Effect of the rolB gene on phenotypic development and tropane alkaloids biosynthesis in Atropa belladonna / 药学学报

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.

Influencing factors for nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus / 临床肝胆病杂志

Objective To investigate related influencing factors in patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD). Methods A total of 252 patients with T2DM who were treated in Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine from May 2021 to March 2022 were enrolled as subjects, and these patients were also included in Metabolic Management Center of China. According to the presence or absence of fatty liver disease, the patients were divided into simple T2DM group ( n =105) and T2DM+NAFLD group ( n =147). Related general data were analyzed, including sex, age, blood pressure, body height, body weight, neck circumference, triglyceride (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, fasting blood glucose, glycosylated hemoglobin, high-sensitivity C-reactive protein, albumin/creatinine ratio in morning urine, thyroid stimulating hormone, uric acid, intrahepatic fat deposition, carotid intima-media thickness, and brachial-ankle pulse wave velocity. The group t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between groups. A multivariate logistic regression analysis was used to investigate the risk factors for T2DM with NAFLD, and the receiver operating characteristic (ROC) curve was used to assess the predictive value of related influencing factors. Results The age-stratified analysis showed that in the < 50 years age group, compared with the patients with T2DM alone, the patients with T2DM and NAFLD had significantly higher levels of body mass index (BMI), visceral fat, TG, brachial-ankle pulse wave velocity, albumin/creatinine ratio in morning urine, and uric acid ( P < 0.05); in the ≥50 years age group, compared with the patients with T2DM alone, the patients with T2DM and NAFLD had significantly higher levels of blood pressure, BMI, visceral fat, TG, brachial-ankle pulse wave velocity, albumin/creatinine ratio in morning urine, and uric acid ( P < 0.05) and a significantly lower level of serum HDL-C ( P < 0.05). The multivariate logistic regression analysis showed that BMI (odds ratio [ OR ]=1.408, 95% confidence interval [ CI ]: 1.136-1.746, P =0.002), HDL-C ( OR =0.031, 95% CI : 0.001-0.647, P =0.025), left brachial-ankle pulse wave velocity ( OR =1.003, 95% CI : 1.001-1.006, P =0.003), and uric acid ( OR =1.011, 95% CI : 1.005-1.016, P < 0.001) were independent influencing factors for T2DM with NAFLD. The ROC curve analysis showed that HDL-C, BMI, left brachial-ankle pulse wave velocity, and uric acid had an area under the ROC curve of 0.695 (95% CI : 0.574-0.812), 0.708 (95% CI : 0.628-0.788), 0.611 (95% CI : 0.523-0.698), and 0.698 (95% CI : 0.617-0.779), respectively, in evaluating T2DM with NAFLD. Conclusion Low levels of HDL-C, BMI, left brachial-ankle pulse wave velocity, and uric acid have a certain value in predicting NAFLD in patients with T2DM.

Deep neck space infections: a retrospective cohort study of surgical risk factors / 中华耳鼻咽喉头颈外科杂志

Objective: To explore risk factors affecting treatment for deep neck space infections (DNSIs) so as to provide guidance for appropriate early managements. Methods: A retrospective cohort study was conducted on inpatients with DNSIs admitted to the Department of Otolaryngology, Head and Neck Surgery, Affiliated Hospital of Qingdao University from March 2013 to February 2021. Patients were divided into surgical and non-surgical groups based on whether they had surgery or not. Information collected included demographic data, disease-related signs and symptoms, treatment history, systemic comorbidities, imaging data and laboratory indicators. Hypothesis testing, univariate Logistic regression and multivariate Logistic regression were used for data processing. Resuts A total of 61 patients were included, including 37 males and 24 females, aged 6-96 years. There were 35 cases (57.4%) in the surgical group and 26 cases (42.6%) in the non-surgical group. Multivariate analysis showed that risk factors for surgery as followings: neck dyskinesia (OR=0.03, 95%CI: 0.00-0.24), dysphagia (OR=0.10, 95%CI: 0.02-0.72), serum white blood cell count≥16.74×109/L (OR=1.18, 95%CI: 1.01-1.39) and interspace gas (OR=0.03, 95%CI: 0.00-0.30). Conclusion: Clinicians should be alert to these risk factors for surgery in the course of treatment and timely surgical treatment for patients who meet the conditions.

Effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on proteomics and autophagy in mice with type 2 diabetes mellitus induced by high-fat diet coupled with streptozotocin / 中国中药杂志

To compare the pancreatic proteomics and autophagy between Rehmanniae Radix-and Rehmanniae Radix Praeparata-treated mice with type 2 diabetes mellitus(T2DM). The T2DM mouse model was established by high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days). The mice were then randomly assigned into a control group, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) catalpol groups, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) 5-hydroxymethyl furfuraldehyde(5-HMF) groups, and a metformin(250 mg·kg~(-1)) group. In addition, a normal group was also set and each group included 8 mice. The pancreas was collected after four weeks of administration and proteomics tools were employed to study the effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on protein expression in the pancreas of T2DM mice. The expression levels of proteins involved in autophagy, inflammation, and oxidative stress response in the pancreatic tissues of T2DM mice were determined by western blotting, immunohistochemical assay, and transmission electron microscopy. The results showed that the differential proteins between the model group and Rehmanniae Radix/Rehmanniae Radix Prae-parata group were enriched in 7 KEGG pathways, such as autophagy-animal, which indicated that the 7 pathways may be associated with T2DM. Compared with the control group, drug administration significantly up-regulated the expression levels of beclin1 and phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR and down-regulated those of the inflammation indicators, Toll-like receptor-4(TLR4) and Nod-like receptor protein 3(NLRP3), in the pancreas of T2DM mice, and Rehmanniae Radix showed better performance. In addition, the expression levels of inducible nitric oxide synthase(iNOS), nuclear factor erythroid 2-related factor 2(Nrf2), and heine oxygenase-1(HO-1) in the pancreas of T2DM mice were down-regulated after drug administration, and Rehmanniae Radix Praeparata demonstrated better performance. The results indicate that both Rehmanniae Radix and Rehmanniae Radix Praeparata can alleviate the inflammatory symptoms, reduce oxidative stress response, and increase the autophagy level in the pancreas of T2DM mice, while they exert the effect on different autophagy pathways.

Data mining in traditional Chinese medicine product quality review / 中国中药杂志

The traditional Chinese medicine(TCM) enterprises have accumulated a large amount of product quality review(PQR) data. Mining these data can reveal the hidden knowledge in production and helps improve pharmaceutical manufacturing technology. However, there are few studies involving the mining of PQR data and thus enterprises lack the guidance to analyze the data. This study proposed a method to mine the PQR data, which consisted of 4 functional modules: data collection and preprocessing, risk classification of variables, risk evaluation by batches, and the regression analysis of quality. Further, we carried out a case study of the formulation process of a TCM product to illustrate the method. In the case study, the data of 398 batches of products during 2019-2021 were collected, which contained 65 process variables. The risks of variables were classified according to the process performance index. The risk of each batch was analyzed through short-term and long-term evaluation, and the critical variables with the strongest impact on the product quality were identified by partial least square regression. The results showed that 1 variable and 13 batches were of high risk, and the critical process variable was the quality of the intermediates. The proposed method enables enterprises to comprehensively mine the PQR data and helps to enhance the process understanding and improve the quality control.

Application of augmented reality navigation in laparoscopic and robot-assisted liver surgery / 中华外科杂志

In recent years, laparoscopic surgery and robotic surgery have been widely used, and various intraoperative image navigation systems have also developed rapidly. However, the liver itself has a complex vessel and duct system, which increase the difficulty of liver surgery. The augmented reality image navigation system combines the three-dimensional reconstructed image of the liver with the real liver anatomy, which presents the specific relationship between the tumor location and the surrounding vessels for the surgeon. Compared with other intraoperative image navigation methods, augmented reality has its unique advantages. This paper provides an overview of current advances in registration technology in augmented reality image navigation system, and focuses on its applications in liver surgery, including laparoscopic surgery and robotic surgery. Finally, the technological problems and difficulties still faced at present are summarized, and future directions worth studying in this field are proposed.

