Fosaprepitant Weekly vs Every 3 Weeks for the Prevention of Concurrent Chemoradiotherapy-Induced Nausea and Vomiting: A Pilot Randomized Clinical Trial.

Importance: Unlike substantial evidence in the prevention of chemotherapy-induced nausea and vomiting (CINV), research in the prevention of nausea and vomiting caused by concurrent chemoradiotherapy (CCRT) is currently lacking. Objective: To compare the efficacy and safety of fosaprepitant weekly vs every 3 weeks for the prevention of nausea and emesis caused by CCRT among patients with nasopharyngeal carcinoma. Design, Setting, and Participants: This pilot randomized clinical trial was conducted at a single cancer center from November 24, 2020, to July 26, 2021, among patients with nasopharyngeal carcinoma who had achieved CINV control after 2 to 3 cycles of induction chemotherapy. Efficacy analyses were performed in the intention-to-treat population. Data were analyzed on November 4, 2022. Interventions: Eligible patients were randomly assigned (1:1) to receive fosaprepitant either weekly or every 3 weeks. Main Outcomes and Measures: The primary end point was the proportion of patients with sustained complete response (defined as no emesis and no rescue therapy) during CCRT. Secondary end points were sustained no emesis, no nausea, no significant nausea, mean time to first emetic episode, quality of life, and 1-year progression-free survival (PFS). Results: A total of 100 patients (mean [SD] age, 46.6 [10.9] years; 83 [83.0%] male) who had achieved CINV control after induction chemotherapy were randomly assigned to receive fosaprepitant weekly (50 patients) or every 3 weeks (50 patients). There was no significantly significant difference in cumulative risk of emesis or rescue therapy in the group that received weekly fosaprepitant compared with those who received fosaprepitant every 3 weeks (subhazard ratio, 0.66 [95% CI, 0.43-1.02]; P = .06). The proportion of patients with sustained no emesis (38% vs 14%; P = .003) or no significant nausea (92% vs 72%; P = .002) was significantly higher in the group that received fosaprepitant weekly vs those who received fosaprepitant every 3 weeks. Treatments were well tolerated. Patients in the weekly group had improved scores for multiple quality-of-life measures. There was no significant difference in survival outcomes between groups (91.8% vs 93.7%; P = .99). In the mean brainstem dose subgroups, a possible treatment interaction effect was observed in sustained complete response (mean brainstem dose ≥36 Gy: hazard ratio [HR], 0.32 [95% CI, 0.15-0.69]; mean brainstem dose <36 Gy: HR, 0.95 [95% CI, 0.55-1.63]) and sustained no emesis (mean brainstem dose ≥36 Gy: HR, 0.21 [95% CI, 0.08-0.53]; mean brainstem dose <36 Gy: HR, 0.73 [95% CI, 0.41-1.28]). Conclusions and Relevance: In this pilot randomized clinical trial, there was no statistically significant difference in the complete response primary end point, but patients receiving weekly fosaprepitant were less likely to experience emesis compared with those who received fosaprepitant every 3 weeks, especially in the subgroup with a mean brainstem dose of 36 Gy or more. Weekly fosaprepitant was well tolerated and improved quality of life of patients without compromising survival. Trial Registration: ClinicalTrials.gov Identifier: NCT04636632.

A novel recombinant human microplasminogen induced complete posterior vitreous detachment without morphological change of retina in juvenile rabbits.

Vitreomacular traction syndrome results from persistent vitreoretinal adhesions in the setting of partial posterior vitreous detachment (PVD). Vitrectomy and reattachment of retina is an effective therapeutic approach. The adhesion between vitreous cortex and internal limiting membrane (ILM) of the retina is stronger in youth, which brings difficulties to induce PVD in vitrectomy. Several clinical investigations demonstrated that intravitreous injection of plasmin before vitrectomy could reduce the risk of detachment. In our study, a novel recombinant human microplasminogen (rhµPlg) was expressed by Pichia pastoris. Molecular docking showed that the binding of rhµPlg with tissue plasminogen activator (t-PA) was similar to plasminogen, suggesting rh µPlg could be activated by t-PA to generate microplasmin (µPlm). Moreover, rhµPlg had higher catalytic activity than plasminogen in amidolytic assays. Complete PVD was found at vitreous posterior pole of 125 µg rhµPlg-treated eyes without morphological change of retina in juvenile rabbits via intraocular injection. Our results demonstrate that rhµPlg has a potential value in the treatment of vitreoretinopathy.

Evaluation of diagnostic efficacy of NRP-1/CD304 in hematological diseases.

