The advances of industrial biotechnology highly depend on the development of industrial bioprocess researches. In China, we are facing several challenges because of a huge national industrial fermentation capacity. The industrial bioprocess development experienced several main stages. This work mainly reviews the development of the industrial bioprocess in China during the past 30 or 40 years: including the early stage kinetics model study derived from classical chemical engineering, researching method based on control theory, multiple-parameter analysis techniques of on-line measuring instruments and techniques, and multi-scale analysis theory, and also solid state fermentation techniques and fermenters. In addition, the cutting edge of bioprocess engineering was also addressed.
Bioengineering ; history ; Bioreactors ; Biotechnology ; Chemical Engineering ; China ; Fermentation ; History, 20th Century ; History, 21st Century

Filamentous fungi are widely used in industrial fermentation. Particular fungal morphology acts as a critical index for a successful fermentation. To break the bottleneck of morphological analysis, we have developed a reliable method for fungal morphological analysis. By this method, we can prepare hundreds of pellet samples simultaneously and obtain quantitative morphological information at large scale quickly. This method can largely increase the accuracy and reliability of morphological analysis result. Based on that, the studies of Aspergillus niger morphology under different oxygen supply conditions and shear rate conditions were carried out. As a result, the morphological responding patterns of A. niger morphology to these conditions were quantitatively demonstrated, which laid a solid foundation for the further scale-up.
Aspergillus niger ; cytology ; Fermentation ; Industrial Microbiology ; Reproducibility of Results

Objective To explore the bone marrow stromal cells,anti-late antigen-4 (VLA-4) antibody (aVLA-4),cytarabine (Ara-C) on the proliferation and apoptosis of leukemia HL-60 cells.Methods The experiment was divided into five groups:HL-60 cells were cultured alone (control group),HL-60 cells and stromal cells group (stromal cells group),HL-60 cells + stromal cells + aVLA-4 (antibody group),HL-60 cells + stromal cells + Ara-C group (drug group),HL-60 cells + stromal cells + aVLA-4 + Ara-C group (antibody +drug group).Cell proliferation or inhibition rate was detected by CCK-8 method,the HL-60 cells apoptosis was detected by flow cytometry.The expression of anti-apoptotic gene bcl-2 in HL-60 cells was determined by Western blot.Results After 24 h and 48 h,treatment,the number of the stromal cells group HL-60 cells were higher than that of the control group with significant difference cultured [(7.2±0.3)×1O5/ml vs (5.3±0.4)×105/ml,(8.4±0.2)×105/ml vs (6.8±0.3)×105/m1,P ＜ 0.001],while the HL-60 cell proliferation inhibition rate [(24.3±2.1) ％,(37.0±2.6) ％,(65.6±3.8) ％] and apoptosis rate [(5.7±0.6) ％,(8.0±0.5) ％,(10.4±0.9) ％,(16.5±0.7) ％] of antibody group,drug group,antibody + drug group were higher than the control group with a difference of statistically significant (P ＜ 0.05),and the increase of antibody + drug group was most obvious.With the decreasing of the bcl-2 protein expression,which was most the decrease of antibody + drug group was most obvious.Conclusion Bone marrow stromal cells can stimulate the proliferation of leukemia cells,aVLA-4 interference the interaction between stromal cells and leukemia cells can enhance the chemosensitivity of leukemia cells to Ara-C.

Objective To evaluate DTI for early diagnosis and prognosis of diffuse axonal injury (DAI)in the moderate and sever traumatic brain injury (sTBI).Methods 30 patients with sTBI and 30 healthy controls were studied with T1 WI and DTI.The frac-tional anisotropy(FA)and ADC were quantified from different regions of interest(ROI)including the genu of corpus callosum(gCC), the trunk of CC,the splenium of CC(sCC)and the integrity CC.The FA and ADC of the same R0I was compared between TBI group and control group,and FA and ADC of the different parts of CC were compared in TBI group.Correlations between the FA or ADC and coma duration of the TBI patients were analyzed by Pearson linear correlation.Results Compared with control group,the FA value decreased significantly in each ROI,while ADC was reversed.The FA or ADC of the different ROI were correlated with co-ma duration in TBI group.Conclusion DTI is sensitive to detect the white matter injury of TBI.FA value detected in the CC can help diagnose DAI earlier and evaluate the degree of injury.