Clinical evaluation of platelet-rich plasma in the treatment of early and middle stage knee osteoarthritis under 3.0T MRI T2 mapping sequence / 中华外科杂志

Objective: To quantitatively evaluate the clinical effect of platelet-rich plasma(PRP) intra-articular injection for early and middle stage knee osteoarthritis(KOA) treatment by 3.0T MRI T2 mapping sequence. Methods: Clinical data of 26 patients with early or middle stage KOA who received treatment from April to December 2021 at Department of Orthopaedic Surgery,the Second Affiliated Hospital,Zhengzhou University were retrospectively analyzed. In total, 8 patients were male and 18 were female,with age of (66.4±12.0)years(range:51 to 94 years). Four patients were bilateral KOA and 22 patients were unilateral KOA.All patients received PRP intra-articular injection. Patients underwent 3.0T MRI T2 mapping sequence scanning pre-treatment,3-month-after and 6-month-after treatment respectively. Those were used to measure and compare T2 values of medial and lateral femoral articular surface and patellofemoral articular surface. Visual analogue scale(VAS) and Western Ontario and McMaster Osteoarthritis Index (WOMAC) score were recorded and evaluated. The results were analyzed using repeated measure ANOVA followed by Bonferroni multiple comparison test.The correlation between WOMAC scores and T2 values at pre-treatment and 6 months post-treatment was analyzed using Pearson correlation test. Results: After treatment, the patients' International Cartilage Regeneration＆Joint Preservation Society(ICRS) classification were partly improved(one case improved from grade Ⅲ to grade Ⅱ, one case improved from grade Ⅱ to grade Ⅰ),and all patients generally improved after treatment in clinical symptoms. Compared with pre-treatment,VAS and WOMAC scores of grade Ⅰ,Ⅱ,and Ⅲ of 6-month after treatment were declined significantly(all P<0.05).The T2 values of articular cartilage declined to varying degrees(the decrease in T2 values was about 2.06 ms in grade Ⅰ, 2.66 ms in grade Ⅱ, and 3.72 ms in grade Ⅲ).Three-month (VAS:4.8±1.3,WOMAC:21.5±4.0) and 6-month (VAS:4.2±1.4,WOMAC:17.2±2.9) after treatment, the VAS and WOMAC score were significantly higher than those before treatment (VAS:6.0±1.2, WOMAC:29.0±2.3) (F=48.846, F=346.746;both P<0.01). Multiple comparisons showed a statistically significant difference between pre-treatment and post-treatment VAS (P<0.01) and it also was significantly different between 3-month and 6-month post-treatment (P<0.01).At 3- and 6-month after treatment,WOMAC scores were significantly different from before treatment.And it also was significantly different between 3-month and 6-month post-treatment (P<0.01).There was a statistically significant improvement in T2 values of patellofemoral articular surface, medial and lateral femoral articular surface at pre-treatment((44.64±4.02)ms,(44.17±3.64)ms and(43.53±3.91)ms) and 3-month ((43.19±3.91)ms,(43.24±3.34)ms and (42.47±3.80)ms), 6-month ((41.49±3.64)ms,(41.83±3.15)ms and (41.10±3.42)ms) after treatment(F=148.845,F=73.657,F=86.268;all P<0.01).The results of the multiple comparisons showed a statistically significant difference in the T2 values of medial and lateral femoral articular surface and patellofemoral articular surface at each time point(all P<0.01).The Pearson correlation analysis suggested that the WOMAC score at pre-treatment was positively correlated with the medial condyle (r=0.856,P<0.01) and the patellofemoral joint surface T2 values (r=0.840,P<0.01);The WOMAC score at 6-month post-treatment was positively correlated with the medial condyle (r=0.731,P<0.01) and the patellofemoral joint surface T2 values (r=0.691,P<0.01). Conclusions: In the treatment of early and mid-stage KOA,MRI T2 mapping sequences are able to indicate the integrity of cartilage morphology and quantitatively evaluate cartilage repair. PRP has a good therapeutic effect on cartilage repair and reconstruction.

Changes and clinical significance of erythrocyte lifespan in megaloblastic anemia / 中华内科杂志

