The Effect of Mitochondrial Damage in Chondrocytes on Osteoarthritis / 生物化学与生物物理进展

The pathogenesis of osteoarthritis (OA) is related to a variety of factors such as mechanical overload, metabolic dysfunction, aging, etc., and is a group of total joint diseases characterized by intra-articular chondrocyte apoptosis, cartilage fibrillations, synovial inflammation, and osteophyte formation. At present, the treatment methods for osteoarthritis include glucosamine, non-steroidal anti-inflammatory drugs, intra-articular injection of sodium hyaluronate, etc., which are difficult to take effect in a short period of time and require long-term treatment, so the patients struggle to adhere to doctor’s advice. Some methods can only provide temporary relief without chondrocyte protection, and some even increase the risk of cardiovascular disease and gastrointestinal disease. In the advanced stages of OA, patients often have to undergo joint replacement surgery due to pain and joint dysfunction. Mitochondrial dysfunction plays an important role in the development of OA. It is possible to improve mitochondrial biogenesis, quality control, autophagy balance, and oxidative stress levels, thereby exerting a protective effect on chondrocytes in OA. Therefore, compared to traditional treatments, improving mitochondrial function may be a potential treatment for OA. Here, we collected relevant literature on mitochondrial research in OA in recent years, summarized the potential pathogenic factors that affect the development of OA through mitochondrial pathways, and elaborated on relevant treatment methods, in order to provide new diagnostic and therapeutic ideas for the research field of osteoarthritis.

Hepatotoxicity and mechanism of Rhododendri Mollis Flos based on zebrafish model / 中国中药杂志

This study used the zebrafish model to explore the hepatotoxicity of Rhododendri Mollis Flos(RMF). The mortality was calculated according to the number of the survival of zebrafish larvae 4 days after fertilization under different concentration of RMF, and the dose-toxicity curve was fitted to preliminarily evaluate the toxicity of RMF. The liver phenotypes under the sublethal concentration of RMF in the treatment group and the blank control group were observed by hematoxylin-eosin(HE) staining and acridine orange(AO) staining. Meanwhile, the activities of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were determined to confirm the hepatotoxicity of RMF. Real-time quantitative polymerase chain reaction(real-time PCR) and Western blot were used to determine the expressions of genes and proteins in zebrafish larvae. Gas chromatography time-of-flight mass spectrometry(GC-TOF-MS) was used to conduct untargeted metabolomics testing to explore the mechanism. The results showed that the toxicity of RMF to zebrafish larvae was dose-dependent, with 1 100 μg·mL~(-1) of the absolute lethal concentration and 448 μg·mL~(-1) of sublethal concentration. The hepatocyte apoptosis and degeneration appeared in the zebrafish larvae under the sublethal concentration of RMF. The content of ALT and AST in zebrafish larvae at the end of the experiment was significantly increased in a dose-dependent manner. Under the sublethal concentration, the expressions of genes and proteins related to apoptosis in zebrafish larvae were significantly increased as compared with the blank control group. The results of untargeted metabolomics showed that the important metabolites related to the he-patotoxicity of RMF were mainly enriched in alanine, aspartic acid, glutamic acid, and other pathways. In conclusion, it is inferred that RMF has certain hepatotoxicity to zebrafish larvae, and its mechanism may be related to apoptosis.

Correlation of probiotic consumption with serum inflammatory cytokines, endotoxin and post-stroke depression severity in patients with ischemic stroke / 国际脑血管病杂志

Objective:To investigate the correlation of probiotic consumption level with serum inflammatory cytokines, endotoxin and post-stroke depression (PSD) severity in patients with ischemic stroke.Methods:Patients with ischemic stroke visited the Department of Neurology, the Third Affiliated Hospital of Naval Medical University from May 2021 to June 2022 were prospectively included. At 6 months after discharge, the outpatient follow-up was conducted to investigate the consumption of probiotic products in the past six months, and depression was evaluated using the Self-rating Depression Scale (SDS). Multiple linear regression analysis was used to determine the correlation of consumption levels of probiotic products and serum inflammatory cytokines, endotoxin, and PSD severity.Results:A total of 168 patients with ischemic stroke were included, including 74 patients (44.0%) in the probiotic product high consumption group and 94 (56.0%) in the low consumption group. The incidence of PSD in the high consumption group was significantly lower than that in the low consumption group (22.97% vs. 38.30%; χ2=6.551, P=0.036). The serum pro-inflammatory cytokine interleukin-6 (IL-6) and endotoxin levels at the follow-up in the high consumption group were significantly lower than those in the low consumption group, while the anti-inflammatory cytokine IL-10 was significantly higher than that in the low consumption group (all P<0.05). Multiple linear regression analysis shows that the probiotic consumption level was significantly negatively correlated with the serum IL-6 ( β=-0.178, P=0.001) and endotoxin ( β=-0.107, P=0.035) at follow-up. PSD severity (SDS score) was negatively correlated with probiotic consumption level ( β=-0.309, P=0.001), and was positively correlated with IL-6 ( β=0.306, P=0.027) and endotoxin ( β=0.360, P=0.017) at follow-up. Conclusion:Probiotic products can reduce the severity of serum pro-inflammatory cytokines, endotoxin and PSD, and may be a non-drug treatment direction for PSD.

