This article reviews the review articles and research papers related to biomanufacturing driven by engineered organisms published in the Chinese Journal of Biotechnology from 2023 to 2024. The content covers 26 aspects, including chassis cells; gene (genome) editing; facilities, tools and methods; biosensors; protein design and engineering; peptides and proteins; screening, expression, characterization and modification of enzymes; biocatalysis; bioactive substances; plant natural products; microbial natural products; development of microbial resources and biopesticides; steroidal compounds; amino acids and their derivatives; vitamins and their derivatives; nucleosides; sugars, sugar alcohols, oligosaccharides, polysaccharides and glycolipids; organic acids and monomers of bio-based materials; biodegradation of polymeric materials and biodegradable materials; intestinal microorganisms, live bacterial drugs and synthetic microbiomes; microbial stress resistance engineering; biodegradation and conversion utilization of lignocellulose; C1 biotechnology; bioelectron transfer and biooxidation-reduction; biotechnological environmental protection; risks and regulation of biomanufacturing driven by engineered organisms, with hundreds of technologies and products commented. It is expected to provide a reference for readers to understand the latest progress in research, development and commercialization related to biomanufacturing driven by engineered organisms.
Biotechnology/methods* ; Gene Editing ; Genetic Engineering ; Metabolic Engineering ; Protein Engineering ; Biosensing Techniques

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.

Objective To explore imaging findings of 10 cases of misdiagnosed IgG4-associated pancreatitis.Methods Ten cases of IgG4-associated pancreatitis misdiagnosed by preoperative CT and/or MRI were retrospectively collected,and intrapancreatic and extra pancreatic manifestations were observed.Results Among 10 cases,diffuse lesions resulted"sausage like"appearance of pancreas were observed in 2 cases,focal lesions were found in 7 cases,including 3 cases in neck,3 cases in head and 1 case in tail of pancreas,while multifocal lesions involved the head,neck and tail of pancreas in 1 case.The lesions mostly presented as slightly low densities and occasional calcifications on non-enhanced CT,slightly low signals on MR T1WI,equal or high signals on T2WI as well as slightly high signals on diffusion weighted imaging,and progressively enhanced after administration of contrast agents.Peripheral halo sign was found in 3 cases,and mild dilatation of main pancreatic duct was observed in 7 cases.Extrapancreatic manifestations mainly included dilatation of bile ducts both inside and outside the liver and involvement of other organs.Conclusion Imaging findings of misdiagnosis IgG4-associated pancreatitis present as focal or diffuse lesions of pancreas with peripheral halo sign and extrapancreatic involvements,which progressively enhanced after administration of contrast agents.

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.

Objective To explore imaging findings of 10 cases of misdiagnosed IgG4-associated pancreatitis.Methods Ten cases of IgG4-associated pancreatitis misdiagnosed by preoperative CT and/or MRI were retrospectively collected,and intrapancreatic and extra pancreatic manifestations were observed.Results Among 10 cases,diffuse lesions resulted"sausage like"appearance of pancreas were observed in 2 cases,focal lesions were found in 7 cases,including 3 cases in neck,3 cases in head and 1 case in tail of pancreas,while multifocal lesions involved the head,neck and tail of pancreas in 1 case.The lesions mostly presented as slightly low densities and occasional calcifications on non-enhanced CT,slightly low signals on MR T1WI,equal or high signals on T2WI as well as slightly high signals on diffusion weighted imaging,and progressively enhanced after administration of contrast agents.Peripheral halo sign was found in 3 cases,and mild dilatation of main pancreatic duct was observed in 7 cases.Extrapancreatic manifestations mainly included dilatation of bile ducts both inside and outside the liver and involvement of other organs.Conclusion Imaging findings of misdiagnosis IgG4-associated pancreatitis present as focal or diffuse lesions of pancreas with peripheral halo sign and extrapancreatic involvements,which progressively enhanced after administration of contrast agents.

