Mesenchymal Stem Cells Ameliorate Fibrosis by Enhancing Autophagy via Inhibiting Galectin-3/Akt/mTOR Pathway and by Alleviating the EMT via Inhibiting Galectin-3/Akt/GSK3β/Snail Pathway in NRK-52E Fibrosis

Background and Objectives@#Epithelial-Mesenchymal transition (EMT) is one of the origins of myofibroblasts in renal interstitial fibrosis. Mesenchymal stem cells (MSCs) alleviating EMT has been proved, but the concrete mechanism is unclear. To explore the mechanism, serum-free MSCs conditioned medium (SF-MSCs-CM) was used to treat rat renal tubular epithelial cells (NRK-52E) fibrosis induced by transforming growth factor-β1 (TGF-β1) which ameliorated EMT. @*Methods@#and Results: Galectin-3 knockdown (Gal-3 KD) and overexpression (Gal-3 OE) lentiviral vectors were established and transfected into NRK-52E. NRK-52E fibrosis model was induced by TGF-β1 and treated with the SF-MSCs-CM for 24 h after modelling. Fibrosis and autophagy related indexes were detected by western blot and immunocytochemistry. In model group, the expressions of α-smooth muscle actin (α-SMA), fibronectin (FN), Galectin-3, Snail, Kim-1, and the ratios of P-Akt/Akt, P-GSK3β/GSK3β, P-PI3K/PI3K, P-mTOR/mTOR, TIMP1/MMP9, and LC3B-II/I were obviously increased, and E-Cadherin (E-cad) and P62 decreased significantly compared with control group. SF-MSCs-CM showed an opposite trend after treatment compared with model group. Whether in Gal-3 KD or Gal-3 OE NRK-52E cells, SF-MSCs-CM also showed similar trends. However, the effects of anti-fibrosis and enhanced autophagy in Gal-3 KD cells were more obvious than those in Gal-3 OE cells. @*Conclusions@#SF-MSCs-CM probably alleviated the EMT via inhibiting Galectin-3/Akt/GSK3β/Snail pathway. Meanwhile, Gal-3 KD possibly enhanced autophagy via inhibiting Galectin-3/Akt/mTOR pathway, which synergistically ameliorated renal fibrosis. Targeting galectin-3 may be a potential target for the treatment of renal fibrosis.

Value of nomogram based on preoperative ultrasound and inflammatory indexes in predicting axillary high nodal burden in early breast cancer / 中华超声影像学杂志

Objective:To explore the values of ultrasound, pathology combined with inflammatory indicators in predicting high nodal burden (HNB) in patients with early breast cancer and to construct a nomogram to provide reference for individualized diagnosis and treatment.Methods:The ultrasonographic, pathological features and preoperative inflammatory indicators of 378 female patients diagnosed with early breast cancer confirmed by pathology in the South Hospital of the Sixth People′s Hospital Affiliated to Shanghai Jiaotong University from January 2014 to July 2022 were retrospectively analyzed. They were randomly divided into training set ( n=302) and test set ( n=76) in a ratio of 8∶2, and the baseline data of the two groups were compared. The optimal cutoff values of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR) were obtained by ROC curve. In the training set, with axillary high lymph node load (≥3 metastatic lymph nodes) as the dependent variable, independent influencing factors of HNB were identified by univariate and multivariate Logistic regression analyses, and the nomogram was established. The test set data were used to verify the model. The discrimination, calibration and clinical applicability of the model were assessed by the area under the ROC curve (AUC), C-index, the calibration curve, Brier score and the decision curve analysis, respectively. Results:There were no significant differences in all variables between the training set and the test set (all P>0.05). ROC curve analysis results showed that AUCs of NLR, PLR and LMR were 0.578, 0.547 and 0.516, respectively, and the optimal cut-off values were 2.184, 150 and 3.042, respectively. Univariate Logistic regression analysis showed that age, pathological type, histological grade, Ki-67, lymphovascular invasion, NLR, PLR, ultrasonic characteristics (maximum diameter of primary tumor, shape, long/short diameter of lymph node, cortical thickness, cortical and medullary boundary, lymph node hilum, lymph node blood flow pattern) were correlated with HNB of early breast cancer (all P<0.05). Multivariate Logistic regression analysis showed that ultrasonic characteristics (maximum diameter of primary tumor >2 cm, effacement of lymph node hilum, non-lymphatic portal blood flow), lymphovascular invasion, Ki-67>14% and NLR>2.184 were independent risk factors for HNB in early breast cancer ( OR=7.258, 8.784, 6.120, 8.031, 3.394 and 3.767, respectively; all P<0.05) and were used to construct the nomogram model. The AUC of the training set was 0.914 (95% CI=0.878-0.949), C-index was 0.914; The AUC of the test set was 0.871 (95% CI=0.769-0.973), C-index was 0.871, indicating good discrimination. Calibration curve and Brier score were 0.090, indicating high calibration degree of the model. The clinical decision curve indicated good clinical benefit. Conclusions:The nomogram based on ultrasonic characteristics (maximum diameter of primary tumor, lymph node hilum, lymph node blood flow pattern), lymphovascular invasion, Ki-67 and NLR can effectively predict the risk of HNB in patients with early breast cancer, and provide a reference for precision diagnosis and treatment to avoid excessive or insufficient treatment.

