Highly efficient production of L-valine by multiplex metabolic engineering of Corynebacterium glutamicum / 生物工程学报

As a branched chain amino acid, L-valine is widely used in the medicine and feed sectors. In this study, a microbial cell factory for efficient production of L-valine was constructed by combining various metabolic engineering strategies. First, precursor supply for L-valine biosynthesis was enhanced by strengthening the glycolysis pathway and weakening the metabolic pathway of by-products. Subsequently, the key enzyme in the L-valine synthesis pathway, acetylhydroxylate synthase, was engineered by site-directed mutation to relieve the feedback inhibition of the engineered strain. Moreover, promoter engineering was used to optimize the gene expression level of key enzymes in L-valine biosynthetic pathway. Furthermore, cofactor engineering was adopted to change the cofactor preference of acetohydroxyacid isomeroreductase and branched-chain amino acid aminotransferase from NADPH to NADH. The engineered strain C. glutamicum K020 showed a significant increase in L-valine titer, yield and productivity in 5 L fed-batch bioreactor, up to 110 g/L, 0.51 g/g and 2.29 g/(L‧h), respectively.

Treatment of intra-articular distal femur fracture by our slot-designed compression bolt combined with bilateral locking compression plates: a biomechanical analysis / 中华创伤骨科杂志

Objective:To evaluate the biomechanical stability of our slot-designed compression bolt (SCB) combined with bilateral locking compression plates (LCPs) in the treatment of intra-articular distal femur fracture.Methods:In 24 adult male knee specimens treated with formalin, the femoral bony part was preserved to establish standard models of intra-articular distal femur fracture (AO type 33-C1). According to the random number table, the fracture models were divided into 2 equal groups: an experimental group ( n=12) subjected to fixation with one SCB combined with bilateral LCPs with 10 locking screws and a control group ( n=12) subjected to fixation with bilateral LCPs with 12 locking screws. In each model, a vertical ballast test was conducted to record the maximum axial displacement of the system and a horizontal torsion test to calculate the torsional stiffness of the system. When the loading pressure was 0-1,000 N in the biomechanical machine, structural abnormalities were observed in the 2 groups of models and the system maximum axial displacement and system torsional stiffness were compared between the 2 groups. Results:When the vertical ballast pressure was 400 N, 600 N, 800 N and 1,000 N, the maximum axial displacement of the system was, respectively, (0.14±0.01) mm, (0.25±0.01) mm, (0.41±0.02) mm and (0.63 ± 0.02) mm in the experimental group, and (0.15 ± 0.01) mm, (0.26 ± 0.01) mm, (0.46 ± 0.03) mm, and (0.67 ± 0.04) mm in the control group. Compared with the control group, the average maximum axial displacement in the experimental group decreased significantly under the axial pressure of 600-1,000 N ( P<0.05). When the horizontal torsion reached 5°, the torsional stiffness was, respectively, (2.00±0.12) Nm/° and (2.02±0.07) Nm/° in the experimental group and the control group, showing no significant difference between the 2 groups ( P>0.05). Conclusions:In the treatment of intra-articular distal femur fracture, compared with simple bilateral LCPs, our SCB combined with bilateral LCPs demonstrate similar torsional stability but better axial biomechanical stability. As our SCB has advantages of bilateral compression and minimal invasion in operation, it may be a new option for the reduction and compression treatment of intra-articular fractures.

Recent advances in mechanism and treatment of fracture-related tension blister / 中华创伤杂志

The presence of tension blister often predicts severe soft tissue damage，which not only increases the risk of wound complications but also prolongs the surgical treatment time. However，the developed tension blister has been proposed as a potential decompressive approach for it may relieve the pressure of osteofascial compartment and improve the likelihood of relieving clinical symptoms，as well as avoid unnecessary surgery in cases of suspected osteofascial compartment syndrome. Recently，the osteofascial system has been increasingly recognized that associations were found between the tension blister and osteofascial self-release processing. Thus，the timing of blister occurrence and regression substantially influences physicians′ clinical decisions，making blister management as part of the treatment of fractures. In this review，the authors give an overview of the characteristics，mechanism，stress reduction effect，prevention，current treatment status and complications of the fracture-related tension blister，hoping to help orthopedic physicians understand and treat the tensile blister.

