AIM: To investigate and analyze serum nitric oxide synthase 4(NOX4)and matrix metalloproteinase(MMP)-2 expressions in patients with diabetes mellitus(DM)complicated with neovascular glaucoma(NVG)and their clinical significance.METHODS: A prospective study was conducted on 161 patients with DM complicated with NVG admitted to Handan City Eye Hospital(The Third Hospital of Handan)from June 2020 to June 2023. Based on whether complications occurred 1 a after trabeculectomy in the study group patients, they were divided into a group with good prognosis(n=90)and a group with poor prognosis(n=71). During the same period, 161 patients with chronic angle-closure glaucoma without iris neovascularization were selected as the control group. ELISA method was applied to detect the expression levels of serum NOX4 and MMP-2. ROC curve was plotted to evaluate the diagnostic value and postoperative complication prediction value of NOX4 and MMP-2 in patients with DM complicated with NVG. Pearson method was applied to analyze the correlation of NOX4 and MMP-2 with vascular endothelial growth factor(VEGF)and interleukin-6(IL-6). Multivariate Logistic regression was applied to analyze the influencing factors of postoperative complications in the study group.RESULTS:The general information of the study group and control group of patients is comparable. Compared with the control group, the expression levels of serum NOX4, MMP-2, VEGF, and IL-6 in the study group were significantly increased(P<0.001). According to Pearson analysis, serum NOX4 and MMP-2 levels significantly positively correlated with VEGF and IL-6 levels, respectively(P<0.001). According to ROC curve, the AUC of NOX4 combined with MMP-2 in the diagnosis of DM complicated with NVG was better than that of individual diagnosis of NOX4(Z=3.341, P<0.05)and MMP-2(Z=2.788, P<0.05). The duration of DM, the proportion of people with intraocular pressure >21 mmHg, and the expression levels of NOX4, MMP-2, VEGF, and IL-6 in the poor prognosis group were all higher than those in the good prognosis group(P<0.001). The duration of DM, intraocular pressure >21 mmHg, the levels of NOX4, MMP-2, VEGF, and IL-6 were all risk factors for poor prognosis in DM patients with NVG(P<0.001). According to ROC curve, the combined prediction of NOX4 and MMP-2 for postoperative complications in patients with DM complicated by NVG was superior to the AUC predicted by NOX4(Z=3.727, P<0.05)and MMP-2(Z=2.219, P<0.05), respectively.CONCLUSION:NOX4 and MMP-2 are upregulated in the serum of patients with DM complicated by NVG. Combined detection of these two markers holds significant clinical value for the early diagnosis and prognosis of patients with DM complicated by NVG.

Objective To evaluate the effect of LifePort combined with polymyxin B in preventing donor-derived infections caused by preservation solution contamination. Methods Clinical data of 110 kidney transplant recipients were retrospectively analyzed. According to the decontamination status of preservation solution, the recipients were divided into the decontamination group (n=62) and the non-decontamination group (n=48). The general data of the two groups were compared, and the preventive effect of polymyxin B on possible donor-derived infections (p-DDI) was analyzed, especially infections associated with multidrug-resistant Gram-negative bacteria (MDR GNB). Results There were no statistically significant differences in baseline data (gender, age, preservation solution contamination status, etc.) between the decontamination group and the non-decontamination group (all P > 0.05). The overall contamination rate of preservation solution was 80.0%, and 68 contaminated samples were with single microorganism and 20 with multiple microorganisms. Coagulase-negative staphylococci, Enterococcus and Klebsiella pneumoniae were the most common microorganisms in the positive samples. Fifteen cases of preservation solution were contaminated by MDR GNB, including 10 cases in the non-decontamination group and 5 cases in the decontamination group, with no statistically significant difference between the two groups (P = 0.053). Postoperative infection-related events occurred in 69 recipients, including 39 cases in the non-decontamination group and 30 cases in the decontamination group, with the incidence rate in the non-decontamination group significantly higher than that in the decontamination group (P < 0.001). Only 10 cases of infections were identified as p-DDI, all of which were positive for preservation solution culture, including 8 cases in the non-decontamination group and 2 cases in the decontamination group (P < 0.05). There were 5 cases of p-DDI related to MDR GNB in the non-decontamination group, while no such cases occurred in the decontamination group (P < 0.05). No adverse reactions related to polymyxin B were observed, and no recipient death or renal allograft dysfunction occurred in either group. Conclusions Adding polymyxin B to the preservation fluid during hypothermic machine perfusion with LifePort before renal transplantation may reduce p-DDI and its potential adverse consequences.

