Value of transrectal multimodal ultrasound combined with prostate specific antigen in predicting clinically organ-confined prostate cancer / 中华健康管理学杂志

Objective:To explore the predictive value of transrectal multimodal ultrasound and prostate specific antigen (PSA) in clinically organ-confined prostate cancer.Methods:It was a cross-sectional study. The clinical data of patients with suspected prostate nodules treated in the First Hospital of Shanxi Medical University from May 2014 to April 2020 were analyzed retrospectively. Of the patients, 48 cases of clinically organ-confined prostate cancer and 51 cases of benign prostatic hyperplasia confirmed by clinical data and pathology were selected as research objects. The characteristics of transrectal multimodal ultrasound in the two groups were compared. Combined with PSA, logistic regression analysis was applied to screen the statistically significant features, and then the diagnosis model was established, and odds ratio of the variables were compared. The receiver operating characteristic (ROC) curve was constructed to analyze the predicting ability of the diagnosis model.Results:Four features were obtained with logistic regression analysis finally, including enhancement type, enhancement degree, elastography mode and PSA. The odds ratio of enhancement degree was higher than those of the other independent variables. The area under ROC curve of the diagnosis model was 0.868 ( P<0.01), the cut-off value was 0.514. The sensitivity and specificity of the diagnosis model in predicting clinically organ-confined prostate cancer was 79.2% and 80.4%, respectively. Conclusions:This combined diagnosis model of transrectal multimodal ultrasound and PSA has a certain clinical value in predicting clinically organ-confined prostate cancer.

Discovery of a highly potent and orally available importin-β1 inhibitor that overcomes enzalutamide-resistance in advanced prostate cancer

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.

Use of recombinant microRNAs as antimetabolites to inhibit human non-small cell lung cancer

During the development of therapeutic microRNAs (miRNAs or miRs), it is essential to define their pharmacological actions. Rather, miRNA research and therapy mainly use miRNA mimics synthesized in vitro. After experimental screening of unique recombinant miRNAs produced in vivo, three lead antiproliferative miRNAs against human NSCLC cells, miR-22-3p, miR-9-5p, and miR-218-5p, were revealed to target folate metabolism by bioinformatic analyses. Recombinant miR-22-3p, miR-9-5p, and miR-218-5p were shown to regulate key folate metabolic enzymes to inhibit folate metabolism and subsequently alter amino acid metabolome in NSCLC A549 and H1975 cells. Isotope tracing studies further confirmed the disruption of one-carbon transfer from serine to folate metabolites by all three miRNAs, inhibition of glucose uptake by miR-22-3p, and reduction of serine biosynthesis from glucose by miR-9-5p and -218-5p in NSCLC cells. With greater activities to interrupt NSCLC cell respiration, glycolysis, and colony formation than miR-9-5p and -218-5p, recombinant miR-22-3p was effective to reduce tumor growth in two NSCLC patient-derived xenograft mouse models without causing any toxicity. These results establish a common antifolate mechanism and differential actions on glucose uptake and metabolism for three lead anticancer miRNAs as well as antitumor efficacy for miR-22-3p nanomedicine, which shall provide insight into developing antimetabolite RNA therapies.

Repeated stellate ganglion blockade for the treatment of ventricular tachycardia storm in patients with nonischemic cardiomyopathy: a new therapeutic option for patients with malignant arrhythmias / 中华心血管病杂志

Objectives: This study sought to describe our institutional experience of repeated percutaneous stellate ganglion blockade (R-SGB) as a treatment option for drug-refractory electrical storm in patients with nonischemic cardiomyopathy (NICM). Methods: This prospective observational study included 8 consecutive NICM patients who had drug-refractory electrical storm and underwent R-SGB between June 1, 2021 and January 31, 2022. Lidocaine (5 ml, 1%) was injected in the vicinity of the left stellate ganglion under the guidance of ultrasound, once per day for 7 days. Data including clinical characteristics, immediate and long-term outcomes, and procedure related complications were collected. Results: The mean age was (51.5±13.6) years. All patients were male. 5 patients were diagnosed as dilated cardiomyopathy, 2 patients as arrhythmogenic right ventricular cardiomyopathy and 1 patient as hypertrophic cardiomyopathy. The left ventricular ejection fraction was 37.8%±6.6%. After the treatment of R-SGB, 6 (75%) patients were free of electrical storm. 24 hours Holter monitoring showed significant reduction in ventricular tachycardia (VT) episodes from 43.0 (13.3, 276.3) to 1.0 (0.3, 34.0) on the first day following R-SGB (P<0.05) and 0.5 (0.0, 19.3) after whole R-SGB process (P<0.05). There were no procedure-related major complications. The mean follow-up was (4.8±1.1) months, and the median time of recurrent VT was 2 months. Conclusion: Minimally invasive R-SGB is a safe and effective method to treat electrical storm in patients with NICM.