BACKGROUND: Previous studies had explored the diagnostic or prognostic value of NRP-1/CD304 in blastic plasmacytoid dendritic cell neoplasm (BPDCN), acute myeloid leukemia (AML), and B-cell acute lymphoblastic leukemia (B-ALL), whereas the expression and application value of NRP-1/CD304 in other common hematological diseases have not been reported. METHODS: Bone marrow samples from 297 newly diagnosed patients with various hematological diseases were collected to detect the expression of NRP-1/CD304 by flow cytometry (FCM). The diagnostic efficacy of NRP-1/ CD304-positive diseases was analyzed by receiver operating characteristic (ROC) curve, and the area under the ROC curve (AUC) was compared. RESULTS: In the research cohort, the total positive rate of NRP-1/CD304 was 14.81% (44/297), mainly distributed in BPDCN (100%, 6/6), B-ALL (48.61%, 35/72), and AML (4.48%, 3/67), with statistically significant differences (p < 0.01). Other diseases, such as T-cell acute lymphoblastic leukemia (T-ALL), B-cell non-Hodgkin lymphoma (B-NHL), T/NK-cell lymphoma and plasma cell neoplasms, did not express NRP-1/CD304. The AUC of NRP-1/CD304 was 0.936 (95% CI 0.898-0.973), 0.723 (95% CI 0.646-0.801), and 0.435 (95% CI 0.435) in BPDCN, B-ALL and AML, respectively. Besides, CD304 was commonly expressed in B-ALL with BCR-ABL1 gene rearrangement (p = 0.000), and CD304 expression was positively correlated with CD34 co-expression (p = 0.009) and CD10 co-expression (p = 0.007). CONCLUSIONS: NRP-1/CD304 is only expressed in BPDCN, B-ALL and AML, but not in other common hematological diseases. This indicates that NRP-1/CD304 has no obvious diagnostic and follow-up study value in hematological diseases other than BPDCN, B-ALL, and AML.

Hyperfractionation compared with standard fractionation in intensity-modulated radiotherapy for patients with locally advanced recurrent nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial.

BACKGROUND: Reirradiation in standard fractionation for locally advanced recurrent nasopharyngeal carcinoma after a previous course of high-dose radiotherapy is often associated with substantial late toxicity, negating its overall benefit. We therefore aimed to investigate the efficacy and safety of hyperfractionation compared with standard fractionation in intensity-modulated radiotherapy. METHODS: This multicentre, randomised, open-label, phase 3 trial was done in three centres in Guangzhou, China. Eligible patients were aged 18-65 years with histopathologically confirmed undifferentiated or differentiated, non-keratinising, advanced locally recurrent nasopharyngeal carcinoma. Participants were randomly assigned (1:1) to either receive hyperfractionation (65 Gy in 54 fractions, given twice daily with an interfractional time interval of at least 6 h) or standard fractionation (60 Gy in 27 fractions, given once a day). Intensity-modulated radiotherapy was used in both groups. A computer program generated the assignment sequence and randomisation was stratified by treatment centre, recurrent tumour stage (T2-T3 vs T4), and recurrent nodal stage (N0 vs N1-N2), determined at the time of randomisation. The two primary endpoints were the incidence of severe late complications defined as the incidence of grade 3 or worse late radiation-induced complications occurring 3 months after the completion of radiotherapy until the latest follow-up in the safety population, and overall survival defined as the time interval from randomisation to death due to any cause in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02456506. FINDINGS: Between July 10, 2015, and Dec 23, 2019, 178 patients were screened for eligibility, 144 of whom were enrolled and randomly assigned to hyperfractionation or standard fractionation (n=72 in each group). 35 (24%) participants were women and 109 (76%) were men. After a median follow-up of 45·0 months (IQR 37·3-53·3), there was a significantly lower incidence of grade 3 or worse late radiation-induced toxicity in the hyperfractionation group (23 [34%] of 68 patients) versus the standard fractionation group (39 [57%] of 68 patients; between-group difference -23% [95% CI -39 to -7]; p=0·023). Patients in the hyperfractionation group had better 3-year overall survival than those in the standard fractionation group (74·6% [95% CI 64·4 to 84·8] vs 55·0% [43·4 to 66·6]; hazard ratio for death 0·54 [95% CI 0·33 to 0·88]; p=0·014). There were fewer grade 5 late complications in the hyperfractionation group (five [7%] nasal haemorrhage) than in the standard fractionation group (16 [24%], including two [3%] nasopharyngeal necrosis, 11 [16%] nasal haemorrhage, and three [4%] temporal lobe necrosis). INTERPRETATION: Hyperfractionated intensity-modulated radiotherapy could significantly decrease the rate of severe late complications and improve overall survival among patients with locally advanced recurrent nasopharyngeal carcinoma. Our findings suggest that hyperfractionated intensity-modulated radiotherapy could be used as the standard of care for these patients. FUNDING: Key-Area Research and Development of Guangdong Province, the National Natural Science Foundation of China, the Special Support Program for High-level Talents in Sun Yat-sen University Cancer Center, the Guangzhou Science and Technology Plan Project, and the National Ten Thousand Talents Program Science and Technology Innovation Leading Talents, Sun Yat-Sen University Clinical Research 5010 Program.