Objective:To explore the clinical effects of free anterolateral thigh perforator flaps in repairing diabetic foot ulcers (DFUs) under a multi-disciplinary team (MDT) cooperation model.Methods:The study was a retrospective observational study. From June 2018 to December 2022, 49 DFU patients who met the inclusion criteria were admitted to the Department of Hand and Foot Microscopy and Wound Repair Surgery of Henan Provincial People's Hospital (People's Hospital of Zhengzhou University), including 28 males and 21 females, aged from 47 to 68 years, with type 2 diabetes history period ranging from 6 months to 21 years. Under a MDT cooperation model, the physicians from department of endocrinology comprehensively assessed the patients, stabilized the patients' general condition, and controlled their complications, the surgeons from department of vascular surgery assessed and improved the patients' lower limb blood supply, the physicians from department of infectious diseases provided anti-infection treatment plans, the physicians from department of anesthesiology and perioperative medicine assessed the patients' perioperative risk and ensured their perioperative safety, and according to the patients' condition, the physicians from departments such as cardiology, neurology, nutrition, and rehabilitation actively and timely participated in the treatment. The surgeons from department of hand and foot microscopy and wound repair surgery prepared the wound base and used free anterolateral thigh perforator flaps to repair the wounds. After once or multiple debridement in the first stage, the wound area ranged from 5.0 cm×4.5 cm to 17.0 cm×10.0 cm. After once or twice vacuum sealing drainage treatment, the free anterolateral thigh perforator flaps were used to repair the wounds with incision area of 6 cm×5 cm to 18 cm×11 cm in the second stage. The descending branches of lateral circumflex femoral artery and the accompanying veins of flaps were anastomosed to the arteries and veins in the recipient sites, respectively. The wounds in the flap donor sites were sutured directly. After surgery, whether the patient's perioperative period was stable, the survival of flaps, the healing of wounds in the flap donor and recipient sites were observed. During the follow-up, the texture and appearance of flaps, whether there was a new ulcer, and the patient's walking ability were observed.Results:All the patients had stable perioperative period. Among them, the flaps in 46 patients survived successfully; the flaps in 2 patients developed complete necrosis, including 1 case whose ulcer was healed after repair of pedicled flap from the lower leg, and 1 case who underwent amputation of the lower leg; the flap in 1 patient developed partial necrosis, which was healed after dressing change and skin grafting. The wounds in the flap donor and recipient sites healed well. During the postoperative follow-up of 6-24 months, the flaps had good texture and appearance with no new ulcers, and the patients had no obvious impairment in daily walk.Conclusions:The MDT cooperation model can sufficiently ensure the perioperative safety of DFU patients. The free anterolateral thigh perforator flaps can repair the DFU wounds achieving good clinical effects with high flap survival rate and decreased amputation rate.

Objective:To investigate the expression of nuclear matrix protein 4 (NMP4) in hepatocellular carcinoma (HCC), and its relationship with clinicopathological features and survival prognosis of patients.Methods:The clinical data of 100 HCC patients who were treated with radical resection of liver cancer in the Department of Hepatobiliary Surgery of the Third Affiliated Hospital of Wenzhou Medical University from July 1, 2014 to July 1, 2019 were retrospectively analyzed. There were 63 males and 37 females, aged (58.5±10.4) years old. Immunohistochemical method was used to detect the expression of NMP4 protein in HCC cancer tissue and the corresponding adjacent normal tissue. According to the expression of NMP4 in HCC tissues, 100 patients were divided into two groups: the NMP4-positive expression group ( n=62) and the NMP4-negative expression group ( n=32). Univariate analysis was performed on the relationship between NMP4 expression and clinical pathological features as well as overall survival of HCC patients. Cox multivariate analysis was performed on the factors influencing postoperative prognosis of HCC patients. Results:Immunohistochemistry results showed that NMP4 was primarily expressed in the nucleus, the positive expression rate of NMP4 in HCC tissues was higher than that in adjacent non-cancerous tissues [62.0% (62/100) vs. 8.0%(8/100)], and the difference was statistically significant ( χ2=2.12, P=0.003). Univariate analysis revealed that the overall survival of HCC patients was correlated with the degree of tumor differentiation, tumor length, BCLC stage, number of tumor foci, vascular tumor thrombus and expression of NMP4 (all P<0.05). Cox multivariate analysis revealed that low differentiation, high BCLC stage (stage C), number of tumor foci (≥3), and positive expression of NMP4 were independent risk factors affecting postoperative survival and recurrence-free survival of HCC patients. The median overall survival and median recurrence-free survival of HCC patients in the NMP4-positive expression group were 22.3 months and 11.5 months, respectively. In contrast, that in the NMP4-negative expression group were 40.6 months and 19.4 months, respectively. The cumulative survival rate and recurrence-free survival rate of HCC patients in the NMP4-positive expression group were lower than those in the NMP4-negative expression group, and the differences were statistically significant (both P<0.05). Conclusion:Positive NMP4 expression was closely correlated with malignant biological progression and poor prognosis of HCC patients.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