ObjectiveTo explore the incremental cost of central line-associated bloodstream infections （CLABSI） after central venous catheterization （CVC） in critically ill patients in the intensive care unit （ICU）， as well as the main cost of nosocomial infection prevention and control. By comparing these two costs， the medical personnel to pay more attention should CLABSI prevention and control from the perspectives of medical quality and economic benefits， and promote the implementation of prevention and control measures. MethodsCluster sampling was used to select 126 critically ill patients who underwent CVC in the ICU of a tertiary traditional Chinese medicine hospital from January 2021 to December 2023， including 65 cases in the CLABSI group and 61 in the non-CLABSI group. Patients’ data were retrospectively collected from the hospital medical records， including the disease type， gender， age， length of hospital stay， outcome， and hospitalization expenses. The costs of different hand hygiene methods and differing approaches to environmental cleaning and disinfection were analyzed and compared. ResultsThere were significant differences in the length of hospital stay （Z=-5.35， P<0.05） and total hospitalization expenses （Z=-6.79， P<0.05） between the CLABSI and non-CLABSI group. Total hospitalization expenses showed significant differences among patients with different lengths of hospital stay （H=43.01， P<0.05）， with much higher median one in those with 60 or more days of hospital stay than other patients. Greater differences of median total hospitalization expenses were found in males than in females （Z=-3.98， P<0.05）， as well as in patients aged 60-80 years than in patients of other ages （Z=-5.79， P<0.05）. ConclusionsThe occurrence of CLABSI significantly increases the ICU patients’ length of hospital stay and hospitalization expenses. There are differences in the costs of different hand hygiene methods and differing approaches to environmental cleaning and disinfection， but these costs are acceptable compared to the incremental costs directly attributable to CLABSI. Therefore， medical institutions should attach importance to the investment in prevention and control of nosocomial infections such as hand hygiene and environmental cleaning and disinfection， formulate practical， reasonable and feasible plans， and ensure their implementation， in order to avoid nosocomial infections， improve the medical quality， effectively control patients’ length of hospital stay and hospitalization costs， and strive to maintain patient safety.

AIM: To compare the clinical outcomes of extended depth-of-focus intraocular lenses(EDOF IOLs)using either micromonovision implantation or mixed implantation of EDOF and diffractive bifocal IOLs.METHODS: This retrospective clinical trial included 130 patients(260 eyes), who were divided into two groups. Group RR comprised 70 patients(140 eyes)bilaterally implanted with ZXR00 IOLs(Tecnis ZXR00, where one target was -0.5 D to -0.75 D and the other was 0 to -0.25 D). Group RM comprised 60 patients(120 eyes)unilaterally implanted with both ZXR00 and ZMB00 IOLs(Tecnis ZMB00, 0 to -0.25 D). Postoperative outcomes were compared after 3 mo, including visual acuity, defocus curves, stereoacuity, modulation transfer functions(MTFs), higher-order aberrations, and Visual Function-14(VF-14)questionnaire responses.RESULTS: Group RR had superior bilateral intermediate vision, while the group RM had superior bilateral near vision(both P<0.05). Group RM also exhibited superior MTFs and reduced higher-order aberrations(both P<0.05). Stereoacuity and VF-14 questionnaire results showed no statistically significant difference between groups(P>0.05).CONCLUSION: The implantation of micromonovision has significantly improved near vision. IOLs and their collocation can be customized according to individual patient needs to achieve precise treatment and provide cataract patients with high-quality vision.