Application of nanotechnology in local anesthetic drug sustained release and light-responsive controlled release / 药学学报

Local anesthetic drugs are commonly used to block the conduction function of patient's nerves temporarily for anesthesia during surgery or to provide targeted analgesia after trauma. Compared with general anesthetics, local anesthetics makes less impact on the physiological status and alleviates pain complications in the presence of clear consciousness. However, its clinical application is still limited by its systemic toxicity, as well as toxicity to nerves and muscles, duration of action and lack of penetration. Nanotechnology can help it penetrate the physiological barrier, prolong the time of nerve block, and reduce toxic side effects. In addition, by building a light-responsive release system, local anesthetics can be released on demand, enhancing drug effectiveness and safety. However, in addition to the problems of poor consistency and high production costs, the system of light response release is still limited in application due to the limitation of the depth of penetration of the tissue. According to the current research progress, this paper briefly introduces and analyzes the main dosage forms, hoping to provide new ideas for the responsive release of local anesthetic drugs.

The Pathology of Primary Familial Brain Calcification: Implications for Treatment / 神经科学通报·英文版

Primary familial brain calcification (PFBC) is an inherited neurodegenerative disorder mainly characterized by progressive calcium deposition bilaterally in the brain, accompanied by various symptoms, such as dystonia, ataxia, parkinsonism, dementia, depression, headaches, and epilepsy. Currently, the etiology of PFBC is largely unknown, and no specific prevention or treatment is available. During the past 10 years, six causative genes (SLC20A2, PDGFRB, PDGFB, XPR1, MYORG, and JAM2) have been identified in PFBC. In this review, considering mechanistic studies of these genes at the cellular level and in animals, we summarize the pathogenesis and potential preventive and therapeutic strategies for PFBC patients. Our systematic analysis suggests a classification for PFBC genetic etiology based on several characteristics, provides a summary of the known composition of brain calcification, and identifies some potential therapeutic targets for PFBC.

Risk factor analysis of lymph node metastasis in endometrial carcinoma combined with molecular types / 中华妇产科杂志

Objective: To investigate the relationships between molecular types of the cancer genome atlas (TCGA) of patients with endometrial carcinoma (EC) and lymph node metastasis and other clinicopathological features. Methods: The clinical pathological information of 295 patients with EC who underwent initial inpatient surgical treatment and accepted the detection of the molecular types of TCGA with next-generation sequencing technology at Peking University People's Hospital were collected during April 2016 and May 2022. The TCGA molecular typing of EC was divided into four types: POLE-ultramutated (15 cases), high microsatellite instability (MSI-H; 50 cases), copy-number low (CNL; 175 cases), and copy-number high (CNH; 55 cases). The differences of clinical pathological features among different molecular types and the risk factors of lymph node metastasis were analyzed retrospectively. Results: Among 295 patients with EC, the average age was (56.9±0.6) years. (1) There was a statistically significant difference in lymph node metastasis (0, 8.0%, 10.3% and 25.5%) among the four molecular types (χ2=12.524, P=0.006). There were significant differences in age, stage, pathological type, grade (only endometrioid carcinoma), myometrium invasion, lymphatic vascular space infiltration, and estrogen receptor among the EC patients of four molecular types (all P<0.05). Among them, while in the patients with CNH type, the pathological grade was G3, the pathological type was non-endometrioid carcinoma, and the proportion of myographic infiltration depth ≥1/2 were higher (all P<0.05). (2) Univariate analysis suggested that pathological type, grade, myometrium infiltration depth, cervical interstitial infiltration, lymphatic vascular space infiltration, and progesterone receptor were all factors which significantly influence lymph node metastasis (all P<0.01); multivariate analysis suggested that the lymphatic vascular space infiltration was an independent risk factor for lymph node metastasis (OR=5.884, 95%CI: 1.633-21.211; P=0.007). (3) The factors related to lymph node metastasis were different in patients with different molecular types. In the patients with MSI-H, the non-endometrioid carcinoma of pathological type was independent risk factor for lymph node metastasis (OR=29.010, 95%CI: 2.067-407.173; P=0.012). In the patients with CNL, myometrium infiltration depth≥1/2 (OR=4.995, 95%CI: 1.225-20.376; P=0.025), lymphatic vascular space infiltration (OR=14.577, 95%CI: 3.603-58.968; P<0.001) were the independent risk factors for lymph node metastasis. While in the CNH type patients pathological type of non-endometrioid carcinoma (OR=7.451, 95%CI: 1.127-49.281; P=0.037), cervical interstitial infiltration (OR=22.938, 95%CI: 1.207-436.012; P=0.037), lymphatic vascular space infiltration (OR=9.404, 95%CI: 1.609-54.969; P=0.013), were the independent risk factors for lymph node metastasis. Conclusions: POLE-ultramutated EC patients have the lowest risk of lymph node metastasis, and CNH patients have the highest risk of lymph node metastasis. The risk factors of lymph node metastasis of different molecular types are different. According to preoperative pathological and imaging data, lymph node metastasis is more likely to occur in patients with non-endometrioid carcinoma in MSI-H and CNH type patients, and lymph node metastasis is more likely to occur in patients with myometrium infiltration depth ≥1/2 in CNL type patients.