A preliminary experience of retroperitoneal approach by partial resection of the tenth rib for repairing Crawford type Ⅳ thoracoabdominal aortic aneurysm and complex abdominal aortic aneurysm / 中华普通外科杂志

Objective:To evaluate a surgical approach for partial resection of the tenth rib through a retroperitoneal approach for the exposure of Crawford type IV thoracoabdominal aortic aneurysm and complex abdominal aortic aneurysm from 2014 to 2019.Methods:A retrospective analysis was conducted on clinical data and follow-up results of 7 patients who underwent treatment for Crawford type IV thoracoabdominal aortic aneurysm and complex abdominal aortic aneurysm through partial resection of the tenth rib via a retroperitoneal approach.Results:One case (14.3%) had associated Marfan syndrome, and 5 cases (71.4%) underwent left renal artery reconstruction. None of the patients experienced severe complications such as cardiopulmonary complications or renal failure postoperatively, and there was no statistically significant difference in serum creatinine levels between preoperative and postoperative stages during hospitalization ( P=0.205). Follow-up examinations showed no long-term vascular stenosis. Conclusions:Partial resection of the tenth rib through a retroperitoneal approach can avoid incisions of the pleura and diaphragm. It allows for the exposure of the aorta below the diaphragm and has the ability to treat aortic diseases below the diaphragm with smaller incisions and lower complication risks.

Mechanism of cucurbitacin B suppresses proliferation of hepatocellular carcinoma Huh-7 cells via inducing ferroptosis / 中国药理学通报

Aim To study the effects of cucurbitacin B (Cu B) on proliferation of hepatocellular carcinoma Huh-7 cells and its mechanism. Methods CCK-8 was used to detect the survival rate of Huh-7 cells with different concentrations of Cu B. Huh-7 cells were treated with Cu B (0. 5, 1, 2 njnol; L

Effect of NMDA receptor blocker in relieving HIV-1/gp120 induced learning and memory disorder in rats and its mechanism / 中国药理学通报

Aim: To investigate the alleviating effect of NMDA receptor blocking on learning and memory impairment induced by gp120 in rats and its mechanism. Methods: (1 ) Thirty-two SD rats were randomly divided into control group, sham operation group, gpl20 group, and gp120 + Memantine group. Except for the control group, the other groups underwent a bilateral hippocampal injection to establish the model of learning and memory impairment in rats. Memantine (10 mg • kg

Evaluating the predictive value of a coagulation-related gene model in glioma.

AIM: The prognosis of glioma, which is the most common and malignant tumor in the central nervous system, requires the identification of additional markers. MATERIAL AND METHODS: The mRNA expression and clinical data of glioma were downloaded from the TCGA and CGGA databases. Coagulation-related genes were downloaded from the KEGG database. The expression model was constructed using LASSO regression. The GBM data were divided into high and low-risk expression groups based on the median risk score, and the differences in overall survival and progression-free survival between them were calculated. The prognostic model was further validated using the TCGA-LGG and CGGA glioma databases, respectively. The accuracy of the risk score was calculated by ROC analysis for 1 year and 3 years. RESULTS: Four model genes, namely the SERPINA5, PLAUR, BDKRB1, and PTGIR, were identified, and risk score = SERPINA5*0.126264111304559 + PLAUR*0.288587629696211 + BDKRB1*0.349215422945011 + PTGIR*0.17334527969703, respectively. Based on glioma data from three groups, patients were divided into high and low-risk groups according to the median risk score. The overall survival, progression-free survival, and risk scores of the high-risk score group were worse than the low-risk group. The ROC curve analysis showed that the AUC values of the coagulation-related gene model at 1 year, 3 years, and 5 years were more than 0.65, validating the reliability of the prognostic model. CONCLUSION: This study established the correlation between the coagulation-related gene model and glioma prognosis, providing deeper insight into the mechanism and treatment of glioma.

Ultrasonographic evaluation of diaphragm function in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis.

