LONP1 ameliorates liver injury and improves gluconeogenesis dysfunction in acute-on-chronic liver failure / 中华医学杂志(英文版)

BACKGROUND@#Acute-on-chronic liver failure (ACLF) is a severe liver disease with complex pathogenesis. Clinical hypoglycemia is common in patients with ACLF and often predicts a worse prognosis. Accumulating evidence suggests that glucose metabolic disturbance, especially gluconeogenesis dysfunction, plays a critical role in the disease progression of ACLF. Lon protease-1 (LONP1) is a novel mediator of energy and glucose metabolism. However, whether gluconeogenesis is a potential mechanism through which LONP1 modulates ACLF remains unknown.@*METHODS@#In this study, we collected liver tissues from ACLF patients, established an ACLF mouse model with carbon tetrachloride (CCl 4 ), lipopolysaccharide (LPS), and D-galactose (D-gal), and constructed an in vitro hypoxia and hyperammonemia-triggered hepatocyte injury model. LONP1 overexpression and knockdown adenovirus were used to assess the protective effect of LONP1 on liver injury and gluconeogenesis regulation. Liver histopathology, biochemical index, mitochondrial morphology, cell viability and apoptosis, and the expression and activity of key gluconeogenic enzymes were detected to explore the underlying protective mechanisms of LONP1 in ACLF.@*RESULTS@#We found that LONP1 and the expressions of gluconeogenic enzymes were downregulated in clinical ACLF liver tissues. Furthermore, LONP1 overexpression remarkably attenuated liver injury, which was characterized by improved liver histopathological lesions and decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in ACLF mice. Moreover, mitochondrial morphology was improved upon overexpression of LONP1. Meanwhile, the expression and activity of the key gluconeogenic enzymes were restored by LONP1 overexpression. Similarly, the hepatoprotective effect was also observed in the hepatocyte injury model, as evidenced by improved cell viability, reduced cell apoptosis, and improved gluconeogenesis level and activity, while LONP1 knockdown worsened liver injury and gluconeogenesis disorders.@*CONCLUSION@#We demonstrated that gluconeogenesis dysfunction exists in ACLF, and LONP1 could ameliorate liver injury and improve gluconeogenic dysfunction, which would provide a promising therapeutic target for patients with ACLF.

Application of Global Leadership Initiative on Malnutrition criteria in patients with liver cirrhosis / 中华医学杂志(英文版)

BACKGROUND@#The Global Leadership Initiative on Malnutrition (GLIM) criteria were published to build a global consensus on nutritional diagnosis. Reduced muscle mass is a phenotypic criterion with strong evidence to support its inclusion in the GLIM consensus criteria. However, there is no consensus regarding how to accurately measure and define reduced muscle mass in clinical settings. This study aimed to investigate the optimal reference values of skeletal muscle mass index for diagnosing sarcopenia and GLIM-defined malnutrition, as well as the prevalence of GLIM-defined malnutrition in hospitalized cirrhotic patients.@*METHODS@#This retrospective study was conducted on 1002 adult patients with liver cirrhosis between January 1, 2018, and February 28, 2022, at Beijing You-An Hospital, Capital Medical University. Adult patients with a clinical diagnosis of liver cirrhosis and who underwent an abdominal computed tomography (CT) examination during hospitalization were included in the study. These patients were randomly divided into a modeling group (cohort 1, 667 patients) and a validation group (cohort 2, 335 patients). In cohort 1, optimal cut-off values of skeletal muscle index at the third lumbar skeletal muscle index (L3-SMI) were determined using receiver operating characteristic analyses against in-hospital mortality in different gender groups. Next, patients in cohort 2 were screened for nutritional risk using the Nutritional Risk Screening 2002 (NRS-2002), and malnutrition was diagnosed by GLIM criteria. Additionally, the reference values of reduced muscle mass in GLIM criteria were derived from the L3-SMI values from cohort 1. Multivariate logistic regression analysis was used to analyze the association between GLIM-defined malnutrition and clinical outcomes.@*RESULTS@#The optimal cut-off values of L3-SMI were 39.50 cm 2 /m 2 for male patients and 33.06 cm 2 /m 2 for female patients. Based on the cut-off values, 31.63% (68/215) of the male patients and 23.3% (28/120) of the female patients had CT-determined sarcopenia in cohort 2. The prevalence of GLIM-defined malnutrition in cirrhotic patients was 34.3% (115/335) and GLIM-defined malnutrition was an independent risk factor for in-hospital mortality in patients with liver cirrhosis ( Wald = 6.347, P  = 0.012).@*CONCLUSIONS@#This study provided reference values for skeletal muscle mass index and the prevalence of GLIM-defined malnutrition in hospitalized patients with liver cirrhosis. These reference values will contribute to applying the GLIM criteria in cirrhotic patients.