AIM: To compare the clinical outcomes of extended depth-of-focus intraocular lenses(EDOF IOLs)using either micromonovision implantation or mixed implantation of EDOF and diffractive bifocal IOLs.METHODS: This retrospective clinical trial included 130 patients(260 eyes), who were divided into two groups. Group RR comprised 70 patients(140 eyes)bilaterally implanted with ZXR00 IOLs(Tecnis ZXR00, where one target was -0.5 D to -0.75 D and the other was 0 to -0.25 D). Group RM comprised 60 patients(120 eyes)unilaterally implanted with both ZXR00 and ZMB00 IOLs(Tecnis ZMB00, 0 to -0.25 D). Postoperative outcomes were compared after 3 mo, including visual acuity, defocus curves, stereoacuity, modulation transfer functions(MTFs), higher-order aberrations, and Visual Function-14(VF-14)questionnaire responses.RESULTS: Group RR had superior bilateral intermediate vision, while the group RM had superior bilateral near vision(both P<0.05). Group RM also exhibited superior MTFs and reduced higher-order aberrations(both P<0.05). Stereoacuity and VF-14 questionnaire results showed no statistically significant difference between groups(P>0.05).CONCLUSION: The implantation of micromonovision has significantly improved near vision. IOLs and their collocation can be customized according to individual patient needs to achieve precise treatment and provide cataract patients with high-quality vision.

The ability of cells to sense and adapt to metabolic changes and environmental variations is essential for their functions. Recent advances in synthetic biology have uncovered increasing mechanisms through which cells detect changes in metabolism and environmental conditions, leading to broader applications. However, a systematic review on the regulation of cellular metabolism and environmental adaption is currently lacking. This article presents a comprehensive overview of this field from three perspectives. First, it introduces key transmembrane and sensor proteins involved in the cellular perception of metabolic and environmental changes. Next, it summarizes the adaptive regulation mechanisms that natural cells employ when confronted with intracellular and extracellular metabolic changes. Finally, the review explores the application scenarios based on cellular adaptive regulation in three aspects: dynamic control, rational metabolic engineering, and adaptive evolution and makes an outlook on the future development directions in this field. This review not only provides a comprehensive perspective on the mechanisms by which cells sense metabolic and environmental variations, but also lays a theoretical foundation for further innovations in the field of synthetic biology. With the continuous advancement of future technologies, a deeper understanding of cellular adaptive regulation mechanisms holds great potential to drive the development and application of novel biomanufacturing platforms.
Adaptation, Physiological ; Synthetic Biology ; Metabolic Engineering/methods* ; Environment ; Bacteria/genetics*

L-valine is an important essential branched-chain amino acid widely used in industries such as feed, pharmaceuticals, and food. In order to further enhance the production performance of L-valine, this study systematically engineered the metabolism of a Corynebacterium glutamicum strain, preserved in the laboratory, which is capable of producing L-valine. First, strain VH-9 was obtained by enhancing the precursor supply, synthesis pathway, and transport system of L-valine. In a 5 L fermenter, the titer, yield, and productivity of L-valine were 76.6 g/L, 0.45 g/g, and 2.39 g/(L·h), respectively. Furthermore, strain VH-18 was obtained by enhancing the uptake of substrate glucose and balancing energy supply to reduce succinate accumulation, with the titer, yield, and productivity of L-valine increased to 82.7 g/L, 0.52 g/g, and 2.58 g/(L·h), respectively. After optimization of fermentation conditions, the titer, yield, and productivity of L-valine in strain VH-18 were further improved to 88.7 g/L, 0.54 g/g, and 2.77 g/(L·h), respectively. This study has achieved the high-efficiency production of L-valine through a systems metabolic engineering strategy.
Corynebacterium glutamicum/genetics* ; Metabolic Engineering/methods* ; Valine/biosynthesis* ; Fermentation ; Glucose/metabolism*