Effects of preoperative diagnostic hysteroscopy on peritoneal cytology and prognosis in patients with non-endometrioid carcinoma / 中华妇产科杂志

Objective: To explore the effects of preoperative hysteroscopic guided biopsy and segmental diagnosis and curettage on the risk of abdominal dissemination and prognosis of non-endometrioid carcinoma. Methods: The clinical and pathological data of 97 patients who underwent surgical treatment and were pathologically confirmed as non-endometrioid carcinoma (including serous carcinoma, clear cell carcinoma, mixed adenocarcinoma, and undifferentiated carcinoma, etc.) from October 2008 to December 2021 in Peking University People's Hospital, were collected for retrospective analysis. According to preoperative diagnostic methods, they were divided into hysteroscopic group (n=44) and non-hysteroscopic group (n=53). The impact of hysteroscopy examination on peritoneal cytology and prognosis was analyzed. Results: (1) There were no statistical differences in age, body mass index, tumor size, pathological characteristics, and treatment methods between the hysteroscopic group and the non-hysteroscopic group (all P>0.05), but the proportion of stage Ⅰ-Ⅱ patients in the hysteroscopic group was significantly higher than that in the non-hysteroscopic group [68% (30/44) vs 47% (25/53); χ2=4.32, P=0.038]. (2) Among 97 patients, 25 (26%, 25/97) of them were cytologically positive for ascites. The hysteroscopic group had a lower positive rate of peritoneal cytology than that in the non-hysteroscopy group, which was significantly different [11% (5/44) vs 38% (20/53); χ2=8.74, P=0.003]. Stratification according to surgical and pathological stages showed that the positive rate of peritoneal cytology in the hysteroscopic group (3%, 1/30) was lower than that in the non-hysteroscopic group (12%, 3/25) in the 55 patients with stage Ⅰ-Ⅱ, and that in the hysteroscopic group (4/14) was also lower than that in the non-hysteroscopic group (61%, 17/28) in the 42 patients with stage Ⅲ-Ⅳ. There were no significant differences (all P>0.05). (3) The 5-year disease-free survival (DFS) rate of the hysteroscopic group and the non-hysteroscopic group were respectively 72.7% and 60.4%, and there was no significant difference between the two groups (P=0.186). After stratification according to staging, the 5-year DFS rate were respectively 90.0% and 72.0% (P=0.051) between the hysteroscopic and non-hysteroscopic groups of patients in stage Ⅰ-Ⅱ, and 35.7% and 50.0% (P=0.218) between the hysteroscopic and non-hysteroscopic groups of patients in stage Ⅲ-Ⅳ, in which there were not statistically significant differences. The 5-year overall survival (OS) rate were respectively 86.4% and 81.1% between the hysteroscopic group and the non-hysteroscopic group, with no significant difference between the two groups (P=0.388). The 5-year OS rate were respectively 93.3% and 96.0% in the hysteroscopic group and non-hysteroscopic group for patients with stage Ⅰ-Ⅱ(P=0.872), and 71.4% and 67.9% in the hysteroscopic group and non-hysteroscopic group in patients with stage Ⅲ-Ⅳ (P=0.999), with no statistical significance. Conclusions: Diagnostic hysteroscopy do not increase the rate of positive peritoneal cytology result at the time of surgery in this cohort, and no significant correlation between preoperative hysteroscopy examination and poor prognosis of non-endometrioid carcinoma is observed. Therefore, preoperative hysteroscopic guided biopsy and segmental diagnosis and curettage in non-endometrioid carcinoma maybe safe.