Mechanism of osteoclast stimulatory transmembrane protein promoting silicosis fibrosis by inducing ferroptosis / 环境与职业医学

Background Osteoclast stimulatory transmembrane protein (OC-STAMP) is involved in silicosis fibrosis induced by silicon oxide (SiO2) exposure. Its role in silicosis fibrosis by inducing ferroptosis of alveolar type II epithelial cells and its related mechanism remain unclear. Objective To explore the effect and possible mechanism of OC-STAMP on ferroptosis of alveolar type II epithelial cells and silicosis fibrosis in rats under SiO2 exposure. Methods Twenty male Wistar rats of SPF grade were randomly divided into two groups: control (Sham) group and SiO2 group, 15 rats in each group. Rats in the SiO2 group were given 1 mL of 50 mg·L−1 SiO2 suspension at one time through the non-exposed intratracheal instillation method to establish an animal model of silicosis, and rats in the Sham group were give 1 mL of 0.9% sodium chloride solution in the same way. Rats were sacrificed after 8 weeks. Samples of lung tissue were fixed in glutaraldehyde or paraformaldehyde for observing ultrastructure of mitochondria by transmission electron microscopy; HE, Masson, VG, and Prussian blue were used to observe changes in lung tissue structure and iron deposition. The expression level of OC-STAMP and the degree of lung fibrosis were evaluated by immunohistochemistry and immunofluorescence. The expression level of OC-STAMP in rat lung tissue was detected and the transfection effect of OC-STAMP was verified by real-time fluorescence quantitative polymerase chain reaction (RT-PCR). Overexpression (OCS group) and inhibition expression (SI-OC group) models were constructed by OC-STAMP plasmid and OC-STAMP small interfering RNA (siRNA) transfection to cultured MLE-12 cells, respectively. The relative expression levels of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and other proteins in lung tissue and MLE-12 were detected by Western blotting. Results The results of HE, Masson, and VG staining showed that the silicosis modeling was successful after 8 weeks of SiO2 exposure. The immunofluorescence results showed that OC-STAMP and ATP binding cassette subfamily A member 3 (ABCA3) co-localized in alveolar type II epithelium. The immunohistochemical results showed that the levels of OC-STAMP and collagen I in the SiO2 group were significantly higher than those in the Sham group (P<0.01). The RT-PCR results showed that the OC-STAMP mRNA in the lung tissue of the SiO2 group was significantly higher than that of the Sham group (P<0.01). The Prussian blue staining in the lung tissue of the SiO2 group showed positive brownish-yellow particles. Compared with the Sham group which showed normal mitochondrial structure, the mitochondrial structure was generally swollen and the mitochondrial cristae dissolved and disappeared in the SiO2 group by transmission electron microscope observation. The Western blotting results showed that the expression levels of SLC7A11 and GPX4 both decreased in the lung tissue of the SiO2 group (P<0.05, P<0.01), and the expression level of Vimentin increased (P<0.01). In the transfected MLE-12 cells, compared with the Sham group, the expression levels of SLC7A11 and GPX4 in the OCS group were significantly reduced (P<0.05, P<0.01). Conclusion OC-STAMP may affect the expression of proteins related to ferroptosis, and promote lung fibrosis induced by SiO2 exposure.