BACKGROUND: Some studies have reported using ultrasonic evaluations to assess diaphragm function in patients with chronic obstructive pulmonary disease (COPD). However, they have limitations and thus cannot provide strong evidence to support ultrasound evaluations for diaphragm function and dysfunction severity assessments in this patient population. Additionally, quantitative studies on the relationship between ultrasound evaluations and diaphragm function do not exist. Therefore, we performed a systematic review and meta-analysis to explore the usefulness of ultrasonography for evaluating diaphragm function in patients with COPD. METHODS: The Cochrane Library, PubMed, Embase, Web of Science, Chinese Biomedical Literature Database, Wanfang Data, China National Knowledge Network, and Chinese Scientific Journal Database (i.e., VIP) databases were searched for literature about ultrasonic evaluations of diaphragm function in patients with COPD for systematic review. We extracted patient demographic, diaphragm mobility, diaphragm thickness, diaphragm thickening score, and other related parameter data using RevMan 5.3 software for the meta-analysis. RESULTS: We included 13 articles in the systematic review, 8 of which (494 participants) were included in the meta-analysis. The degree of diaphragm offset in patients with COPD was significantly lower than that in healthy controls (weighted mean difference [WMD] = -1.34; 95% confidence interval [CI]: -2.15, 0.53; P < .05). The diaphragm deviation was lower in the severe COPD group than in the mild-to-moderate COPD group (WMD = 0.50; 95% CI: -0.01, 1.01; P = .06), but the difference was not significant. CONCLUSION: Ultrasonography effectively evaluates diaphragm function in patients with COPD. The diaphragm offset can be used as an auxiliary diagnostic index for COPD, which is also related to disease severity.

Role of CaMK II in pancreatic injury in mice with severe acute pancreatitis / 南方医科大学学报

OBJECTIVE@#To investigate the expression of Ca2+/calmodulin-dependent protein kinase II (CaMK Ⅱ) in pancreatic tissues of mice with severe acute pancreatitis (SAP) and explore the protective effect of KN93, a CaMK Ⅱ inhibitor, against pancreatic injury in SAP and the possible mechanism.@*METHODS@#Thirty-six healthy male C57 mice were randomly divided into sham operation group, SAP group, KN93 group and SAP + KN93 group (n=9). Serum and pancreatic tissue samples were collected 24 h after modeling. The pathological changes in the pancreatic tissues were observed using HE staining. Serum lipase and amylase activities and the levels of inflammatory factors were detected using ELISA. Western blotting was used to detect the expressions of CaMK Ⅱ, p-CaMK Ⅱ, p-NF-κB, MAPK and p-MAPK in mouse pancreas.@*RESULTS@#Compared with those in sham operation group, the expressions of p-CaMK Ⅱ, p-NF-κB and p-MAPK were significantly increased in SAP group (P < 0.05). KN93 treatment obviously alleviated pathological injuries of the pancreas in SAP mice, and significantly lowered serum levels of lipase, amylase and inflammatory factors (TNF-α and IL-6) and phosphorylation levels of NF-κB, ERK and MAPK proteins (P < 0.05).@*CONCLUSION@#The activity of CaMK Ⅱ is significantly increased in the pancreatic tissue of SAP mice. KN93 can alleviate pancreatic injury and inflammation in SAP mice possibly through the ERK/MAPK signaling pathway.

Pathogenic detection and molecular tracing of a bacillary dysentery outbreak by Shigella sonnei in Huainan city / 中华预防医学杂志

Objective: To understand the virulence gene and drug resistance profile of Shigella sonnei outbreak in Huainan city, and conduct pathogenic traceability analysis. Methods: Water samples and feces related to an infectious diarrhea outbreak in Huainan city in August 2020 were collected for multiple pathogen detection. Virulence gene, drug sensitivity, pulse-field gel electrophoresis and whole genome sequencing of Shigella isolates were analyzed respectively. Results: 38 strains of Shigella sonnei were detected in 56 samples of mucilage feces with a positive rate 67.86%, and all serotypes were Shigella sonnei Phase I. Three strains of Shigella sonnei were detected by fluorescence PCR in the Gram-negative (GN) bacterial enrichment solution of terminal water and well water. Virulence genes were ipaH positive (38), ipaH/ial (31) and ipaH/ial/sen positive (1), respectively. The drug resistance spectrum showed that 9 of 14 antibiotics were 100% resistant, and only imipenem, chloramphenicol, ceftazidime and ciprofloxacin were effective drugs. XbaⅠ restriction enzyme map type of 36 isolates was completely consistent, and the ST type analysis of 3 strains was ST152. Whole genome sequencing and analysis verified that the outbreak was caused by a single clonal group of strains, and revealed that the isolates of the outbreak were clustered into a large cluster with 3 Chinese strains and 1 Korean strain in the database, far away from the strains of other countries. Conclusion: The outbreak is caused by a single clone of Shigella sonnei, which are low virulence strains and have multiple drug resistance.