Prognosis analysis of radical or modified radical hysterectomy and simple hysterectomy in patients with stage Ⅱ endometrial cancer / 中华妇产科杂志

Objective: To compare the prognosis and perioperative situation of patients with stage Ⅱ endometrial cancer (EC) between radical hysterectomy/modified radical hysterectomy (RH/mRH) and simple hysterectomy (SH). Methods: A total of 47 patients diagnosed EC with stage Ⅱ [International Federation of Gynecology and Obstetrics (FIGO) 2009] by postoperative pathology, from January 2006 to January 2021 in Peking University People's Hospital, were analyzed retrospectively. The patients were (54.4±10.7) years old, and the median follow-up time was 65 months (ranged 9-138 months). They were divided into RH/mRH group (n=14) and SH group (n=33) according to the scope of operation. Then the prognosis of patients between the groups were compared, and the independent prognostic factors of stage Ⅱ EC were explored. Results: (1) The proportions of patients with hypertension in RH/mRH group and SH group were 2/14 and 45% (15/33), the amounts of intraoperative blood loss were (702±392) and (438±298) ml, and the incidence of postoperative complications were 7/14 and 15% (5/33), respectively. There were significant differences (all P<0.05). (2) The median follow-up time of RH/mRH group and SH group were 72 vs 62 months, respectively (P=0.515). According to Kaplan-Meier analysis and log-rank method, the results showed that there were no significant difference in 5-year progression-free survival (PFS) rate (94.3% vs 84.0%; P=0.501), and 5-year overall survival rate (92.3% vs 92.9%; P=0.957) between the two groups. Cox survival analysis indicated that age, pathological type, serum cancer antigen 125 (CA125), and estrogen receptor (ER) status were associated with 5-year PFS rate (all P<0.05). But the scope of hysterectomy (RH/mRH and SH) did not affect the 5-year PFS rate of stage Ⅱ EC patients (P=0.508). And level of serum CA125 and ER status were independent prognostic factors for 5-year PFS rate (all P<0.05). Conclusions: This study could not find any survival benefit from RH/mRH for stage Ⅱ EC, but increases the incidence of postoperative complications. Therefore, the necessity of extending the scope of hysterectomy is questionable.

Retrospective Clinical Study on Integrated Chinese and Western Medicine in Treatment of Limited-Stage Small Cell Lung Cancer / 中国结合医学杂志

OBJECTIVE@#To investigate the efficacy of integrated Chinese and Western medicine extending the progression-free survival (PFS) and overall survival (OS) of limited-stage small cell lung cancer (LS-SCLC) patients after the first-line chemoradiotherapy.@*METHODS@#The data of 67 LS-SCLC patients who received combined treatment of CM and Western medicine (WM) between January 2013 and May 2020 at the outpatient clinic of Guang'anmen Hospital were retrospectively analyzed. Thirty-six LS-SCLC patients who received only WM treatment was used as the WM control group. The medical data of the two groups were statistically analyzed. Survival analysis was performed using the product-limit method (Kaplan-Meier analysis). The median OS and PFS were calculated, and survival curves were compared by the Log rank test. The cumulative survival rates at 1, 2, and 5 years were estimated by the life table analysis. Stratified survival analysis was performed between patients with different CM administration time.@*RESULTS@#The median PFS in the CM and WM combination treatment group and the WM group were 19 months (95% CI: 12.357-25.643) vs. 9 months (95% CI: 5.957-12.043), HR=0.43 (95% CI: 0.27-0.69, P<0.001), respectively. The median OS in the CM and WM combination group and the WM group were 34 months (95% CI could not be calculated) vs. 18.63 months (95% CI: 16.425-20.835), HR=0.40 (95% CI: 0.24-0.66, P<0.001), respectively. Similar results were obtained in the further stratified analysis of whether the duration of CM administration exceeded 18 and 24 months (P<0.001).@*CONCLUSION@#The combination treatment of CM and WM with continuing oral administration of CM treatment after the first-line chemoradiotherapy for LS-SCLC patients produced better prognosis, lower risks of progression, and longer survival than the WM treatment alone. (Registration No. ChiCTR2200056616).