Nephrotoxicity caused by polymyxin in the treatment of drug-resistant Gram-negative bacterial infections：a meta-analysis / 中国药房

OBJECTIVE To evaluate the incidence of nephrotoxicity in patients with drug-resistant Gram-negative bacterial infections after the use of polymyxin， and to provide evidence-based reference for clinical rational drug use. METHODS PubMed， Embase， Web of Science， the Cochrane Library， Wanfang database， CNKI， VIP and SinoMed were searched to collect randomized controlled trials （RCTs） or cohort studies about the polymyxin （trial group） versus other antibiotics （control group） or polymyxin B （trial group） versus polymyxin E （control group）. After literature screening， data extraction and quality evaluation， RevMan 5.4.1 software was used for meta-analysis. RESULTS A total of 37 studies were included， including 4 RCTs and 33 cohort studies， with a total of 5 871 patients. The meta-analysis results showed that in RCT [RR＝2.64，95%CI （1.43，4.87），P＝0.002] and in cohort studies [RR＝1.59， 95%CI （1.27， 1.98）， P＜0.000 1]， the incidence of nephrotoxicity in the trial group was significantly higher than control group. The results of the subgroup analysis of cohort studies showed that the incidence of nephrotoxicity in the trial group （receiving polymyxin） was significantly higher than control group （receiving new β-lactam and β-lactamase inhibitors and tigecycline）； when Kidney Disease Improving Global Outcomes （KDIGO）， renal replacement therapy or 0.5 times increase in serum creatinine were used as the standard of nephrotoxicity， the incidence of nephrotoxicity in the trial group was significantly higher than the control group （P＜0.05）. The incidence of nephrotoxicity in patients receiving polymyxin E was significantly higher than those using polymyxin B [RR＝0.57， 95%CI （0.39，0.84）， P＝0.005]. CONCLUSIONS In the treatment of drug-resistant Gram-negative bacteria infections， the incidence of nephrotoxicity caused by polymyxin is relatively high. The TYU108F）； incidence of nephrotoxicity caused by polymyxin E is higher than polymyxin B.

Incidence and prognosis of olfactory and gustatory dysfunctions related to infection of SARS-CoV-2 Omicron strain: a national multi-center survey of 35 566 population / 中华耳鼻咽喉头颈外科杂志

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.

Discussion of Application Status and Key Attentions on Registration for Ossicular Replacement Prosthesis / 中国医疗器械杂志

The ossicular replacement prosthesis should have good biocompatibility, stability, easy to install, and excellent sound transmission capacity. In this study, the characteristics of ideal materials for the ossicular replacement prosthesis were analyzed by searching the types of materials used in clinical practice and comparing the advantages and disadvantages of various materials and structures. At the same time, in combination with the current evaluation requirements and evaluation experience, the focus of the performance research project of ossicular replacement prosthesis in the process of registration is discussed to clarify the performance evaluation requirements of these products, so as to provide reference for the future work of manufacturers and regulators. The performance evaluation of ossicular replacement prosthesis focuses on its mechanical properties, fixation stability, sound transmission characteristics, biological characteristics, and magnetic resonance compatibility.

Xingnao Kaiqiao acupuncture on promoting wake-up of consciousness disorder in children with early severe traumatic brain injury / 中国针灸

OBJECTIVE@#To observe the awakening effect and safety of Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture on consciousness disorder in children with early severe traumatic brain injury (STBI) based on western medicine treatment.@*METHODS@#A total of 62 children with STBI were randomly divided into an observation group (31 cases,1 case dropped off) and a control group (31 cases, 1 case dropped off). The control group was treated with routine rehabilitation therapy (6 times a week for 30 days), and intravenous drip of cattle encephalon glycoside and ignotin injection (once a day for 28 days). On the basis of the treatment in the control group, the observation group was treated with Xingnao Kaiqiao acupuncture at Neiguan (PC 6), Shuigou (GV 26), Yintang (GV 24+), Baihui (GV 20), Sanyinjiao (SP 6), Zusanli (ST 36), etc., and supplementary acupoints according to clinical symptoms, once a day, 6 times a week for 30 days. The scores of Glasgow coma scale (GCS), coma recovery scale-revised (CRS-R) and modified Barthel index (MBI) were observed before treatment and 10, 20 and 30 d into treatment. Electroencephalogram (EEG) grading before and after treatment was observed in the two groups, and safety was evaluated.@*RESULTS@#After 10, 20 and 30 days of treatment, the scores of GCS, CRS-R and MBI in the two groups were increased compared before treatment (P<0.05), and those in the observation group were higher than the control group (P<0.05). After treatment, EEG grading of both groups was improved compared with that before treatment (P<0.05), and the observation group was better than the control group (P<0.05). There were no adverse events or adverse reactions in the two groups during treatment.@*CONCLUSION@#On the basis of western medicine treatment, Xingnao Kaiqiao acupuncture plays a remarkable role in wakening the early STBI children, can improve the level of consciousness disorder and daily living ability, and it is safe and effective.

