[Clinical and genetic characteristics of 21 children with Rubinstein-Taybi syndrome].

Objective: To investigate the phenotypes of Rubinstein-Taybi syndrome (RSTS) caused by variants in the CREBBP or EP300 gene, and the correlation between genotype and phenotype. Methods: This case series study was performed on pediatric patients who were referred to the Children's Hospital of Capital Institute of Pediatrics between January 2013 and July 2022. Both point variant and copy number deletion in CREBBP or EP300 gene were detected by whole exome sequencing, chromosomal microarray analysis, or copy number variation sequencing (CNV-seq). The variant categories were summarized and phenotype numbers were re-visited for RSTS patients. Based on variant types, the patients were divided into different groups (point variant or copy number deletion, EP300 or CREBBP point variant, and loss of function or missense variant). Phenotype counts between different groups were compared using the rank-sum test of two independent samples. Results: A total of 21 RSTS patients were recruited, including 12 males and 9 females, with ages ranging from 1 month to 14 years and 2 months. Among them, 67% (14/21) had point variants, and 33% (7/21) had copy number deletions. Out of these, 20 variants (95%) were de novo. Among 20 patients finishing phenotype count during re-visit, 95% (19/20) of the patients exhibited developmental delays before the age of 2 years. Additionally, 80% (16/20) of the patients had distinctive facial features. Considering phenotype count, no statistically significant difference was found between point variant (14 cases) and copy number deletion (6 cases) (5.0 (3.0, 7.0) vs. 5.0 (2.5, 5.3), Z=0.75, P=0.452), CREBBP (10 cases) and EP300 gene (4 cases) point variant (5.0 (3.8, 7.0) vs. 4.0 (2.0, 6.0), Z=1.14, P=0.253), and loss of function (9 cases) and missense (5 cases) variant (6.0 (4.5, 7.0) vs. 3.0 (2.5, 5.5), Z=1.54, P=0.121). Conclusions: Patients with RSTS primarily exhibit developmental delays in early childhood. Specific facial features serve as suggested signs of genetic testing. However, no significant genotype-phenotype correlation is found.

17ß-estradiol regulates adenosine triphosphate-binding cassette transporters A1 expression via estrogen receptor A to increase macrophage cholesterol efflux.

The liver is the focus of research on the effects of estrogen on cholesterol metabolism. Few studies have investigated the effects of estrogen on macrophages despite the significance of cells in atherosclerosis. The purpose of this study is to examine the effect of estrogen on macrophage cholesterol efflux. Macrophage cholesterol efflux, oil red O staining, RT-qPCR, Western blotting analyses were used to determine cholesterol metabolize and the expressions of adenosine triphosphate (ATP)-binding cassette transporter G1 (ABCG1) and ATP-binding cassette transporter A1 (ABCA1) in J774A.1 cells, and the effect of these treatments was compared to without adding 17ß-estradiol (E2). Gain and loss of estrogen receptor alpha (ERα), liver X receptor α (LXRα) were conducted to study interactions between E2, ERα, LXRα and ABCA. Finally, in mice, we validate the relationship between ERα and ABCA1. E2 increases cholesterol efflux from macrophages and decreases the formation of lipid droplets and positively regulates the expression of ABCA1. This suggests that estrogen receptors (ERs) directly regulate ABCA1 translation. We suppressed ERα, which decreased the mRNA and protein expression of ABCA1. At the mRNA level, E2 treatment could partially counteract these phenomena, but not at the protein level. ABCA1 expression decreased after LXRα was inhibited. This suggests that ABCA1 translation is directly regulated by ERα. In the ovariectomized mouse model of ABCA1 protein expression was significantly reduced in the peritoneal macrophages of the ovariectomy (OVX) group. ABCA1 protein expression was greater in the E2+OVX group than in the OVX group. E2 contributes to the positive regulation of ABCA1 expression and promotes cholesterol efflux in macrophages by binding to ERα. The effect is independent of ABCA1 transcription regulation by LXRα.

[Safety of double and a half layered esophagojejunal anastomosis in radical gastrectomy: A prospective, multi-center, single arm trial].