Applicability Analysis of Gender Selection in Mitochondrial Replacement Technology / 中国医学伦理学

Whether gender selection should be conducted is a controversial topic in ethical research on mitochondrial replacement technology. Scholars put forward different moral judgments based on different positions, and after reviewing these judgments, it was found that those who support gender selection mainly rely on the utility theory and rights theory, while those who oppose gender selection mainly rely on the dignity theory and community theory. It is not difficult to find that relying on traditional moral theory to defend moral judgments or actions often leads to endless debates among "moral strangers" , and does not provide effective guidance for solving specific problems. Principlism is a systematic and comprehensive analytical approach constructed with a series of clear and effective frameworks, which can reasonably solve the differences and disagreements between different value systems and cultural concepts. In the discussion of whether gender selection should be conducted in mitochondrial replacement technology, principlism refined and balanced it through the method of reflective equilibrium, and finally obtained the best judgment plan that allows for gender selection. To truly achieve the humane purpose of avoiding harm in gender selection, it is necessary to clearly limit the objects and stages of use, and regulate them from the dual dimensions of ethics and morality, as well as policy regulation.

Current Status of Drug Development and Implementation for Diseases Included in the Second Catalog of Rare Diseases / 罕见病研究

The National Health Commission of the People′s Republic of China and six other departments jointly released the Second Catalog of Rare Diseases, which expanded the definition of rare diseases in China. The expansion of the catalog means greater attention to rare diseases at the national level, and is also expected to accelerate the launch of relevant rare disease drugs and benefit more rare disease patients. When the new rare disease catalog released, it is necessary to quickly sort out the availability of drugs and find out the base number for the advancement of subsequent relevant measures. This paper searched official medical information websites and medical databases such as the National Medical Products Administration (NMPA), the Center for Drug Evaluation (CDE), and foreign drug regulatory agencies, and sorted out and summarized the subject categories of diseases included in the Second Catalog of Rare Diseases, the corresponding global research and development and implementation of drugs, as well as the medical insurance access situation in China, elaborates on the differences in the accessibility of orphan drugs at home and abroad. As China′s prevention, treatment and protection of rare diseases has reached a new point, plans and prospects are made for the introduction of relevant policies in the future, as well as the promotion of research and development and protection and other key tasks.