Objective: To investigate the lifespan of erythrocytes in megaloblastic anemia (MA) patients. Methods: A prospective cohort study analysis. Clinical data from 42 MA patients who were newly diagnosed at the Department of Hematology, Lanzhou University Second Hospital from January 2021 to August 2021 were analyzed, as were control data from 24 healthy volunteers acquired during the same period. The carbon monoxide breath test was used to measure erythrocyte lifespan, and correlations between erythrocyte lifespan and laboratory test indexes before and after treatment were calculated. Statistical analysis included the t-test and Pearson correlation. Results: The mean erythrocyte lifespan in the 42 newly diagnosed MA patients was (49.05±41.60) d, which was significantly shorter than that in the healthy control group [(104.13±42.62) d; t=5.13,P=0.001]. In a vitamin B12-deficient subset of MA patients the mean erythrocyte lifespan was (30.09±15.14) d, and in a folic acid-deficient subgroup it was (72.00±51.44) d, and the difference between these two MA subsets was significant (t=3.73, P=0.001). The mean erythrocyte lifespan after MA treatment was (101.28±33.02) d, which differed significantly from that before MA treatment (t=4.72, P=0.001). In MA patients erythrocyte lifespan was positively correlated with hemoglobin concentration (r=0.373), and negatively correlated with total bilirubin level (r=-0.425), indirect bilirubin level (r=-0.431), and lactate dehydrogenase level (r=-0.504) (all P<0.05). Conclusions: Erythrocyte lifespan was shortened in MA patients, and there was a significant difference between a vitamin B12-deficient group and a folic acid-deficient group. After treatment the erythrocyte lifespan can return to normal. Erythrocyte lifespan is expected to become an informative index for the diagnosis and treatment of MA.

4E-BP1 counteracts human mesenchymal stem cell senescence via maintaining mitochondrial homeostasis

Although the mTOR-4E-BP1 signaling pathway is implicated in aging and aging-related disorders, the role of 4E-BP1 in regulating human stem cell homeostasis remains largely unknown. Here, we report that the expression of 4E-BP1 decreases along with the senescence of human mesenchymal stem cells (hMSCs). Genetic inactivation of 4E-BP1 in hMSCs compromises mitochondrial respiration, increases mitochondrial reactive oxygen species (ROS) production, and accelerates cellular senescence. Mechanistically, the absence of 4E-BP1 destabilizes proteins in mitochondrial respiration complexes, especially several key subunits of complex III including UQCRC2. Ectopic expression of 4E-BP1 attenuates mitochondrial abnormalities and alleviates cellular senescence in 4E-BP1-deficient hMSCs as well as in physiologically aged hMSCs. These f indings together demonstrate that 4E-BP1 functions as a geroprotector to mitigate human stem cell senescence and maintain mitochondrial homeostasis, particularly for the mitochondrial respiration complex III, thus providing a new potential target to counteract human stem cell senescence.

Comparative Study of the Two High-Efficient Strategies for in vitro Generation of Human Umbilical Cord Blood-derived Natural Killer Cells / 中国实验血液学杂志

OBJECTIVE@#To explore the similarities and variations of biological phenotype and cytotoxicity of human umbilical cord blood natural killer cells (hUC- NK) after human umbilical cord blood-derived mononuclear cells (hUC-MNC) activated and expanded by two in vitro high-efficient strategies.@*METHODS@#Umbilical cord blood mononuclear cells (MNC) from healthy donor were enriched by Ficoll-based density gradient centrifugation. Then, the phenotype, subpopulations, cell viability and cytotoxicity of NK cells derived from Miltenyi medium (denoted as M-NK) and X-VIVO 15 (denoted as X-NK) were compared using a "3IL" strategy.@*RESULTS@#After a 14-day's culture, the contents of CD3-CD56+ NK cells were elevated from 4.25%±0.04% (d 0) to 71%±0.18% (M-NK) and 75.2%±1.1% (X-NK) respectively. Compared with X-NK group, the proportion of CD3+CD4+ T cells and CD3+CD56+ NKT cells in M-NK group decreased significantly. The percentages of CD16+, NKG2D+, NKp44+, CD25+ NK cells in X-NK group was higher than those in the M-NK group, while the total number of expanded NK cells in X-NK group was half of that in M-NK group. There were no significant differences between X-NK and M-NK groups in cell proliferation and cell cycle, except for the lower percentage of Annexin V+ apoptotic cells in M-NK group. Compared with X-NK group, the proportion of CD107a+ NK cells in M-NK group were higher under the same effector-target ratio (E∶T) (P<0.05).@*CONCLUSION@#The two strategies were adequate for high-efficient generation of NK cells with high level of activation in vitro, however, there are differences in biological phenotypes and tumor cytotoxicity.