Objective: To explore the change of bone mass density(BMD) and micronutrients in middle-aged and old patients with iron overload and the effect on levels of micronutrients.Methods: BMD was measured by dual energy X-ray absorptiometry(DXA) in 19 middle-aged and old patients with iron overload and 41 age-and gender-matched healthy subjects.Serum selenium(Se)was measured by fluorospectrophotometry.Serum zinc(Zn) was measured by inductively coupled plasma atomic emission spectrometry(ICP-AES).Plasma vitamin A,D and E were measured by HPLC.The levels of blood lipid and plasma homocysteine were measured by automatic biochemical analyzer.Results: Plasma vitamin E of 19 iron overload patients was significantly lower than control group,and the levels of triglyceride and homocysteine increased significantly(P

Objective To analyze the status of information release and the ability to identify public needs for hypertension prevention and control information in Shanxi and Hebei areas. Methods A systematic data collection method was used to obtain various information about hypertension prevention and control published in Shanxi and Hebei provinces. Based on the Delphi method, sensitive and evaluation indicators for the tertiary prevention of hypertension were determined. To evaluate the degree to which public needs were met in the two areas, the authority, timeliness, continuity, systematicness, and credibility of identifying public needs were calculated. Results The release of information on hypertension prevention and control in Shanxi and Hebei lagged behind that in World Health Organization (WHO) for 2 and 27 years, respectively, and this was mainly carried out by research institutes, with no response from professional associations and government agencies. Information on primary and secondary prevention was first released in 1980 in Shanxi province, while primary prevention information was first released in 2005 in Hebei province. Regarding hypertension prevention and treatment, Shanxi province could meet 6.11% of the public need, and Hebei province could meet 3.57% of it. The five dimensions of authority, timeliness, continuity, systematicness, and credibility of identifying the public need were 11.34%, 25.29%, 0, 50.31%, and 0 in Shanxi province, and 6.86%, 14.54%, 0, 50.00%, and 0 in Hebei province, respectively. Conclusions The ability to identify the public need for information on hypertension prevention and control in Shanxi and Hebei provinces is relatively low. Relevant departments should take measures to enhance the two‐way communication of information and improve the public's knowledge and participation.

Objective:To investigate the effects of disialyllacto-N-tetraose (DSLNT) on low molecular weight metabolic profile of intestinal contents in neonatal rats with necrotizing enterocolitis (NEC), in an attempt to explore the protective mechanism of DLSNT on intestinal tract of neonates.Methods:Immediately after birth, SD rats were randomly divided into the control group, the NEC group and the NEC+ DSLNT group according to random number tale method.All rats were hand-fed by special formula milk.Rats in the NEC group and NEC+ DSLNT group were exposed to hypoxia (950 mL/L nitrogen, 10 min, thrice per day) and cold stress (4 ℃, 10 min, thrice per day) for continuous 3 days to establish rodent NEC model.Rats in the NEC+ DSLNT group were hand-fed with special formula containing 300 μmol/L DSLNT.All rats were sacrificed after 72 h, and intestinal contents were collected from ileum and colon, followed by untargeted metabolomic determination with the ultrahigh-performance liquid chromatography Q extractive mass spectrometry (UHPLC-QE-MS) method.The terminal ileum was examined by hematoxylin-eosin staining.The metabolome data were analyzed with multivariable analysis using SIMCA 14.1.The metabolites that met both variable importance in the projection (VIP) >1 in the orthogonal partial least squares analysis (OPLS-DA) model and P<0.05 in the t-test were screened as differential metabolites between groups. Results:DSLNT reduced the incidence of NEC and pathological scores of ileum tissue from neonatal rats with NEC [3.0(2.0, 3.0) scores vs.1.0(1.0, 2.0) scores, P<0.01], and also significantly suppressed inflammatory infiltration.OPLS-DA model based on the metabolome data determined by UHPLC-QE-MS could perform effective discrimination between the NEC group and the control group, as well as the NEC+ DSLNT group and the NEC group.There were 64 differential metabolites between the NEC group and the control group (VIP value>1 and P<0.05 for the OPLS-DA model). These metabolites included docosahexaenoic acid (+ 288.0%, P=0.028), xanthine (+ 372.1%, P=0.007), L-arginine (+ 233.1%, P=0.027), L-leucine (+ 232.7%, P=0.015), N-acetylneuraminic acid (-41.6%, P=0.014), and so forth.These metabolites were associated with 34 metabolic pathways.Among them, such 6 pathways as arginine biosynthesis, arginine and proline metabolism were the most disturbed pathways affected by NEC.There were 15 diffe-rential metabolites in between NEC+ DSLNT group and NEC group, which included D-mannose (-73.5%, P=0.032), xanthine (-63.4%, P=0.008), linoleic acid (+ 137.9%, P=0.047), nicotinamide adenine dinucleotide (+ 278.2%, P=0.005), and so forth.These metabolites were mapped to 7 metabolic pathways, among them, linoleic acid metabolism pathway was the most relevant differential pathway affected by DSLNT.There were 8 overlapped meta-bolites in both comparison strategies, and the variation trend of these overlapped metabolites in the NEC group was significantly reversed by DSLNT supplementation. Conclusions:DSLNT could significantly attenuate the NEC pathological damage caused by hypoxia/cold stress in neonatal rats.This protective effect is associated with the improvement of the metabolic profile of intestinal contents caused by NEC and the modulation of the linoleic acid metabolic pathway.The early preventive supplementation of DSLNT is of great significance in maintaining neonatal intestinal homeostasis and preventing the process of NEC.

