Energy metabolism regulation plays a pivotal role in metabolic engineering. It mainly achieves the balance of material and energy metabolism or maximizes the utilization of materials and energy by regulating the supply intensity and mode of ATP and reducing electron carriers in cells. On the one hand, the production efficiency can be increased by changing the distribution of material metabolic flow. On the other hand, the thermodynamic parameters of enzyme-catalyzed reactions can be altered to affect the reaction balance, and thus the production costs are reduced. Therefore, energy metabolism regulation is expected to become a favorable tool for the modification of microbial cell factories, thereby increasing the production of target metabolites and reducing production costs. This article introduces the commonly used energy metabolism regulation methods and their effects on cell factories, aiming to provide a reference for the efficient construction of microbial cell factories.
Energy Metabolism/physiology* ; Metabolic Engineering/methods* ; Adenosine Triphosphate/metabolism* ; Industrial Microbiology/methods*

Objective:To discuss the classification and treatment of ureteroileal anastomotic stricture (UAS) after radical cystectomy.Methods:The clinical data of 34 patients with UAS after radical cystectomy in the Department of Urology of Tongji Hospital from January 2017 to January 2022 were reviewed and analyzed. There were 25 males and 9 females. The average age was (66.3±7.7)years, including 2 cases of bilateral hydronephrosis and 32 cases of unilateral hydronephrosis. The average time of UAS was detected (14.7±6.5)months after radical cystectomy. There were 32 patients of unilateral hydronephrosis and 2 patients of bilateral hydronephrosis. Two patients had undergone nephrostomy in an external hospital. Three patients had elevated leukocytes in blood routine. Among them, two patients had fever. First, nephrostomy on the hydronephrosis side and anti-infection treatment were performed. After routine blood tests showed that the white blood cells were normal and antibiotics were stopped for 24 hours without fever, the operation was performed. 34 patients had preoperative hydronephrosis of (2.7±0.6) cm. Of the 34 cases in this group, 5 cases were injected with methylene blue through a preoperative nephrostomy tube, and 29 were injected with methylene blue through the renal pelvis using an 18G puncture needle under ultrasound guidance. Using a ureteroscope to observe in the ileal bladder, methylene blue was seen in 4 cases. Methylene blue was used to guide the search for the stenosis and a super smooth guide wire was inserted. Among them, 3 cases were dilated with a 5 mm ureteral dilation balloon catheter, 1 case was dilated with a F14 ureteral access sheath, and then a F6 single J stent was inserted. Methylene blue was not seen in the ileal conduit in 30 cases, of which 16 cases were treated with a flexible ureteroscope through the nephrostomy to locate the stenosis, incised with a 30 W holmium laser. 9 cases were treated with 5 mm ureteral dilation balloon catheter, and 7 cases were treated with a F14 ureteral access sheath, and then an F6 single J stent was inserted. 14 cases were unable to find the stenosis by antegrade method. According to the operation time and patient's condition, it was decided to perform immediate or second stage dual endoscope surgery. Through the nephrostomy, a flexible ureteroscope was used to enter the stenosis along the super slide guide wire. A rigid ureteroscope was used to observe the stenosis through the ileal conduit, and the stenosis was found. The stenosis was found in 10 cases and incised with a 30 W holmium laser. 8 cases were treated with 5 mm ureteral dilation balloon catheter, and 2 cases were treated with a F14 ureteral access sheath, and then an F6 single J stent was inserted. 4 cases were still unable to accurately locate the stenosis using the dual endoscope surgery(one case was bilateral stenosis, and one side was relieved), and continued indwelling nephrostomy. The definition of successful removal of stricture in this study is that an F6 single J stent can be inserted into the ureter.Results:UAS were classified into four types based on the severity of the intraoperative findings: Type Ⅰ, the narrow ureteral lumen is more than 50% narrower than the normal ureteral lumen, but methylene blue can pass through in strands; Type Ⅱ, needle like stricture of the ureteral lumen, allowing only methylene blue filaments to pass through; Type Ⅲ, membranous atresia of the ureter, with a narrow segment of 1 to 3 mm in length, and methylene blue cannot pass through; Type Ⅳ, long segment stenosis. Of the 34 cases in this group, 4 cases were type Ⅰ, and the stenosis was dredged by retrograde method; 16 cases were type Ⅱ, and the stenotic segments were dredged by antegrade method; 10 cases were type Ⅲ, and the stenosis was dredged by the dual endoscope surgery; Four cases were of type Ⅳ (one case was of bilateral UAS, one side was of type Ⅲ, and the other side was of type Ⅳ, which was classified as type Ⅳ). The stenotic segment could not be solved through the above methods. Among the 34 patients, 30 patients were successfully relieved of anastomotic obstruction, and 1 patient with bilateral obstruction was unilaterally relieved of anastomotic obstruction. In the other 3 cases, because the stenosis segment was too long, 2 cases were changed to nephrostomy, and 1 case was changed to open surgery, with a success rate of 88.2%. UAS was classified into 4 types based on the severity of UAS seen during surgery. No serious complications occurred during and after the operation. During the follow-up of 6-24 months, the imaging evaluation of 4 patients showed that hydronephrosis was aggravated, with an average increase in creatinine of (32.5±10.9)μmol/L, requiring replacement of a single J tube. The imaging evaluation of the remaining 26 patients showed that the postoperative hydronephrosis was 0.9 ± 0.6 cm less than the preoperative hydronephrosis 2.6 ± 0.6 cm, with a statistically significant difference ( P<0.01). The quality of life score at 3 months after surgery was (1.9±0.6), which was significantly improved compared to the preoperative indwelling nephrostomy period (5.2±0.7), with a statistically significant difference ( P<0.01) Conclusions:The treatment of UAS after radical cystectomy with retrograde, antegrade, and dual endoscope surgery has a high success rate, which can help some patients avoid the inconvenience of indwelling external drainage tubes and the risk of open surgery. Choosing an appropriate surgical method can achieve the goal of treating UAS with minimal trauma.