Determination of H2S in rat brain tissues by GC-MS based on bispentafluorobenzyl sulphide / 中国药理学通报

Aim To establish a method for the determination of hydrogen sulfide ( H2S) in rat brain tissues by gas chromatogra- phy-mass spectrometry (GC-MS) on bispentafluorobenzyl sulfide ( C6F5CH2SCH2C6F5 ).Methods Chromatographic conditions: Hie column was HP-5MS(30 m x 250 jxm x 0.25 |xm) and temperature programmed, the injection port temperature was 280 V..Mass spectrometry conditions: The electron bombardment ion source was 20 eV.'Hie ion source, quadrupole and interface temperature was kept at 230.150 and 280 XI, respectively, The MRM mode was used to quantitatively and qualitatively analyze the C6F5CH2SCH2C6F5 ion pair (m/z 394->181, m/z 181->161 ), Results The concentration of sodium hydro- sulfide( NaHS) in brain tissue samples had good linearity in the range of 0.25 ~256 jxmol • L~'.'Hie limit of detection was 0.1 jxmol • L~'.'Hie intra-day and inter-day precision were both less than 15%.There was no obvious matrix effect and the recover)' rate was more than 90%.'Hie H2S concentration in brain tissues could be selectively determined.'Hie basic H2S concentration in rat brain cortex was measured to be ( 11.84 ±0.38) jxmol • L_l.After intravenous injection of NaHS.the H2S concentration in brain tissues increased significantly in a dose-de- pendent manner.Conclusions The GC-MS method based on C6F5CH2SCH2C6F3 established here is reliable and effective to investigate H2S in brain tissues, and H2S could enter brain tissues through the blood-brain barrier.

Role of H2S produced by CSE in cerebral ischemia-reperfusion injury in mice and its relationship with RhoA-ROCK2 signaling pathway / 中国药理学通报

Aim To investigate the role of H2S pro¬duced by CSE in cerebral ischemia-reperfusion ( I/R) injury and its relationship with RhoA-ROCK2 signaling pathway.Methods Bilateral common carotid artery ligation was used to prepare a mouse cerebral ischemia- reperfusion injury model.Laser speckle method was used to detect cerebral blood flow, HE staining method was used to observe the pathological changes of brain hippocampus, and the activity of LDH, NSE, RhoA and ROCK,, H,S content and ROCK, protein expres¬sion were detected.Results The H,S synthase CSE substrate L-Cys ( 3(X) mg • kg-1) could significantly promote the recovery of cerebral blood flow in brain 1/ R mice, improve the pathological damage of hippocam¬pus , inhibit the increase of LDH activity in serum and NSE, RhoA and ROCK2 activity in brain tissues, and inhibit the decrease of serum H2S content and the in¬crease of ROCK2 protein expression in brain tissues.But the above effects of L-Cys could be significantly at¬tenuated by the CSE inhibitor PPG (50 mg • kg~ 1 ) ; the H2S donor NaHS (4.8 mg • kg"1 ) also had the same effect as L-Cys did.Conclusions H2S pro¬duced by CSE has a protective effect on mouse brain 1/ R injury, and its effect may be related to inhibiting RhoA-ROCK signaling pathway and increasing cerebral blood flow.

