(+)-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.

Objectives:To investigate the association between social determinants of health(SDOH)and incident stroke and analyze the main risk factors for stroke among resident with different SDOH levels. Methods:From 2012 to 2015,30 036 residents(≥35 years old)from 30 districts in 14 provincial-level administrative divisions in China were enrolled this study based on stratified multi-stage-random-sampling method.The prevalence of cardiovascular diseases and related risk factors were investigated,and stroke events were followed up in 2018 to 2019.Principal component analysis was performed to establish SDOH scores based on 9 indicators related to socioeconomic and healthcare resources,participants were divided into low SDOH group(n=8 343)when it was≥-2.01 to<-1.14,middle SDOH group(n=7 257)when it was≥-1.14 to<0.10,and high SDOH group(n=8 457)when it was≥0.10 to≤5.79.Multivariate Cox regression was applied to estimate the association of SDOH levels with incident stroke.The random survival forest method was used to analyze the major risk factors in different SDOH levels. Results:A total of 24 057 participants were finally included,669(2.8%)participants developed stroke during a mean of(4.7±0.8)years follow-up.The incidence densities of stroke in the low,medium,and high SDOH groups were 468.39,628.85,and 700.39/100 000 person-years,respectively(Pdifference<0.05,Ptrend=0.01).Compared with individuals with low SDOH level group,fully HR for incident stroke among those with medium and high were 1.91(95%CI:1.54-2.36)and 1.59(95%CI:1.30-1.95),respectively(Ptrend<0.001).Advanced age is the primary risk factor for stroke in the population,especially in districts with high SDOH level.In districts with medium SDOH level,diabetes is an important risk factor for stroke.High blood pressure and alcohol consumption are important modifiable risk factors in low SDOH level districts. Conclusions:Present study shows that higher levels of SDOH are associated with increased risk of stroke.The main risk factors for stroke differ among participants with different SDOH level districts.Targeted interventions should be implemented to improve the prevention and treatment of stroke in populations with different levels of SDOH.

Objective To investigate the feasibility and safety of transanal total mesorectal excision (TaTME) in re-operation for anastomosis recurrence rectal cancer. Methods Five patients with anastomosis recurrence rectal cancer underwent TaTME at Ruijin Hospital between April 2020 and December 2021 were retrospectively enrolled in this study. The peri-operative situation, pathological examination, and short-term follow-up results were analyzed. Results All cases were operated laparoscopic TaTME successfully. The operative time was (206.00±19.49) min without intraoperative complications. One case encountered incorrect dissection plane. Anastomotic leakage occurred in one case and anastomotic stenosis developed in another case. The specimens quality of mesorectum deemed complete in all cases without both positive circumferential resection margin and positive distal resection margin. There was (15.20±2.39) months of median follow-up and one case found defecation disorder. Tumor recurrence, metastasis and tumor-related death were not found. Conclusions For patients with anastomosis recurrence rectal cancer, laparoscopic TaTME procedure is novel type and would be safe and effective surgical approach with satisfactory short-term follow-up.

ObjectiveTo investigate the related factors of hypertension and comorbid hypertension-diabetes mellitus （HT-DM） among rural residents in Shanghai， China. MethodsA total of 2 159 residents over 35 years old were randomly selected from a rural community in the suburbs of Shanghai through cluster random sampling. Their basic sociological characteristics and blood lipid levels were investigated. Chi-square test was used to analyze the relationship between hypertension （or HT-DM） and gender， age， education levels， marital status， original household registration and current household registration. The relationship between hypertension （or HT-DM） and blood lipid level was analyzed by a conditional logistic regression model. ResultsThe prevalence of hypertension was 26.35% and that of HT-DM was 4.68% in the study population. Chi-square test analysis showed that hypertension was significantly associated with age， marital status， educational level， and rural household registration， while HT-DM was significantly associated with age， educational level， and rural household registration. Chi-square trend analysis indicated that the prevalence of hypertension and HT-DM increased with age in both male and female populations （χ²=129.82， 193.04，both P<0.001， and χ²=9.29， 40.57， both P<0.01）. The unconditional logistic regression analysis indicated that the lower level of high-density lipoprotein cholesterol （HDL-C） and higher level of triglyceride （TG） were associated with an increased the risk of hypertension by 2.79 times and 2.06 times， respectively. The lower level of HDL-C increased risk of HT-DM by 4.21 times. ConclusionThe prevalence of hypertension in the rural population in Shanghai is relatively high. Age， education level， rural household registration and HDL-C are common related factors of hypertension and HT-DM.

