Therapeutic effects of estrogen-intervened EPCs transplantation on diabetic ischemic stroke rats / 药学实践杂志

Objective To explore the therapeutic effects of estrogen-intervened endothelial progenitor cells( EPCs) transplantation on diabetic ischemic stroke rats. Methods PKH26-labeled diabetic EPCs and estrogen-intervened diabetic EPCs were injected into rats via the tail vein 24 h after cerebral ischemia. Cerebral ischemic volume, behavioral changes, ischemic site vascularization and homing of EPCs were measured 3 d after EPCs injection. Results Compared with diabetic ischemic rats, estrogen-intervened EPCs transplantation had reduced infarct volumes, improved behavioral scores and ischemic site revascularization and promoted homing of EPCs to sites of injury(P<0.05). Conclusion Estrogen-intervened EPCs transplantation had a better therapeutic effect on diabetic ischemic stroke by promoting EPCs homing to injury site and EPCs-medicated neovascularization .

Benefits and risks of prolonged dual antiplatelet therapy after percutaneous coronary intervention with drug-eluting stent in patients with stable coronary artery disease and diabetes / 中华心血管病杂志

Objective: To compare the efficacy and safety of prolonged dual antiplatelet therapy (DAPT>1 year) in patients with stable coronary artery disease (CAD) and diabetes who were event-free at 1 year after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) in a large and contemporary PCI registry. Methods: A total of 1 661 eligible patients were selected from the Fuwai PCI Registry, of which 1 193 received DAPT>1 year and 468 received DAPT ≤1 year. The primary endpoint was major adverse cardiac and cerebrovascular event (MACCE) and Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding, MACCE was defined as a composite of all-cause death, myocardial infarction or stroke. Multivariate Cox regression analysis and inverse probability of treatment weighting (IPTW) Cox regression analysis were performed. Results: After a median follow-up of 2.5 years, patients who received DAPT>1 year were associated with lower risks of MACCE (1.4% vs. 3.2%; hazard ratio (HR) 0.412, 95% confidence interval (CI) 0.205-0.827) compared with DAPT ≤1 year, which was primarily caused by the lower all-cause mortality (0.1% vs. 2.6%; HR 0.031, 95%CI 0.004-0.236). Risks of cardiac death (0.1% vs. 1.5%; HR 0.051, 95%CI 0.006-0.416) and definite/probable ST (0.3% vs. 1.1%; HR 0.218, 95%CI 0.052-0.917) were also lower in patients received DAPT>1 year than those received DAPT ≤ 1 year. No difference was found between the two groups in terms of BARC type 2, 3, or 5 bleeding (5.3% vs. 4.1%; HR 1.088, 95%CI 0.650-1.821). Conclusions: In patients with stable CAD and diabetes who were event-free at 1 year after PCI with DES, prolonged DAPT (>1 year) provides a substantial reduction in ischemic cardiovascular events, including MACCE, all-cause mortality, cardiac mortality, and definite/probable ST, without increasing the clinically relevant bleeding risk compared with ≤ 1-year DAPT. Further well-designed, large-scale randomized trials are needed to verify the beneficial effect of prolonged DAPT in this population.

Effect and mechanism of estrogen on EPCs function in diabetic rats / 药学实践杂志

Objective To explore the effect and mechanism of estrogen on endothelial progenitor cells（EPCs）function in diabetic rats. Methods EPCs were isolated from bone marrow of rats and characterized by fluorescence microscopy and flow cytometry. Rat diabetic model was established via streptozotocin induction. The bone marrow was taken to culture EPCs. EPCs of diabetes were incubated with Estrogen 10 nmol/L for 24h. The functions and proliferation of EPCs in vitro were detected. The levels of MnSOD and NO in EPCs and TSP-1 in supernatant were assayed. Results Compared with control group, EPCs proliferation, adhesion and angiogenesis functions were impaired in diabetic rats. The level of MnSOD and NO in diabetic EPCs were significantly decreased, while TSP-1 protein level in the supernatant increased. The above changes can be reversed with estrogen incubation. Conclusion Estrogen improved the EPCs migration and tubule formation in diabetic rats. The mechanism may be related to the reduction of oxidative stress and downregulation of TSP-1 expression in diabetic EPCs.