Analysis on repetitive reporting of hepatitis B in Fujian province, 2016-2020 / 中华流行病学杂志

Objective: To analyze the repetitive reporting of hepatitis B in Fujian province during 2016-2020, and provide evidence for the improvement of hepatitis B surveillance. Methods: The reporting cards from the China Information System for Disease Control and Prevention were collected and divided into repetitive reporting cards and non-repetitive reporting cards from the report cards collected according to the valid ID number on the cards, and the proportion of repetitive report cards and related factors were analyzed by using software SAS 9.4. Results: A total of 314 551 hepatitis B reporting cards were submitted in Fujian from 2016 to 2020, in which 90.93% (286 020/314 551) were included in the analysis. The repetitive reporting cards accounted for 10.48% (29 982/286 020). The annual proportion of the repetitive reporting cards from 2016 to 2020 was between 2.98% and 3.71%, showing an overall increasing trend year by year (Z=2.26, P=0.024). The proportions of the repetitive reporting cards in 1-5 years were 3.17%, 5.40%, 7.74%, 9.27% and 10.48%, respectively, showing an increase trend with year (Z=128.16, P<0.001). The proportions of the repetitive reporting cards in 10 areas of Fujian ranged from 5.44% to 13.48% with significant difference (χ2=2 050.41, P<0.001) and increased with the increase of reported incidence of hepatitis B (Z=26.92, P<0.001). There were significant differences in relationships between repetitive reporting proportion and sex, age and type of the cases between the areas with high incidence and low incidence of hepatitis B. Conclusions: The reported incidence of hepatitis B was seriously affected by the repetitive reporting in Fujian from 2016 to 2020. A cross-year and cross-area surveillance mechanism for hepatitis B should be established and targeted measures should be taken to strengthen the control of the repetitive reporting and improve the surveillance for hepatitis B.

Sperm-specific protein ACTL7A as a biomarker for fertilization outcomes of assisted reproductive technology / 亚洲男科学杂志(英文版)

Obtaining high-quality embryos is one of the key factors to improve the clinical pregnancy rate of assisted reproductive technologies (ART). So far, the clinical evaluation of embryo quality depends on embryo morphology. However, the clinical pregnancy rate is still low. Therefore, new indicators are needed to further improve the evaluation of embryo quality. Several studies have shown that the decrease of sperm-specific protein actin-like 7A (ACTL7A) leaded to low fertilization rate, poor embryo development, and even infertility. The aim of this study was to study whether the different expression levels of ACTL7A on sperm can be used as a biomarker for predicting embryo quality. In this study, excluding the factors of severe female infertility, a total of 281 sperm samples were collected to compare the ACTL7A expression levels of sperms with high and low effective embryo rates and analyze the correlation between protein levels and in-vitro fertilization (IVF) laboratory outcomes. Our results indicated that the ACTL7A levels were significantly reduced in sperm samples presenting poor embryo quality. Furthermore, the protein levels showed a significant correlation with fertilization outcomes of ART. ACTL7A has the potential to be a biomarker for predicting success rate of fertilization and effective embryo and the possibility of embryo arrest. In conclusion, sperm-specific protein ACTL7A has a strong correlation with IVF laboratory outcomes and plays important roles in fertilization and embryo development.

Arthroscopic debridement combined with platelet-rich plasma injection for the treatment of Kellgren-Lawrence gradeⅠ-Ⅲ knee osteoarthritis / 中国骨伤

OBJECTIVE@#To explore clinical effect of arthroscopic debridement combined with platelet-rich plasma (PRP) injection for Kellgren-Lawrence(K-L) gradeⅠ-Ⅲ knee osteoarthritis (KOA) .@*METHODS@#Totally 117 patients with KOA who underwent arthroscopic debridement combined with injection from November 2015 to January 2019 were retrospectively analyzed. According to different injection drugs, the patients were divided into sodium hyaluronate group(group A) and PRP group(group B). In group A, there were 60 patients, including 27 males and 33 females, aged from 49 to 67 years old with an average age of (54.1±4.8) years old;12 patients with gradeⅠ, 23 patients with gradeⅡand 25 patients with grade Ⅲ according to K-L clssification, 2 ml(20 g) sodium hyaluronate was injected into knee joint after intraoperative, 1, 2, 3 weeks after operation for 4 times. In group B, there were 57 patients, including 25 males and 32 females, aged from 47 to 70 years old with an average of (55.8±5.0) years old, 10 patients with gradeⅠ, 20 patients with gradeⅡand 27 patients with grade Ⅲ according to K-L classification, injected 5 ml PRP at the same time. Postoperative complications was recorded between two groups. Postoperative visual analogue scale(VAS) and Lysholm score at 3, 6, 12 months were used to evaluate improvement of knee pain and joint function.@*RESULTS@#All patients were followed up for 12 to 19 months with an average of (14.1±1.6) months. There was no significant difference in postopertaive complications between group A and group B (P>0.05). Postoperative VAS score in group A at 3, 6, 12 months were 3.0±0.8, 2.0±0.8, 2.6±0.9 respectively, and 2.9±0.8, 1.9±0.7, 2.2±0.8 in group B respectively; and no differnece at 3 and 6 months after operation between two groups (P<0.05), while VAS score in group B was higher than group A at 12 months after operation(P<0.05). Postoperative Lysholm score in group A at 1, 6, 12 months (86.6±1.8, 93.1±2.0, 86.7±1.7) were lower than group B(88.9±1.9, 95.0±2.0, 89.0±1.9)(P<0.05).@*CONCLUSION@#Arthroscopic debridement combined with sodium hyaluronate or PRP injection for K-L gradeⅠ-Ⅲ KOA could effectively relieve pain and improve joint function with higher safety in short term, but the medium-long-term effect of PRP injection is stable.