Construction and optimization of a novel plasma membrane model for membrane affinity assay based on polydiacetylene vesicles / 药学学报

Most drugs need to interact with cell membrane to reach the biological target, so that membrane affinity assay is an important early screening step in drug discovery. However, at present, the traditional oil-water distribution method is still used, a new, simple and accurate method for membrane affinity assay is urgently needed. In this study, according to the colorimetric principle, a new assay model based on polydiacetylene vesicles was optimized through a series of experiments including different concentrations of vesicle solution, temperature, or pH reaction environment. On this basis, tetracaine hydrochloride, 2-methylimidazole and histamine were used as model drugs to measure the membrane affinity constants and verify the between-batch precision of the optimized assay model (relative standard deviation less than 5%). In addition, polydiacetylene vesicles were stable for up to 180 days, demonstrating the potential application of the assay model. This strategy is simple, stable, reliable, with high reproducibility, low cost and easy to promote, which provided a new tool and a new direction for the high-throughput assay of membrane affinity.

Research on monitoring method of dripping pills dripping process based on laser detection and multivariate data analysis technology / 药学学报

At present, the digitalization and intelligence level of dripping pills production process is low, and there is a lack of process monitoring methods, which makes it difficult to effectively control the quality of dripping pills. Therefore, this paper proposed an online monitoring method for the dripping process of dripping pills based on laser detection technology and multivariate data analysis (MVDA) technology. Firstly, the width data of the falling droplets during the dripping process of the dripping pills were collected by the laser detector at a high frequency. Secondly, based on the width data, the nodes were selected for each droplet and the features were extracted. Then, the principal component analysis (PCA) model was established based on the feature dataset under normal process conditions, and Hotelling's T2 or DModX statistic was selected to determine whether the droplets in the dripping process were abnormal, and the abnormalities were classified and diagnosed by the principal component score map combined with K-nearest neighbor (KNN) algorithm. In this study, the feasibility of this method was investigated by taking the dripping process of Ginkgo biloba leaf dripping pills as an example. The results showed that the obtained model has good detection and diagnosis ability for abnormal valve opening, abnormal liquid temperature, and abnormal liquid volume. This method can provide some reference for the industrial production of dripping pills.

Effect of modified Chufeng Yisun Decoction on ocular surface inflammation after pterygium surgery / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effect of modified Chufeng Yisun Decoction on ocular surface inflammation after pterygium surgery.METHODS: A total of 60 patients(60 eyes)with primary pterygium who underwent pterygium surgery were randomly divided into control group and study group, with 30 cases(30 eyes)in each group. In the control group, patients were treated with pranoprofen eye drops, tobramycin dexamethasone eye drops, and deproteinized calf blood extract eye gel after the surgery. In the study group, patients were treated by oral modified Chufeng Yisun Decoction in addition to the treatments in the control group. The changes of ocular irritation symptoms, ocular inflammatory signs, tear interleukin 6(IL-6)levels, and tear ferning test(TFT)of patients in the two groups were assessed.RESULTS: The visual analogue scale(VAS)in patients of both groups was significantly lower at 2d and 1wk after the surgery than that at 1d after the surgery(all P&#x0026;#x003C;0.01), and the VAS of the study group was significantly better than that of the control group at 2d and 1wk after surgery(P&#x0026;#x003C;0.01). The ocular signs integrals(OSI)and TFT results of both groups at 1wk were significantly lower than those at 1d after the surgery(all P&#x0026;#x003C;0.01), and the OSI and TFT were also lower in the study group than in the control group at 1wk after the surgery(all P&#x0026;#x003C;0.01). In addition, the concentration of tear IL-6 in both groups was significantly lower at 1wk after the surgery than 1d after the surgery(all P&#x0026;#x003C;0.01), and it was also significantly lower in the study group than in the control group at 1wk after the surgery(P&#x0026;#x003C;0.05).CONCLUSION: The combination of Chufeng Yisun Decoction and conventional treatment of western has a better effect on controlling ocular surface inflammation after pterygium surgery.