The therapeutic effects of endoscopic ultrasound-guided coil embolization for gastric varices (with video) / 中华消化内镜杂志

Objective:To investigate the safety and efficacy of endoscopic ultrasound-guided coil embolization for gastric varices.Methods:Patients with portal hypertension who received endoscopic ultrasound-guided coil embolization for the prophylaxis of gastric variceal bleeding between November 2016 and August 2020 at Zhongshan Hospital, Fudan University were included in the study. The primary evaluation index was the post-operative loss of blood flow in gastric varices, and the secondary indices included the safety of coil embolization, rebleeding rate, portal vein thrombosis changes and patient survival.Results:A total of 13 patients with isolated gastric varices and portal systemic shunt were enrolled, including 6 males and 7 females with the median age of 58 years. The median maximum diameter of the target vessel was 40 mm and the median number of coils used was 2.7. All puncture sites were in the lower part of the esophagus near the cardia, and no active bleeding occurred after deployment of coils. Flow in the gastric varices were confirmed absent by Doppler imaging. In a median follow-up period of 403 days, 2 patients had rebleeding, with the one-year rebleeding rate of 9.1%.Two patients developed portal venous thrombosis after the operation. Two patients died, and the one-year survival rate was 90.0%.Conclusion:Endoscopic ultrasound-guided coil embolization might be an effective option for the treatment of isolated gastric varices with portal systemic shunts.

Mechanism of Huanglian Houpotang on Ulcerative Colitis by Network Pharmacology and Experimental Verification / 中国实验方剂学杂志

ObjectiveTo explore the active components and underlying mechanism of Huanglian Houpotang （HHD） against ulcerative colitis（UC） based on network pharmacology and animal experiments. MethodThe active components of HHD were preliminarily obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM） and screened out by TCMSP， SwissADME， and SwissTargetPrediction， and their targets were predicted. Relevant microarrays were searched for disease genes with the help of Gene Expression Omnibus （GEO）. The common targets of HHD and disease genes were screened out to obtain the potential targets of HHD against UC. The drug-active component-target-disease network was constructed using Cytoscape 3.7.2. The potential therapeutic targets were imported into the DAVID 6.8 for GO-Biological process （GO-BP） analysis to predict related biological processes which were subsequently verified by the animal experiment. Enzyme-linked immunosorbent assay （ELISA） was used to detect the effect of HHD on inflammatory factors in colon tissues of mice. Western blot was used to detect the protein expression of B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and cysteinyl aspartate-specific protease 3 （Caspase-3）. The IVIS system was used to detect the content of reactive oxygen species （ROS） in colon tissues of mice in each group. ResultNineteen active components of HHD were screened out， involving 32 potential therapeutic targets against UC and 158 biological processes. The results of the animal experiment showed that HHD exerted its anti-UC effect by inhibiting the expression of inflammatory factors tumor necrosis factor （TNF）-α and interleukin-1β （IL-1β）， reducing the content of apoptotic proteins， and regulating the expression of ROS. ConclusionThis study revealed the rationality of predictions and guidance of network pharmacology in experimental design， and confirmed that HHD could exert its effects by participating in biological processes such as immune inflammation， apoptosis， and ROS， which is expected to provide a basis for the mechanism research of HHD in the treatment of UC.

Molecular Mechanism of Shengxiantang in Treating Myasthenia Gravis： Based on Network Pharmacology and Molecular Docking / 中国实验方剂学杂志

ObjectiveTo predict the pharmacodynamic basis and core target of Shengxiantang in the treatment of myasthenia gravis （MG） by network pharmacology and molecular docking and to further verify the molecular mechanism through animal experiment. MethodThe active components and potential targets of Shengxiantang were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and the disease-related targets from GeneCards and other databases. Then the common targets of the decoction and the disease were screened out， followed by the construction of protein-protein interaction （PPI） network， and Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment of the common targets based on STRING database and Cytoscape 3.8.2. Afterward， Cytoscape 3.8.2 was employed to construct the disease-active component-target network. AutoDock and PyMOL were used for molecular docking of key components and hub genes. Finally， we used the Rα97-116 peptide to induce experimental autoimmune myasthenia gravis （EAMG） in rats and then verified the core target yielded in the docking with the model rats. ResultA total of 655 disease-related targets， 118 active components of the decoction， 21 common targets of the disease and the decoction， and 3 hub genes were screened out. The common targets were mainly involved in the GO terms of regulation of active oxygen metabolism， positive regulation of protein transport， and positive regulation of protein localization， and the KEGG pathways of toll-like receptor signaling pathway， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， hypoxia inducible factor-1 （HIF-1） signaling pathway， and T cell receptor signaling pathway. The results of molecular docking showed that quercetin and Akt1 had the lowest and stable binding energy and interacted with each other through the amino acid residue LYS-30. Western blot demonstrated that Shengxiantang significantly inhibited the expression of p-Akt protein in the spleen of EAMG rats. ConclusionThe pharmacological mechanism of Shengxiantang in the treatment of MG may be that the main chemical components regulate the expression of the core protein Akt， and then may participate in and affect PI3K/Akt signaling pathways， laying a theoretical and experimental basis for further research.