Activation of renal outer medullary potassium channel in the renal distal convoluted tubule by high potassium diet / 生理学报

Renal outer medullary potassium (ROMK) channel is an important K+ excretion channel in the body, and K+ secreted by the ROMK channels is most or all source of urinary potassium. Previous studies focused on the ROMK channels of thick ascending limb (TAL) and collecting duct (CD), while there were few studies on the involvement of ROMK channels of the late distal convoluted tubule (DCT2) in K+ excretion. The purpose of the present study was mainly to record the ROMK channels current in renal DCT2 and observe the effect of high potassium diet on the ROMK channels by using single channel and whole-cell patch-clamp techniques. The results showed that a small conductance channel current with a conductance of 39 pS could be recorded in the apical membrane of renal DCT2, and it could be blocked by Tertiapin-Q (TPNQ), a ROMK channel inhibitor. The high potassium diet significantly increased the probability of ROMK channel current occurrence in the apical membrane of renal DCT2, and enhanced the activity of ROMK channel, compared to normal potassium diet (P < 0.01). Western blot results also demonstrated that the high potassium diet significantly up-regulated the protein expression levels of ROMK channels and epithelial sodium channel (ENaC), and down-regulated the protein expression level of Na+-Cl- cotransporter (NCC). Moreover, the high potassium diet significantly increased urinary potassium excretion. These results suggest that the high potassium diet may activate the ROMK channels in the apical membrane of renal DCT2 and increase the urinary potassium excretion by up-regulating the expression of renal ROMK channels.

Difference in Nocturnal Erectile Function Between SRPE Patients and Normal People / 中山大学学报(医学科学版)

ObjectiveTo compare the nocturnal erectile function between SRPE patients and normal people. MethodsFrom July 1st， 2019 to December 15th， 2022， a clinical comparative study was conducted on 29 SRPE patients （experimental group） and 58 volunteers （control group） who visited our urology department. The Rigiscan System was used to monitor sleep monitoring time， the number of nocturnal erections and the rigidity， duration and circumference growth of the penis when the erection reached 60%～79% and 80%～100%， respectively. The patients and volunteers were asked to make written records when they woke up， and then the total number of awakenings and the number of awakenings when the penis erection reached 60% and 80% were compared between the two groups. ResultsAge was eliminated by matching. There was no statistically significant difference in sleep monitoring time， rigidity， circumference growth and duration of the penis when the erection reached 60%～79% and 80%～100%. between the two groups. In terms of sleep， there was a statistically significant difference in the total number of awakenings between the two groups［3（2 ~ 4）vs 0（0 ~ 0），P<0.01］ .And the same was true for the number of awakenings when the penis erection exceeded 60%～79% ［1（0 ~ 1）vs 0（0 ~ 0），P<0.01］and 80%～100% ［2（1 ~ 3）vs 0（0 ~ 0），P<0.01］. ConclusionRigiscan monitoring showed that there was no difference between SRPE patients and normal male in nocturnal penile erection function. Painful awakening usually occurs when the penis erection reaches 60%～79% or 80%～100%， which reveals that SRPE may be caused by abnormal sensation of nocturnal erections or pain sensitivity in some of these patients.

Research Advances on the Relationship between Overt Hyperthyroidism and Risk of Erectile Dysfunction / 中国医学科学院学报

Studies have demonstrated the detrimental effects of overt hyperthyroidism on sexual functioning.Here,we comprehensively reviewed the studies that focused on the association between overt hyperthyroidism and erectile dysfunction (ED).After the systematic searching for relevant studies,we find that overt hyperthyroidism is significantly associated with the high risk of ED.The prevalence of ED in patients with hyperthyroidism ranges from 3.05% to 85%,while that in general population is 2.16% to 33.8%.A study reported that the erectile functioning of the hyperthyroidism patients was improved (International Index of Erectile Function:22.1±6.9 vs. 25.2±5.1) after the achievement of euthyroidism.The underlying mechanism of the increase in the risk of ED by overt hyperthyroidism might be correlated to the dysfunction of hypothalamus-pituitary-thyroid axis,dysregulation of sex hormones,abnormal expression of thyroid hormone receptors,and psychiatric or psychological disturbances (e.g.,depression,anxiety,and irritability).Since limited clinical trials have been conducted,additional well-designed cohorts with sizable samples are warranted to elucidate the evidence and mechanism of hyperthyroidism predisposing to ED.The present review indicates that overt hyperthyroidism and the risk of ED are associated,which reminds the clinicians should assess the thyroid stimulating hormone in hyperthyroidism patients presenting with ED,especially in those without positive conventional laboratory findings for causing ED.

