Tropane alkaloids (TAs) are a class of anticholinergic drugs widely used in clinical practice and mainly extracted from plant, among which Atopa belladonna is the main commercial drug source. It is of great industrial value to obtain TAs in large quantities by plant metabolic engineering. In TAs pathway, cytochrome oxidase CYP82M3 catalyze the synthesis of tropinone and then tropinone reductase I (TRI) compete with TRII for tropinone to form tropine leading to the TAs synthesis (drainage). In this study, based on the "increasing flow and drainage" metabolic engineering strategy, two genes, namely HnCYP82M3 and DsTRI from Hyoscyamus niger and Datura stramonium, respectively, were overexpressed in the hair roots of A. belladonna, with a view to promote the TAs accumulation. The HnCYP82M3 gene was cloned from the root of H. niger, and it encoded amino acid with 91.7% sequence identity with AbCYP82M3 from A. belladonna. Overexpression of HnCYP82M3 alone did not affect the content of TAs in hair roots of A. belladonna, indicating that CYP82M3 was not a key enzyme in TAs biosynthesis. Simultaneous overexpression of HnCYP82M3 and DsTRI greatly promoted the accumulation of the three TAs, and the contents of hyoscyamine, anisodamine and scopolamine were 4.97 times, 2.83 times and 2.19 times that of the control, respectively, and the increase amplitude was greater than that of single overexpression of DsTRI. This study showed that the "increasing flow and drainage" strategy of enzyme genes co-expression at branch points was a promising metabolic engineering method to effectively improve the biosynthesis of TAs in A. belladonna, and laid a theoretical and technical foundation for the large-scale industrial acquisition of TAs.

The rol genes on pRiA4 plasmid of Agrobacterium rhizogenes are potent genes that promote secondary metabolism. Molecular breeding of Atropa belladonna can be conducted by introducing rol genes to increase tropane alkaloids (TAs) content in A. belladonna. In this study, the rolB gene was overexpressed in A. belladonna plants to study the effect of rolB gene on the biosynthesis of TAs. The phenotype, TAs content and expression levels of key enzyme genes in the pathway of TAs biosynthesis of transgenic A. belladonna were analyzed. The results showed that transgenic A. belladonna had developed root system, enlarged leaves, increased leaf fresh weight, deepened leaf color, enlarged flowers, changed flower shape, reduced pistil height and decreased pollen vitality. The content of TAs in the stems of transgenic A. belladonna was significantly higher than that of the control, and the contents of scopolamine, anisodamine, hyoscyamine can reach 2.11-2.91, 1.23-2.37 and 4.88-5.20 times of the control, respectively. Compared with the control group, the expressions of key enzymes putrescine N-methyltransferase (PMT), type III polyketide synthase (PYKS), tropinone reductase I (TRI), aromatic amino acid aminotransferase 4 (ArAT4), UDP-glycosyltransferase 1 (UGT1) and hyoscyamine 6-β-hydroxylase (H6H) in the TAs biosynthesis pathway were up-regulated, and the expression of tropinone reductase II (TRII) as a metabolic shunting gene was down-regulated. The results indicated that rolB gene enhanced TAs synthesis ability in roots and accumulation in stems of A. belladonna by enhancing metabolic flow of TAs synthesis pathway and weakening the metabolic shunt of competing pathway. This study laid a foundation for molecular breeding of A. belladonna with high-yield TAs content using rolB gene.