Anti-inflammation and Regulation of HIF-1α/VEGF of 3 Kinds of Borneolum in Prevention and Treatment of AMI Model Rats / 中国实验方剂学杂志

ObjectiveTo investigate the possible mechanism of different doses of L-Borneolum，Borneolum，and Borneolum Syntheticum in the electrophysiology，anti-inflammation，and regulation of hypoxia inducible factor-1α （HIF-1α）/vascular endothelial growth factor （VEGF） cardiovascular protection of the experimental acute myocardial infarction （AMI） rats. MethodSD male adult rats were randomly divided into thirteen groups according to their body weight，namely the sham operation group，the model group，the solvent model group，the nitroglycerin group，the Borneolum high，medium，and low-dose （0.6，0.3， 0.15 g·kg-1） groups，the L-Borneolum high，medium，and low-dose （0.2，0.1， 0.05 g·kg-1） groups，and the Borneolum Syntheticum high，medium，and low-dose （0.2，0.1， 0.05 g·kg-1） groups，with 10 rats in each group. Rats were given 10 mL·kg-1 by gavage for 3 d of pre-administration. Thirty minutes after the last administration，the left anterior descending coronary artery （LAD） was ligated to induce the model，and the successful rat model was continuously treated for 3 d. BL-420N biosystem was used to analyze the electrocardiogram （ECG） and heart rate variability （HRV） before and after modeling and after 3 d of treatment. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to determine the mRNA expressions of interleukin-1β （IL-1β） and interleukin-6 （IL-6） in the myocardial tissue Western blot and immunohistochemistry were used to determine the protein expression levels of VEGF receptor 1 （VEGFR1），HIF-1α，and CD34. ResultCompared with the sham operation group，the model group significantly increased the heart rate，ECG ST wave，T wave，QRS duration，QTC interval，and Q wave on the day of modeling and after 3 d of treatment，and significantly changed HRV and T wave （P<0.05，P<0.01）. As compared with the solvent model group，on the day of modeling，the heart rate of the L-Borneolum medium and low-dose groups and the Borneolum groups，the ST wave of the L-Borneolum groups，the Borneolum high and medium-dose groups，and the Borneolum Syntheticum high-dose group，HRV parameters of the L-Borneolum groups，the Borneolum medium and low-dose groups，and the Borneolum Syntheticum high-dose group，LF/HF of the L-Borneolum high and medium-dose group，the Borneolum low-dose group，and the Borneolum Syntheticum groups，T wave of the L-Borneolum high-dose group，the Borneolum Syntheticum high-dose group，and Borneolum medium-dose group，QTC interval of the L-Borneolum medium and low-dose groups and the Borneolum high and medium-dose groups，and QRS duration of the L-Borneolum high and low-dose groups，the Borneolum high and low-dose groups，and the Borneolum Syntheticum groups were significantly reduced or shortened （P<0.05，P<0.01）. After 3 d of treatment，the heart rate of the L-Borneolum groups，the Borneolum high and medium-dose groups，and the Borneolum Syntheticum medium-dose group，ST wave of the L-Borneolum group，the Borneolum high and medium-dose groups，and the Borneolum Syntheticum high-dose group，OTC interval，ORS duration，and Q wave of the L-Borneolum high-dose group，the Borneolum high-dose group，and the Borneolum Syntheticum high and medium-dose groups，QRS duration of the L-Borneolum medium-dose group，QTC interval of the Borneolum medium-dose group，and Q wave of the Borneolum Syntheticum low-dose group were all significantly reduced or shortened（P<0.01）. The mRNA expressions of IL-1β and IL-6 in the L-Borneolum medium and low-dose groups，the Borneolum medium and low-dose groups，and the Borneolum Syntheticum high and medium-dose groups were significantly down-regulated（P<0.01），and LF/HF in the L-Borneolum high and medium-dose groups，the Borneolum high and medium-dose groups，and the Borneolum Syntheticum high and low-dose groups were significantly reduced （P<0.05，P<0.01）. HRV in the L-Borneolum high-dose group，the Borneolum groups，and the Borneolum Syntheticum high and low-dose groups，and T wave in the Borneolum high and medium-dose groups and the Borneolum Syntheticum high-dose group were increased significantly. The protein expressions of HIF-1α，VEGFR1，and CD34 in the L-Borneolum medium and low-dose groups，the Borneolum low-dose group，and the Borneolum Syntheticum high-dose group were significantly up-regulated，as well as those of VEGFR1 and CD34 in the Borneolum medium-dose group （P<0.05，P<0.01）. ConclusionThe 3 kinds of Borneolum improves the heart rate，heart rate variability，and electrocardiogram of AMI model rats to different degrees，and may play a myocardial protective effect by anti-inflammation and promotion of angiogenesis. The combined effect suggests that L-Borneolum has the superior effect next to Borneolum，and Borneolum Syntheticum has the inferior effect.