Objective: To evaluate the safety of double and a half layered esophagojejunal anastomosis in radical gastrectomy. Methods: This prospective, multi-center, single-arm study was initiated by the Affiliated Cancer Hospital of Zhengzhou University in June 2021 (CRAFT Study, NCT05282563). Participating institutions included Nanyang Central Hospital, Zhumadian Central Hospital, Luoyang Central Hospital, First Affiliated Hospital of Henan Polytechnic University, First Affiliated Hospital of Henan University, Luohe Central Hospital, the People's Hospital of Hebi, First People's Hospital of Shangqiu, Anyang Tumor Hospital, First People's Hospital of Pingdingshan, and Zhengzhou Central Hospital Affiliated to Zhengzhou University. Inclusion criteria were as follows: (1) gastric adenocarcinoma confirmed by preoperative gastroscopy;(2) preoperative imaging assessment indicated that R0 resection was feasible; (3) preoperative assessment showed no contraindications to surgery;(4) esophagojejunostomy planned during the procedure; (5) patients volunteered to participate in this study and gave their written informed consent; (6) ECOG score 0-1; and (7) ASA score I-III. Exclusion criteria were as follows: (1) history of upper abdominal surgery (except laparoscopic cholecystectomy);(2) history of gastric surgery (except endoscopic submucosal dissection and endoscopic mucosal resection); (3) pregnancy or lactation;(4) emergency surgery for gastric cancer-related complications (perforation, hemorrhage, obstruction); (5) other malignant tumors within 5 years or coexisting malignant tumors;(6) arterial embolism within 6 months, such as angina pectoris, myocardial infarction, and cerebrovascular accident; and (7) comorbidities or mental health abnormalities that could affect patients' participation in the study. Patients were eliminated from the study if: (1) radical gastrectomy could not be completed; (2) end-to-side esophagojejunal anastomosis was not performed during the procedure; or (3) esophagojejunal anastomosis reinforcement was not possible. Double and a half layered esophagojejunal anastomosis was performed as follows: (1) Open surgery: the full thickness of the anastomosis is continuously sutured, followed by embedding the seromuscular layer with barbed or 3-0 absorbable sutures. The anastomosis is sutured with an average of six to eight stitches. (2) Laparoscopic surgery: the anastomosis is strengthened by counterclockwise full-layer sutures. Once the anastomosis has been sutured to the right posterior aspect of the anastomosis, the jejunum stump is pulled to the right and the anastomosis turned over to continue to complete reinforcement of the posterior wall. The suture interval is approximately 5 mm. After completing the full-thickness suture, the anastomosis is embedded in the seromuscular layer. Relevant data of patients who had undergone radical gastrectomy in the above 12 centers from June 2021 were collected and analyzed. The primary outcome was safety (e.g., postoperative complications, and treatment). Other studied variables included details of surgery (e.g., surgery time, intraoperative bleeding), postoperative recovery (postoperative time to passing flatus and oral intake, length of hospital stay), and follow-up conditions (quality of life as assessed by Visick scores). Result: [1] From June 2021 to September 2022,457 patients were enrolled, including 355 men and 102 women of median age 60.8±10.1 years and BMI 23.7±3.2 kg/m2. The tumors were located in the upper stomach in 294 patients, mid stomach in 139; and lower stomach in 24. The surgical procedures comprised 48 proximal gastrectomies and 409 total gastrectomies. Neoadjuvant chemotherapy was administered to 85 patients. Other organs were resected in 85 patients. The maximum tumor diameter was 4.3±2.2 cm, number of excised lymph nodes 28.3±15.2, and number of positive lymph nodes five (range one to four. As to pathological stage,83 patients had Stage I disease, 128 Stage II, 237 Stage III, and nine Stage IV. [2] The studied surgery-related variables were as follows: The operation was successfully completed in all patients, 352 via a transabdominal approach, 25 via a transhiatus approach, and 80 via a transthoracoabdominal approach. The whole procedure was performed laparoscopically in 53 patients (11.6%), 189 (41.4%) underwent laparoscopic-assisted surgery, and 215 (47.0%) underwent open surgery. The median intraoperative blood loss was 200 (range, 10-1 350) mL, and the operating time 215.6±66.7 minutes. The anastomotic reinforcement time was 2 (7.3±3.9) minutes for laparoscopic-assisted surgery, 17.6±1.7 minutes for total laparoscopy, and 6.0±1.2 minutes for open surgery. [3] The studied postoperative variables were as follows: The median time to postoperative passage of flatus was 3.1±1.1 days and the postoperative gastrointestinal angiography time 6 (range, 4-13) days. The median time to postoperative oral intake was 7 (range, 2-14) days, and the postoperative hospitalization time 15.8±6.7 days. [4] The safety-related variables were as follows: In total, there were 184 (40.3%) postoperative complications. These comprised esophagojejunal anastomosis complications in 10 patients (2.2%), four (0.9%) being anastomotic leakage (including two cases of subclinical leakage and two of clinical leakage; all resolved with conservative treatment); and six patients (1.3%) with anastomotic stenosis (two who underwent endoscopic balloon dilation 21 and 46 days after surgery, the others improved after a change in diet). There was no anastomotic bleeding. Non-anastomotic complications occurred in 174 patients (38.1%). All patients attended for follow-up at least once, the median follow-up time being 10 (3-18) months. Visick grades were as follows: Class I, 89.1% (407/457); Class II, 7.9% (36/457); Class III, 2.6% (12/457); and Class IV 0.4% (2/457). Conclusion: Double and a half layered esophagojejunal anastomosis in radical gastrectomy is safe and feasible.