Genetically predicted insomnia causally increases the risk of erectile dysfunction / 亚洲男科学杂志(英文版)

Sleep has attracted extensive attention due to its significance in health. However, its association with erectile dysfunction (ED) is insufficiently investigated. To investigate the potential causal links between sleep traits (insomnia, sleep duration, and chronotype) and ED, this study was performed. The single-nucleotide polymorphisms (SNPs) associated with insomnia, sleep duration, and chronotype were retrieved from previous genome-wide association studies (GWAS). A conventional two-sample Mendelian randomization (MR) was used to estimate the causal links between sleep traits and ED. The summary statistics of ED were from individuals of European ancestry (6175 cases vs 217 630 controls). As shown by the random effect inverse-variance-weighting (IVW) estimator, genetically predicted insomnia was causally associated with a 1.15-fold risk of ED (95% confidence interval: 1.07-1.23, P < 0.001). Sleep duration and morningness were not causally associated with ED, as indicated by the IVW (all P > 0.05). These findings were consistent with the results of sensitivity analyses. Based on genetic data, this study provides causal evidence that genetically predicted insomnia increases the risk of ED, whereas sleep duration and chronotype do not.

Safety and immunogenicity of freeze-dried rabies vaccine (Vero-cells) for human use in healthy people aged 9-65 years / 中华预防医学杂志

Objective: To assess the safety and immunogenicity of freeze-dried rabies vaccine (Vero-cells) for human use on different immunization procedures in healthy people aged 9-65 years. Methods: A randomized, blind, positive-controlled clinical study was conducted in March 2015. The eligible residents aged 9-65 were recruited in Dengfeng city and Biyang County, Henan Province. A total of 1 956 subjects were enrolled. The subjects were randomly (1∶1∶1) assigned to 5-dose control group, 4-dose trial group and 5-dose trial group, with 652 subjects in each group. The subjects of 5-dose control group were immunized with control vaccine on days 0, 3, 7, 14 and 28. The subjects of 4-dose trial group were immunized with trial vaccine on days 0, 7 and 21 (2-1-1 phases) and the subjects of 5-dose trial group were immunized with trial vaccine on days 0, 3, 7, 14 and 28. A combination of regular follow-up and active reporting was used to observe local and systemic adverse reactions till 30 days after the first and full immunization, and the incidence rate of adverse reactions in three groups was analyzed and compared. The venous blood was collected before the first immunization, 7 days after the first immunization, 14 days after the first immunization and 14 days after the full immunization. The neutralizing antibody of rabies virus was detected by rapid fluorescent focus inhibition test (RFFIT), and the seropositive conversion rate and geometric mean concentration (GMC) of antibody were calculated. Results: The adverse reaction rates in 5-dose control group, 4-dose trial group and 5-dose trial group were 41.87% (273/652), 35.43% (231/652) and 34.97% (228/652), respectively. The adverse reaction rates of 4-dose trial group and 5-dose trial group were lower than those of the 5-dose control group (P<0.05). The local reactions were mainly pain, itching, swelling and redness in injection site, while the systemic reactions were mainly fever, fatigue, headache and muscle pain. The severity of adverse reactions was mainly mild (level 1), accounting for 85.33% (518/607), 89.02% (373/419) and 88.96% (427/480) of the total number of adverse reactions in each group. At 14 days after the first immunization and 14 days after the full immunization, the antibody positive conversion rates of three groups were all 100%. At 7 days, 14 days after the first immunization and 14 days after the full immunization, the GMCs of three groups were 0.60, 0.72, 0.59 IU/ml, 20.42, 23.99, 24.38 IU/ml and 22.95, 23.52, 24.72 IU/ml, respectively, with no significant difference (P>0.05). Conclusion: The freeze-dried rabies vaccine (Vero-cells) for human use has good safety and immunogenicity when inoculated according to 5-dose and 4-dose immunization procedures.