Clinical characteristics and long-term follow-up results of radiofrequency ablation for the treatment of ventricular tachycardia in patients with arrhythmogenic left ventricular cardiomyopathy / 中华心血管病杂志

Objective: To investigate the acute and long-term outcome of catheter ablation for the treatment of ventricular tachycardia (VT) in patients with arrhythmogenic left ventricular cardiomyopathy (ALVC). Methods: This retrospective, cross-sectional study enrolled ALVC patients undergoing radiofrequency ablation for the treatment of VT at the First Affiliated Hospital of Nanjing Medical University from January 2011 to December 2018 and collected their clinical characteristics and intraoperative electrophysiological examination. Patients were followed up every 6 months after radiofrequency ablation until August 2021. Echocardiographic results and VT recurrence post radiofrequency ablation were analysed. Results: Totally 12 patients were enrolled (mean age: (42±15) years, 11 males(11/12)). The mean of left ventricular end diastolic diameter (LVDd) and left ventricular ejection fraction (LVEF) were (51±5)mm and (65±5)%, respectively. Twelve VTs were induced in 10 patients during the electrophysiological study, and the mean tachycardia cycle length was (293±65) ms. Three-dimensional substrate mapping revealed the diseased area at endocardial site in one patient, at epicardial sites in the other 11 patients (involved endocardial sites in 2 cases) with the basal part near the mitral annulus being the predilection for the substrate (10/11). After the catheter ablation at the endocardial and epicardial sites respectively, the complete procedure endpoint was achieved in all patients (VT cannot be induced post ablation). The median follow-up time was 65 (25, 123) months. One patient was lost to follow-up, and the other 11 patients survived without VT. No significant cardiac function deterioration was detected by the echocardiographic examination ((51±5)mm vs. (52±5)mm, P>0.05 for LVDd, (65±5)% vs. (60±6)%, P>0.05 for LVEF) at the end of follow-up. Conclusion: After radiofrequency ablation, the complete procedure endpoint is achieved in ALVC patients, and the catheter ablation provides long-term ventricular tachycardia control during the long-term follow-up.

Risk factors of long-term mortality in patients with acute pulmonary embolism and the predictive value of echocardiography / 中华全科医师杂志