Spectrum-effect relationship of anti-gastric ulcer effect of Shaoyao gancao decoction / 中国药房

OBJECTIVE To study the sp ectrum-effect relationship of anti-gastric ulcer effect of Shaoyao gancao decoction. METHODS Eleven batches of Shaoyao gancao decoction were prepared ；gastric ulcer model was established by anhydrous ethanol modeling method. Using Weikangling as positive control ，the effects of Shaoyao gancao decoction on the contents of defensive factors [nitric oxide （NO），epidermal growth factor （EGF），superoxide dismutase （SOD）] and attack factor [malondialdehyde （MDA）] in gastric tissue of model rats were investigated. HPLC fingerprints of 11 batches of Shaoyao gancao decoction were established and similarity evaluation was performed with Similarity Evaluation System of Traditional Chinese Medicine Chromatographic Fingerprint （2004A edition ）； common peaks were identified by comparing with mixed control. The spectrum-effect relationship of Shaoyao gancao decoction against gastric ulcer was analyzed based on the grey correlation analysis. RESULTS Eleven batches of Shaoyao ganyao decoction could significantly decrease the content of MDA in gastric tissue ，while increased the contents of NO ，EGF and SOD in gastric ulcer model rats （P＜0.01），and had a certain inhibitory effect on the gastric ulcer. There were 23 common peaks in chromatograms of 11 batches of samples ，and the similarity with the control fingerprint was not less than 0.9. By comparing with mixed control ，7 common peaks were identified ，namely gallic acid （peak 5），albiflorin（peak 9），paeoniflorin（peak 10），liquiritin（peak 12），isoliquiritin apioside （peak 14），isoliquiritoside（peak 15）， glycyrrhizic acid （peak 22）. The average correlation degree of 7 identified common peaks and pharmacodynamic indexes were greater than 0.6，of which peak 22（glycyrrhizic acid ），peak 10（paeoniflorin）and peak 12（liquiritin）had the largest correlation ， and their values were 0.807，0.772 and 0.770 respectively. RESULTS The anti-gastric ulcer effect of Shaoyao gancao decoction is the result of the synergistic effect of multiple components ，among which glycyrrhizic acid ，paeoniflorin and liquiritin may be the main pharmacodynamic components.

CHINA PH ARMACY Volume 33，Number 12，June 30，2022 Semimonthly Table of Contents Construction of total q uality managemen t system of clinica l comprehens ive evaluation of drugs in China / 中国药房

OBJECTIVE To provide reference for scientifi c and standardized development of clinical comprehensive evaluation of drugs in China. METHODS Guided by the theory of total quality management （TQM），drawing lessons from the successful experience of the British and German conducting evaluation ，combining with plan-do-check-act cycle and other quality management methods and tools ，drug clinical comprehensive evaluation of total quality management system was constructed in accordance with the requirements for our country related policy and local practice. RESULTS & CONCLUSIONS To construct total quality management system of clinical comprehensive evaluation of drugs in China from 5 aspects of organization system ，management process，assessment system ，evaluation and supervision platform ，support and guarantee mechanism. The organization system included national ，provincial and medical institutions ；management process should focus on the key links in the 3 stages of theme selection，evaluation and implementation ，and result transformation and application ；assessment system ，evaluation and supervision platform，support and guarantee mechanism should be established together so as to further improve the scientificity ，rationality， practicality and standardization of total quality management of clinical comprehensive evaluation of drugs. The development of total quality management is an effective starting point to promote the continual improvement of the drug clinical comprehensive evaluation；relevant government departments and the implementation of evaluation of medical institutions should further set up quality management consciousness ，establish report quality feedback mechanism and the results co-constructing and sharing mechanism and strengthen professional personnel training and innovation synergy regulation mode to ensure that the authenticity and reliability of evaluation results.