Trend in incidence of stroke in Nanshan District from 2010 to 2021 / 预防医学

Objective@#To investigate the trend in incidence of stroke in Nanshan District, Shenzhen City from 2010 to 2021, so as to provide the evidence for formulating the integrated strategy for stroke control.@* Methods@#The data of stroke morbidity in Nanshan District from 2010 to 2021 were collected through Shenzhen Chronic Disease Prevention and Control Management System. The incidence of stroke was calculated, and standardized by the population of the Chinese Sixth National Census in 2010. The trends in stroke incidence were evaluated in Nanshan District from 2010 to 2021 using annual percent change (APC) and average annual percent change (AAPC), and gender-, age- and subtype-specific incidence of stroke was descriptively analyzed. @*Results@#A total of 30 377 cases with stroke were reported in Nanshan District from 2010 to 2021, with a crude incidence rate of 190.45/105 and a standardized incidence rate of 405.65/105. The crude incidence rate of stroke appeared a tendency towards a rise in Nanshan District from 2010 to 2021 (APC=5.38%, t=4.678, P=0.001), and a higher crude incidence rate of stroke was seen among men than among women (227.57/105 vs. 148.40/105; χ2=1 309.580, P<0.001). The incidence of stroke appeared a tendency towards a rise with age (χ2trend =435.717, P<0.001), and there was a tendency towards a rise in stroke incidence among residents under 40 years of age (APC=2.89%, t=2.538, P=0.029). The crude incidence of ischemic stroke was 151.24/105, which was higher than that of hemorrhagic stroke (39.21/105) (χ2=10 521.000, P<0.001). @*Conclusions@#The incidence of stroke appeared a tendency towards a rise in Nanshan District from 2010 to 2021, with ischemic stroke as the predominant subtype of stroke. Males and middle-aged and elderly residents should be given a high priority for stroke prevention and treatment.

Light-driven CO2 conversion system: construction, optimization and application / 生物工程学报

The use of light energy to drive carbon dioxide (CO2) reduction for production of chemicals is of great significance for relieving environmental pressure and solving energy crisis. Photocapture, photoelectricity conversion and CO2 fixation are the key factors affecting the efficiency of photosynthesis, and thus also affect the efficiency of CO2 utilization. To solve the above problems, this review systematically summarizes the construction, optimization and application of light-driven hybrid system from the perspective of combining biochemistry and metabolic engineering. We introduce the latest research progress of light-driven CO2 reduction for biosynthesis of chemicals from three aspects: enzyme hybrid system, biological hybrid system and application of these hybrid system. In the aspect of enzyme hybrid system, many strategies were adopted such as improving enzyme catalytic activity and enhancing enzyme stability. In the aspect of biological hybrid system, many methods were used including enhancing biological light harvesting capacity, optimizing reducing power supply and improving energy regeneration. In terms of the applications, hybrid systems have been used in the production of one-carbon compounds, biofuels and biofoods. Finally, the future development direction of artificial photosynthetic system is prospected from the aspects of nanomaterials (including organic and inorganic materials) and biocatalysts (including enzymes and microorganisms).

Metabolic engineering of Escherichia coli for adipic acid production / 生物工程学报

Adipic acid is a high-value-added dicarboxylic acid which is primarily used in the production of nylon-66 for manufacturing polyurethane foam and polyester resins. At present, the biosynthesis of adipic acid is hampered by its low production efficiency. By introducing the key enzymes of adipic acid reverse degradation pathway into a succinic acid overproducing strain Escherichia coli FMME N-2, an engineered E. coli JL00 capable of producing 0.34 g/L adipic acid was constructed. Subsequently, the expression level of the rate-limiting enzyme was optimized and the adipic acid titer in shake-flask fermentation increased to 0.87 g/L. Moreover, the supply of precursors was balanced by a combinatorial strategy consisting of deletion of sucD, over-expression of acs, and mutation of lpd, and the adipic acid titer of the resulting E. coli JL12 increased to 1.51 g/L. Finally, the fermentation process was optimized in a 5 L fermenter. After 72 h fed-batch fermentation, adipic acid titer reached 22.3 g/L with a yield of 0.25 g/g and a productivity of 0.31 g/(L·h). This work may serve as a technical reference for the biosynthesis of various dicarboxylic acids.