Objective: To study the incidence of bloodstream infections, pathogen distribution, and antibiotic resistance profile in patients with hematological malignancies. Methods: From January 2018 to December 2021, we retrospectively analyzed the clinical characteristics, pathogen distribution, and antibiotic resistance profiles of patients with malignant hematological diseases and bloodstream infections in the Department of Hematology, Nanfang Hospital, Southern Medical University. Results: A total of 582 incidences of bloodstream infections occurred in 22,717 inpatients. From 2018 to 2021, the incidence rates of bloodstream infections were 2.79%, 2.99%, 2.79%, and 2.02%, respectively. Five hundred ninety-nine types of bacteria were recovered from blood cultures, with 487 (81.3%) gram-negative bacteria, such as Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Eighty-one (13.5%) were gram-positive bacteria, primarily Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium, whereas the remaining 31 (5.2%) were fungi. Enterobacteriaceae resistance to carbapenems, piperacillin/tazobactam, cefoperazone sodium/sulbactam, and tigecycline were 11.0%, 15.3%, 15.4%, and 3.3%, with a descending trend year on year. Non-fermenters tolerated piperacillin/tazobactam, cefoperazone sodium/sulbactam, and quinolones at 29.6%, 13.3%, and 21.7%, respectively. However, only two gram-positive bacteria isolates were shown to be resistant to glycopeptide antibiotics. Conclusions: Bloodstream pathogens in hematological malignancies were broadly dispersed, most of which were gram-negative bacteria. Antibiotic resistance rates vary greatly between species. Our research serves as a valuable resource for the selection of empirical antibiotics.
Humans ; Bacteremia/epidemiology* ; Cefoperazone ; Sulbactam ; Retrospective Studies ; Drug Resistance, Bacterial ; Microbial Sensitivity Tests ; Hematologic Neoplasms ; Sepsis ; Anti-Bacterial Agents/pharmacology* ; Gram-Negative Bacteria ; Gram-Positive Bacteria ; Piperacillin, Tazobactam Drug Combination ; Escherichia coli

OBJECTIVE To evaluate the effect and mechanism of Qili Huanshao Formula(QLHSF)in ameliorating sex hormone disturbance and oxidative damage in testicular tissues of D-galactose-induced subacute aging mice.METHODS 105 male mice were randomly divided into the normal group,model group,low,medium and high doses of QLHSF group,vitamin E(VE)group and Jin Gui Shen Qi Wan(JGSQW)group.The subacute senescence model was established by continuous intraperitoneal injection of D-galac-tose(D-gal)and treated by intragastric administration,as well.The testicular histopathological damage was detected by HE staining.The levels of relevant sex hormones in serum were detected by ELISA.The expression of oxidative stress factors was detected by related kits.The apoptotic cells in testicular tissue were detected by TUNEL assay,and the expressions of oxidative stress and apop-totic related proteins in the testicular tissues of mice were detected by Western blot.RESULTS Compared to the aging model mice,all dose groups of QLHSF could obviously improve testicular tissue pathological damage.The levels of T,E2 and GnRH levels were in-creased,while LH and FSH were decreased in serum(P<0.01).Meanwhile,the SOD activity(P<0.01)and the levels of GSH(P<0.01)were increased,while MDA levels(P<0.01)were decreased in serum and testicular tissues.The medium dose group of QLHSF significantly inhibited testicular cell apoptosis(P<0.01),increased the expression of Nrf2,HO-1 protein and Bcl-2/Bax ratio(P<0.05),and down-regulated the expressions of Cleaved-Caspase-3/Caspase-3,Cleaved-Caspase-9/Caspase-9 apoptotic protein in the testis of mice(P<0.05).CONCLUSION QLHSF can effectively improve sex hormone disturbance and protect testicular tissue in aging mice,and the mechanism of action might be related to the inhibition of oxidative stress-induced apoptosis in testicular tissues.The study will provide reference and lay the foundation for the clinical application and functional anti-aging product develop-ment of Lycium barbarum and its formulations.

Potato skin may turn green, purple or sprout when stored improperly.At this time the content of its metabolite sola- nine increases significantly.Although solanine is toxie,it also has certain medicinal value.It has been found that solanine has effects like anti-cancer, anti-inflammation, detumescence, treatment of pulmonary hypertension, and diabetes.This paper searches the relevant literature for the research on the medicinal application of solanine,and systematically summarizes the solanine medicinal value.For a more effective development and utilization of the plant resources,this paper hopes to provide the theoretical and application basis for the development of natural medicine with high efficiency and small adverse reactions in the treatment of cancer, inflammation, tumescence, pulmonary hypertension and diabetes.