Dosimetric study of 125I seed implantation guided by 4D template for advanced malignant tumors / 中华放射肿瘤学杂志

Objective:To investigate the safety and dose of 4D template (real-time adjustable angle template) in the treatment of advanced malignant tumors with 125I seeds. Methods:98 patients with advanced malignant tumors admitted to Department of Thoracic Surgery of Shaanxi Provincial Tumor Hospital were treated with 4D template-navigated radioactive 125I seed implantation from June 2018 to December 2019. Preoperative TPS plan, intraoperative optimization, postoperative verification of immediate dose and postoperative evaluation of implantation dose were performed. The treatment results were observed. Results:All 98 patients completed the seed implantation. The implantation dose of GTV of implantation site receiving external irradiation was (12 489±414) cGy and the dose of no external irradiation was (15 036±514) cGy. V 100% was 84.7%-94.1%, and 88.2%-93.7%. The implantation dose of CTV was (7 450±621) cGy, and (9 080±761) cGy. The quality of dose implantation was evaluated as: excellent in 89 cases (91%, 89/98), good in 7 cases (7%, 7/98), fair in 2 cases (2%, 2/98), and poor in 0 case, respectively. The symptom relief rate of patients with pain was 92%(36/39). The 1-and 2-year local control rates were 61%, 36% and 82%, 54% in patients treated with and without external irradiation, respectively. The difference was statistically significant ( P=0.02). The incidence rates of pneumothorax and hemoptysis were 19%(9/48) and 10%(5/48). No corresponding complications were observed in other parts of the patients. Conclusion:4D template-assisted 125I seed therapy is safe and effective for malignant tumors, and intraoperative adjustment of needle angle and dose optimization can realize the precise control of implantation dose.

Exploration and reflection on the online teaching of physiology under the COVID-19 epidemic / 中华医学教育探索杂志

Facing the challenge of the COVID-19 epidemic to the classroom teaching, the physiology teaching team of Qiqihar Medical University constructed a blended teaching model based on "small private online course (SPOC)+ live real audio" to carry out online teaching. Through the joint efforts of all team members, the online teaching has been carried out in a stable order for 4 weeks, thus ensuring the teaching effect of physiology. Taking the physiology teaching of 236 nursing undergraduates in Batch 2019 as an example, this paper introduces the teaching design, implementation measures, teaching effect and teaching reflection of carrying out online teaching under the epidemic situation, and provides practical experience for further promoting online teaching in medical colleges and universities during epidemic prevention and control.

Correlation of prolongation of PR interval with carotid atherosclerosis in middle-aged and elderly patients with type 2 diabetes mellitus / 中华内分泌代谢杂志

Objective:To investigate the relationship between prolonged PR interval and carotid atherosclerosis(CAS)in middle-aged and elderly patients with type 2 diabetes mellitus(T2DM).Methods:A total of 537 middle-aged and elderly inpatients with T2DM in the Southern Branch of the Sixth People′s Hospital of Shanghai Jiaotong University from January 2019 to January 2021 were selected as the research objects. Color Doppler ultrasound was used to detect bilateral carotid artery intima-media thickness(CIMT). The subjects were divided into carotid atherosclerosis group(CAS group, n=352)and non-carotid atherosclerosis group(NCAS group, n=185). The difference in the PR interval of ECG between the two groups was compared. Pearson or Spearman rank correlation analysis was used for evaluating the correlation of PR interval and CAS lesions with various clinical index. The relationship between PR interval and CAS lesions was adopted by multivariate logistic regression analysis. Results:The average PR interval of middle-aged and elderly patients with T2DM was(164.57±23.02)ms. The average PR interval in CAS group was significantly higher than that in NCAS group [(169.76±24.28) vs (154.70±16.42)ms, P<0.01]. The results of multifactorial logistic regression analysis showed that age, low density lipoprotein-cholesterol, serum osteocalcin, and PR interval were independent factors influencing the development of CAS lesions in middle-aged and elderly patients with T2DM( OR=1.079, 1.936, 0.879, 1.039, respectively, P<0.05 or P<0.01)where each 1 ms increase in PR interval was associated with a 3.9% increase in the risk of CAS in middle-aged and elderly patients with T2DM( OR=1.039, 95% CI 1.006-1.073, P=0.020). Multivariate logistic regression analysis showed that middle-aged and elderly type 2 diabetic patients with PR interval≥158 ms were 4.072 times more likely to have CAS lesions than those with PR interval<158 ms( OR=4.072, 95% CI 1.417-11.702, P<0.01). Conclusion:The PR interval of electrocardiogram is correlated with CAS lesions in middle-aged and elderly patients with T2DM. Middle-aged and elderly type 2 diabetic patients with significantly prolonged PR interval should be reminded to screen for CAS lesions early.