Effect of different incubation time of aminolevulinic acid on photodynamic inhibition of Propionibacterium acnes biofilms / 中华皮肤科杂志

Objective:To investigate the effect of different incubation time of aminolevulinic acid (ALA) on photodynamic inhibition of Propionibacterium acnes biofilms. Methods:Propionibacterium acnes biofilms were formed in 24-well plates with pre-placed cell slides and 96-well plates. The formation of the biofilm structure was observed by confocal laser scanning microscopy (CLSM) , and the growth activity of the biofilm was assessed by the tetrazolium salt XTT assay. The in vitro successfully constructed biofilm models were divided into 6 groups: negative control group receiving neither ALA treatment nor LED radiation, ALA group incubated with ALA alone for 30 minutes, LED group receiving LED radiation alone, ALA-PDT1 group, ALA-PDT2 group and ALA-PDT3 group incubated with ALA for 15, 30 and 60 minutes respectively followed by LED radiation. After the treatment, CLSM was performed to observe the biofilm structure, as well as to determine the dead/living bacteria ratio, and XTT assay to assess the growth activity of the biofilm. Differences among groups were analyzed using one-way analysis of variance and least significant difference- t test. Results:CLSM showed that the Propionibacterium acnes biofilm model was successfully constructed in vitro. The dead/living bacteria ratios were 0.90 ± 0.16, 1.75 ± 0.19, and 2.57 ± 0.32 in the ALA-PDT1 group, ALA-PDT2 group and ALA-PDT3 group respectively, which were significantly higher than the dead/living bacteria ratio in the negative control group (0.31 ± 0.01; t= 55.56, 138.62, 74.64, respectively, all P<0.001) ; the biofilm viability value was significantly lower in the ALA-PDT1 group, ALA-PDT2 group and ALA-PDT3 group (0.35 ± 0.02, 0.26 ± 0.02, 0.18 ± 0.01, respectively) than in the negative control group (0.43 ± 0.00; t= 35.66, 2.64, 110.96, respectively, all P < 0.001) . CLSM showed that the structure of the Propionibacterium acnes biofilm was destroyed under the action of ALA-PDT, and the destruction was aggravated with the prolongation of incubation time of ALA. Conclusion:The prolongation of incubation time of ALA can enhance the inhibitory effect of ALA-PDT on Propionibacterium acnes biofilms.

Two-staged hybrid ablation versus thoracoscopic epicardial ablation for long-standing persistent atrial fibrillation: Mid-long term result of a randomized controlled trial / 中国胸心血管外科临床杂志

@#Objective    To evaluate the efficacy of hybrid ablation through compared with thoracoscopic epicardial ablation. Methods    In this study, 108 patients with all long-standing persistent atrial fibrillation (LSPAF) received thoracoscopic epicardial ablation (TEA) after enrollment. There were 82 males and 26 females at age of 56.5±9.4 years. After blanking-period, patients off antiarrhythmic therapy with sinus rhythm were divided into a hybrid ablation (HA) group (50 patients) and a TEA group (58 patients). Only patients in the HA group received catheter ablation after randomization subsequently. In at least two-year observation period, cardiovascular risk factors were observed in all groups’ patients. Results    The mean follow-up duration was 17.3-41.8 (26.9±6.1) months and there was no significant difference between two groups [8.2-40.6 (27.5±5.7) months in the HA group and 17.3-41.8 (26.4±6.7) months in the TEA group]. The off antiarrhythmic agents (AADs) sinus rhythm rate was significantly higher in the HA group than that in the TEA group at the time of postoperative 6, 12, 24 and 36 months ［96.0%, 90.0%, 83.7%, 83.7% versus 79.3%, 75.9%, 67.3%, 63.1%, HR=0.415 (95%CI 0.206-0.923)]. Conclusion    We can conclude that the efficacy of two-staged hybrid ablation for LSPAF is superior to thoracoscopic epicardial ablation alone. Patients can obtain benefit from a supplemental radiofrequency catheter ablation after blanking-period of surgical ablation, instead of those without a supplemental ablation.

