(+)-Borneol, the main component of "Natural Borneol" in the Chinese Pharmacopoeia, is a high-end spice and precious medicine. Plant extraction cannot meet the increasing demand for (+)-borneol, while microbial biosynthesis offers a sustainable supply route. However, its production was extremely low compared with other monoterpenes, even with extensively optimizing the mevalonate pathway. We found that the key challenge is the complex and unusual dephosphorylation reaction of bornyl diphosphate (BPP), which suffers the side-reaction and the competition from the cellular dephosphorylation process, especially lipid metabolism, thus limiting (+)-borneol synthesis. Here, we systematically optimized the dephosphorylation process by identifying, characterizing phosphatases, and balancing cellular dephosphorylation metabolism. For the first time, we identified two endogenous phosphatases and seven heterologous phosphatases, which significantly increased (+)-borneol production by up to 152%. By engineering BPP dephosphorylation and optimizing the MVA pathway, the production of (+)-borneol was increased by 33.8-fold, which enabled the production of 753 mg/L under fed-batch fermentation in shake flasks, so far the highest reported in the literature. This study showed that rewiring dephosphorylation metabolism was essential for high-level production of (+)-borneol in Saccharomyces cerevisiae, and balancing cellular dephosphorylation is also helpful for efficient biosynthesis of other terpenoids since all whose biosynthesis involves the dephosphorylation procedure.

Objective:To evaluate the value of 18F-FDG PET/CT for preoperative localization of epileptogenic foci in refractory epilepsy patients with negative MRI. Methods:Clinical data (550 lobes) of 55 epilepsy patients (38 males, 17 females, age (20.0±8.1) years) with negative MRI who underwent preoperative 18F-FDG PET/CT-MRI between January 2014 and June 2020 at the First Affiliated Hospital of Jinan University were retrospectively analyzed. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of 18F-FDG PET/CT, video electroencephalogram (VEEG), PET/CT+ VEEG and PET/CT-VEEG for localizing epileptogenic foci were calculated using stereoelectroencephalography (SEEG) and the outcomes of at least 1 year of postoperative follow-up as reference standards. χ2 test was used to compare the efficiencies of different examination modalities for unilobar, multilobar and all patients. Results:The correct lateralization rate of epileptogenic foci was 92.6%(25/27) using PET/CT. The sensitivity, specificity, accuracy, PPV and NPV of PET/CT for localization of epileptogenic foci were 65.1%(54/83), 77.9%(364/467), 76.0%(418/550), 34.4%(54/157) and 92.6%(364/393), respectively. The sensitivities of PET/CT-VEEG for localization of epileptogenic foci in all patients and patients with multilobar epilepsy were higher than those of VEEG alone (75.9%(63/83) vs 45.8%(38/83), 68.6%(35/51) vs 31.4%(16/51); χ2 values: 15.80, 14.16, both P<0.001). The specificities of PET/CT+ VEEG for localization of epileptogenic foci in all patients and patients with unilobar epilepsy were higher than those of VEEG alone (97.6%(456/467) vs 94.6%(442/467), 97.9%(282/288) vs 94.1%(271/288); χ2 values: 5.66, 5.48; P values: 0.017, 0.019). The sensitivity of PET/CT-VEEG (PET/CT and VEEG concordance) for localization of epileptogenic foci was higher than that of PET/CT+ VEEG (PET/CT and VEEG discordance) (8/9 vs 28.4%(21/74); χ2=10.40, P=0.001), and its specificity and accuracy were higher than those of PET/CT-VEEG (PET/CT and VEEG discordance) (93.4%(57/61) vs 71.7%(291/406), 92.9%(65/70) vs 72.1%(346/480); χ2 values: 13.23, 13.96; both P<0.001). Conclusions:18F-FDG PET/CT can localize and lateralize epileptogenic foci in patients with negative MRI. The combination of 18F-FDG PET/CT and VEEG improves the sensitivity, specificity, and accuracy for epileptogenic foci detection. 18F-FDG PET/CT is more accurate in detecting epileptogenic foci when it is concordant with VEEG.