Postoperative pulmonary complications in older patients undergoing elective surgery with a supraglottic airway device or tracheal intubation.

The two most commonly used airway management techniques during general anaesthesia are supraglottic airway devices and tracheal tubes. In older patients undergoing elective non-cardiothoracic surgery under general anaesthesia with positive pressure ventilation, we hypothesised that a composite measure of in-hospital postoperative pulmonary complications would be less frequent when a supraglottic airway device was used compared with a tracheal tube. We studied patients aged ≥ 70 years in 17 clinical centres. Patients were allocated randomly to airway management with a supraglottic airway device or a tracheal tube. Between August 2016 and April 2020, 2900 patients were studied, of whom 2751 were included in the primary analysis (1387 with supraglottic airway device and 1364 with a tracheal tube). Pre-operatively, 2431 (88.4%) patients were estimated to have a postoperative pulmonary complication risk index of 1-2. Postoperative pulmonary complications, mostly coughing, occurred in 270 of 1387 patients (19.5%) allocated to a supraglottic airway device and 342 of 1364 patients (25.1%) assigned to a tracheal tube (absolute difference -5.6% (95%CI -8.7 to -2.5), risk ratio 0.78 (95%CI 0.67-0.89); p < 0.001). Among otherwise healthy older patients undergoing elective surgery under general anaesthesia with intra-operative positive pressure ventilation of their lungs, there were fewer postoperative pulmonary complications when the airway was managed with a supraglottic airway device compared with a tracheal tube.

[Estimate the population size of transgender women based on the capture-recapture method in Tianjin].

Objective: To investigate the population size of transgender women (TGW) in Tianjin and analyze the characteristics of their sexual behaviors to provide a basis for AIDS prevention and control. Methods: To estimate the population size of TGW in Tianjin using the capture-recapture method. At the same time, an anonymous questionnaire was collected to conduct a multi-factor logistic analysis of the TGW population's sexual behavior. Results: A total of 213 TGW were investigated. Tianjin's estimated TGW population size was 599 (95%CI: 407-792). Multivariate logistic analysis of the use of condoms consistently showed that compared with TGW without regular sex partners, those with regular sex partners had a lower proportion of consistent condom use (aOR=0.44, 95%CI: 0.23-0.82) and had received HIV tests in the last year were more likely to adhere to condom use than those who had not been tested (aOR=2.73, 95%CI: 1.06-6.99). Conclusion: It is necessary to strengthen HIV mobilization testing among the TGW population and their regular sexual partners to improve condom use.

[Application status of CFD technology in occupational hazard control].