Objective:To investigate the risk factors of long-term mortality in patients with acute pulmonary embolism (APE) and to explore the predictive value of echocardiography.Methods:A total of 109 APE patients admitted in First Hospital of Shanxi Medical University between December 2010 and November 2014 were enrolled in this study. APE was diagnosed by computed tomography pulmonary angiography (CTPA) or ventilation-perfusion pulmonary scintigraphy. Transthoracic echocardiography (TTE) parameters and clinical parameters within 48 h of onset were collected. All the patients were treated with standard anticoagulation, thrombolysis, or thrombectomy. Regular follow-up was carried out, with the average follow-up period of (7.20±1.04) years. The patients were divided into survival group and fatal group according to their follow-up results. The echocardiographic parameters and primary biochemical laboratory parameters within 48 h after onset were compared between the survival group and the fatal group by t test or χ 2 test. Cox regression analysis was conducted to analyze the influencing factors of long-term prognosis of patients with APE. Survival analysis was performed in patients with echocardiographic assessment of right ventricular (RV) enlargement and/or dysfunction and without RV enlargement and/or dysfunction by Kaplan-Meier method, and the survival curves were plotted. The comparison between the two groups was performed by log-rank test. Results:The average follow-up period was (7.20±1.04) years. Fourteen patients were lost in the follow-up, and 95 patients were included in the final analysis, among whom 58 survived and 37 died with a fatality rate of 39.0%. Cox regression analysis showed that age ( HR=2.32, 95% CI:1.31-4.13, P=0.004), malignancy ( HR=6.49, 95% CI:2.32-18.14, P<0.001), right atrial (RA)/left atrial (LA) area ratio ( HR=2.01, 95% CI:1.16-3.48, P=0.013), RV enlargement and/or dysfunction ( HR=5.90, 95% CI: 1.45-23.94, P=0.013), Charlson comorbidity index (CCI) score ( HR=1.75, 95% CI: 1.04-2.96, P=0.035), low oxygen saturation ( HR=1.70, 95% CI:1.14-2.53, P=0.009) were independent risk factors associated with long-term mortality in patients with APE. Kaplan Meier survival curve analysis showed that the cumulative survival rates of patients with RV enlargement and/or dysfunction at 1, 3, 5 and 7 years were 92.8%, 66.7%, 59.4% and 52.2% respectively, and those without RV enlargement and/or dysfunction were 96.2%, 92.3%, 84.6% and 84.6%,respectively (log rank test, P=0.006). Conclusions:Patients with APE have high long-term mortality. Early echocardiographic RV enlargement and/or dysfunction, RA/LA area ratio, age, malignant tumor, CCI score and low oxygen saturation are independent risk factors related to long-term mortality in patients with APE. Ultrasound evaluation of patients with RV enlargement and/or dysfunction has a certain value in predicting long-term mortality in patients with pulmonary embolism.

Xintahua water extract improves the disease indexes of atherosclerosis model rats / 中国临床药理学与治疗学

AIM: To investigate the effect of water extract of Ziziphora clinopodioides Lam (WEZ) on improving atherosclerosis model rats. METHODS: Sixty SD rats were randomly selected and 50 rats of them were randomly selected for atherosclerosis model with high-fat emulsion and vitamin D3, and then randomly divided into atherosclerosis (AS) model group, low, medium, high WEZ group and the positive control group. After 8 weeks of drug intervention, the plasma of each group of rats was collected to detect total cholesterol (TC), triglyceride (TG), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and trimethylamine oxide (TMAO) level. The correlation between plasma TMAO and TNF-α and IL-6 levels in AS rats was detected. The aortic tissue-embedded sections of rats in each group were taken out to compare the aortic plaque area/aortic lumen area (PA/LA) ratio. RESULTS: Compared with the blank control group, the serum TC and TG levels of the AS model group increased significantly, and the difference was statistically significant (P<0.01). Compared with the AS model group, the serum TC and TG levels of the middle and high dose WEZ group and the positive control group were significantly decreased, and the difference was statistically significant (P<0.05). Compared with the blank control group, the serum TNF-α and IL-6 levels in the AS model group increased significantly, and the difference was statistically significant (P<0.01). Compared with the AS model group, the serum TNF-α and IL-6 levels of the high-dose WEZ group and the positive control group were significantly decreased, and the difference was statistically significant (P<0.05). Compared with the blank control group, the plasma TMAO level of rats in the AS model group increased significantly, and the difference was statistically significant (P<0.01). Compared with the AS model group, the plasma TMAO levels of rats in the high-dose WEZ group and the positive control group decreased significantly, and the difference was statistically significant (P<0.05). The analysis of the correlation between TMAO level and TNF-α/IL-6 level showed that TMAO level was positively correlated with TNF-α level (P=0.001, r=0.673), and positively correlated with IL-6 level (P=0.002, r= 0.646). Compared with the blank control group, the PA/LA ratio of the AS model group increased significantly, and the difference was statistically significant (P<0.01). Compared with the AS model group, the PA/LA ratio of rats in the medium and high dose WEZ group and the positive control group decreased significantly, and the difference was statistically significant (P<0.05). CONCLUSION: WEZ may regulate TMAO levels, down-regulate TNF-α and IL-6 levels, and reduces TC and TG levels, thereby improving AS, but its mechanism still needs further study.