Correlation between consumption of probiotic products and post-stroke depression in patients with ischemic stroke / 国际脑血管病杂志

Objective:To investigate the correlation between the consumption level of probiotic products and post-stroke depression (PSD).Methods:Patients with ischemic stroke visited the Department of Neurology, the Third Affiliated Hospital of Naval Medical University from May 2021 to January 2022 were prospectively enrolled. According to self-rating depression scale (SDS), they were divided into PSD group (SDS score ≥53) and non-PSD group (SDS score <53). The influence factors of PSD were determined by comparing the demographic data, clinical data and consumption level of probiotic products between the two groups. Multivariate logistic regression analysis was used to determine the independent correlation between PSD and the consumption level of probiotic products. Results:A total of 120 patients with ischemic stroke were enrolled, including 39 (32.5%) in the PSD group and 81 (67.5%) in the non-PSD group. Multivariate logistic regression analysis showed that after adjusting for potential confounding factors, the severity of infarction (odds ratio 1.276, 95% confidence interval 1.138-1.432; P<0.001) and the consumption level of probiotic products (odds ratio 0.300, 95% confidence interval 0.098-0.916; P=0.035) were the independent influencing factors of PSD. Conclusion:The consumption level of probiotic products is an independent protective factor for PSD, and higher consumption level of probiotic products is associated with lower PSD incidence.

Qi-Tai-Suan, an oleanolic acid derivative, ameliorates ischemic heart failure via suppression of cardiac apoptosis, inflammation and fibrosis / 中国天然药物

Although anti-thrombotic therapy has been successful for prevention of deaths from acute myocardial infarction (MI), by far, there are few preventive and therapeutic options for ischemic heart failure (IHF) after MI. Qi-Tai-Suan (QTS) is an oleanolic acid (OA) derivative which once underwent a clinical trial for treating hepatitis. In this study, we investigated the potential cardioprotective effect of QTS on IHF. IHF mouse model was constructed by coronary artery ligation in male C57BL/6J mice, and the protective effects of QTS on IHF were examined by echocardiography measurement, histological and TUNEL analysis, etc. We found that QTS exhibited promising cardioprotective effect on IHF. QTS treatment significantly improved cardiac function of IHF mice and the symptoms of heart failure. Notably, QTS had much better oral bioavailability (F = 41.91%) in mice than its parent drug OA, and took effects mainly as its original form. Mechanistically, QTS ameliorated ischemic heart failure likely through suppression of cardiac apoptosis, inflammation and fibrosis. Taken together, QTS holds great promise as a preventive and therapeutic agent for ischemic heart failure and related diseases.

Correlation analysis between corneal biomechanical parameters and high-order aberrations in myopia children / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate the correlation between corneal biomechanical parameters measured by the corneal visualization Scheimpflug Technology(Corvis ST)and corneal high-order aberrations(HOAs)in children with mild to moderate myopia.METHODS:A cross-sectional study. A total of 255 pediatric patients with myopia enrolled from April to July 2021 in Tianjin Medical University Eye Hospital were continuously collected, and all the right eyes were taken for analysis. Corneal biomechanical parameters were obtained from Corvis ST. Pentacam three-dimensional anterior segment analyzer was used to measure total corneal higher-order aberrations(RMSh), third order aberrations(RMS3)and fourth order aberrations(RMS4).RESULTS:RMS3 was positively correlated with the second applanation time(A2T)(r=0.175, P=0.009)and negatively correlated with the axis length(AL)(r=-0.155, P=0.014). RMS4 was negatively correlated with the highest concavity radius(HCR)(r=-0.165, P=0.009). RMSh was negatively correlated with HCR and AL(r=-0.152, P=0.037; r=-0.175, P=0.005).CONCLUSION:There is a correlation between corneal biomechanical parameters and HOAs in children with myopia. Cornea with higher stiffness and stronger deformation resistance has smaller RMS3, RMS4 and RMSh.

Clinical Randomized Controlled Observation of Modified Wuhutang in Treatment of Acute Asthma in Children / 中国实验方剂学杂志

ObjectiveTo explore the clinical effect of modified Wuhutang in the treatment of children with acute asthma. MethodA total of 130 children with acute asthma were randomly divided into an observation group and a control group， with 65 cases in each group. The observation group was treated with modified Wuhutang and the control group was treated with procaterol hydrochloride for one week. The scores of primary symptoms （wheezing， cough， shortness of breath， and chest tightness） and secondary symptoms （mental status， runny nose， dry mouth， tongue texture， tongue coating， stool， etc.）， lung functions， immunoglobulin E （IgE） expression， eosinophil （EOS） count， and serum inflammatory factors， including interleukin （IL）-5， IL-6， IL-8， and IL-1β in two groups before and after treatment were compared. ResultThe data of 126 children were statistically analyzed. As revealed by the results， compared with the conditions before treatment， the scores of primary symptoms and secondary symptoms， serum levels of IL， IgE expression， and EOS count were both reduced in two groups （P<0.05）， lung functions were increased in the two groups（P<0.05）. Compared with the control group after treatment， the observation group showed decreased scores of cough and secondary symptoms （P<0.05）， and insignificant decrease in IL-1β （P<0.05）. The improvement in lung functions， IgE expression， and EOS count in observation group was equivalent to that in control group. ConclusionModified Wuhutang for treatment of acute asthma in children （phlegm-heat obstructing lung syndrome） can significantly relieve the clinical symptoms， improve lung functions， and reduce IgE， IL-5， IL-6， IL-8， IL-1β expression levels and EOS count， and its overall clinical efficacy is superior or equivalent to that of tprocaterol hydrochloride.