Objective:To investigate the efficacy and safety of anlotinib in the treatment of advanced gastric cancer.Methods:Eighty patients with advanced gastric cancer in Longhua District Central Hospital of Shenzhen City from February 2015 to May 2016 were selected. The patients were randomly divided into anlotinib group (anlotinib 12 mg) and placebo group by random number table method. The anlotinib or placebo was given once a day for two weeks and discontinued for one week, and three weeks were a course of treatment. The relief situation, total survival time as well as adverse reactions after treatment of all patients were compared between the two groups.Results:The remission rate in the anlotinib group was higher than that in the placebo group [61.6% (37/60) vs. 5.0% (1/20)], and the difference was statistically significant ( χ2 = 19.315, P < 0.05). The overall survival time of the anlotinib group was longer than that of the placebo group [(22.8±1.0) months vs. (10.3±0.9) months], and the difference was statistically significant ( P < 0.01). The adverse reactions mainly included hypertension, diarrhea, nausea and vomiting, liver damage, etc. The adverse reactions were mild, and no drug-related deaths occurred. There was no statistically significant difference in the incidence of adverse reactions between the two groups (all P > 0.05). Conclusion:Anlotinib is effective and safe in the treatment of advanced gastric cancer.

OBJECTIVE: To study the mechanism of osteopontin (OPN) in viral myocarditis by observing the expression of OPN and collagen I (Col I) in mice myocardium. METHODS: The viral myocarditis models were achieved by infection with myocarditic coxsackievirus B3 (CVB3). The myocardium of mice was stained by HE and Masson staining, and the pathological scores and the collagen volume fraction (CVF )of myocardium were tabulated. The expression of Col I mRNA was measured by RT-PCR. The expression of OPN was detected by RT-PCR and ELISA. RESULTS: The histopathological examination revealed a prevalence of myocardial cell necrosis and obvious inflammation changes at the 7th day post-infection. Subsequently the inflammatory lesions were gradually absorbed. At the 28th day, the inflammatory cells had almost disappeared and obvious fibrosis occurred. The pathological scores and the expression of OPN mRNA were higher than those of the control group (P<0.05), and reached the highest level at the 7th day (P<0.05). From the 14th day, these parameters decreased,reflected also in the ELISA results. At the 7th day and the 14th day, the Col I expression was similar to that of control. Col I expression at the 21th and 28th days was higher than those of the control (P<0.05), and correlated positively to the CVF results. CONCLUSION The OPN mRNA expression increased in acute stage of VMC, and higher than that of the control group when in recovery stage, suggesting that OPN might be related to the inflammatory response in acute stage of, and promote the collagen synthesis of recovery stage.
Animals ; Collagen Type I ; genetics ; metabolism ; Coxsackievirus Infections ; metabolism ; Enterovirus B, Human ; isolation & purification ; Male ; Mice ; Mice, Inbred BALB C ; Myocarditis ; metabolism ; virology ; Osteopontin ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism

Objective To investigate the peri-nasopharyngeal invasion patterns of nasopharyngeal carcinoma (NPC) on MRI and its relationship with tumor staging. Methods One thousand five hundred and seventy-three patients with newly diagnosed NPC which were histo-pathologically proved were retrospectively studied. The MRI manifestations and invasion patterns of the NPCs were elevated according to the 2008 Tstaging system of NPC. Z test was used to analyze the rate of adjacent structures invasion in NPCs. Results The structures invaded by NPCs included pharyngobasilar fascia in 1299 cases (82. 58% ); parapharyngeal space, 1090 ( 69. 29% ); nasal cavities, 304 ( 19. 33% ); oropharynx, 49 ( 3. 12% ); carotid space,514(32. 68% ); medial pterygoid muscle, 661 (42. 02% ); lateral pterygoid muscle, 210( 13. 35% ); skull base bones, 943(59. 95% ); cranial nerves, 630(40. 05% ) and paranasal sinuses, 242 ( 15.38% ). The T-stage distribution was T1, 242 cases ( 15.38% ); T2, 288 ( 18. 31% ); T3, 410 (26. 06% ) and T4,633 (40. 24% ). Among the cases with nasal cavities invasion, 90. 46% (275/304)showed the involvement of the structures seen in T3 or T4 stage, which was found in all cases with oropharynx invasion. In addition,69. 14% (457/661) of cases with medial pterygoid muscle invasion and 92. 15% (223/242) of cases with paranasal sinuses invasion showed the involvement of structures seen in T4 stage. As for the invasion patterns of NPC, the lateral invasion of pharyngobasilar fascia was more frequent than upward invasion of skull base (Z = 14. 025, P ＜ 0. 01 ) and downward invasion of oropharynx ( Z = 45.032, P ＜ 0. 01 ), and the downward invasion of oropharynx was less frequent than upward invasion of skull base ( Z = 34. 301, P ＜ 0. 01 ) and forward invasion of nasal cavities ( Z = 14. 404, P ＜ 0. 01 ). Conclusion NPC has a predilection of lateral invasion rather than upward and downward invasion, and its upward and forward invasion are more common than downward invasion.