Objective: To explore the clinical manifestations and treatment plans of chronic recurrent parotitis (CRP), and to provide a reference for the clinical diagnosis and treatment of CRP. Methods: Approval was obtained from the hospital’s Medical Ethics Committee, and a retrospective analysis and summary of the clinical features, imaging characteristics, diagnosis, and treatment of 41 CRP patients with complete data were performed. Results: Among the 41 patients with CRP, 14 were male and 27 were female, with a male-to-female ratio of approximately 1:2 (14/27). The age at first-time onset ranged from 3 to 23 years, with a median age of 6 years, and there were 38 patients (92.7%, 38/41) with the first onset age of under 18 years old. The age of the first visit to our hospital ranged from 4 to 72 years old, with an average age of (41.0 ± 17.3) years; the disease duration was 0.5 to 66 years, with an average of 35.0 ± 16.1 years. Twenty-five cases had bilateral parotid gland involvement (61.0%, 25/41). The clinical manifestations of CRP are repeated swelling of one or both parotid glands, along with discomfort, and this may be accompanied by mild edema or skin flushing and pus or jelly-like secretions at the duct openings. The typical manifestations of parotid angiography are: the dominant duct and branch ducts of the parotid gland do not have specific dilation or narrowing, and the peripheral ducts show characteristic “punctate, spherical, or cavitary” dilation and delayed emptying. Of the cases, 34 had abnormal enlargement of the main duct orifice (82.9%, 34/41), and 37 presented with abnormal anterior displacement of the accessory glands (90.2%, 37/41). The treatment plan of “antibiotic perfusion + aspiration and removal of obstruction (or aspiration after obstruction dissolution)+ postprandia massage along the direction of the parotid duct (from posterior to anterior) with multiple courses for consolidation”achieved favorable outcomes. The mean follow-up period of this group was(71.1+21.9)months, and no recurrence was observed during the follow-up period. Conclusion CRP is more prevalent in young females and frequently presents with bilateral involvement. Congenital anatomical defects, such as abnormal enlargement of the main duct orifice and abnormal anterior displacement of the accessory glands, are important predisposing factors. The multi-course comprehensive therapy centered on antibiotic infusion, removal and dissolution of obstructions, and post-prandial massage along the direction of the parotid duct has significant therapeutic effects and deserves clinical application.

Objective:To analyze the blood-transition prototype components and metabolites of Fengliaoxing Fengshi Dieda medicinal liquor.Methods:Ultra-high performance liquid chromatographyquadrupole/electrostatic field orbital trap high resolution mass spectrometry (UHPLC-Q Exactive Focus MS/MS) technique was used to compare the chromatogram differences of Fengliaoxing Fengshi Dieda medicinal liquor extract, blank serum and drug-containing serum. According to the retention time, relative molecular weight and the ratio with primary and secondary ion fragments provided by MS, the prototype components and metabolites of Fengliaoxing Fengshi Dieda medicinal liquor extract were analyzed in serum of rats after oral administration. The detection conditions were as follows: the mobile phase of methanol (A)-0.1% formic acid solution (B) for elution gradient (0-5 min, 5%A; 5-60 min, 5%-95%A; 60-65 min, 95%A), the flow rate of 0.3 ml/min, heated electrospray ionization, detection range of m/z 80-1 200, positive and negative ion scanning modes.Results:A total of 31 transitional components were detected in the serum, of which 9 were prototype components and 22 were metabolites. The 9 prototype components were identified as phenylacetaldehyde, baogongteng C/ erycibellin, p-coumaric acid, 5-Hydroxymethylfurfural, quinic acid, paeonol, 3-Hydroxybenzaldehyde, salicylic acid, and isourecumenol. The 22 metabolites mainly consist of 11 organic acid components, 3 indole components, 2 organic phenolic components, 2 alkaloid components, 1 nucleoside component, 1 amino acid component, 1 lactone component, and 1 sulfonic component. The metabolic pathways were mainly glucuronidation, sulfation and others, which by phase Ⅱ metabolism.Conclusion:Organic phenols and organic acids are the main components that enter the body of Fengliaoxing Fengshi Dieda Medicinal Liquor, while alkaloid compounds and organic acid components may be potential active ingredients for its pharmacological effects.

The theory of "origin essence-origin qi-origin spirit" is rooted in the theory of "essence-qi-spirit", which explains that origin essence, origin qi, origin spirit as the important material foundation, energy power and regulation center in the process of growth and development of the organism, are mutual and complementary to each other, and operate orderly under the guidance of the ministerial fire. Tumor is essentially an abnormal disorder of the growth and development process of the organism, and its occurrence and development are directly related to the mutation of origin essence and the alienation of ministerial fire, and closely related to the attenuation of origin qi, the departure of ministerial fire, and the inefficiency of origin spirit, and the delusional movement of ministerial fire. Based on the theory of "origin essence-origin qi-origin spirit", the tumor can be treated in the clinic by regulating the ministerial fire suppressing origin essence to inhibit the tumor development, strengthening the spleen and benefiting the qi to slow down the attenuation of origin qi, and nourishing the heart and cultivating the mind to stabilize the power of origin spirit in order to further improve the understanding of TCM on the etiology of tumors, and at the same time, to provide a new direction and ideas for the clinical treatment of tumors.