Anti-inflammation and Regulation of HIF-1α/VEGF of 3 Kinds of Borneolum in Prevention and Treatment of AMI Model Rats / 中国实验方剂学杂志

ObjectiveTo investigate the possible mechanism of different doses of L-Borneolum，Borneolum，and Borneolum Syntheticum in the electrophysiology，anti-inflammation，and regulation of hypoxia inducible factor-1α （HIF-1α）/vascular endothelial growth factor （VEGF） cardiovascular protection of the experimental acute myocardial infarction （AMI） rats. MethodSD male adult rats were randomly divided into thirteen groups according to their body weight，namely the sham operation group，the model group，the solvent model group，the nitroglycerin group，the Borneolum high，medium，and low-dose （0.6，0.3， 0.15 g·kg-1） groups，the L-Borneolum high，medium，and low-dose （0.2，0.1， 0.05 g·kg-1） groups，and the Borneolum Syntheticum high，medium，and low-dose （0.2，0.1， 0.05 g·kg-1） groups，with 10 rats in each group. Rats were given 10 mL·kg-1 by gavage for 3 d of pre-administration. Thirty minutes after the last administration，the left anterior descending coronary artery （LAD） was ligated to induce the model，and the successful rat model was continuously treated for 3 d. BL-420N biosystem was used to analyze the electrocardiogram （ECG） and heart rate variability （HRV） before and after modeling and after 3 d of treatment. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to determine the mRNA expressions of interleukin-1β （IL-1β） and interleukin-6 （IL-6） in the myocardial tissue Western blot and immunohistochemistry were used to determine the protein expression levels of VEGF receptor 1 （VEGFR1），HIF-1α，and CD34. ResultCompared with the sham operation group，the model group significantly increased the heart rate，ECG ST wave，T wave，QRS duration，QTC interval，and Q wave on the day of modeling and after 3 d of treatment，and significantly changed HRV and T wave （P<0.05，P<0.01）. As compared with the solvent model group，on the day of modeling，the heart rate of the L-Borneolum medium and low-dose groups and the Borneolum groups，the ST wave of the L-Borneolum groups，the Borneolum high and medium-dose groups，and the Borneolum Syntheticum high-dose group，HRV parameters of the L-Borneolum groups，the Borneolum medium and low-dose groups，and the Borneolum Syntheticum high-dose group，LF/HF of the L-Borneolum high and medium-dose group，the Borneolum low-dose group，and the Borneolum Syntheticum groups，T wave of the L-Borneolum high-dose group，the Borneolum Syntheticum high-dose group，and Borneolum medium-dose group，QTC interval of the L-Borneolum medium and low-dose groups and the Borneolum high and medium-dose groups，and QRS duration of the L-Borneolum high and low-dose groups，the Borneolum high and low-dose groups，and the Borneolum Syntheticum groups were significantly reduced or shortened （P<0.05，P<0.01）. After 3 d of treatment，the heart rate of the L-Borneolum groups，the Borneolum high and medium-dose groups，and the Borneolum Syntheticum medium-dose group，ST wave of the L-Borneolum group，the Borneolum high and medium-dose groups，and the Borneolum Syntheticum high-dose group，OTC interval，ORS duration，and Q wave of the L-Borneolum high-dose group，the Borneolum high-dose group，and the Borneolum Syntheticum high and medium-dose groups，QRS duration of the L-Borneolum medium-dose group，QTC interval of the Borneolum medium-dose group，and Q wave of the Borneolum Syntheticum low-dose group were all significantly reduced or shortened（P<0.01）. The mRNA expressions of IL-1β and IL-6 in the L-Borneolum medium and low-dose groups，the Borneolum medium and low-dose groups，and the Borneolum Syntheticum high and medium-dose groups were significantly down-regulated（P<0.01），and LF/HF in the L-Borneolum high and medium-dose groups，the Borneolum high and medium-dose groups，and the Borneolum Syntheticum high and low-dose groups were significantly reduced （P<0.05，P<0.01）. HRV in the L-Borneolum high-dose group，the Borneolum groups，and the Borneolum Syntheticum high and low-dose groups，and T wave in the Borneolum high and medium-dose groups and the Borneolum Syntheticum high-dose group were increased significantly. The protein expressions of HIF-1α，VEGFR1，and CD34 in the L-Borneolum medium and low-dose groups，the Borneolum low-dose group，and the Borneolum Syntheticum high-dose group were significantly up-regulated，as well as those of VEGFR1 and CD34 in the Borneolum medium-dose group （P<0.05，P<0.01）. ConclusionThe 3 kinds of Borneolum improves the heart rate，heart rate variability，and electrocardiogram of AMI model rats to different degrees，and may play a myocardial protective effect by anti-inflammation and promotion of angiogenesis. The combined effect suggests that L-Borneolum has the superior effect next to Borneolum，and Borneolum Syntheticum has the inferior effect.