Saikosaponin A Changes Drug Resistance of A549/DDP Cells Through Wnt/β-Catenin Pathway / 中国实验方剂学杂志

Objective:To investigate the effect and mechanism of saikosaponin A （SSA） on the reversal of cisplatin （DDP） resistance in human lung cancer cell line A549/DDP. Methods:The resistance of A549 and A549/DDP cells to DDP and the inhibitory effects of SSA against the proliferation of A549 and A549/DDP cells were detected using cell counting kit-8 （CCK-8）. The apoptosis rates of A549/DDP cells treated with SSA or DDP or SSA combined with DDP and the changes in reactive oxygen species （ROS） were determined by flow cytometry. The mRNA expression levels of C-myc， B-cell lymphoma 2 （Bcl-2） and cysteinyl aspartate-specific protease-3 （Caspase-3） were detected by real-time polymerase chain reaction （Real-time PCR）， followed by the determination of <italic>β</italic>-catenin transcriptional activity using the TopFish dual-luciferase reporter assay system and the measurement of <italic>β</italic>-catenin protein expression in A549/DDP cells by Western blot. Results:The results of CCK-8 assay showed that the DDP resistance of A549/DDP cells was 12.82 times that of A549 cells （<italic>P</italic><0.05）. SSA inhibited the viability of A549 cells with the half maximal inhibitory concentration （IC₅₀） being 34.9 μmol·L^-1， and also suppressed the viability of A549/DDP cells in a concentration-dependent manner. Since the inhibition rate of 20 μmol/L SSA against A549/DDP cells was less than 10%， the reversal concentration was set at 20 μmol/L. Flow cytometry revealed that compared with the control， DDP alone increased the apoptosis rate of A549/DDP cells （<italic>P</italic><0.05）， stimulated the accumulation of intracellular ROS （<italic>P</italic><0.05）， down-regulated the mRNA expression levels of C-myc and Bcl-2 in A549/DDP cells， up-regulated Caspase-3 mRNA expression， and reduced the transcriptional activity of <italic>β</italic>-catenin （<italic>P</italic><0.05）. Compared with the DDP group， the SSA+DDP group exhibited obviously increased apoptosis of A549/DDP cells， enhanced accumulation of intracellular ROS， down-regulated C-myc and Bcl-2 mRNA expression， up-regulated Caspase-3 mRNA expression （<italic>P</italic><0.05）， and weakened <italic>β</italic>-catenin transcription （<italic>P</italic><0.05）. DDP combined with SSA better decreased the <italic>β</italic>-catenin protein expression in contrast to that of control or DDP （<italic>P</italic><0.05）. Conclusions:SSA enhances the sensitivity of A549/DDP cells to DDP possibly by inhibiting the activation of Wnt/<italic>β</italic>-catenin pathway.

Protective Effect of Total Ginsenoside Ginseng Root on Learning and Memory Impairment and Anxiety in Rats Induced by Hindlimb Suspension / 中国实验方剂学杂志

Objective:To investigate the effect of total ginsenoside ginseng root on the learning and memory impairment and anxiety of hindlimb suspension rats by detecting the performance of rats in the water maze， elevated plus maze， and the expression of hypothalamic-pituitary-adrenal （HPA） axis， inflammatory factors and tryptophan pathway related factors through the intervention of ginsenosides in hindlimb suspension rats. Method:The Wistar male rats were divided into normal group， hindlimb suspension model group， Huperzine A group （0.1 mg·kg^-1）， and total ginsenoside ginseng root low and high dose groups （100， 200 mg·kg^-1）， with 8 rats in each group. Except for the normal group， the rats in the other groups maintained a -30° hindlimb suspension state for 24 h. The normal group and the model group received intragastric administration of 10 mL·kg^-1 pure water . After 28 days of continuous administration， the water maze and elevated plus maze behavioral tests were performed. After the tests， blood was taken from the abdominal aorta， and the rat brain cortex was peeled off on ice， quenched with liquid nitrogen， and stored at -80 ℃ for later use. LC-MS/MS was used to detect neurotransmitter levels of dopamine， acetylcholine， glutamate， <italic>γ</italic>-aminobutyric acid and tryptophan pathway metabolites （tryptophan， 5-hydroxytryptamine， 5-hydroxyindoleacetic acid， kynurenine， 3-hydroxykynurenine， and kynurenine） in rat brain cortex. An enzyme-linked immunosorbent assay （ELISA） kit was used to detect the levels of inflammatory factors interleukin-6 （IL-6）， interleukin-10 （IL-10， the HPA axis-related hormone corticotropin （ACTH）， and the level of corticosterone （CORT）. Result:Compared with the normal group， the escape latency in the water maze significantly increased， the number of crossings was significantly reduced， and the number of open-arm entry and the percentage of open-arm entry were significantly reduced in the elevated plus maze in model group （<italic>P</italic><0.05，<italic> P</italic><0.01）， the content of dopamine， acetylcholine， glutamic acid， and <italic>γ</italic>-aminobutyric acid in the cortex decreased， kynurenine and kynurenic acid showed an upward trend， 3-hydroxykynurenine， 5-hydroxytryptamine， 5-hydroxyindole acetic acid showed a downward trend， and the levels of IL-6， IL-10， ACTH， and CORT in the serum significantly increased （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the model group of rats， total ginsenoside ginseng root low and high dose groups group reduced the avoidance latency in the water maze， and increased the number of crossings and the number of open arms of the elevated plus maze， dopamine， acetylcholine， glutamate， and <italic>γ</italic>-aminobutyl content increased， while kynurenine and kynurenic acid showed a downward trend， 3-hydroxykynurenine， serotonin， and 5-hydroxyindole acetic acid showed an upward trend， and IL-6， IL-10， ACTH， and CORT factor levels were down-regulated（<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:Hindlimb suspension for 28 days in simulated microgravity can impair the learning and memory ability of rats and cause anxiety-like behaviors. Total ginsenoside ginseng root can improve their learning and memory impairment and anxiety-like behaviors. The mechanism may be mainly related to inhibiting body inflammation and regulating HPA axis imbalance.