This paper reports the clinical characteristics and ZNF526 gene mutation in a child with Dentici-Novelli neurodevelopmental syndrome, who was admitted to the Department of Pediatrics at the First Affiliated Hospital of Henan University of Traditional Chinese Medicine in June 2021, and reviews the relevant literature.The male child, 5 years and 1 month old, presented with distinctive facial features, intellectual and motor retardation, language development delays, scattered Mongolian spots on the back and buttocks, brain tissue involvement, visual impairment, and epilepsy.The whole-exome sequencing of the family revealed that the child suffered compound heterozygous mutations, c.1430G>T and c. 475C>T, in the ZNF526 gene.At present, 7 mutation sites in the ZNF526 gene have been reported globally to be associated with neurodevelopmental disorders, and the 2 mutations in this case have not been reported in the literature, broadening the phenotype and mutation spectrum of this disease.

Objective To evaluate the safety of the low glucoside composites of Epimedii Folium and clarify the pharmacokinetic characteristics of its five low glucosides.Methods Four groups of KM mice were orally administrated of corn oil,1 968,2 625 and 3 500 mg·kg-1 low glucoside composites of Epimedii Folium,respectively.Then,the living conditions,toxic symptoms,and death of the mice were observed for 7 consecutive days.After the mice were dissected,the viscera/body ratio and the viscera/brain ratio were calculated.Besides,the contents of alanine aminotransferase(ALT)and aspartate transaminase(AST)in plasma were determined by ELISA,and the pathological changes of the liver were observed by HE staining.C57BL/6J mice were intravenously or orally administered of baohuoside I,baohuoside II,sagittatoside A,sagittatoside B and sagittatoside C.Then,blood samples were collected at different time points.The plasma concentrations of the five low glucosides were measured by UHPLC-MS/MS.Results When compared with the control group,no significant differences were found in the body mass,viscera/body ratio,viscera/brain ratio,contents of ALT and AST in plasma after oral administration of different doses of low glucoside composites to mice.Moreover,no pathological changes or damages were found in the liver sections.After intravenous injection,the AUC0-t values of baohuoside Ⅰ,baohuoside Ⅱ,sagittatoside A,sagittatoside B and sagittatoside C in mice were 4.82,82.54,276.64,88.77 and 178.02 min·μg·mL-1,respectively.Meanwhile,the t1/2 values were 60.42,115.27,67.63,131.61 and 129.87 min,respectively.After oral administration,the AUC0-t values of the five low glucosides were 31.64,18.59,3.48,2.41 and 2.42 min·μg·mL-1,respectively.The Cmax values were 147.23,86.76,15.58,24.34 and 26.12 ng·mL-1,respectively.The tmax values were 21.00,78.00,78.00,30.00 and 28.00 min,respectively.The bioavailability of baohuosideⅠ,baohuosideⅡ,sagittatoside A sagittatoside B and sagittatoside C were 1.91%,0.51%,0.05%,0.06%and 0.04%,respectively.Conclusion The low glucoside composites of Epimedii Folium has high safety,and no hepatotoxicity were observed at dose of 3 500 mg·kg-1.The 5 low glucosides are quickly absorbed and rapidly eliminated in mice,and all of them have low bioavailability.