Interstitial pneumonia with autoimmune features.

BACKGROUND: Cardiac tamponade is a medical emergency. This study was carried out to determine the etiologies of cardiac tamponade and review the management and outcomes. METHODS: We retrospectively analysed case records of patients who underwent pericardiocentesis for cardiac tamponade during the two consecutive years (1 January 2018 to 31 December 2019) at Hospital Sultanah Nora Ismail, Batu Pahat, in Johor, Malaysia. RESULTS: There were ten patients (eight males, two females; age range 20 to 70 years old, mean age 36 years old) who underwent pericardiocentesis for cardiac tamponade during the said period. Malignancy (40%), tuberculosis (30%), idiopathic (20%), and bacterial (10%) were among the common causes of the pericardial effusion in this center. The commonest symptoms were breathlessness (90%), chest pain (60%), cough (50%), and unexplained fever (20%). Pulsus paradoxus was the most speciÿ c sign (100%) for the presence of echocardiographic feature of cardiac tamponade. Two of the patients with tuberculous pericarditis had retroviral disease; one patient had bacterial pericarditis due to salmonella typhi. CONCLUSION: This study has conÿ rmed that there are many etiologies and presentation of cardiac tamponade; clinicians should be alert as urgent pericardiocentesis is lifesaving.

Analysis of clinical features and prognosis of 27 patients with mantle cell lymphoma / 天津医药

Objective To study the clinical features, effects of therapeutic regimen and prognosis of patents with mantle cell lymphoma (MCL). Methods Clinical data of 27 MCL patients admitted in Tianjin Medical University Cancer Institute&Hospital from January 2008 to December 2014 were retrospectively analyzed. Cox regression analysis was used to analyze influencing factors of prognosis of MCL. Results The median age was 68 years old for 27 patients, and the male-to-female ratio was 4.4∶1. Ann Arbor staging showed that 25 cases were stageⅢ-Ⅳ(92.6%), 8 cases were heptosplenomegaly (29.6%), 7 cases showed extranodal involvement (25.9%). ECOG scoring showed that 4 cases with scores of 2-4 (14.8%), 8 cases were 0-3 (29.6%), 14 cases were 4-5 (51.9%) and 5 cases were 6-11 (18.5%). The Ki-67 index≤30%was found in 9 cases (33.3%), and>30%was found in 18 cases (67.7%). Patients with B symptom was found in 10 (37.0%). The elevated lactate dehydrogenase (LDH) was found in 17 cases (63.0%). The increased Beta 2- microglobulin was found in 8 cases (29.6%). Seven patients were found with bone marrow involvement. The total effective rate (ORR) was 81.8%in group with R-CHOP method, and the ORR was 68.8%in group with CHOP method. Multivariate analysis showed that age, LDH and Ki-67 were independent factors influencing the prognosis of MCL (P60 years, elevated LDH and Ki-67 index>30%are with poor prognosis.

GABAB receptor-mediated tonic inhibition regulates the spontaneous firing of locus coeruleus neurons in developing rats and in citalopram-treated rats.