Low-frequency transcranial magnetic stimulation can relieve depression and improve cognitive functioning among the elderly / 中华物理医学与康复杂志

Objective:To explore any effect of repeated application of low-frequency transcranial magnetic stimulation (rTMS) on depression and the cognition of depressed elderly persons.Methods:Eighty-six elderly persons with depression were randomly divided into an rTMS group and a control group, each of 43. In addition to anti-depressant treatment, the rTMS group was given 20 minutes of 1Hz rTMS daily applied over the right dorsolateral prefrontal cortex, five times a week for 4 weeks. The control group was given sham treatment on the same schedule. Before the experiment and after 1, 2, 3, 4, 6 and 8 weeks of the treatment, depression in both groups was evaluated using the Hamilton Depression Scale (HAMD-24). At the 4- and 8-week evaluations the Wisconsin Card Sorting Test (WCST) and the Trail Making Test Part A (TMT-A) were also administered.Results:Before the treatment there were no significant differences in the 2 groups′ average HAMD or WCST scores. At each subsequent evaluation both groups′ average HAMD score had decreased significantly. After 3 weeks the average HAMD score of the rTMS group consistently remained significantly lower than the control group′s average. At the 4- and 8-week evaluations both groups′ WCST and TMT-A scores had improved significantly compared with before the treatment, with significantly greater improvement in the rTMS group′s average WCST result, though not in their TPT-A result. There was no signi-ficant difference in the incidence of adverse reactions between the 2 groups.Conclusion:As a supplement to antidepressant treatment, right-side low-frequency rTMS can relieve depressive symptoms and improve the cognitive functioning of depressed elderly persons. It is well tolerated with few adverse reactions.

Application of the second derivative-based small monitor unit beam deletion optimization to CyberKnife planning of heads / 中华放射医学与防护杂志

Objective:To investigate the effects of different small monitor unit (MU) beam deletion optimization method in the CyberKnife treatment planning system on the calculated planned dose to brain tumors.Methods:A total of 17 patients with brain metastases treated in our hospital from June, 2021 to February, 2022 were selected for this study. A treatment plan was designed for each patient using the multiPlan system in the CyberKnife VSI system as the group without optimization. To improve the efficiency, the generated original plans should be optimized first by deleting some small MUs, forming an experience group and an optimization group for each patient. For the experience group, beams below 30 MU were deleted according to experience. For the optimization group, beams below the MU value calculated based on the second derivative method were deleted. Finally, the parameters of the two groups were statistically compared. The main evaluation parameters included the node number, the beam number, the total number of MUs, the estimated treatment duration, doses to 2% and 95% planning target volumes (PTV D2 and PTV D95), average dose to PTV ( Dmean), average dose to brain tissue ( Dmean-Brain), conformity index (CI), new conformity index (nCI), gradient index (GI), coverage, and the maximum doses to the brainstem and left and right lens ( Dmax-BS, Dmax-LL, and Dmax-RL), and the average doses to the dose shells 20 mm and 40 mm away from PTV (Shell20 and Shell40). Results:The two optimization method met the requirements for the prescription dose delivery to more than 98% PTV. There were statistical differences in the node number ( H = 7.97, P< 0.05) and estimated treatment duration ( H = 6.60, P < 0.05) among the group without MP optimization, the experience group, and the optimization group, with the estimated treatment duration and node number of the optimization group less than those of the group without MP optimization ( P < 0.05). There were no statistically significant differences in other parameters among the three groups ( P > 0.05). The PTV was moderately positively correlated with the treatment duration ( r=0.79, P < 0.01) and beam number ( r=0.78, P < 0.01) of the experience group, and was also moderately positively correlated with the treatment duration ( r=0.69, P < 0.01) and beam number ( r=0.71, P < 0.01) of the optimization group. Conclusions:For the CyberKnife planning of heads, the small MU beam deletion optimization method based on the second derivative can further shorten the treatment duration while ensuring no significant differences in the distribution of doses to organs at risk and targets. Moreover, this method is more effective in optimizing the plans for a large PTV volume.