Objective:To investigate the accuracy of magnetic resonance imaging (MRI) for quantitative determination of liver fat and iron content through a rat model of non-alcoholic fatty liver disease (NAFLD) induced by methionine-choline deficient (MCD) diet.Methods:Sixty SD rats were randomly divided into experimental (MCD-diet group, n = 30) and normal control group (normal diet, n = 30). Rats were subjected to special MRI examinations at the ends of 2, 4, and 8 weeks. Proton density fat fraction (PDFF) and R2* value were obtained, and then the rats were sacrificed. The liver tissues were stained with HE, Prussian blue, etc. Liver tissue non-heme iron (NHI) homogenate was determined by flame atomic absorption spectrometry. According to different data, one-way analysis of variance, t-test or χ2 test was used for statistical analysis. Results:PDFF and R2 * values in the MCD diet group at 2, 4 and 8 weeks were 23.37% ± 9.20%, 28.07% ± 6.84%, 25.40% ± 7.04% ( P < 0.01) and 90.58 ± 15.92, 104.12 ± 13.47, 106.35 ± 15.76 ( P < 0.05), respectively, which were significantly higher than the normal control group PDFF (2.39% ± 0.50%, 2.45% ± 0.45%, 3.26% ± 0.80%) and R2* (48.93 ± 7.90, 54.71 ± 5.91, 64.25 ± 15.76). Additionally, with the disease progression, R2 * had gradually increased, which was consistent with the NHI trend in liver tissue homogenates of each group. Conclusion:MRI, as a non-invasive quantitative method, can accurately assess liver fat and iron content in fatty liver disease, and with the degree of severity of fat changes, iron deposits tend to increase.

Objective:To analyze the correlation between serum ferritin and steatosis in non-alcoholic fatty liver disease.Methods:Data of 167 cases who underwent liver biopsy in the Affiliated Hospital of Hangzhou Normal University were collected. Hydrogen proton magnetic resonance spectroscopy were performed within one week. The pathological results of liver biopsy were used as the gold standard to analyze the case data, serological indicators, magnetic resonance spectroscopy-proton density fat fraction.Results:Pathological monitoring result showed that the serum ferritin in patients without steatosis, and with mild, moderate and severe steatosis were (206.20 ± 189.83), (286.65 ± 200.80), (326.55 ± 214.71), (391.50 ± 184.93) ng/ml, respectively, P < 0.005. Serum ferritin was correlated to body mass index, PDFF, alanine aminotransferase, gamma glutamyltransferase, low-density lipoprotein, high-density lipoprotein. The area under ??the receiver operating characteristic curve with ferritin for the diagnosis of non-alcoholic fatty liver disease was 0.716, and the optimal diagnostic threshold was 214.56 ng/ml. The sensitivity and specificity were 80.1%, and 68.8%, respectively. There was no statistically significant difference between the intralobular inflammation, fibrosis, and ferritin. Prussian blue iron staining had no apparent deposition of iron particles. Conclusion:Ferritin has significant positive correlation with the results of pathological and magnetic resonance imaging for liver steatosis. Therefore, it can be used as a non-invasive diagnostic method for liver steatosis evaluation.

Objective To explore the prevalent challenges in the construction and operation of SPD(Supply,Process-ing,and Distribution)projects for medical consumables and to propose corresponding strategies,thereby offering hospital supply managers insights for references.Methods Based on the questionnaire survey,the scope of difficulties was assessed across 23 hospitals.scores of each difficult point were calculated with descriptive statistics methods according to various stages,and the causes were analyzed.Results The overall scores of the survey ranged from 50 to 77 points,with the highest in each category being system interface docking(77 points),system stability(73 points),inventory carry-over(61 points),and the professional capability of SPD service provider(66 points).Conclusion In the construction and operation of SPD projects,it is essential to select an SPD model and service provider that aligns with the hospital's own characteristics.Establishing robust assessment mechanisms for SPD service providers and personnel training,as well as a comprehensive system audit and testing framework,can ensure system stability.Additionally,effective work assignment and performance evaluation of SPD personnel should be well-man-aged.