KEY POINTS: Noradrenaline (NA)-releasing neurons in the locus coeruleus (LC) provide NA to the forebrain and play important roles in regulating many brain functions. LC neurons are subject to tonic inhibition mediated by GABAB receptors (GABAB Rs) and that the extent of the effect varies with ambient GABA levels. GABAB R-mediated tonic inhibition can effectively tune the spontaneous firing rate (SFR) of LC neurons; it is developmentally regulated and is responsible for maintaining a constant SFR of LC neurons during development. In male, but not female rats, chronic perinatal treatment with citalopram, a selective serotonin reuptake inhibitor, results in downregulation of GABAB R-mediated tonic inhibition of LC neurons that partially accounts for increased SFR in male, but not female, rats receiving such treatment. Our results show that GABAB R-mediated tonic inhibition could be an important player in the development of normal and abnormal behaviours/brain functions associated with the LC-NA system. Noradrenaline (NA)-releasing neurons in the locus coeruleus (LC) provide NA to the forebrain. Their activity is believed to be a key factor regulating the wakefulness/arousal level of the brain. In this study, we found that the activity of NA-releasing neurons in the LC (LC neurons) was subject to γ-aminobutyric acid (GABA) tonic inhibition through GABAB receptors (GABAB Rs), but not GABAA receptors. The intensity of GABAB R tonic inhibition was found to depend on ambient GABA levels, as it was dramatically increased by blockade of GABA reuptake. It also varied with the function of GABAB Rs. The GABAB R activity on LC neurons was found to increase with postnatal age up to postnatal days 8-10, resulting in increased tonic inhibition. Interestingly, there was no significant difference in the spontaneous activity of LC neurons at different postnatal ages unless GABAB R tonic inhibition was blocked. These results show that, during postnatal development, there is a continuous increase in GABAB R tonic inhibition that maintains the activity of LC neurons at a proper level. In male, but not female, rats, chronic perinatal treatment with citalopram, a selective serotonin reuptake inhibitor, reduced GABAB R activity and tonic inhibition, which might result in the significantly higher spontaneous activity of LC neurons seen in these animals. In conclusion, our results show that GABAB R-mediated tonic inhibition has a direct impact on the spontaneous activity of LC neurons and that the extent of the effect varies with ambient GABA levels and functionality of GABAB R signalling.

Association of SOX9 expression and prognosis in patients with gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the association of SOX9 expression and clinicopathologic factors and prognosis of gastric cancer.</p><p><b>METHODS</b>A retrospective cohort study including 112 gastric cancer patients admitted to the Zhejiang Provincial People's Hospital from 2004 to 2006 was performed. Immunohistochemical analysis was used to evaluate the expression of SOX9 in the 112 specimens of gastric cancer tissues and 70 non-cancerous tissues adjacent to the tumor.</p><p><b>RESULTS</b>Low expression of SOX9 was seen in 5(7.1%) tissues out of 70 non-cancerous tissues adjacent to the tumor. A total of 94(83.9%) patients had varying expression of SOX9, of whom 51(45.4%) had overexpression. Univariate analysis demonstrated that the expression of SOX9 was significantly associated with Lauren classification (P<0.05), tumor invasion(P<0.01), lymph node metastasis(P<0.05), distant metastasis(P<0.05) and tumor stage(P<0.05), however there was no significant association between SOX9 expression and sex, age, histological type, histology differentiation or tumor size. Kaplan-Meier analysis showed that the 5-year survival rate of patients with SOX9 over-expression was significantly lower than that of patients with low expression(29.4% vs. 49.2%, P=0.031). Multivariate Cox regression analysis showed that histology differentiation(P=0.046), tumor invasion(P=0.001), and distant metastasis(P<0.01) were independent prognostic factors for gastric cancer, however the over-expression of SOX9 was not significant(P=0.948).</p><p><b>CONCLUSIONS</b>The expression SOX9 is associated with the growth, invasion, and metastasis of gastric cancer, as well as the prognosis. However, SOX9 expression is not an independent factor for the prognosis in patients with gastric cancer.</p>