Objective:To explore the effects of neonatal stimulator of interferon genes (STING) innate immune signaling pathway of HBsAg-positive mothers on non/hypo-response to hepatitis B vaccine (HepB) in their infants.Methods:From November 2019 to June 2022, HBsAg-positive mothers and their infants in the Third People's Hospital of Taiyuan were recruited as the study subjects. The epidemiological and clinical data were collected by questionnaire survey and medical records review. The key molecular proteins of STING innate immune signaling pathway (STING, pIRF3) and immune cells associated with vaccine response (DC, T and B and plasma cells) in neonatal cord blood were detected by flow cytometry. Follow up was conducted for infants for 1-2 months after the full vaccination of HepB. Serum hepatitis B surface antibody (anti-HBs) was detected by chemiluminescence microparticle immunoassay. Unconditional logistic regression model, nomogram and Bayesian network model were used to evaluate the effect of STING innate immune signaling pathway on non/hypo-response to HepB and related factors in infants, and the relationship between various factors.Results:A total of 195 pairs of HBsAg-positive mothers and infants were recruited, the rate of non/hypo-response to HepB in the infants was 12.31% (24/195). High maternal HBV DNA load, low expression of neonatal STING, low expression of pIRF3 and low percentage of plasma cells were risk factors for non/hypo-response to HepB in the infants ( OR=4.70, 3.46, 3.18 and 2.20, all P<0.05). The nomogram constructed by these factors had good predictive efficacy (area under curve=0.81, 95% CI: 0.63-0.83). The results of Bayesian network model showed that the infants with a high maternal HBV DNA load had a higher conditional probability of low STING expression (62.50%) and a higher conditional probability of low pIRF3 expression (58.54%). The conditional probabilities of low expression of DC, T, B and plasma cells were 53.16%, 60.20%, 68.42% and 57.14%, respectively. Conclusion:Maternal HBV DNA might inhibit STING innate immune signaling pathways in infants and immune cells associated with HepB response, resulting in non/hypo-response to HepB in infants of HBsAg-positive mothers.

Objective:To investigate the bacterial composition and antimicrobial resistance profile of clinical isolates from bloodstream infections in China.Methods:The clinical bacterial strains isolated from blood culture were collected during January 2020 to December 2020 in member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS). Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical Laboratory Standards Institute(CLSI, USA). WHONET 5.6 was used to analyze data.Results:During the study period, 10 043 bacterial strains were collected from 54 hospitals, of which 2 664 (26.5%) were Gram-positive bacteria and 7 379 (73.5%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (38.6%), Klebsiella pneumoniae (18.4%), Staphylococcus aureus (9.9%), coagulase-negative Staphylococci (7.5%), Pseudomonas aeruginosa (3.9%), Enterococcus faecium (3.3%), Enterobacter cloacae (2.8%), Enterococcus faecalis (2.6%), Acinetobacter baumannii (2.4%) and Klebsiella spp (1.8%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus aureus were 27.6% and 74.4%, respectively. No glycopeptide- and daptomycin-resistant Staphylococci were detected. More than 95% of Staphylococcus aureus were sensitive to rifampicin and SMZco. No vancomycin-resistant Enterococci strains were detected. Extended spectrum β-lactamase (ESBL) producing Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were 48.4%, 23.6% and 36.1%, respectively. The prevalence rates of carbapenem-resistance in Escherichia coli and Klebsiella pneumoniae were 2.3% and 16.1%, respectively; 9.6% of carbapenem-resistant Klebsiella pneumoniae strains were resistant to ceftazidime/avibactam combination. The prevalence rate of carbapenem-resistance in Acinetobacter baumannii was 60.0%, while polymyxin and tigecycline showed good activity against Acinetobacter baumannii. The prevalence rate of carbapenem-resistance of Pseudomonas aeruginosa was 23.2%. Conclusions:The surveillance results in 2020 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while Escherichia coli was the most common pathogen, and ESBL-producing strains declined while carbapenem-resistant Klebsiella pneumoniae kept on high level. The proportion and the prevalence of carbapenem-resistant Pseudomonas aeruginosa were on the rise slowly. On the other side, the MRSA incidence got lower in China, while the overall prevalence of vancomycin-resistant Enterococci was low.