In the process of occupational hazard management, computational fluid dynamics technology can be used to reflect the distribution pattern of occupational hazards in the production process, so as to quickly and accurately guide the formulation of occupational disease prevention and control programs. This paper summarizes and analyzes the current research results on the prevention and control of occupational hazards in workplaces through computational fluid dynamics technology, and describes the application of these research results in the process of occupational disease prevention and control. On this basis, this paper presents the problems and application limitations of existing research and points out the future key research directions, which are of great reference value for guiding further systematic and in-depth research on simulation, experimentation and management of occupational hazards that can cause occupational diseases.

[Clinical and genetic characteristics of congenital isolated adrenocorticotropic hormone deficiency].

Objective: To investigate the clinical and genetic characteristics of congenital isolated adrenocorticotropic hormone (ACTH) deficiency. Methods: The clinical and laboratory characteristics of 5 cases with congenital isolated ACTH deficiency diagnosed in the Department of Endocrinology of the Children's Hospital, Capital Institute of Pediatrics from January 2019 to March 2021 were retrospectively analyzed. The general conditions, clinical manifestations, laboratory examinations, genetic charcteistics, treatment and follow-up (up to October 2021) were analyzed. Results: Of the 5 cases, 1 was female and 4 were males, aged from 13 months to 6 years at the time of consultation. The symptoms of hypoglycemia and convulsion were presented in infancy, and 4 cases had infantile cholestasis. Glucose level of 5 cases ranged from 0.79-2.20 mmol/L, ACTH ranged from <1.00-4.17 ng/L, and cortisol ranged from 0.2-3.8 µg/L. Whole exon sequencing revealed that 3 cases carried homozygous TBX19 variations, and 2 cases had compound heterozygous TBX19 variations, including 3 variants that had been reported before and 3 novel variants were found. After the diagnosis was confirmed, all the cases were treated with hydrocortisone. Hypoglycemia was all corrected during the follow-up, and 4 cases no longer had convulsions. Conclusion: Congenital isolated ACTH deficiency should be considered in neonates and infants with cholestasis and hypoglycemia, and the diagnosis can be confirmed by genetic testing.

[Analysis on psychoactive substances use in men who have sex with men in Tianjin].

Objective: To understand the use of psychoactive substances and its related factors in men who have sex with men (MSM) in Tianjin. Methods: A cross-sectional survey was conducted in MSM recruited in Tianjin by snowball sampling from September 2017 to December 2020, the information about their social demographic information, use of psychoactive substances and behavioral characteristics were collected, meanwhile the blood samples were taken from them for HIV/syphilis detections. Multivariate logistic regression was used to explore related factors about psychoactive substances use. Results: A total of 9 218 MSM were included in the study, in whom 43.5% (4 013/9 218) had ever used psychoactive substances, including 92.6% (3 718/4 013)who used Rush and 17.2% (692/4 013) who used multi substances. Multivariate analysis showed that, the OR of psychoactive substances use in MSM who were in Han ethnic group was 0.68 (95%CI:0.51-0.91) compared with those who were in minor ethnic group; the OR of psychoactive substances use in MSM who were married or cohabited, divorced or widowed were 0.65 (95%CI: 0.57-0.71), 0.80 (95%CI: 0.65-0.97) respectively compared with those who were unmarried; the OR of psychoactive substances use in MSM who had the first homosexual sex at age of ≥30 years was 0.57 (95%CI: 0.44-0.74) compared with those who had the first homosexual sex at age of <30 years; the OR of psychoactive substances use in local MSM in Tianjin was 1.12 (95%CI: 1.03-1.23) compared with those who were not local residents in Tianjin; the OR of psychoactive substances use in MSM with education level of college or above was 1.29 (95%CI: 1.12-1.49) compared with those with education level of junior middle school or below; the OR of psychoactive substances use in MSM who had anal sex in the past six months was 1.93 (95%CI: 1.34-2.77) compared with those who had no anal sex; the OR of psychoactive substances use in MSM who had >2 homosexual partners in the last week was 1.62 (95%CI: 1.41-1.87) compared with those who had ≤2 homosexual partners; the OR of psychoactive substances use in MSM who had homosexual commercial sex in the past six months was 1.99 (95%CI: 1.62-2.45) compared with those who had no homosexual commercial sex; the OR of psychoactive substances use in MSM who had sexually transmitted diseases in the last year was 2.39 (95%CI: 1.82-3.12) compared with those who had no sexually transmitted diseases and the OR of psychoactive substances use in MSM who received peer education services in the last year was 1.63 (95%CI: 1.50-1.78) compared with those who received no peer education services. Conclusion: The prevalence of psychoactive substances use is high in MSM in Tianjin, and there are many influencing factors. It is necessary to conduct targeted interventions according to the influencing factors.