Risk factors and early neurological deterioration in proximal single subcortical infarction: comparison with distal single subcortical infarction / 国际脑血管病杂志

Objective:To investigate the risk factors for different types of single subcortical infarction (SSI) in middle cerebral artery territory and the risk factors for early neurologic deterioration (END).Methods:Patients with SSI in middle cerebral artery territory admitted to the Department of Neurology, People's Hospital Affiliated to Jiangsu University from January 2020 to April 2021 were enrolled retrospectively. According to the distribution of infarction, the patients were divided into proximal SSI (pSSI) and distal SSI (dSSI). The demographics, vascular risk factors and baseline clinical data were collected. END was defined as new signs and/or symptoms of neurological deficit or aggravation of any neurological deficit within 2 weeks after onset. Multivariate logistic regression analysis was used to determine the independent risk factors for pSSI and END. Results:Seventy-six patients with acute SSI in the middle cerebral artery territory were included, 41 patients (53.9%) in the pSSI group, 35 (46.1%) in the dSSI group; 13 (17.1%) in the END group, and 63 (82.9%) in the non-END group. There were no significant differences in age, gender, vascular risk factors and baseline National Institutes of Health Stroke Scale score between the pSSI group and the dSSI group. The total cholesterol, fasting blood glucose levels and the ratio of pSSI in the END group were significantly higher than those in the non-END group ( P<0.05), while the high-density lipoprotein cholesterol level was significantly lower than that of the non-END group ( P<0.05). Multivariate logistic regression analysis showed that pSSI was an independent risk factor for the occurrence of END in patients with SSI (odds ratio 6.75, 95% confidence interval 1.26-36.23; P=0.026). Conclusion:There was no significant difference in risk factors between pSSI and dSSI, but patients with pSSI were more prone to END.

Research Progress of Pharmacological Intervention of Sevoflurane-induced Nerve Injury in the Developing Brain / 中国医学科学院学报

Sevoflurane is one of the most commonly used inhaled anesthetics in obstetric and pediatric general anesthesia.According to related literature,this article reviews major possible mechanisms including myelin formation damage,nerve inflammation,cell apoptosis,oxidative stress,inhibition of histone acetylation,synapsis and receptor changes of sevoflurane-induced neurotoxicity in animal experiments.Furthermore,we summarize the neuroprotection effects and functioning mechanisms of anti-anemia medicine,plant-based drugs,alpha 2 adrenoceptor agonists and others,aiming to provide a basis for the brain protection of fetuses and infants during the perioperative period.

Low-intensity pulsed ultrasound ameliorates angiotensin II-induced cardiac fibrosis by alleviating inflammation via a caveolin-1-dependent pathway / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

OBJECTIVES@#Cardiac hypertrophy and fibrosis are major pathological manifestations observed in left ventricular remodeling induced by angiotensin II (AngII). Low-intensity pulsed ultrasound (LIPUS) has been reported to ameliorate cardiac dysfunction and myocardial fibrosis in myocardial infarction (MI) through mechano-transduction and its downstream pathways. In this study, we aimed to investigate whether LIPUS could exert a protective effect by ameliorating AngII-induced cardiac hypertrophy and fibrosis and if so, to further elucidate the underlying molecular mechanisms.@*METHODS@#We used AngII to mimic animal and cell culture models of cardiac hypertrophy and fibrosis. LIPUS irradiation was applied in vivo for 20 min every 2 d from one week before mini-pump implantation to four weeks after mini-pump implantation, and in vitro for 20 min on each of two occasions 6 h apart. Cardiac hypertrophy and fibrosis levels were then evaluated by echocardiographic, histopathological, and molecular biological methods.@*RESULTS@#Our results showed that LIPUS could ameliorate left ventricular remodeling in vivo and cardiac fibrosis in vitro by reducing AngII-induced release of inflammatory cytokines, but the protective effects on cardiac hypertrophy were limited in vitro. Given that LIPUS increased the expression of caveolin-1 in response to mechanical stimulation, we inhibited caveolin-1 activity with pyrazolopyrimidine 2 (pp2) in vivo and in vitro. LIPUS-induced downregulation of inflammation was reversed and the anti-fibrotic effects of LIPUS were absent.@*CONCLUSIONS@#These results indicated that LIPUS could ameliorate AngII-induced cardiac fibrosis by alleviating inflammation via a caveolin-1-dependent pathway, providing new insights for the development of novel therapeutic apparatus in clinical practice.