Clinicopathological characteristics and prognosis of early gastric cancer after gastrectomy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Assessment of lymph node metastasis (LNM) is important in early gastric cancer (EGC) and affects treatment decisions. However, the relationship between clinicopathological characteristics and LNM in EGC remains unclear. This study therefore explored favorable predictors of LNM in EGC.</p><p><b>METHODS</b>A total of 716 specimens from gastric cancer patients who underwent curative gastrectomy between 1996 and 2003 at Zhejiang Provincial People's Hospital were reviewed. Forty-five cases were EGC, and clinicopathological characteristics such as gender, age, tumor size, location, gross type, differentiation, invasion depth, and vessel involvement were assessed to identify predictive factors for LNM and survival time.</p><p><b>RESULTS</b>The overall cumulative 5-year survival rate of EGC patients was 88.92%. Among these, 22.4% developed LNM, which was associated with a poor 5-year survival rate of only 72.7%. Patients with tumors larger than 2 cm in diameters, with depth of tumor invasion to the submucosa, and with positive lymphatic or nerve involvement were also inclined to have poorer survival performances. EGC limited to the mucosa but poorly differentiated also had a high risk for LNM. Multivariate analysis identified lymphatic invasion and tumor size as independent prognosis factors related to survival in EGC patients.</p><p><b>CONCLUSIONS</b>Careful planning is required in EGC patients at high risk of lymph node metastases. Endoscopic mucosal resection or endoscopic submucosal dissection and laparoscopic partial gastrectomy should be cautiously used in EGC, and curative gastrectomy including lymphatic dissection and postoperative adjuvant therapy might be considered to improve the prognosis.</p>

Application of purse-string suture for management of duodenal stump in radical gastrectomy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Gastric cancer (GC) is the second leading cause of cancer mortality worldwide, and surgical resection is currently the only possible curative approach. Duodenal stump leakage is the most serious complication after radical gastrectomy, and optimal treatment is still lacking.</p><p><b>METHODS</b>We retrospectively reviewed 2034 cases of total or subtotal gastrectomy for GC from January 1995 to December 2009, including 465 cases of duodenal stump closure using purse-string suture (group A), 835 cases of duodenal stump treated with linear cutting stapler and seromuscular layer suture (group B), and 734 cases of duodenal stump closure using full-thickness and seromuscular layer suture (group C). We evaluated the surgical cost, operative time for duodenal stump closure, short-term postoperative complications, perioperative blood loss, and postoperative recovery.</p><p><b>RESULTS</b>There was no perioperative mortality in any group. Ninety-four postoperative (within 1 month) complications occurred: 18 abdominal bleeding, 14 anastomotic leakage, 15 abdominal infection, 36 wound infection, and 11 duodenal stump leakage. There was no significant difference among the groups in intra-abdominal hemorrhage, anastomotic leakage, abdominal infection and wound infection. No postoperative duodenal stump leakage occurred in group A, which had a significant difference compared with groups B and C (6 cases in group B and 5 cases in group C suffered duodenal stump leakage. P < 0.01). The surgical cost in groups A and C was significantly lower than in group B (P < 0.01), with no significant difference between groups A and C. The processing time for duodenal stump closure in groups A and B was significantly shorter than in group C (P < 0.01), with no significant difference between groups A and B. There was no significant difference in blood loss and postoperative recovery among the groups.</p><p><b>CONCLUSIONS</b>Duodenal stump closure using purse-string suture seems to be a promising approach with shorter operative time, and lower cost and incidence of duodenal stump leakage in radical gastrectomy.</p>

Effects of additives on the selectivity of byproducts and dry removal of fluorine for abating tetrafluoromethane in a discharge reactor.

The removal efficiency of tetrafluoromethane (CF(4)) was significantly enhanced by adding additives (H(2), O(2), H(2)+O(2), H(2)O) in an atmospheric-pressure microwave plasma reactor. However, large amounts of fluorine (F(2)) were produced in this study. Moreover, the selectivity of F(2) was apparently greater than that of HF (in H(2)-based condition) or COF(2) (in O(2)-based abatement). Notably, in an O(2)-rich environment, more F(2) and a larger amount of CO(2) were produced. Subsequently, F(2) can be effectively removed by reacting with CaO to form CaF(2) at 200 degrees C via an in situ dry, chemical absorption process in the low-temperature afterglow discharge zone within the same plasma reactor.