[Analysis on incidence trend of liver cancer in China, 2005-2016].

Objective: To understand the incidence trend of liver cancer in China from 2005 to 2016, and explore the correlation between the incidence trend of liver cancer and the incidence trend of hepatitis B. Methods: The incidence data of liver cancer in China from 2005 to 2016 were collected from the Annual Report of Cancer Registry in China. The incidence data of hepatitis B were collected from China Public Health Science Data Center. World standardized incidence rate (WSR) was calculated according to the World Segi's population. Joinpoint regression model was used to analyze the trend of WSR of liver cancer [measured by average annual percentage change (AAPC)]. The age-period-cohort model was fitted to analyze the age, period and cohort effects in people aged 20- years and above. Pearson correlation coefficient was used to explore the correlation between the incidence of liver cancer and the incidence of hepatitis B. Results: The crude incidence of liver cancer in China showed a trend of first increase before 2009 and then relatively stable. The world standardized morbidity rate of liver cancer in China decreased from 19.11 per 100 000 in 2005 to 17.74 per 100 000 in 2016 (AAPC=-0.5%, 95%CI: -1.3%-0.3%, P=0.240). The incidence of liver cancer in male decreased significantly (AAPC=-1.0%, 95%CI: -1.5%--0.5%, P=0.001). The incidence of liver cancer in women increased from 2005 to 2010 [annual percentage change (APC)=1.7%, 95%CI: -0.1%-3.4%, P=0.059] but showed a significant decrease trend from 2010 to 2016 (APC=-1.6%, 95%CI: -2.3%--1.0%, P=0.001). From 2005 to 2016, the incidence of liver cancer showed a decreasing trend in urban areas (AAPC=-0.3%, 95%CI: -0.8%-0.3%, P=0.316) and rural areas (AAPC=-3.9%, 95%CI: -4.4%--3.3%, P<0.001). Risk for liver cancer increased with age, while the period effect showed a trend of first increase then decrease and cohort effect showed a decrease trend. The morbidity rates of both hepatitis B and liver cancer showed decrease trends from 2009 to 2016, and there was a significant correlation (r=0.71, 95%CI: 0.01-0.94, P=0.048). Conclusions: From 2005 to 2016, the morbidity rate of liver cancer in China showed a decrease trend, and there were significant gender and urban-rural area specific differences. Age effect had a great impact on the risk for liver cancer. With the progress of population aging in China, liver cancer is still a public health problem, to which close attention needs to be paid.

Population pharmacokinetics of bedaquiline in patients with drug-resistant TB.

OBJECTIVE: To develop a population pharmacokinetic (PK) model for bedaquiline (BDQ) to describe the concentration-time data from patients with multidrug-resistant TB (MDR-TB) in China.METHOD: A total of 306 PK observations from 69 patients were used in a non-linear, mixed-effects modelling (NONMEM) approach. BDQ PK can be adequately described by a three-compartment model with a transit absorption model. The impact of baseline covariates, including age, sex, height, weight, alanine aminotransferase (ALT), aspartate aminotransferase (AST), apolipoprotein (ALP), total bilirubin (TBIL), direct bilirubin (DBIL), creatinine (CR), potassium (K+), calcium (Ca++) and magnesium (Mg++) on the oral clearance (CL/F) of BDQ were investigated.RESULTS: In final population PK model, no significant covariates were found in the population PK model for BDQ. The population PK parameter estimate values for oral clearance (CL/F); CL/F between central compartment and peripheral compartment (Q1/F, Q2/F); peripheral volume of distribution (Vp1/F, VP2/F) were respectively 1.50 L/h (95% CI 1.07-1.93), 2.54 L/h (95% CI 1.67-3.41), 1,250 L (95% CI 616.9-1883.1), 2.00 L/h (95% CI 1.10-2.90) and 4,960 L (95% CI 1647.6-8272.4). Inter-individual variability on CL/F was 65.0%.CONCLUSION: This is the first study to establish a population PK model for BDQ in Chinese patients with MDR-TB. The final model adequately described the data and had good simulation characteristics. Despite some limitations, the final population PK model was stable with good accuracy of parameter estimation.