Modular engineering of Escherichia coli for high-level production of l-tryptophan / 生物工程学报

As an essential amino acid, l-tryptophan is widely used in food, feed and medicine sectors. Nowadays, microbial l-tryptophan production suffers from low productivity and yield. Here we construct a chassis E. coli TRP3 producing 11.80 g/L l-tryptophan, which was generated by knocking out the l-tryptophan operon repressor protein (trpR) and the l-tryptophan attenuator (trpL), and introducing the feedback-resistant mutant aroGfbr. On this basis, the l-tryptophan biosynthesis pathway was divided into three modules, including the central metabolic pathway module, the shikimic acid pathway to chorismate module and the chorismate to tryptophan module. Then we used promoter engineering approach to balance the three modules and obtained an engineered E. coli TRP9. After fed-batch cultures in a 5 L fermentor, tryptophan titer reached to 36.08 g/L, with a yield of 18.55%, which reached 81.7% of the maximum theoretical yield. The tryptophan producing strain with high yield laid a good foundation for large-scale production of tryptophan.

Application of cutinase in the degradation of biodegradable polyester poly(butylene adipate-co-terephthalate) / 生物工程学报

With the environmental pollution caused by waste plastics becoming increasingly serious, biodegradable polyester has become the focus of public attention. Poly(butylene adipate-co-terephthalate) (PBAT) is a biodegradable polyester formed by the copolymerization of aliphatic and aromatic groups, which has excellent performance of both. The degradation of PBAT under natural conditions requires strict environmental conditions and long degradation cycle. To address these shortcomings, this study explored the application of cutinase in PBAT degradation and the impact of butylene terephthalate (BT) content on the biodegradability of PBAT, so as to improve the degradation rate of PBAT. Five Polyester degrading enzymes from different sources were selected to degrade PBAT to pick out the most efficient enzyme. Subsequently, the degradation rate of PBAT materials with different BT content were determined and compared. The results showed that cutinase ICCG was the best enzyme for PBAT biodegradation, and the higher the BT content, the lower the degradation rate of PBAT. Furthermore, the optimum temperature, buffer type, pH, the ratio of enzyme to substrate (E/S) and substrate concentration in the degradation system were determined to be 75 ℃, Tris HCl, 9.0, 0.4% and 1.0% respectively. These findings may facilitate the application of cutinase in PBAT degradation.

“Liquid seal to detoxification – drying and puffing” of two stage processing technology design and pharmacodynamic study of aconite (Aconiti Lateralis Radix Praeparata) processed by microwave / 药学学报

Establish a production line with controllable process and high intelligence, contribute to improve the quality and production efficiency of aconite processed by microwave, and promote the transformation and application of aconite processed by microwave. According to the principle of aconite detoxification and the characteristics of industrial microwave equipment, an industrial production line of aconite processed by microwave was established with diester alkaloids and monoester alkaloids as indicators, and pilot production was carried out. At the same time, the content of active constituents and efficacy were compared with that of the main processed products, such as Shengfupian, Baifupian and Heishunpian. The results showed that the industrial production of aconite processed by microwave can be divided into two stages: "Liquid seal to detoxification - drying and puffing". The content of monoester alkaloids in 10 batches of aconite processed by microwave was 0.071%-0.166% and the content of diester alkaloids was 0.004%-0.016%, which met the relevant requirements of the Chinese Pharmacopoeia in 2020. Compared with Heishunpian and Baifupian, the retention rate of the effective components of aconite processed by microwave was higher. Pharmacological experiments showed that aconite processed by microwave not only retained the anti-inflammatory and analgesic activities of Heishunpian and Baifupian, but also significantly increased the levels of leukocytes and lymphocytes in mice with liver cancer chemotherapy, enhanced the CD4/CD8 ratio in spleen cells of mice (P < 0.05), thus regulating the body's immunity. However, this effect of Baifupian was weak, while Heishunpian and Shengfupian had no such effect. Through the above research, this study established microwave processing line with controllable process and high intelligence, as well produced the aconite processed by microwave with low toxicity and stable quality. It laid a foundation for the industrialized continuous production and clinical positioning of aconite by microwave processed, and provided scientific support for the development and application of microwave technology in the field of traditional Chinese medicine. All animal experiments in this study were reviewed and approved by the Experimental Animal Ethics Committee of Chengdu University of Traditional Chinese Medicine before being carried out (Approval No. 2020-28).