Effect of CBS-derived H2S from mouse nerve cells on proliferation and migration of brain microvascular endothelial cells and its relationship with VEGFR2 / 中国药理学通报

Aim To study the effect of H2S synthase CBS-derived H2S from mouse nerve cells on the proliferation and migration of the brain vascular endothelial cells and its relationship with VEGFR2. Methods CCK-8 method was used to detect cell proliferation, cell scratch method and Transwell method were used to detect cell migration, methyl blue method was used to detect H2S content, and calcium fluorescence imaging method was used to detect intracellular free Ca2 + concentration. HT22 cells were co-cultured with bEnd. 3 cells by using Transwell system. Results The H2S donor NaHS( 1 xlO"8-1 X 10"3'5 mol • L'1) significantly increased the proliferation and migration of HU- VEC cells and bEnd. 3 cells, while the VEGFR2 blocker SU5416 (10 (xmol • L"1) markedly inhibited the NaHS- increased proliferation and migration; in the co-culture system,the substrate of H2S synthase CBS, L-Cys (100 |xmol • L"1) , significantly promoted the proliferation and migration of bEnd. 3 cells, and increased intracellular Ca2 + fluorescence intensity in bEnd. 3 cells and the H2S content in the co-culture. However, CBS inhibitor AO A A (1 mmol • L"1 ) and SU5416 significantly attenuated the effects of L-Cys on the proliferation and migration and intracellular Ca2 + fluorescence intensity. Conclusions The CBS-derived H2S from neurons can promote the proliferation and migration of mouse cerebral vascular endothelial cells, which may be related to activation of VEGFR2 and subsequently increase of intracellular free Ca2+ concentration.

Role of S-sulfhydration of RhoA kinase in neuroprotection of hydrogen sulfide against hypoxic injury / 中国药理学通报

Aim To investigate the role of S-sulfhydration of RhoA kinase 2 in the neuroprotection of hydrogen sulfide (H2S) against hypoxic injury. Methods Rat hippocampal neurons were primarily cultured and treated with exogenous H2S donor NaHS (50, 100, 200 (xmol • L"1 ) and S-sulfhydration inhibitor DTT (50 (xmol • L"1 during 4 hours of hypoxia and 12 hours of reoxygenation. Cell viability, the lactate dehydrogenase (LDH) activity and neuron-specific enolase (NSE) activity released from injured neuron to culture supernatant, and the proportion of apoptotic cells were measured to assess the neuroprotection of H2S, and the role of S-sulfhydration in the neuroprotection of H2S was preliminarily explored. In addition, the S-sulf- hydrated proteins in neurons were isolated and purified by modified biotin-switch assay. And then, the RhoA kinase 2 (ROCK2) expression and activity, and S-sul- fhydrated ROCK2 were detected to further confirm the role H2S on the S-sulfhydrated ROCK2 by Western blot and assay kits, respectively. Results The decrease of cell viability, and the increase of LDH and NSE released from injured neuron to culture supernatant and cell apoptosis after hypoxia/ reoxygenation ( H/R) were significantly inhibited by 100 and 200 |imol • L"1 NaHS. Compared with the effect of 200 jimol • L"1 NaHS, the neuroprotection of 200 (xmol • L"1 NaHS could be inhibited by co-application with DTT. Furthermore, 100 and 200 (junol • L"1 NaHS could reduce the expression of R0CK2 protein and restrain ROCK2 activity via promoting the S-sulfhydryl modification of ROCK2 protein in hippocampal neurons. Conclusions H2S exerts protective effect on H/R injury of rat hippocampal neurons via down-regulation of ROCK2 expression and inhibition of R0CK2 activity by S-sulfhydration modification.

Association between periodontal indexes and biomarkers in gingival crevicular fluid and preterm birth in pregnancy: a nested case-control study / 华西口腔医学杂志

OBJECTIVES@#This study aimed to investigate the association between periodontal indexes and biomarkers in gingival crevicular fluid (GCF) and preterm birth (PTB) in pregnancy, as well as to assess the clinical value of these indexes as predictors of PTB.@*METHODS@#A nested case-control study was conducted. A total of 300 systematically healthy pregnant women were selected within 36 weeks of gestation and grouped according to the enrolled weeks. Periodontal indexes, including probing depth (PD), bleeding index (BI), gingival index (GI), and five biomarkers in GCF, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2), and 8-hydroxy-2-deoxyguanosine (8-OHdG) were measured at the enrolled date. The detailed birth outcome was recorded.@*RESULTS@#Only women at 24-28 weeks of gestation per PTB case (four full-term births) were selected as controls subjects, PTB displayed significantly greater GI, BI, and 8-OHdG (@*CONCLUSIONS@#Increased BI and 8-OHdG at 24-28 weeks of gestation are risk factors for PTB. Their combined detection may have some value in the prediction of PTB, but further studies with a larger sample size are needed to explore it and thus provide experiment evidence for establishing an early warning system for PTB in pregnant women with periodontal disease.