Effects of lipids and surfactants on the fermentation production of echinocandin B by Aspergillus nidulans.

AIMS: Echinocandin B (ECB) is a kind of lipopeptide antifungal antibiotic, as well as the key precursor of antifungal drug Anidulafungin. Its efficient bioproduction plays an important role in promoting the industrial production of Anidulafungin. METHODS AND RESULTS: In this study, methyl oleate and Tween 80 were firstly used to enhance the ECB fermentation by Aspergillus nidulans, the results showed that the ECB titre was significantly enhanced with the addition of methyl oleate and Tween 80. Among the lipids, methyl oleate was found to play a pivotal role in increasing the ECB titre to 2123 mg l-1 , which was more than five times higher than that of the control. The addition of Tween 80 in the medium resulted in ECB titre increased to 2584 mg l-1 . The scanning electron microscope (SEM) and N-phenyl-1-naphthylamine (NPN) assay indicated that Tween 80 could influence the cell membrane permeability of A. nidulans, and enhance the intracellular and extracellular substance exchange, therefore lead to the increasing of ECB titre. CONCLUSIONS: Methyl oleate and Tween 80 are optimal carbon sources and surfactants for efficient ECB biosynthesis respectively. SIGNIFICANCE AND IMPACT OF THE STUDY: Surfactant was used in ECB fermentation for the first time, which provided feasible ideas for optimizing the fermentation process of other fungi.

Kaempferol suppresses proliferation and induces apoptosis and DNA damage in human gallbladder cancer cells through the CDK4/CDK6/cyclin D1 pathway.

OBJECTIVE: Kaempferol has been reported to play an anti-tumor role in various human cancers, while its role in gallbladder cancer (GBC) is unclear. MATERIALS AND METHODS: We found that kaempferol significantly inhibited the growth, invasion and migration, meanwhile induced apoptosis through cells arrested at G0/G1 phase of GBC cell lines, including GBC-SD and SGC996 cells in vitro. RESULTS: Kaempferol promoted the release of cytochrome C from the mitochondria to cytoplasm, the activation of c-caspase-3 and c-caspase-9 and increased the expression levels of pro-apoptotic factor Bax, meanwhile decreased the expression levels of anti-apoptotic factor Bcl-2. In addition, the expression levels of CDK4, CDK6 and cyclin D1, which are members of the CDK4/CDK6/cyclin D1 signaling pathway, were also decreased by kaempferol. Moreover, kaempferol could efficiently prevent tumor progression of GBC in the xenograft in vivo. CONCLUSIONS: Our results demonstrated that kaempferol suppressed GBC progression through activation of the CDK4/CDK6/cyclin D1 signaling pathway, suggesting that it might be a potential anti-tumor agent for clinical treatment of GBC.

Enhanced O-succinyl-l-homoserine production by recombinant Escherichia coli ΔIJBB*TrcmetL/pTrc-metAfbr -Trc-thrAfbr -yjeH via multilevel fermentation optimization.

AIMS: Constructing a strain with high yield of O-succinyl-l-homoserine (OSH) and improving the titre through multilevel fermentation optimization. METHODS AND RESULTS: OSH high-yielding strain was first constructed by deleting the thrB gene to block the threonine biosynthesis. Single-factor experiment was carried out, where a Plackett-Burman design was used to screen out three factors (glucose, yeast and threonine) from the original 11 factors that affected the titre of OSH. The Box-Behnken response surface method was used to optimize the fermentation conditions. Through gene editing and medium optimization, the titre of OSH increased from 7·20 to 8·70 g l-1 in 500 ml flask. Furthermore, the fermentation process and fed-batch fermentation conditions including pH, temperature, feeding strategy and feeding medium were investigated and optimized. Under the optimal conditions, the titre of OSH reached 102·5 g l-1 , which is 5·6 times higher than before (15·6 g l-1 ). CONCLUSIONS: O-succinyl-l-homoserine fermentation process was established and the combination of response surface methodology and metabolic pathway analysis effectively improved the titre of OSH. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, the titre of OSH reached the needs for industrial production and the metabolic pathway of OSH was demonstrated for further optimization.

