ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

Objective:To construct a deep learning model based on YOLOV8-Seg algorithm to conduct automatic segmentation for the central gland(CG)and peripheral zone(PZ)of prostate,so as to provide a reliable basis for clinical diagnosis and treatment.Methods:The sequence data of T2-weighted imaging(T2WI)of horizontal relaxation time of 158 patients were selected from a public data set of magnetic resonance imaging(MRI)for prostate MRI,which was provided by the Charité University Hospital in Berlin,were selected.The all data were divided into a training set(109 cases),a validation set(16 cases),and a test set(33 cases)as the ratio of 7 to1 to 2.A lightweight asymmetric decoupled head(LADH)structure and the large kernel UniRepLKNetBlock module were integrated into the YOLOV8-Seg algorithm to enhance the capabilities of model's extraction feature,and the new model was named as YOLOV8-URLK.The assessment model with mean Average Precision(mAP),Dice Similarity Coefficient(DSC),95%Hausdorff Distance(HD95),and Average Surface Distance(ASD)was adopted to segment performance of the detection at prostate CG and PZ.Comparative experiments were conducted among that and YOLOV8-Seg,TransU-Net,and U-Net network,so as to validate the effectiveness of YOLOV8-URLK for detection and segmentation at prostate zone.Results:On the test set,the mAP@0.5(box)of YOLOV8-URLK model was 0.878,and the mean Dice coefficients,the mean HD95 values and the ASD values of that at CG and PZ were respectively(0.867,17.123 and 1.461)and(14.902,0.898 and 1.112).On the test set,the mAP@0.5(box)of YOLOV8-Seg model was 0.860,and the mean Dice coefficients of that at CG and PZ were 0.851 and 0.884,the mean HD95 values of that at them were 19.174 and 15.298,and ASD values of that at them were 1.781 and 1.219,respectively.On test set,the mean Dice coefficients of TransU-Net model at CG and PZ were 0.864 and 0.824,and the mean HD95 values of that at them were 18.134 and 19.402,and ASD values of that at them were 1.698 and 1.717,respectively.On the test set,the mean Dice coefficients of the U-Net model at CG and PZ were 0.857 and 0.690,and the mean HD95 values of that at them were 18.976 and 26.934,and ASD values of that at them were 1.753 and 2.135.The YOLOV8-URLK model can better reappear the segmentation trend of manual annotations.Conclusion:The YOLOV8-URLK model demonstrates higher precision in the detection and segmentation of MRI images of prostate,which were superior to YOLOV8-Seg,TransU-Net and U-Net.It can enhance the efficiency of the detection and segmentation.

Biomanufacturing has emerged as a crucial driving force for efficient material conversion through engineered cells or cell-free systems. However, the intrinsic spatiotemporal heterogeneity, complexity, and dynamic characteristics of these processes pose significant challenges to systematic understanding, optimization, and regulation. This review summarizes essential methodologies for multi-omics data acquisition and analyses for bioprocesses and outlines modelling approaches based on multi-omics data. Furthermore, we explore practical applications of multi-omics and modelling in fine-tuning process parameters, improving fermentation control, elucidating stress response mechanisms, optimizing nutrient supplementation, and enabling real-time monitoring and adaptive adjustment. The substantial potential offered by integrating multi-omics with computational modelling for precision bioprocessing is also discussed. Finally, we identify current challenges in bioprocess optimization and propose the possible solutions, the implementation of which will significantly deepen understanding and enhance control of complex bioprocesses, ultimately driving the rapid advancement of biomanufacturing.
Fermentation ; Genomics/methods* ; Biotechnology/methods* ; Proteomics/methods* ; Models, Biological ; Metabolomics/methods* ; Bioreactors ; Multiomics