Clinical Value of Translocator Protein Gene in Evaluating the Efficacy of FLT3-ITD/DNMT3A R882 Double-Mutated Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To observe the clinical significance of translocator proteins (TSPO) gene in the treatment of FLT3-ITD/DNMT3A R882 double-mutated acute myeloid leukemia (AML).@*METHODS@#Seventy-six patients with AML hospitalized in the Department of Hematology of the Affiliated People's Hospital of Ningbo University from June 2018 to June 2020 were selected, including 34 patients with FLT3-ITD mutation, 27 patients with DNMT3A R882 mutation, 15 patients with FLT3-ITD/DNMT3A R882 double mutation, as well as 19 patients with immune thrombocytopenia (ITP) hospitalized during the same period as control group. RNA was routinely extracted from 3 ml bone marrow retained during bone puncture, and TSPO gene expression was detected by transcriptome sequencing (using 2-deltadeltaCt calculation).@*RESULTS@#The expression of TSPO gene in FLT3-ITD group and DNMT3A R882 group at first diagnosis was 2.02±1.04 and 1.85±0.76, respectively, which were both higher than 1.00±0.06 in control group, but the differences were not statistically significant (P=0.671, P=0.821). The expression of TSPO gene in the FLT3-ITD/DNMT3A R882 group was 3.98±1.07, wich was significantly higher than that in the FLT3-ITD group and DNMT3A R882 group, the differences were statistically significant (P=0.032, P=0.021). The expression of TSPO gene in patients who achieved complete response after chemotherapy in the FLT3-ITD/DNMT3A R882 group was 1.19±0.87, which was significantly lower than that at first diagnosis, and the difference was statistically significant (P=0.011).@*CONCLUSION@#TSPO gene may be used as an indicator of efficacy in FLT3-ITD /DNMT3A R882 double-mutated AML.

High-throughput "read-on-ski" automated imaging and label-free detection system for toxicity screening of compounds using personalised human kidney organoids / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Organoid models are used to study kidney physiology, such as the assessment of nephrotoxicity and underlying disease processes. Personalized human pluripotent stem cell-derived kidney organoids are ideal models for compound toxicity studies, but there is a need to accelerate basic and translational research in the field. Here, we developed an automated continuous imaging setup with the "read-on-ski" law of control to maximize temporal resolution with minimum culture plate vibration. High-accuracy performance was achieved: organoid screening and imaging were performed at a spatial resolution of 1.1 μm for the entire multi-well plate under 3 min. We used the in-house developed multi-well spinning device and cisplatin-induced nephrotoxicity model to evaluate the toxicity in kidney organoids using this system. The acquired images were processed via machine learning-based classification and segmentation algorithms, and the toxicity in kidney organoids was determined with 95% accuracy. The results obtained by the automated "read-on-ski" imaging device, combined with label-free and non-invasive algorithms for detection, were verified using conventional biological procedures. Taking advantage of the close-to-in vivo-kidney organoid model, this new development opens the door for further application of scaled-up screening using organoids in basic research and drug discovery.

MBOAT1 homozygous missense variant causes nonobstructive azoospermia / 亚洲男科学杂志(英文版)

Nonobstructive azoospermia (NOA) is a common cause of infertility and is defined as the complete absence of sperm in ejaculation due to defective spermatogenesis. The aim of this study was to identify the genetic etiology of NOA in an infertile male from a Chinese consanguineous family. A homozygous missense variant of the membrane-bound O-acyltransferase domain-containing 1 (MBOAT1) gene (c.770C>T, p.Thr257Met) was found by whole-exome sequencing (WES). Bioinformatic analysis also showed that this variant was a pathogenic variant and that the amino acid residue in MBOAT1 was highly conserved in mammals. Quantitative polymerase chain reaction (Q-PCR) analysis showed that the mRNA level of MBOAT1 in the patient was 22.0% lower than that in his father. Furthermore, we screened variants of MBOAT1 in a broader population and found an additional homozygous variant of the MBOAT1 gene in 123 infertile men. Our data identified homozygous variants of the MBOAT1 gene associated with male infertility. This study will provide new insights for researchers to understand the molecular mechanisms of male infertility and will help clinicians make accurate diagnoses.

