDCT) in characterizing regional lymph node (LN) status of colorectal cancer.Methods:From August 2019 to May 2020, 101 patients with colorectal cancer confirmed by pathology in the First Affiliated Hospital of Sun Yat-sen University were retrospectively collected. The largest regional LNs were matched with surgical pathology one by one and divided into metastatic LNs group (42 cases) and nonmetastatic LNs group (59 cases) according to pathological results. Based on preoperative venous phase contrast enhanced SDCT images he short-axis diameter (S) and the of the largest regional LN was measured, then its border and enhancement homogeneity were evaluated. Outlining the ROI along the edge of the LN on its widest cross section, the iodine density (ID) and effective atomic number (Z eff) were measured, then the normalized ID (nID) and normalized Z eff (nZ eff) were calculated. The χ 2 test, Fisher′s exact test, independent samples t-test or Mann-Whitney U test were used to compare the differences of each parameter between pathologically metastatic and nonmetastatic LNs and a logistic regression model was constructed. The ROC curves and area under the curve (AUC) were performed to evaluate the diagnostic performance of each parameter. DeLong test was used to compare the differences of each AUC. Results:The S, border, enhancement homogeneity, ID, Z eff, nID and nZ eff of LNs all showed significant differences between metastatic and nonmetastatic LNs (all P<0.001). The regression model constructed by S and Z eff of LNs had the highest value in differentiating metastatic and nonmetastatic LNs, with an AUC of 0.935, sensitivity and specificity of 85.7% and 89.8%, respectively. Its diagnostic value was higher than that of S, border, enhancement homogeneity (AUC 0.674-0.832, all P<0.05) and SDCT quantitative parameters (AUC 0.863-0.906, all P<0.05) of LNs. Conclusion:SDCT quantitative parameters facilitate the accurate diagnosis of regional metastatic LNs in patients with colorectal cancer, among which the multi-parameter regression model has the highest diagnostic value.

From November to December 2019, a cross-sectional study including 1 243 children aged 8~13 years was conducted in one primary school in Huantai County, and 1 238 children with complete data were finally included. A total of 1 238, 146, and 83 children were included in the first, second and third visit of the follow-up, respectively. With the follow-up visits increasing, the systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels of the 83 children who were followed up across all three different visits decreased significantly across three different visits (both Pfor trend<0.05). The prevalence of elevated blood pressure across the three visits was 11.8%, 6.8% and 4.0% ( P for trend<0.001); the prevalence of elevated SBP was 11.4%, 6.5%, and 4.0% ( P for trend<0.001); the prevalence of elevated DBP was 1.1%, 1.0%, and 0.4%, respectively ( P for trend>0.05).

From November to December 2019, a cross-sectional study including 1 243 children aged 8~13 years was conducted in one primary school in Huantai County, and 1 238 children with complete data were finally included. A total of 1 238, 146, and 83 children were included in the first, second and third visit of the follow-up, respectively. With the follow-up visits increasing, the systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels of the 83 children who were followed up across all three different visits decreased significantly across three different visits (both Pfor trend<0.05). The prevalence of elevated blood pressure across the three visits was 11.8%, 6.8% and 4.0% ( P for trend<0.001); the prevalence of elevated SBP was 11.4%, 6.5%, and 4.0% ( P for trend<0.001); the prevalence of elevated DBP was 1.1%, 1.0%, and 0.4%, respectively ( P for trend>0.05).

Objective To analyze the policy texts related to the contracted service of family physicians, and probe into the key points and existing problems of the policy in the process of promoting the contracted service of family physicians in China, for the purpose of providing references for the optimization and perfection of the system. Methods A total of 54 relevant policy texts issued by the Central Government from 2011 to 2019 were selected, for establishing a two-dimensional analysis framework based on policy tools and stakeholders.By means of quantitative analysis of policy text and literature research method, we analyzed the relevant policy texts. Results Study of the 54 texts found 52.8% (124/235)mentioned commands and regulatory tool use, 27.2% (64/235) mentioned capacity building tool use, 13.2% (31/235) mentioned information and exhortation tool use, 5.1% (12/235)only mentioned incentive tool use, and 1.7% (4/235) only mentioned system change tool use; while most of them(34.3% and 32.7% )mentioned government and physicians, and only a few(17.6% and 15.4% )mentioned patients and medical entities. Conclusions It is suggested to optimize the policy tools mixture, and increase the use of incentive tools to physicians, and explore new forms of system change tools.It is also proposed to pay more attention to resource allocation of primary medical institutions, and to patient awareness and satisfaction.