Effect of Licochalcone A on Apoptosis in Human Breast Cancer MDA-MB-231 Cells / 中国实验方剂学杂志

Objective:To investigate the effect of licochalcone A （LCA） on apoptosis in human breast cancer MDA-MB-231 cells， and to explore its possible mechanism. Method:MDA-MB-231 cells were treated with LCA of different concentrations， and<italic> </italic>cell counting kit-8 （CCK-8） assay was used to detect the cell viability. The cells were treated with LCA （10， 20， and 40 μmol·L^-1） for 24 h， and apoptosis was detected by Annexin V staining with fluorescein isothiocyanate （FITC） and propidium iodide （PI） （Annexin V-FITC/PI）. The level of intracellular reactive oxygen species （ROS） was detected by 2′，7′-dichlorodihydrofluorescein diacetate （DCFA-DA） fluorescent probe. Mitochondrial membrane potential （MMP） was detected by 5， 5′， 6， 6′-tetrachloro-1， 1′， 3， 3′-tetraethyl-imidacarbocyanine （JC-1） fluorescence probe. Western blot was used to detect the expression of cell apoptosis-related proteins， such as B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax）， and endoplasmic reticulum （ER） stress-related proteins， such as C/EBP homologous protein （CHOP）， activating transcription factor 4 （ATF4）， protein kinase R-like ER kinase （PERK）， p-PERK， eukaryotic translation initiation factor 2 alpha （eIF2<italic>α</italic>）， and p-eIF2<italic>α</italic>. Result:With the increase in the drug concentration （starting from 5 μmol·L^-1）， the cell viability decreased （<italic>P<</italic>0.05） with IC₅₀of 19.05 μmol·L^-1 as compared with the normal group. Additionally， the apoptosis rates of the LCA groups （10， 20， 40 μmol·L^-1） significantly increased （<italic>P</italic><0.05）， which reached 30.2% （<italic>P</italic><0.05） at LCA concentration of 40 μmol·L^-1. LCA （10， 20， and 40 μmol·L^-1） decreased the expression of Bcl-2 （<italic>P<</italic>0.05） and increased Bax expression （<italic>P<</italic>0.05） in a dose-dependent manner. Besides， the intracellular ROS level was elevated （<italic>P<</italic>0.05） and mitochondrial MMP was reduced （<italic>P<</italic>0.05） after LCA （10， 20， and 40 μmol·L^-1） treatment in a dose-dependent manner， leading to mitochondrial dysfunction. LCA （10， 20， and 40 μmol·L^-1） induced ER stress to up-regulate the expression of CHOP， ATF4， p-PERK， and p-eIF2<italic>α</italic> （<italic>P<</italic>0.05） in a dose-dependent manner. Conclusion:LCA can induce MDA-MB-231 cell apoptosis by increasing intracellular ROS level and reducing MMP to trigger mitochondrial dysfunction and ER stress.

Performance analysis of clinical skills friendship competition between Chinese and French medical students / 中华医学教育探索杂志

Objective:To understand the clinical diagnosis and treatment ability of Chinese and French medical students, so as to improve the education of clinical medicine in China, improve the diagnosis and treatment ability of medical students, and provide reference for improving training quality of medical personnel.Methods:Retrospective analysis was made on the clinical skills competition of Chinese and French medical students, and the percentages of three categories of students' scores were compared (1 team of general practice residents, 3 teams of Chinese undergraduates, and 3 teams of French undergraduates).Results:In clinical basic skills such as electrocardiogram and imaging interpretation site, the scores of general practice residents were higher than those of Chinese and French undergraduates, and there was no significant difference between Chinese and French undergraduates. In clinical virtual case sites, except for few items in surgery site, general practice residents and Chinese undergraduates were better than French undergraduates in many evaluation items. In the internal medicine site, 6 out of 8 scoring items of French undergraduates were higher than those of Chinese undergraduates. In the medical team comprehensive first-aid site, 8 out of 10 scoring items of Chinese undergraduates were higher than those of French undergraduates.Conclusion:Clinical thinking and decision-making of undergraduates in our university need to be improved compared with that of French students. The general practice residents in our school need to be strengthened in the aspects of clinical thinking, decision-making and the cooperation with emergency team.