The anti-neoplastic activities of aloperine in HeLa cervical cancer cells are associated with inhibition of the IL-6-JAK1-STAT3 feedback loop / 中国天然药物

Cervical cancer (CC) is recognized as the most common neoplasm in the female reproductive system worldwide. The lack of chemotherapeutic agents with outstanding effectiveness and safety severely compromises the anti-cipated prognosis of patients. Aloperine (ALO) is a natural quinolizidine alkaloid with marked anti-cancer effects on multiple malignancies as well as favorable activity in relieving inflammation, allergies and infection. However, its therapeutic efficacy and underlying mechanism in CC are still unclear. In the current study, MTT assay was employed to evaluate the viability of HeLa cells exposed to ALO to preliminarily estimate the effectiveness of ALO in CC. Then, the effects of ALO on the proliferation and apoptosis of HeLa cells were further investigated by plate colony formation and flow cytometry, respectively, while the migration and invasion of ALO-treated HeLa cells were evaluated using Transwell assay. Moreover, nude mice were subcutaneously inoculated with HeLa cells to demonstrate the anti-CC properties of ALO in vivo. The molecular mechanisms underlying these effects of ALO were evaluated by Western blot and immunohistochemical analysis. This study experimentally demonstrated that ALO inhibited the proliferation of HeLa cells via G2 phase cell cycle arrest. Simultaneously, ALO promoted an increase in the percentage of apoptotic HeLa cells by increasing the Bax/Bcl-2 ratio. Additionally, the migration and invasion of HeLa cells were attenuated by ALO treatment, which was considered to result from inhibition of epithelial-to-mesenchymal transition. For molecular mechanisms, the expression and activation of the IL-6-JAK1-STAT3 feedback loop were markedly suppressed by ALO treatment. This study indicated that ALO markedly suppresses the proliferation, migration and invasion and enhances the apoptosis of HeLa cells. In addition, these prominent anti-CC properties of ALO are associated with repression of the IL-6-JAK1-STAT3 feedback loop.

Research progress in mechanism of mesenchymal stem cells-derived exosomes treating spinal cord injury / 中华创伤杂志

Secondary injury and the glial scar after spinal cord injury can adversely affect nerve regeneration in the microenvironment, leading to treatment difficulties. Mesenchymal stem cells (MSCs) have multi-differentiation, self-renewal ability, participation in immune regulation and other functions and can be used to treat spinal cord injury, but they are not easy to pass the blood spine barrier and have high tumorigenicity and other disadvantages. MSCs-derived exosomes are nanometer exosomes secreted by MSCs, which contain many active substances. These exosomes have a strong neurorepair effect in spinal cord injury research, and have advantages of easy penetration, stability and low tumorigenicity, etc. These exosomes make up for the disadvantages of MSCs treatment, and are expected to replace MSCs in treatment of spinal cord injury. The authors review the biological characteristics of MSCs-derived exosomes and its mechanism in the treatment of spinal cord injury, so as to provide references for the treatment of spinal cord injury.

Epidemiological characteristics of the notifiable infectious diseases reported in Zhejiang Province, 2020 / 预防医学