Ulcerative colitis (UC) is a chronic non-specific intestinal inflammatory disease. Whether surgical treatment should be taken is a difficult and focus decision of clinical practice. Studies have shown that severe complications, combined with severe infection, poor laboratory indices, and ineffective medical treatment are the evaluation elements of UC surgery. This article reviewed the advances in study on high risk factors of surgery with UC.

Inflammatory bowel disease (IBD) involves extra-intestinal organs, and pulmonary disease associated with IBD is easy to be ignored because of its low incidence. This article summarizes the pulmonary disease associated with IBD, which improves the clinicians′understandings and provides references.

Objective:To explore efficacy and safety of endovascular therapy combined with hyperbaric oxygen (HBO) intervention in acute anterior circulation macrovascular occlusion stroke.Methods:A total of 150 patients with acute anterior circulation macrovascular occlusive stroke admitted in No.902 Hospital of the CPLA Joint Logistic Support Force were selected and randomly divided into endovascular treatment group and combined treatment group (endovascular+ HBO). Endovascular therapy was adopted in the treatment of all patients. Modified thrombolytic flow grading (mTICI) was used to evaluate vascular recanalization after operation, and the incidences of complications of hemorrhage transformation and vascular re-occlusion were recorded. National institutes of health stroke scale (NIHSS) was used to evaluate the neurological functions on admission, at 24 hours after the operation, and one course after HBO therapy. The prognosis was evaluated by observing the changes of blood homocysteine (HCY) and high-sensitivity C-reactive protein (hs-CRP) levels before and after treatment. The patients had been followed up by the modified Rankin Scale (mRS) for 90 days. At the same time, 75 patients with acute anterior circulation macrovascular occlusive stroke without taking endovascular treatment were selected as the control group.Results:Among 150 patients, 126 cases had a grade of mTICI≥2b, while 24 cases had a grade of mTICI<2b. Postoperative vascular re-occlusion occurred in 3 cases, and symptomatic intracranial hematoma occurred in 6 cases. The NIHSS score at 24 hours after the operation was significantly lower than that on admission, and the NIHSS score was further improved after HBO treatment. Ninety days after the operation, mRS showed 98 cases of good prognoses, while 52 cases of poor prognoses. The levels of HCY and hs-CRP were significantly lower than those before the treatment.Conclusion:Endovascular therapy for acute anterior circulation macrovascular occlusive stroke is safe and effective. Postoperative HBO therapy can significantly improve the prognosis and the quality of life of patients.

Inflammatory bowel disease (IBD) involves extra-intestinal organs, and pulmonary disease associated with IBD is easy to be ignored because of its low incidence. This article summarizes the pulmonary disease associated with IBD, which improves the clinicians′understandings and provides references.

Objective:To explore efficacy and safety of endovascular therapy combined with hyperbaric oxygen (HBO) intervention in acute anterior circulation macrovascular occlusion stroke.Methods:A total of 150 patients with acute anterior circulation macrovascular occlusive stroke admitted in No.902 Hospital of the CPLA Joint Logistic Support Force were selected and randomly divided into endovascular treatment group and combined treatment group (endovascular+ HBO). Endovascular therapy was adopted in the treatment of all patients. Modified thrombolytic flow grading (mTICI) was used to evaluate vascular recanalization after operation, and the incidences of complications of hemorrhage transformation and vascular re-occlusion were recorded. National institutes of health stroke scale (NIHSS) was used to evaluate the neurological functions on admission, at 24 hours after the operation, and one course after HBO therapy. The prognosis was evaluated by observing the changes of blood homocysteine (HCY) and high-sensitivity C-reactive protein (hs-CRP) levels before and after treatment. The patients had been followed up by the modified Rankin Scale (mRS) for 90 days. At the same time, 75 patients with acute anterior circulation macrovascular occlusive stroke without taking endovascular treatment were selected as the control group.Results:Among 150 patients, 126 cases had a grade of mTICI≥2b, while 24 cases had a grade of mTICI<2b. Postoperative vascular re-occlusion occurred in 3 cases, and symptomatic intracranial hematoma occurred in 6 cases. The NIHSS score at 24 hours after the operation was significantly lower than that on admission, and the NIHSS score was further improved after HBO treatment. Ninety days after the operation, mRS showed 98 cases of good prognoses, while 52 cases of poor prognoses. The levels of HCY and hs-CRP were significantly lower than those before the treatment.Conclusion:Endovascular therapy for acute anterior circulation macrovascular occlusive stroke is safe and effective. Postoperative HBO therapy can significantly improve the prognosis and the quality of life of patients.