Screening and validation of RT-qPCR reference genes of Viola yedoensis under different light intensities / 中国中药杂志

Screening the reference genes that were stably expressed under different light intensities for Viola yedoensis could provide reference for the related molecular research. In this study, 11 candidate reference genes were detected by RT-qPCR for tissues of V. yedoensis treated with different light intensities. Ge Norm, Norm Finder, Best Keeper, and Ref Finder website were used to comprehensively evaluate the reference genes, and verify the stability of the reference gene based on CAT1. Finally, the ideal reference gene was determined. The results showed that CYP, Actin, and SAMDC had small Ct value ranges and stable expression. Ge Norm demonstrated that CYP, SAMDC, and Actin were suitable reference genes. Norm Finder showed that the expression of α-TUB was the most stable. Best Keeper recommended CYP, Actin, and SAMDC as reference genes. Ref Finder assessed that SAMDC, CYP, α-TUB, and Actin had better stability, while GAPDH had the worst stability. The expression trend of CAT1 gene was consistent when calibrated with SAMDC, CYP, and Actin, while it was quite different from that calibrated with GAPDH. In summary, SAMDC, CYP, and Actin can be used as ideal reference genes for the gene expression profiling of V. yedoensis under different light intensities.

Process in application of subthreshold micropulse laser / 国际眼科杂志(Guoji Yanke Zazhi)

@#Subthreshold micropulse laser(SML)consists of short repetitive pulses of laser. This kind of treatment is safe and cheap, and contrary to conventional laser photocoagulation(LPC), SML doesn't involve destruction of retinal cells and leave no scars. The possible mechanism of SML is to stimulate retinal pigment epithelium(RPE)cells for the production of heat shock proteins(HSPs)and regulate its metabolism and improve its function. The clinical indication of SML includes central serous chorioretinopathy(CSC), diabetic retinopathy edema(DME), nonproliferative diabetic retinopathy(NPDR)and proliferative diabetic retinopathy(PDR)and macular edema(ME)secondary to retinal vein occlusion(RVO). This article discussed the mechanism and safety of SML and reviewed the updates of its application.

Regulatory Mechanism of Youguiwan on Articular Cartilage Degeneration via IL-6/STAT3 Signaling Pathway in Rats with Knee Osteoarthritis / 中国实验方剂学杂志