Meta-analysis on efficacy of PCI treatment or conservative treatment among patients with chronic total occlusions / 中华心血管病杂志

Objective: To compare the efficacy between percutaneous coronary intervention (PCI) and conservative medication treatment in chronic total occlusions (CTO) patients. Methods: It was a meta-analysis.Articles on drug therapy and PCI for complete coronary artery occlusion were retrieved from Pubmed, Embase and Web of Science databases. The search time was from the database construction to May 10, 2020, and the following search criteria were used for the search "chronic total occlusion" "percutaneous coronary intervention" and "medical therapy". References from searched literatures were also searched to identify more eligible studies. Randomized controlled trials (RCT) and cohort studies comparing efficacy of PCI versus oral medication as well as medication as initial therapy option for CTO patients with single or multiple lesions were included. The primary endpoints included all-cause death, cardiac death, recurrent myocardial infarction, re-revascularization, major adverse cardiac events (MACE) and stroke. Data were analyzed with ReviewManager5.3.0 software. Pooled effect size RR and 95%CI were calculated by randomization effect model. Heterogeneity was evaluated by I2. Bege test was used to evaluate publication bias. Subgroup analyses were performed for RCT and cohort studies. Results: A total of 1 079 articles were retrieved and 16 studies (RCT=4, cohort study=12) were included with 12 223 patients. Fourteen publications (RCT=4, cohort study=10) reported all-cause death post PCI and/or drug therapy. Results showed that risk of all-cause death was significantly lower in PCI group than in drug therapy group (RR=0.45,95%CI 0.39-0.53,P<0.001);subgroup analysis showed that risk of all-cause death was significantly lower in PCI group than in drug therapy group from cohort studies (RR=0.44,95%CI 0.38-0.52,P<0.001),but comparable in RCT (P=0.27). Thirteen studies (RCT=3, cohort study=10) reported cardiac death post PCI and/or drug therapy. Results showed that risk of cardiac death was significantly lower in PCI group than in drug therapy group (RR=0.44,95%CI 0.35-0.55,P<0.001);subgroup analysis showed that risk of cardiac death was significantly lower in PCI group than in drug therapy group in cohort studies (RR=0.43,95%CI 0.34-0.54,P<0.001),but not in RCT (P=0.25). Fourteen publications (RCT=4, cohort study=10) reported recurrent myocardial infarction post PCI and/or drug therapy. Results showed that risk of recurrent myocardial infarction was significantly lower in PCI group than in drug therapy group (RR=0.62,95%CI 0.44-0.88,P=0.007);subgroup analysis showed that risk of recurrent myocardial infarction was significantly lower in PCI group than in drug therapy group from cohort studies (RR=0.56,95%CI 0.40-0.78,P=0.000 5),but comparable in RCT (P=0.17). Fourteen publications (RCT=4, cohort study=10) reported re-revascularization post PCI and/or drug therapy. Results showed that risk of re-revascularization was comparable between PCI group and drug therapy group (P=0.91);subgroup analysis showed that risk of re-revascularization was comparable between PCI group and drug therapy group both in cohort study and RCT (P=0.60 and 0.41, respectively). Eleven publications (RCT=3, cohort study=8) reported MACE post PCI and/or drug therapy. Results showed that risk of MACE was significantly lower in PCI group than in drug therapy group (RR=0.74,95%CI 0.59-0.93,P=0.03);subgroup analysis showed that risk of MACE was significantly lower in PCI group than in drug therapy group in cohort studies (RR=0.72,95%CI 0.56-0.93,P=0.01), but not in RCT (P=0.8). Six publications (RCT=2, cohort study=4) reported stroke post PCI and/or drug therapy. Results showed that risk of stroke was comparable between PCI and drug therapy groups (RR=0.62,95%CI 0.32-1.20, P=0.15);subgroup analysis showed that risk of stroke was comparable between PCI and drug therapy groups both in cohort studies and RCT (P=0.48 and 0.32, respectively). Conclusion: Compared with oral drug therapy, PCI may have better efficacy for CTO patients based on results from this cohort study.