Objective To investigate the expression and prognostic value of microRNA-29b-2-5p(miR-29b-2-5p)and syntaxin 16(STX16)in hepatocellular carcinoma(HCC).Methods The cancer tissues and adjacent tissues of 88 HCC patients diagnosed in Nantong Tumor Hospital from January 2013 to September 2020 were collected.The expressions of miR-29b-2-5p and STX16 in cancer tissues and adjacent tissues were analyzed by real-time fluorescent quantitative PCR.The expression of STX16 protein in cancer tissues and adjacent tissues were analyzed by immunohistochemistry.Pearson correlation analysis was used to analyze the correlation be-tween miR-29b-2-5p and STX16.Non-parametric χ2 test was used to analyze the relationship between the ex-pression of the two proteins and clinicopathological parameters,and Kaplan-Meier survival curve was used to analyze the relationship between the expression of the two proteins and prognosis.Results The relative ex-pression level of miR-29b-2-5p was 0.780(0.351,1.708)in cancer tissues and 1.014(0.458,3.124)in adja-cent tissues in 88 HCC patients.The relative expression level of miR-29b-2-5p in cancer tissues was signifi-cantly lower than that in adjacent tissues(P=0.012).The relative expression level of STX16 mRNA was 0.775(0.406,0.946)in cancer tissues and 0.368(0.080,1.301)in adjacent tissues in 88 HCC patients.The relative expression level of STX16 mRNA in cancer tissues was significantly higer than that in adjacent tissues(P<0.01).Immunohistochemical results showed that STX16 was expressed in the cytoplasm,and the expres-sion of STX16 in cancer tissues was higher than that in adjacent tissues(P<0.05).The expression of miR-29b-2-5p in cancer tissues was related to cancer stage(P<0.05),and the expression of STX16 was related to cancer stage and alpha-fetoprotein(P<0.05).Patients with low miR-29b-2-5p expression had a shorter over-all survival(OS)than those with high miR-29b-2-5p expression,and patients with high STX16 expression had a shorter OS than those with low STX16 expression(P<0.05).Conclusion The expression of miR-29b-2-5p is low and STX16 is high in HCC tissues.The combined detection of miR-29b-2-5p and STX16 can effectively evaluate the prognosis of HCC patients.

Objective To explore the diagnostic value of dual-low-dose CT energy spectral imaging combined with adaptive statis-tical iterative reconstruction-Veo(ASIR-V)in distinguishing benign and malignant thyroid nodules.Methods A total of 242 patients with thyroid nodules were included.In part Ⅰ,the initial 90 patients were randomly and equally assigned to the conventional scan group,the low radiation dose group,and the dual-low-dose group.Both subjective and objective image qualities,the radiation dose,and contrast agent dosage in these three groups were evaluated,respectively.In part Ⅱ,the remaining 152 patients underwent dual-low-dose CT energy spectral scanning.Radiographic features of thyroid nodules in benign and malinant groups were observed,fol-lowed by spectral imaging analysis.The iodine concentration(IC)value,normalized iodine concentration(NIC)value,effective atomic number(Eff-Z),and λHU value of benign and malignant nodules were measured and compared,respectively.Results There were significant differences in nodule morphology,sign of edge truncation,enhancement characteristics and nodule boundary enhancement between benign and malignant thyroid nodules(P<0.05).There were statistically significant differences in IC value,NIC value,and λHU value in the venous phase among the three groups(P<0.05).The sensitivity and specificity of IC,NIC,λHU were 81.6%and 60.0%,86.4%and 67.5%,88.8%and 65.0%,respectively.The area under the curve(AUC)of combining the three energy spectral parameters with radiographic fea-tures via binary logistic regression model was 0.905,and the sensitivity and specificity were 82.4%and 87.5%,respectively.The effective dose(ED)in the dual-low-dose group was reduced by 60.13%com-pared to the conventional scan group,and the contrast agent dos-age was reduced by 38.56%.Conclusion The dual-low-dose CT energy spectral imaging combined with ASIR-V significantly reduced the radiation dose and the contrast agent dosage,and might help in distinguishing between benign and malignant thyroid nodules,demonstrating considerable clinical application value.

The hepatic vascular microenvironment(HVM)plays a pivotal role in maintaining liver function homeostasis,including metabolism,detoxification,and coagulation.The maintenance of HVM homeostasis is governed by an intricate interplay of mechanical forces,chemical signals,and neuroelectrophysiological conduction.Recent studies have shown that an imbalance in HVM promotes the progression of chronic liver disease(CLD),which is characterized by sinusoidal capillarization,vascular deformation and remodeling,and the arterialization of blood supply.This review sum-marizes the dynamic regulatory mechanisms that underpin HVM in physiological conditions,and the primary pathological manifestations observed at various stages of CLD progression,aiming to provide a robust framework for the development of therapeutic strategies targeting HVM homeostatic imbanlance in CLD.