<b>Objective::To observe the effect of Youguiwan on the levels of cartilage transducers and activators of transcription 3 (STAT3) and interleukin-6 (IL-6) in rats with knee osteoarthritis (KOA). <b>Method::Sixty SD rats were randomly divided into six groups: sham control group, model group, glucosamine sulfate group and Youguiwan (high, middle and low-dose) groups. The modified Hulth method was used to prepare KOA models for 6 weeks. The shame control group and the model group were treated with normal saline, Youguiwan high, middle, low-dose groups received Youguiwan 4.8, 2.4, 1.2 g·kg^-1 by gavage respectively, and the glucosamine sulfate group was treated with glucosamine sulfate 0.17 g·kg^-1. The rats were administrated for 8 weeks according to the dose. After intervention, each group was put to death by femoral artery blood collection, and the keen cartilages of the rats were collected. The pathological changes were observed by htoxylin eosin (HE) staining method, and Mankin score was evaluated. The expressions of STAT3, superoxide dismutase3(SOD3) and Wnt inhibitory factor 1(WIF1) in articular cartilage were detected by immunohistochemistry. The expressions of IL-6 mRNA in articular cartilage were detected by quantitative real-time fluorescence polymerase chain reaction (Real-time PCR). The expression of WIF1 in articular cartilage was detected by Western blot. <b>Result::Compared with the sham control group, the Makin score was obviously increased in the model group, the protein expression of STAT3 was increased significantly, the mRNA of IL-6 was raised significantly, but the protein expression of WIF1 was decreased significantly (<italic>P</italic><0.01), articular cartilage was seriously damaged, and chondrocytes were arranged in disorder. Compared with the model group, the Makin score was declined obviously in the high-dose Youguiwan group, the protein expression of STAT3 was significantly reduced, the mRNA expression of IL-6 was significantly reduced in Youguiwan treatment group, while the protein expression of WIF1 was significantly increased (<italic>P</italic><0.05, <italic>P</italic><0.01), the cartilage structure returned to be normal, the chondrocytes distribution was uneven, and articular cartilage surface was not smooth. <b>Conclusion::Youguiwan could significantly improve the articular cartilage degeneration of KOA rats, and inhibit the inflammation of chondrocytes, which may be related to the suppression of STAT3 and IL-6 expression.

Reflections on the Establishment of Clinical Comprehensive Evaluation Mechanism for Drugs in China / 中国药房

OBJECTIVE：To prom ote the implementation of clinical comprehensive evaluation of drugs in China ，promote the return of drugs to clinical value ，improve the utilization efficiency of limited resources ，and provide reference for decision makers of health departments. METHODS ：By combing the relevant policy documents and literatures of clinical comprehensive evaluation of drugs，the evolution and research progress of relevant policies in China were introduced ；the advanced experiences （including evaluation subjects ，evaluation value dimensions ，evaluation methods ，evaluation procedures and results applications ）of Canada ，the United States ，the United Kingdom ，Australia，Europe，International Society for Pharmacoeconomics and Outcomes Research and other countries （regions/organizations）were analyzed and summarized ；relevant suggestions on the construction of China ’s clinical comprehensive evaluation mechanism for drugs were put forward. RESULTS & CONCLUSIONS ：It is suggested that the following measures should be taken to construct the clinical comprehensive evaluation mechanism of drugs in China including that the development goal and orientation of clinical comprehensive evaluation of drugs should be further clarified with the guidance of decision-making needs ；the government should play a leading role and strengthen inter departmental cooperation and policy coordination；the traceability quality control system of internal and external standards should be established ，adhere to openness ， fairness and fair ；at the same time ，it is suggested to give full play to the role of informatization and big data ，strengthen the exploration of evaluation methodology and standards ，strengthen the transformation and application of evaluation results ，and promote the service of evaluation results to policy decision-making.

Epigenetic role of N 6-methyladenosine (m6A) RNA methylation in the cardiovascular system / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

As the most prevalent and abundant transcriptional modification in the eukaryotic genome, the continuous and dynamic regulation of N6-methyladenosine (m6A) has been shown to play a vital role in physiological and pathological processes of cardiovascular diseases (CVDs), such as ischemic heart failure (HF), myocardial hypertrophy, myocardial infarction (MI), and cardiomyogenesis. Regulation is achieved by modulating the expression of m6A enzymes and their downstream cardiac genes. In addition, this process has a major impact on different aspects of internal biological metabolism and several other external environmental effects associated with the development of CVDs. However, the exact molecular mechanism of m6A epigenetic regulation has not been fully elucidated. In this review, we outline recent advances and discuss potential therapeutic strategies for managing m6A in relation to several common CVD-related metabolic disorders and external environmental factors. Note that an appropriate understanding of the biological function of m6A in the cardiovascular system will pave the way towards exploring the mechanisms responsible for the development of other CVDs and their associated symptoms. Finally, it can provide new insights for the development of novel therapeutic agents for use in clinical practice.