Multidisciplinary diagnosis and treatment of advanced metastatic prostate cancer: a case report / 中华泌尿外科杂志

We reported an advanced prostate cancer patient underwent muti-disciplinary treatment with long time survival. After 18 months of androgen deprive therapy, the disease progressed to metastatic castration-resistant prostate cancer(mCRPC) stage. So enzalutamide was added and combined with radiotherapy for bone metastases, which achieved excellent survival benefits. From the diagnosis to September 2021, the patients survived for 97 months, including 79 months in the mCRPC stage. the tumor related symptoms disappeared, the PSA remained < 0.003ng/ml, and the imaging lesions remained stable.

Tumor-derived neomorphic mutations in ASXL1 impairs the BAP1-ASXL1-FOXK1/K2 transcription network

Additional sex combs-like 1 (ASXL1) interacts with BRCA1-associated protein 1 (BAP1) deubiquitinase to oppose the polycomb repressive complex 1 (PRC1)-mediated histone H2A ubiquitylation. Germline BAP1 mutations are found in a spectrum of human malignancies, while ASXL1 mutations recurrently occur in myeloid neoplasm and are associated with poor prognosis. Nearly all ASXL1 mutations are heterozygous frameshift or nonsense mutations in the middle or to a less extent the C-terminal region, resulting in the production of C-terminally truncated mutant ASXL1 proteins. How ASXL1 regulates specific target genes and how the C-terminal truncation of ASXL1 promotes leukemogenesis are unclear. Here, we report that ASXL1 interacts with forkhead transcription factors FOXK1 and FOXK2 to regulate a subset of FOXK1/K2 target genes. We show that the C-terminally truncated mutant ASXL1 proteins are expressed at much higher levels than the wild-type protein in ASXL1 heterozygous leukemia cells, and lose the ability to interact with FOXK1/K2. Specific deletion of the mutant allele eliminates the expression of C-terminally truncated ASXL1 and increases the association of wild-type ASXL1 with BAP1, thereby restoring the expression of BAP1-ASXL1-FOXK1/K2 target genes, particularly those involved in glucose metabolism, oxygen sensing, and JAK-STAT3 signaling pathways. In addition to FOXK1/K2, we also identify other DNA-binding transcription regulators including transcription factors (TFs) which interact with wild-type ASXL1, but not C-terminally truncated mutant. Our results suggest that ASXL1 mutations result in neomorphic alleles that contribute to leukemogenesis at least in part through dominantly inhibiting the wild-type ASXL1 from interacting with BAP1 and thereby impairing the function of ASXL1-BAP1-TF in regulating target genes and leukemia cell growth.

Content determination of five flavonoids in Tibetan medicine Rhododendron anthopogonoides by quantitative analysis of multi-components by single marker (QAMS) / 中国中药杂志

To establish a quantitative analysis of multi-components by single marker(QAMS) method for five flavonoids in Rhododendron anthopogonoides and verify its feasibility and applicability in the medicinal materials of R. anthopogonoides. With hyperoside as the internal reference, relative correction factors(RCF) of rutin, quercetin, quercitrin and kaempferol were established by high-performance liquid chromatography(HPLC) analysis. RCFs were used to calculate the content of each component, system durability and relative retention time. Simultaneously, QAMS and external standard method(ESM) were used to determine the content of five flavonoids in 12 batches of R. anthopogonoides from different origins. The results were statistically analyzed to verify the accuracy and feasibility. The fingerprints and cluster analysis data of R. anthopogonoides analyzed and discussed differences among the batches. According to the results, the RCFs of rutin, quercetin, quercetin and kaempferol in R. anthopogonoides were 1.242 6, 0.990 5, 0.535 0, and 0.781 3, respectively. The RCFs represented a good reproducibility under different experimental conditions. Besides, there was no significant difference between QAMS and ESM. Besides, the fingerprint and cluster analysis data showed the consistency between the classification and with the origin distribution of the herbs. In conclusion, the QAMS method shows a good stability and accuracy in the quality control of R. anthopogonoides.