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.

Objective: To assess the relationship between hemoglobin A₁c (HbA₁c) and hemorrhagic cerebral infarction (HI) in patients with acute cerebral infarction. Methods: From January 2014 to June 2016, in the Lianyungang Hospital Affiliated to Xuzhou Medical University, 426 patients with acute anterior circulation infarction were included. The blood sugar status before stroke was expressed by HbA₁c. HbA₁c and fasting blood glucose (FBG) were measured on the second day after admission. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the severity of neurological function at admission. The modified Rankin scale (mRS) was used to evaluate the prognosis at discharge. CT or MRI/SWI examination was performed to determine whether there was HT. Logistic regression was used to evaluate the risk factors for HT and short-term prognosis after cerebral infarction. Results: Of the 426 patients enrolled, 93 (21.8%) appeared HT, 60 (14.1%) had hemorrhagic cerebral infarction (HI) and 33 (7.7%) had parenchymal hemorrhage (PH). Multivariate analysis showed that HbA₁c and infarct volume were independent predictor of HT. When patients were grouped according to fasting blood glucose (FBG<7.8 mmol/L or ≥ 7.8 mmol/L), the predictive effect of HbA₁c on HT was found in both groups. In multiple Logistic regression analysis, HbA₁c was also a predictor of poor prognosis after stroke (OR=1.482, 95% CI 1.228 -1.788). Conclusions In patients with ischemic stroke, elevated HbA₁c is independently associated with post-infarction HT, and this result doesn′t change even in patients with well-controlled blood glucose. HbA₁c is also a predictor of poor prognosis after stroke. These findings are important for blood glucose management in patients with diabetes and acute anterior circulation infarction.

Preventing and mitigating major risk exposure is an important task for modern countries to maintain sustained and healthy economic development and overall social stability. In this manuscript, the authors introduced Israel′s current medical and health care risk prevention system, including the regional health emergency response coordination mechanism, hospital′s external emergency rescue capacity building and hospital′s internal security system. Israel′s risk prevention system has been tested by wars and terrorist attacks, as well as many infectious diseases outbreaks. Thus the authors expected that its successful experiences can be introduced as a reference for improving China′s medical and health care risk prevention system.

Objective To evaluate the effect of hydrogen on mitochondrial fusion during myocardial ischemia-reperfusion (I/R) in aged rats.Methods One hundred and fifty pathogen-free healthy male Sprague-Dawley rats,aged 18 months old,weighing 400-500 g,were divided into 5 groups (n=30 each) using a random number table:control group (group C),sham operation group (group S),group I/R,normal saline group (group NS) and hydrogen-rich saline group (group H).Group C received no treatment.The anterior descending branch was only exposed but not ligated in group S.Myocardial I/R was induced by occlusion of the anterior descending branch of the left coronary artery for 30 rmin followed by reperfusion in I/R,NS and H groups.Hydrogen-rich saline 1 ml/100 g was injected intraperitoneally at 5 min before reperfusion in group H,while normal saline 1 ml/100 g was injected intraperitoneally at 5 min before reperfusion in group NS.The rats were sacrificed at 12 and 24 h of reperfusion,and hearts were removed for examination of the pathological changes and for determination of apoptosis in cardiomyocytes (by TUNEL) and expression of Mfn1 and Mfn2 protein and mRNA in myocardial tissues (by Western blot or real-time polymerase chain reaction).The apoptosis index was calculated.Results Compared with C and S groups,the apoptosis index of cardiomyocytes was significantly increased and the expression of Mfn1 and Mfn2 protein and mRNA in myocardial tissues was down-regulated at 12 and 24 h of reperfusion in I/R,NS and H groups (P＜0.05).Compared with NS and I/R groups,the apoptosis index of cardiomyocytes was significantly decreased and the expression of Mfn1 and Mfn2 protein and mRNA in myocardial tissues was up-regulated at 12 and 24 h of reperfusion in group H (P＜0.05).The pathological changes of myocardial tissues were significantly attenuated in group H when compared with group I/R.Conclusion The mechanism by which hydrogen attenuates myocardial I/R injury is related to promoting mitochondrial fusion and inhibiting apoptosis in cardiomyocytes of aged rats.