Objective:To investigate the prognostic impact of perineural invasion in patients with stageⅢ colon cancer and to clarify its guidance value for the duration of postoperative adjuvant chemotherapy.Methods:This study employed a retrospective cohort study method. It analyzed 426 patients with stageⅢ colon cancer who underwent radical surgery at Sun Yat-sen University Cancer Center and Longyan First Affiliated Hospital of Fujian Medical University, between April 2008 and June 2020. Inclusion criteria: patients received at least 3 months of adjuvant CapeOX therapy post-surgery, had complete pathological data, and were followed up for at least 12 months after the last chemotherapy. Among these patients, 231 were male, the median age was 59 (50~67) years, and 263 tumors were located in the right-sided colon. Postoperative pathology indicated that 107 cases (25.12%) had neural invasion, and 131 patients (30.75%) had vascular tumor thrombus. All patients received at least 4 cycles of postoperative CapeOX adjuvant chemotherapy, with 193 patients receiving 8 cycles and 233 patients receiving 4 to 7 cycles of adjuvant chemotherapy. The study analyzed the impact of neural invasion status and the duration of adjuvant chemotherapy on disease-free survival (DFS). Furthermore, within subgroups stratified by different risk levels (referencing the criteria proposed by the IDEA study: high risk: T4, N2 or T4N2; low risk: T3N1) and different neural invasion statuses, the impact of the duration of adjuvant chemotherapy on prognosis was analyzed.Results:The median follow-up time for the entire cohort was 94.00 months (55.27-128.80 months). Multivariate Cox analysis indicated that pathological T stage T4 (HR = 2.457, 95%CI: 1.499-4.029, P<0.001) and postoperative pathological confirmation of perineural invasion (HR = 2.465, 95% CI: 1.519-4.000, P<0.001) were independent adverse prognostic factors for 5-year DFS. In the perineural invasion-positive group, the 5-year DFS for patients who received 8 cycles of postoperative adjuvant CapeOX chemotherapy was 86.90%, compared to 58.22% for those who received 4-7 cycles, with statistically significant differences (both P<0.05). In the perineural invasion-negative group, the 5-year DFS for patients who received 8 cycles was 88.66%, compared to 90.99% for those who received 4-7 cycles, with no statistically significant differences ( P=0.929). Among IDEA high-risk patients with perineural invasion, the 5-year DFS was 91.81% for those who received 8 cycles versus 50.66% for those who received 4-7 cycles, showing a statistically significant difference ( P=0.003). In IDEA high-risk patients without perineural invasion, the 5-year DFS for those who received 8 cycles was 82.28% compared to 87.32% for those who received 4-7 cycles, with no statistically significant difference ( P=0.806). In the IDEA low-risk patients, no differences were observed in the 5-year DFS between patients receiving 8 cycles and those receiving 4-7 cycles of adjuvant CapeOX chemotherapy in both perineural invasion-positive and negative subgroups (both P>0.05). Conclusion:Perineural invasion serves as a significant prognostic factor for 5-year DFS in stage Ⅲ colon cancer patients who have undergone radical surgery and postoperative adjuvant chemotherapy. It can also be considered an important reference factor in deciding the duration of postoperative adjuvant chemotherapy.

Spontaneous coronary artery dissection is a non-atherosclerotic cause of acute coronary syndrome, particularly among young women. A 46-year-old female without a family history of cardiac disease and traditional atherosclerotic risk factors presented to hospital with non-ST-segment elevation myocardial infarction. Diagnostic coronary angiography revealed moderate stenosis of the left main coronary artery and the left anterior descending artery with blood flow thrombolysis in myocardial infarction grade 3. The left circumflex artery was observed hypoplastic without significant stenosis. Intravascular ultrasound revealed an extensive intramural hematoma from the middle of the left anterior descending branch to the left main trunk and a compressed lumen with intact intima. The patient underwent conservative treatment and remained asymptomatic 11 months after discharge. Repeat coronary computed tomography angiography showed haematoma absorption with stenosis relief. Spontaneous coronary artery dissection of the left main coronary artery is relatively rare. Its management is based on the patient’s clinical condition and lesion characteristics.

Spontaneous coronary artery dissection is a non-atherosclerotic cause of acute coronary syndrome, particularly among young women. A 46-year-old female without a family history of cardiac disease and traditional atherosclerotic risk factors presented to hospital with non-ST-segment elevation myocardial infarction. Diagnostic coronary angiography revealed moderate stenosis of the left main coronary artery and the left anterior descending artery with blood flow thrombolysis in myocardial infarction grade 3. The left circumflex artery was observed hypoplastic without significant stenosis. Intravascular ultrasound revealed an extensive intramural hematoma from the middle of the left anterior descending branch to the left main trunk and a compressed lumen with intact intima. The patient underwent conservative treatment and remained asymptomatic 11 months after discharge. Repeat coronary computed tomography angiography showed haematoma absorption with stenosis relief. Spontaneous coronary artery dissection of the left main coronary artery is relatively rare. Its management is based on the patient’s clinical condition and lesion characteristics.

The hepatic vascular microenvironment(HVM)plays a pivotal role in maintaining liver function homeostasis,including metabolism,detoxification,and coagulation.The maintenance of HVM homeostasis is governed by an intricate interplay of mechanical forces,chemical signals,and neuroelectrophysiological conduction.Recent studies have shown that an imbalance in HVM promotes the progression of chronic liver disease(CLD),which is characterized by sinusoidal capillarization,vascular deformation and remodeling,and the arterialization of blood supply.This review sum-marizes the dynamic regulatory mechanisms that underpin HVM in physiological conditions,and the primary pathological manifestations observed at various stages of CLD progression,aiming to provide a robust framework for the development of therapeutic strategies targeting HVM homeostatic imbanlance in CLD.