Study on liver diseases with zebrafish as an important tool / 中国中药杂志

With the increasing incidence of hepatobiliary diseases, it is particularly important to understand the role of molecular, cellular and physiological factors in the clinical diagnosis and treatment with traditional Chinese medicine(TCM) in the development of liver disease. Appropriate animal models can help us identify the possible mechanisms of relevant diseases. Danio rerio(zebrafish) model was traditionally used to study embryonic development, and has been gradually used in screening and evaluation of liver diseases and relevant drug in recent years. Zebrafish embryos develop rapidly and the digestive organs of 5-day-old juvenile fish are all mature. At this stage, they may develop hepatobiliary diseases induced by developmental defects or compounds. Zebrafish liver is similar to human liver in cell composition, function, signal transduction, response to injury and cell process mediating liver disease. Furthermore, due to the high conservation of genes and proteins between humans and zebrafish, zebrafish becomes an alternative system for studying basic mechanisms of liver disease. Therefore, genetic screening could be performed to identify new genes involving specific disease processes, and chemical screening could be made for drugs in specific processes. This paper briefly introduced the experimental properties of zebrafish as model system, emphasized the study progress of zebrafish models for pathological mechanism of liver diseases, especially fatty liver, and drug screening and evaluation, so as to provide ideas and techniques for the future liver toxicity assessment of TCM.

NLRP3 inflammasome and development of diabetic cardiomyopathy / 中国药理学通报

Diabetic cardiomyopathy(DCM) is a specific cardiac complication of diabetes, which occurs independently of coronary artery disease, hypertension or valvular heart disease. Although diabetic cardiomyopathy is increasingly recognized, the underlying mechanisms are still under controversial. Recently, the putative pathological mechanism involves hyperglycemia, protein nonenzymatic glycosylation, oxidative stress, abnormal calcium ion transport, etc. Inflammation is an independent risk factor for left ventricular diastolic dysfunction. NLRP3 inflammation is the most common inflammasome, which can secrete pro-inflammatory cytokines such as IL-1β, IL-18, and mediate pyroptosis after activated. It manifests a high level of NLRP3 inflammasomes in DCM animal model, which aggravates the damage of pancreatic β-cell function, myocardial injury and the process of myocardial fibrosis. It has been confirmed that Chinese herbal medicine can affect the initiation and activation of NLRP3 inflammasomes, as well as the expression of downstream genes, and then improve the cardiac function of diabetic cardiomyopathy. In this paper, we have summarized the involvement of NLRP3 inflammasomes in the process of diabetic cardiomyopathy and the therapeutic effects of Chinese herbal medicine.

Research Progress on Processing of Polygalae Radix / 中国实验方剂学杂志

Polygalae Radix， a traditional Chinese medicine， has the functions of improving intelligence， calming nerves， relieving cough and eliminating phlegm. Its processing methods are various， but the purpose of processing is to reduce toxicity and increase efficiency. In this paper， the methods of ancient processing， such as cleansing， cutting， processing with excipient and processing without excipient， were summarized， the processing methods of Polygalae Radix in the different versions of Chinese Pharmacopoeia and the local processing specifications were summarized， in order to compare the differences and research progress of different processing methods. On this basis， taking the modern research of processed products of Polygalae Radix as the breakthrough point， this paper reviewed the modern research on processed products of Polygalae Radix from the aspects of processing technology， chemical composition changes and pharmacodynamics changes before and after processing， and the mechanism of reducing toxicity and increasing efficiency. Based on the research status of processing of Polygalae Radix， some existing problems were analyzed in this paper， including not many ancient processing methods used in modern times， lack of standardized research on processing technology， few studies on the ingredients introduced by excipients， etc. The author thinks that it is necessary to strengthen the research on the ancient processing of Polygalae Radix combined with processing methods with local characteristics. While discussing the processing technology， combining with the composition and efficacy， we should carry out in-depth research on the processing mechanism of different processing products of Polygalae Radix， so as to provide scientific basis for the rationality of processing of Polygalae Radix and ensure the clinical safety of medication.