[Current status and prospects of population exposure assessment of nanomaterials consumer products].

With the wide application of nanomaterials in consumer products in the market, it is necessary to understand the existence and release of nanomaterials in consumer products, as well as the current situation of exposure assessment of consumers. China has been a large industrial producer with a huge consumer market, but the supervision of consumer goods with nanomaterials is almost blank. This article summarized and classified the existing consumer products of nanomaterials in the international market, and discussed the release of key nanomaterials in consumer products and the exposure assessment methods of consumers, in order to provide a scientific basis for the establishment of a regulatory system for consumer products of nanomaterials in China in the future.

[The effect of blocking penile blood drainage on stem cells therapy for rats with erectile dysfunction].

Objective: To investigate the effect of blocking penile blood drainage at the root of the rat penis on cell retention, penile erectile function, and histopathological changes when erectile dysfunction (ED) is treated by intracavernous injection (ICI) of stem cells. Methods: Thirty male SD rats were randomly divided into sham operation group (n=6), ED model group (n=6), treatment group A (blockade group, n=9) and treatment group B (non-blockade group, n=9). Twenty-four hours after the model was established, group A and group B were treated by ICI of 1 × 10(6) adipose-derived stem cells (ADSCs). Before ICI, the penile blood drainage in group A was temporarily blocked with a rubber tourniquet at the root of the penis which was removed 5 minutes after the injection. The dynamic changes of the local fluorescent signal of the penis and the expression of the fluorescent signal in the lung were detected after ICI. The maximum intracavernous pressure/mean arterial pressure (ICPmax/MAP) was measured to evaluatethe erectile function, and histopathological changes of the penis were observed after 28 days. Results: At different time points (0, 10 and 60 min), the intensity of the bioluminescent signal (×10(6)·p·s(-1)·sr·cm(-2)) in group A had a similar trend when compared with that in group B, and the differences were not statistically significant (8.76±1.17 vs 8.16±1.12, 6.45±1.47 vs 6.72±0.69, 3.77±0.30 vs 3.36±1.06, all P>0.05). A large number of ADSCs could be found in the lungs in both treatment groups after 60 min of ICI. There was no statistically significant difference in erectile function (0.44±0.11 vs 0.43±0.07) and histopathological change (0.08±0.02 vs 0.08±0.03) regardless of the occlusion of blood drainage at the root of the penis (all P>0.05). Conclusion: Temporarily blocking of penile blood drainage has no obvious advantage in improving cell retention and efficacy when ADSCs are used to treat ED of rat models.

Improvement of gibberellin production by a newly isolated Fusarium fujikuroi mutant.

AIMS: To obtain and investigate the potential mechanism for GA3 production in Fusarium fujikuroi GA-251, a high GA3 producer. METHODS AND RESULTS: Fusarium fujikuroi IMI 58289 was bred with Cobalt-60 (60 Co) radiation and lithium chloride treatment. The best mutant strain GA-251 was obtained for the subsequent optimization of fermentation conditions. The yield of GA3 by GA-251 was 2100 mg l-1 , while the wild-type strain was 100 mg l-1 , which is a 21-fold increase in the yield. To elucidate the mechanism of high GA3 yield of GA-251, the genome was sequenced and compared with wild-type strain IMI 58289. The results showed 2295 single nucleotide polymorphisms, 1242 small indels and 30 structural variants. These mutations were analysed and enriched in the MAPK signalling pathway, the mRNA surveillance pathway and endocytosis. The potential reasons for the improved GA3 biosynthesis were investigated. CONCLUSIONS: The potential mechanism of high GA3 yield was attributed to endocytosis pathway and histone modification proteins family. SIGNIFICANCE AND IMPACT OF THE STUDY: A mutant strain GA-251 in this work that could potentially be utilized in the industrial yield of GA3 . The comparative genome analysis would shed light onto the mechanism of yield improvement and be a theoretical guide for further metabolic engineering.