Adult-onset foveomacular vitelliform dystrophy (AFVD) is characterized by gradually loss of vision,subretinal vitelliform macular lesions and retinal pigment epithelium (RPE) atrophy.The electrooculogram (EOG) is usually normal or reduce slightly.On optical coherence tomography (OCT),there are vitelliform substance which deposited between the photoreceptor layer and the RPE layer,and thinner outer nuclear layer above these deposits.OCT angiography can show the superficial and deep retinal capillaries plexus (DCP) above the yolk-like deposits,the choroidal capillary blood flow is reduced and the DCP blood flow is increased near macular.On indocyanine green angiography (ICG),there is choroidal neovascularization under vitelliform substance at early stage and fluorescence leakage in the corresponding retinal region at late stage.There is no effective treatment for AFVD at present,monogenic gene therapy is the most worth looking forward to.Understanding AFVD clinical manifestations,multi-mode imaging features and new advances in treatment can provide a reference for diagnosis and treatment options

Objective To observe the alterations of vascular density of superficial or deep retinal vascular plexus and the area of foveal avascular zone (FAZ) in acute central serous chorioretinopathy (CSC) eyes. Methods This is a retrospective study including 22 patients with unilateral CSC in acute stages. The patients were divided into group A (22 affected eyes) and B (22 fellow eyes). Twenty eyes of 20 age and gender-matched healthy volunteers (group C) were enrolled in this study. All subjects underwent optical coherence tomography (OCT) angiography examinations. The observation index included signal intensity of blood flow in choroidal capillary, vessel density and FAZ on the superficial capillary plexus (SCP) and deep capillary plexus (DCP). Results The FAZ on DCP in group A was larger than that in group B and C (t=4.28, 5.57; P=0.00、0.00), but there was no significant difference of FAZ on SCP among 3 groups (t=0.28, 0.80; P=0.78, 0.43). The vessel density of SCP and DCP in group A and B were decreased than those in group C (t=-4.40, -2.91; P=0.00, 0.00). The type of choroidal capillaries dilation had two different manifestations by OCTA, which was circumscribed in 12 eyes and diffuse in 10 eyes. The subretinal fluid in macular area which presented dark chamber with weak reflection was observed by en-face OCT. Conclusions The vessel density of SCP and DCP in both eyes of acute CSC are lower than those in normal eyes. The FAZ of DCP in affected eyes of acute CSC is larger than that in fellow eyes and normal eyes. The blood flow of dilated choroidal capillary can be manifested as different morphological enhancements.

This study summarized the experiences of disease-specific performance appraisal at tertiary hospitals in Shanghai,which was launched since year 2013 by Shanghai Hospital Development Center (SHDC). 38 tertiary hospitals in Shanghai were included in the study. A disease-specific performance appraisal system centering on quality and performance, by means of case-mix model, classified surgery management and typical disease screening, and leveraging disease and surgery difficulties analysis, and inter-hospital performance appraisal of typical diseases. This reform has established appraisal criteria of disease difficulty management,coding criteria and data norms,guiding such hospitals to consolidate their functional positioning of focusing on difficult,urgent and complicated cases in the medical service delivery system.All these efforts have paved the way for the reforms to build a hierarchical medical service system, pricing per disease, payment per disease, and consolidate performance appraisal of medical workers.

To sum up the reform of internal performance appraisal system and income allocation system of Shanghai municipal hospitals.The internal performance appraisal index system,evaluation methods and corresponding income allocation system,featuring two breaks,one change and eight elements.The reforms highlight public welfare nature of public hospitals,which is expected to create profound impacts on hospital operation and medical staff behavior.