Research progress on role of programmed cell death in silicosis and its possible mechanisms / 环境与职业医学

Silicosis is a common occupational disease caused by long-term inhalation of large amounts of free SiO2 dust and deposition in lung tissues, characterized by the formation of silicon nodules and diffuse fibrosis of lung tissues. Silicosis is one of the most common and serious occupational diseases in China, and its treatment imposes a huge economic burden on individuals and the country. The formation mechanism of silicosis is very complex, and no early screening indicators, effective drugs, and treatment methods are available yet. The current diagnosis of silicosis is based on occupational history and chest radiography findings, and it is irreversible once pulmonary fibrosis develops. Moreover, as silicosis is a continuously progressive disease, even if silicosis patients stop exposure to free SiO2 dust, their pulmonary fibrosis will continue to develop and deteriorate. Programmed cell death (autophagy, apoptosis, ferroptosis, etc.) is a key factor involved in the development of silicosis. This article summarized the important roles of programmed cell death, including autophagy, apoptosis, and ferroptosis, in silicotic fibrosis, and concluded that regulating different programmed cell death and related signaling pathways through effective means may delay the process of silicosis fibrosis, providing new ideas and clues for exploring potential mechanisms of silicosis formation and formulating prevention and treatment strategies.

Practice and study on the establishment of transformation-oriented scientific research program in medical field: Taking a medical new research & development institution of Haihe Laboratory of Cell Ecosystem as an example / 中华医学科研管理杂志

Objective:To explore the innovation mode of independent transformation-oriented science and technology research program approval by medical new research & development (R&D) institution.Methods:Through analyzing the program layout, funds, review experts, undertaking units, chief experts and interdisciplinarity to summarize the experiences of the independent transformation-oriented municipal program approval by Haihe laboratory of Cell Ecosystem in 2022.Results:As a new medical R&D institution, which vigorously constructed by Tianjin, Haihe laboratory of Cell Ecosystem has carried out the practice of the independent transformation-oriented municipal program through the measures of layout of full-chain transformation, conducting transformation-oriented review, gathering high-level research talents, and emphasizing interdisciplinarity.Conclusions:The experiences of Haihe laboratory of Cell Ecosystem make significance for medical new R&D institutions to explore and cultivate scientific research program with transformation potential and to promote the transformation of scientific and technological achievements, which are powerful factors for new R&D institutions to play a role of pilot and provide important support to scientific and technological innovation and transformation.

Colonoscopy follow-up in patients with simultaneous multiple primary colorectal cancer and patients with sporadic colorectal cancer: a matched-pair study / 中华消化杂志

Objective:To investigate the incidences of metachronous advanced adenoma (MAA) in patients with simultaneous multiple primary colorectal cancer (CRC) and patients with sporadic CRC.Methods:From January 1, 2008 to September 30, 2022, at Beijing Shijitan Hospital, Capital Medical University, CRC patients who underwent surgery and 3 years follow-up with endoscopy were enrolled. The patients completed colonoscopy at least 2 times during follow-up in 6 to 36 months after surgery, and the interval between the 2 times colonoscopies was over 6 months. Clinical data including age, gender, and tumor location, stage, pathological features, combined underlying diseases, preoperative carcinoembryonic antigen, hemoglobin and other laboratory results, baseline colonoscopy results, and detection of MAA were collected. According to age (±2 years old), gender, location of primary lesion and stage of tumor, patients with simultaneous CRC or sporadic CRC were matched at 1∶1 ratio by propensity score matching. The cumulative risks of MAA in patients with simultaneous multiple primary CRC and patients with sporadic CRC were calculated. Cox proportional hazard regression was used to analyze the influencing factors in the occurrence of MAA.Results:A total of 814 CRC patients were enrolled and matched. After paired matching, there were 36 cases of simultaneous multiple primary CRC (78 lesions) and 78 cases of sporadic CRC (78 lesions). The cumulative incidences of MAA at 1, 2 and 3 years of simultaneous CRC group were 11.1%(4/36), 22.2%(8/36) and 33.3%(12/36), respectively. The cumulative incidences of MAA at 1-, 2- and 3-year of sporadic CRC group were 3.8%(3/78), 12.8%(10/78) and 20.5%(16/78), respectively.Simultaneous CRC was correlated with an increase in the 3-year cumulative incidence of MAA ( HR=4.163, 95% confidence interval(95% CI) 1.032 to 4.721, P=0.047). Especially in left-sided CRC, the risk of MAA in simultaneous CRC increased ( HR=7.186, 95% CI 1.602 to 20.787, P=0.010). The results of multivariate cox-regression analysis indicated that detection of simultaneous advanced adenoma at baseline endoscopy was an independent risk factor of MAA ( HR=3.175, 95% CI 1.411 to 7.142, P=0.005). Conclusion:Colouoscopy follow-up should be strengthened in patients with simultaneous multiple primary CRC and simultaneous advanced adenomas.