Fabrication of conventional complete dentures involves a complex restoration method, requiring significant time and typically involving primary impressions, definitive impressions, jaw relation records, clinic try-in, and complete denture placement, which has been used for nearly a century without change. A novel digital system named Functionally Suitable Denture (FSD) was researched and developed so as to reduce clinical steps, operation difficulties and errors of complete denture restoration. It pioneered a unique diagnostic complete denture aided by computer aided design (CAD) & 3D printing, by which, the functional impression, jaw relation, and try-in (3 steps) were simplified to 1 step, thus the number of visits to the dentist was reduced by 2 times. Moreover, for the first time, it put forward a CAD software of template matching based on the expert design, which was an efficient and intelligent design scheme, and the excellent denture experts' experience and skills could be inherited and iterated. The system included the 3D scanner with appropriate accuracy and high efficiency, the CAD software, the special 3D printer and process software, and the innovative clinical operation process. The Patent Cooperation Treaty (PCT) patent international search report showed that all the 15 claims of the technology were of novelty, creativity and industrial utility. All the digital products were independently developed and made by Peking University School and Hospital of Stomatology, China. The design and manufacture process of denture prosthesis was fast, simple and accurate. At the same time, personalized functional and aesthetic matching of the patients after wearing prosthesis was realized. It effectively solved the global problems of "slow, difficult and inaccurate" of the traditional manual technology of complete denture, and brought good news to edentulous patients. Compared with the traditional complete denture treatment, FSD system has a wide range of applications for different types of edentulous patients, including those with severe resorption of the alveolar ridge or a high occlusal force. Furthermore, the low-cost of 3D printers, compared with expensive milling machines, may make the approach more accessible. This review describes that our research is related to the development of the FSD system, including multi-source data acquisition technology, three generations of complete denture design software, 3D printing systems of individual tray and complete denture pattern, the clinical and laboratory operation process of the FSD system.
China ; Computer-Aided Design ; Creativity ; Denture, Complete ; Humans ; Mouth, Edentulous

The positive human leukocyte antigen (HLA) antibody present in kidney transplant recipients affects both surgery and rejection, and also affects the long-term survival of the transplanted kidney. During the third kidney transplant, bilateral axillary fossa and iliac vessel were destroyed. It was very difficult for selection or separation of surgical vessels because the adhesions and scar formation was easy to damage blood vessels and intestinal tubes. A case with strong positive HLA antibody undergoing the third kidney transplant in our hospital was successfully solved the problems, such as less transplant space and vascular scar adhesion. Rituximab, rabbit anti-human thymocyte immunoglobulin, and methylprednisolone treated-antibodies were used in the operation. The immune function test was used to develop individualized treatment after the operation. The postoperative creatinine and urine volume tended to be stable, and the 16-month follow-up renal function was good.
Antibodies ; Humans ; Kidney ; Kidney Diseases ; surgery ; Kidney Transplantation ; Nephrectomy ; Rituximab

Objective:To investigate the impact of age and gender on kinetic visual acuity (KVA) and static visual acuity (SVA) in school children accepting physical activities. Methods:From May, 2018 to September, 2019, 1465 school children from various schools of Suzhou City were measured SVA and KVA with standard logarithmic visual chart and KVA detector. Results:KVA increased with age as six to nine years old, and decreased as eleven to 14. KVA was better in boys than in girls (t = 5.147, P < 0.001). SVA decreased with age as six to eight years old, fluctuated as eight to eleven, and decreased as eleven to 14, especially for girls. SVA was also better in boys than in girls (t = 3.692, P < 0.001). The prevalence of myopia increased with age as six to eight years old, and increased more significantly as eleven to 14. There was a low positive correlation between age and KVA (r = 0.046, P < 0.05), and a moderate negative correlation between age and SVA (r = -0.364, P < 0.05). KVA was positively correlated with SVA (r = 0.409, P < 0.05). Age, gender, KVA, right SVA and left SVA were the factors related with SVA. Conclusion:Vision is better in school boys than in girls. There is positive correlation between age and KVA. It is necessary to develop physical exercise according to age and gender to improve vision development, especially at the sensitive stage of visual function.

Objective:To observe the effect of football, badminton and table tennis on kinetic visual acuity for children in grade one to three at elementary schools. Methods:From February to June, 2019, A total of 123 children aged seven to nine years from four elementary schools were divided into control group (n = 32), badminton group (n = 33), table tennis group (n = 30) and football group (n = 28). The children in the experimental groups accepted ball playing training for 16 weeks, while the control group did not attended any training course. The kinetic visual acuity was measured before and after training. Results:The kinetic visual acuity improved after training in the experimental groups (t > 2.196, P < 0.05), but not in the control group (t = 1.570, P > 0.05). The rates of improvement of kinetic visual acuity were: football (26.82%), badminton (25.44%) and table tennis (19.21%). Conclusion:The ball games play a positive role in improving kinetic visual acuity for children in junior grades, especially the big ball games.