Objective@#To analyze the epidemiological characteristics of notifiable infectious diseases reported in Zhejiang Province in 2020 for prevention and control.@*Methods@#Data of notifiable infectious diseases reported in Zhejiang Province in 2020 were extracted from China Information System for Disease Control and Prevention. The incidence and death of notifiable infectious diseases were analyzed and compared with the averages from 2015 to 2019; then the characteristics of some key diseases such as coronavirus disease 2019 ( COVID-19 ), influenza and other infectious diarrhea were summarized. @*Results@#Totally 487 271 cases of 30 kinds of infectious diseases were reported. The incidence and mortality rate was 832.94/100 000 and 0.615 4/100 000, which were 7.05% and 14.60% lower than the average value of 2015-2019.The weekly morbidity of Class A and Class B infectious diseases fluctuated between 1.24/100 000 and 3.68/100 000, and hit the bottom in the sixth to eighth week. The morbidity of Class C infectious diseases was 154.19/100 000 in the first week, then dropped to 4.83/100 000 in the second to sixth week and maintained at a low level. High morbidity of infectious diseases were reported in Hangzhou ( 1 412.62/100 000 ), Jinhua ( 960.35/100 000 ) and Ningbo ( 921.25/100 000 ). The morbidity of class C infectious diseases in Hangzhou was 1 248.80/100 000, which was far higher than that of other ten prefecture-level cities. The diseases with high reported morbidity were influenza (438.45/100 000), other infectious diarrhea (140.29/100 000 ), hand-foot-and-mouth disease ( 99.64/100 000 ), pulmonary tuberculosis ( 41.92/100 000 ), syphilis (41.37/100 000) and viral hepatitis ( 30.48/100 000 ). More deaths were reported in AIDS and pulmonary tuberculosis, and the mortality were 0.482 1/100 000 and 0.116 2/100 000. A total of 1 306 confirmed cases, 302 asymptomatic infections and 1 death of COVID-19 were reported. @*Conclusion@#In 2020, the incidence rate of notifiable infectious diseases in Zhejiang decreased compared with the average value of 2015-2019. Pulmonary tuberculosis, syphilis and hepatitis B still have high morbidity, and the COVID-19 epidemic spread widely. The morbidity of some respiratory infectious diseases and imported infectious diseases have dropped significantly compared with previous years.

Risk assessment of public health emergencies in Zhejiang Province, March 2021 / 预防医学

Objective@#To assess the risk of public health emergencies in Zhejiang Province, March 2021. @*Methods@#An expert counsel was conducted to assess the risk of coronavirus disease 2019 ( COVID-19 ) , enteritis due to norovirus, chicken pox and influenza by professionals in Zhejiang CDC, based on the information from infectious disease and public health emergency surveillance in Zhejiang Province, domestic health administrative departments, World Health Organization, and European CDC. @*Results@#In March 2021, the risk of imported COVID-19 epidemic will be high in Zhejiang Province, and the possibility of local spread could not be ruled out. The possibility of a large-scale outbreak of enteritis due to norovirus and a small-scale outbreak of chickenpox in schools and kindergartens could not be ruled out after the new term begins. An increased risk of influenza epidemic is predicted in collective units such as schools and kindergartens, yet the risk of a large-scale one will be low.@*Conclusion@#High attention should be paid to COVID-19 and enteritis due to norovirus, and general attention should be paid to chicken pox and influenza outbreak.

Superior effects of thoracic epidural block for analgesia in patients with severe acute pancreatitis / 中华麻醉学杂志

Objective:To evaluate the superior effect of thoracic epidural block (TEB) used for analgesia in patients with severe acute pancreatitis (SAP).Methods:Fifty patients of both sexes, aged 18-64 yr, with SAP, with Japanese severity score (JSS) ≥3, onset time of SAP≤12 h, were divided into conventional analgesia group (group C) and TEB group.Sufentanil was intravenously infused for analgesia in group C. TEB was performed for analgesia in group TEB.In group C, sufentanil was intravenously infused at a rate of 0.2-0.3 μg·kg -1·h -1 after admission to hospital.In group TEB, an epidural catheter was placed at T 9, 10 interspace, and 0.66% lidocaine mixed with 0.33% ropivacaine was epidurally infused at a rate of 3-5 ml/h for 120 h after admission to hospital.Visual analog scale (VAS) score and intra-abdominal pressure (IAP) were recorded at 1, 24, 48, 72 and 120 h of analgesia.HR, respiratory rate (RR), oxygenation index, computed tomography severity index (CTSI), JSS and Ranson scores were recorded at 24, 72 and 120 h of analgesia, and the de-criticalization within 72 h following analgesia was evaluated. Results:Compared with group C, VAS score and IAP were significantly deceased at each time point ( P<0.05), the rate of de-criticalization (60%/90%) was increased ( P<0.05), and Ranson score, CTSI score and JSS score were decreased at 120 h of analgesia in group TEB ( P<0.05). Conclusion:TEB can not only produce good analgesic effect, but also improve the development of the disease, which has superior effect compared with routine analgesia when used for the treatment of SAP.