Mechanism Analysis of Strengthening Anti-cerebral Ischemia Injury of Chuanxiong Rhizoma Processed with Wine Based on UHPLC-Q-Orbitrap HRMS and Integrated Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo analyze the differential components in water extract of Chuanxiong Rhizoma before and after processing with wine， and to explore the molecular mechanism of Chuanxiong Rhizoma processed with wine in enhancing anti-cerebral ischemia injury. MethodUltra high performance liquid chromatography tandem quadrupole orbitrap high resolution mass spectrometry （UHPLC-Q-Orbitrap HRMS） was used to qualitatively analyze the main chemical components in water extract of Chuanxiong Rhizoma based on the spectral information of compound， comparison of reference substance and references. The chemical pattern recognition method was used to screen the differential components of Chuanxiong Rhizoma before and after processing. Based on these differential components， the potential targets of differential components were predicted by online databases， and the related targets of cerebral ischemia were searched. Cytoscape 3.6.0 was used to establish the network diagram of differential components-action targets-diseases of Chuanxiong Rhizoma processed with wine. The protein-protein interaction （PPI） network of intersection targets was constructed by STRING 11.5. The potential targets of differential components against cerebral ischemia were analyzed by Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis through DAVID 6.8. At the same time， the chemical compounds with high relative content and increased peak area after wine processing were docked with their corresponding targets to verify the mechanism of enhanced effect after wine processing. ResultA total of 71 chemical components were identified from Chuanxiong Rhizoma， 34 differential components and 603 potential targets were screened out. At the same time， a total of 769 disease targets and 60 intersection targets were obtained. Seven key targets were identified through PPI network analysis， including JUN， signal transducer and activator of transcription 3 （STAT3）， mitogen-activated protein kinase 3 （MAPK3）， interleukin-1β （IL-1β）， vascular endothelial growth factor A （VEGFA）， Caspase-3 （CASP3） and mtrix metalloproteinase 9 （MMP9）. Tumor necrosis factor （TNF） signaling pathway was the main differential signaling pathway. The results of molecular docking showed that differential components （senkyunolide K， senkyunolide F， 3-n-butylphthalide， Z，Z′-6，8′，7，3′-diligustilide， ferulic acid and Z-ligustilide） and corresponding targets had good binding activities. ConclusionThe synergistic mechanism of Chuanxiong Rhizoma processed with wine may be related to the enhanced inhibitory effect of inflammatory reaction.

Comparison of dynamic hip screw plus anti-rotation screw versus three cannulated compression screws in treatment of femoral neck fractures with comminuted posterior wall / 中华创伤骨科杂志

Objective:To compare the efficacy of 2 fixation modes [dynamic hip screw (DHS) plus anti-rotation screw versus 3 cannulated compression screws (CCS)] in the treatment of femoral neck fractures complicated with comminuted posterior wall.Methods:The data were analyzed retrospectively of the 109 patients who had been treated for femoral neck fractures complicated with comminuted posterior wall at Department of Orthopaedics, Shenzhen Hospital, University of Chinese Academy of Sciences from February 2017 to December 2019. They were divided into 2 groups according to 2 fixation modes. There were 42 males and 16 females with an age of 48.5 (40.0, 55.3) years in CCS group of 58 cases subjected to fixation with 3 CCSs; there were 31 males and 20 females with an age of 47.0 (38.0, 53.0) years in DHS group of 51 cases subjected to fixation with DHS plus anti-rotation screw. The length of incision, operation time, intraoperative bleeding, weight-bearing time for the affected limb, visual analog scale (VAS), hip Harris score, and incidence of postoperative complications were compared between the 2 groups.Results:The comparison of preoperative general data between the 2 groups was not statistically significant, showing comparability between groups ( P>0.05). In the CCS group, the incision length [3.0 (2.9, 4.5) cm] and operation time [90.0 (73.8, 125.0) min] were significantly shorter than those in the DHS group [10.0 (9.0, 12.0) cm and 135.0 (110.0, 165.0) min], the intraoperative bleeding [40.0 (10.0, 100.0) mL] was significantly less than that in the DHS group [200.0 (150.0, 300.0) mL], the partial and complete weight-bearing durations of the affected limb [12.0 (12.0, 13.0) weeks and 24.0 (21.0, 25.0) weeks] were significantly longer than those in the DHS group [11.0 (10.0, 12.0) weeks and 19.0 (18.0, 20.0) weeks], and the perioperative VAS pain score [2.0 (2.0, 3.0) points] was significantly lower than that in the DHS group [5.0 (4.0, 6.0) points], but the incidence of follow-up complications [56.9% (33/58)] was significantly higher than that in the DHS group [33.3% (17/51)] (all P<0.05). There was no significant difference between the DHS group and the CCS group in the excellent and good rate of Harris hip score at one year after operation [94.1% (48/51) versus 91.4% (53/58)] ( P>0.05). Conclusions:In the treatment of femoral neck fractures complicated with comminuted posterior wall, DHS plus anti-rotation screw and 3 CCSs can both result in fine therapeutic outcomes but a relatively high incidence of complications at late follow-up. However, the former fixation mode can shorten the weight-bearing time for the affected limb and reduce complications but is more invasive than the latter fixation mode.