Prenatal diagnosis and intrauterine treatment of a giant fetal hepatic hemangioma:a case report / 中华围产医学杂志

This article reported a case of fetal giant hepatic hemangioma with cardiomegaly managed with intrauterine treatment. At 23 weeks of gestation, the patient was referred to Guangdong Women and Children Hospital due to abnormal abdominal echogenicity of the fetus, which was suspected to be a hepatic hemangioma or a hepatic arteriovenous fistula. The prenatal ultrasound at 26 weeks of gestation revealed an enlarged fetal hepatic hemangioma of 45 mm×35 mm×42 mm and an enlarged heart (cardiothoracic area ratio of 0.50). So, with the patient's informed consent, the fetus was treated with intrauterine administration of propranolol and dexamethasone and closely monitored by ultrasound. The volume of the lump still increased at the beginning of the medication, but started to shrink in the 7th week. Besides, the fetal cardiac load was reduced and the condition was controlled. The patient delivered at 37 weeks of gestation. The baby received a CT examination on the fourth day after birth which revealed an abdominal mass of 40 mm×30 mm×44 mm requiring no treatment, and no abnormalities were reported during a one-year follow-up.

Comparison of long-term clinical outcomes between transvaginal mesh and pelvic floor reconstruction with native tissue repair in the treatment of advanced pelvic organ prolapse / 中华妇产科杂志

Objective:To study the long-term clinical effect of transvaginal mesh (TVM) and pelvic floor reconstruction with native tissue repair (NTR) in the treatment of advanced pelvic organ prolapse (POP).Methods:Totally 207 patients with advanced POP who were treated in Hunan Provincial Maternal and Child Health Care Hospital from Jan. 2016 to Sep. 2019 were enrolled. The patient′s pelvic organ prolapse quantification were all at degree Ⅲ or above, and they all complained for different degree of symptoms. They were divided into two groups according to the different surgical methods, TVM group and NTR group. In TVM group, the mesh was implanted through the vagina for pelvic floor reconstruction, while in NTR group, the traditional transvaginal hysterectomy combined with uterosacral ligament suspension and anterior and posterior wall repair, as well as perineal body repair were performed. The median follow-up time was 60 months, during the follow up time, 164 cases (79.2%, 164/207) had completed follow-up, including 76 cases in TVM group and 88 cases in NTR group. The perioperative data and complication rates of the two groups were compared, and the subjective and objective outcomes of the two groups at 1, 3 and 5 years were observed, respectively. The objective efficacy was evaluated by three composite criteria, namely: (1) the distance from the farthest end of the prolapse of the anterior and posterior wall of the vagina to the hymen is ≤0 cm, and the descending distance of the top is ≤1/2 of the total length of the vagina; (2) determine the disappearance of relevant POP symptoms according to “Do you often see or feel vaginal mass prolapse？”; (3) no further operation or pessary treatment was performed due to prolapse. If the above three criteria were met at the same time, the operation is successful; otherwise, it was recurrence. The subjective efficacy was evaluated by the pelvic floor distress inventory-short form 20 (PFDI-20) and pelvic floor impact questionnaire-short form 7 (PFIQ-7).Results:The median follow-up time of the two groups was 60 months (range: 41-82 months). Five years after the operation, the subjective and objective cure rates of TVM group were 89.5% (68/76) and 94.7% (72/76), respectively. The subjective and objective cure rates in NTR group were 80.7% (71/88) and 85.2% (75/88), respectively. There were significant differences in the subjective and objective cure rates between the two groups ( χ2=9.869, P=0.002; χ2=3.969, P=0.046). The recurrence rate of TVM group was 5.3% (4/76), and that of NTR group was 14.8% (13/88). There was a significant difference between the two groups ( P=0.046). The postoperative PFDI-20 and PFIQ-7 scores of the two groups were significantly lower than those before surgery, and there were significant differences of the two groups before and after surgery (all P<0.05). Postoperative mesh exposure in TVM group was 1.3% (1/76). Conclusions:The long-term outcomes between the two groups show that the subjective and objective outcomes of pelvic floor reconstruction in TVM group are significantly higher than those in NTR group, and the recurrence rate is significantly lower than that in NTR group. TVM has certain advantages in the treatment of advanced POP.