Secukinumab demonstrates high efficacy and a favorable safety profile over 52 weeks in Chinese patients with moderate to severe plaque psoriasis / 中华医学杂志(英文版)

BACKGROUND@#Psoriasis is a chronic inflammatory skin disease, affecting about 0.6% of the Chinese population. Many patients are not well controlled by conventional treatments, thus there is need for new treatment regimens. In this study, we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis.@*METHODS@#This study was a 52-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 trial. A sub-population of study participants (≥18 years) of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab, or placebo. The co-primary endpoints were psoriasis area severity index (PASI) 75 and Investigator's Global Assessment (IGA) 0/1 at Week 12.@*RESULTS@#A total of 441 Chinese patients were enrolled in this study. Co-primary outcomes were achieved; 300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75 (97.7% and 87.2% vs. 3.7%, respectively; P < 0.001), and IGA 0/1 (82.3% and 69.7% vs. 2.7%; P < 0.001) at Week 12. Treatment efficacy was maintained until Week 52. There was no increase in overall adverse events with secukinumab relative to placebo throughout the 52-week period.@*CONCLUSION@#Secukinumab is highly effective and well tolerated in Chinese patients with moderate to severe plaque psoriasis.@*TRIAL REGISTRATION@#ClinicalTrials.gov, NCT03066609; https://clinicaltrials.gov/ct2/show/record/NCT03066609.

Effects of alprostadil in β-aminopropanitrile induced aortic dissection in a murine model / 中华心血管病杂志

Objective: To investigate the protective role of alprostadil on aortic dissection. Methods: 26 C57BL6 male mice were divided into control group (normal drinking water, n=13) and model group (1 g·kg-1·d-1 BAPN via drinking water, n=13). On day 14, mRNA expression of inflammatory-related genes as well as EP receptor families were detected by RT-PCR (n=6 each) and EP4 protein levels were determined by Western blot (n=7 each). Another 88 mice were divided into 3 groups: control group (n=22), model group (n=33) and treatment group (n=33). The mice in model group and treatment group were applied with BAPN (1 g·kg-1·d-1) via drinking water. The mice in treatment group received additional intraperitoneal injection with alprostadil (80 μg·kg-1·d-1) for 28 days. The mice in the control and model group received equal volume intraperitoneal injection with 0.9% saline respectively. The body weight and systolic blood pressure, the mortality and morbidity were monitored from the beginning until the designed end of the study. On day 28, the mice were sacrificed and aorta were fixed, embedded and sliced, followed by staining with HE and Victoria Blue. The distribution of EP4 was determined by immunohistochemistry in control (n=6) and model group (n=6). Furthermore, the concentration of PGE1 were tested among model (n=3) and treatment group (n=4). EP4 protein expression was determined in model group (n=7) and treatment group (n=6). Results: On day 14, mRNA expression level of MCP-1 ((2.74±1.55) vs. (1.00±0.49),<0.05) and MMP2((1.38±0.42) vs. (1.00±0.27), P<0.05) was significantly upregulated in model group compared with control group. Protein expression of EP4 receptor also increased in aorta in model group compared with control group (1.48±0.51 vs. 1.00±0.19, P<0.05). In the dissection area, the EP4 expression was also enriched compared with non-dissection area, particularly in endothelial cells and inflammatory cells on day 28. BAPN applied in drinking water (model and treatment groups) successfully induced the aortic dissection in mice, some mice died of the rupture. The elastic fibers were fractured, and the infiltrated immune cells were visible in dissected tissue. False lumen was formed. There was no dissection and death in the control group. Compared with control group, the morbidity and mortality rates were significantly increased in the model group (60.6%, 20/33, 30.3%, 10/33) and the treatment group (72.7%, 24/33, 24.2%, 8/33). The mortality and morbidity rates were similar between model and treatment groups. There is no difference in terms of SBP among three groups (P>0.05). Further study showed that after alprostadil injection, the blood concentration of PGE1 was increased in treatment group ((0.540±0.041 vs. 0.436±0.012)μmol/L, P<0.05). Besides, the EP4 receptor expression was downregulated in the treatment group compared to model group (0.60±0.30 vs. 1.00±0.20, P<0.05). Conclusion: EP4 expression is upregulated in BAPN induced aortic dissection mouse model. No protective effects are observed post alprostadil treatment in this model probably due to the reduced expression of EP4.

Correlation between Coronary Artery Tortuosity and Stenosis in Patients with Myocardial Bridge / 中国医学科学院学报

Objective To analyze the correlation between tortuosity and stenosis in patients with myocardial bridge(MB)on the left anterior descending artery(LAD). Methods Data of patients with MB on the LAD,which was discovered by coronary computed tomography angiography(CCTA),in the Affiliated Hospital of North China University of Science and Technology from October 2015 to December 2018 were retrospectively analyzed.Among them 278 patients with tortuosity on LAD and 278 patients without tortuosity were selected.The clinical charateristics(age,gender,hypertension,hyperlipidemia,diabetes,smoking history,and family history)as well as the incidence and severity of stenosis of LAD were recorded and compared. Results The incidence of coronary artery stenosis in the non-tortuosity group(57.6%)was significantly lower than that in the tortuosity group(71.9%)($\bar{χ}$=12.608,