Mechanistic analysis for the origin of diverse diterpenes in Tripterygium wilfordii

Tripterygium wilfordii is a valuable medicinal plant rich in biologically active diterpenoids, but there are few studies on the origins of these diterpenoids in its secondary metabolism. Here, we identified three regions containing tandemly duplicated diterpene synthase genes on chromosomes (Chr) 17 and 21 of T. wilfordii and obtained 11 diterpene synthases with different functions. We further revealed that these diterpene synthases underwent duplication and rearrangement at approximately 2.3-23.7 million years ago (MYA) by whole-genome triplication (WGT), transposon mediation, and tandem duplication, followed by functional divergence. We first demonstrated that four key amino acids in the sequences of TwCPS3, TwCPS5, and TwCPS6 were altered during evolution, leading to their functional divergence and the formation of diterpene secondary metabolites. Then, we demonstrated that the functional divergence of three TwKSLs was driven by mutations in two key amino acids. Finally, we discovered the mechanisms of evolution and pseudogenization of miltiradiene synthases in T. wilfordii and elucidated that the new function in TwMS1/2 from the terpene synthase (TPS)-b subfamily was caused by progressive changes in multiple amino acids after the WGT event. Our results provide key evidence for the formation of diverse diterpenoids during the evolution of secondary metabolites in T. wilfordii.

Synthesis of selective PAK4 inhibitors for lung metastasis of lung cancer and melanoma cells

The p21 activated kinase 4 (PAK4) is serine/threonine protein kinase that is critical for cancer progression. Guided by X-ray crystallography and structure-based optimization, we report a novel subseries of C-3-substituted 6-ethynyl-1H-indole derivatives that display high potential and specificity towards group II PAKs. Among these inhibitors, compound 55 exhibited excellent inhibitory activity and kinase selectivity, displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line B16. Compound 55 exhibited potent in vivo antitumor metastatic efficacy, with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models, respectively. Further mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition (EMT).

Experimental study on the regulation of subchondral bone plate osteoprotegerin/receptor activator of nuclear factor kappa-B ligand system by berberine to retard the development of osteoarthritis in rabbits / 中国骨伤

OBJECTIVE@#To investigate the effect of intra-articular berberine injection on the structural remodeling of subchondral bone plate and osteoprotegerin/receptor activator of nuclear factor kappa-B ligand(OPG/RANKL) system expression in rabbits with osteoarthritis(OA).@*METHODS@#Forty 12-month-old male rabbits with an average of(2.73±0.18) kg of body weight, underwent left anterior cruciate ligament transection(ACLT), and were divided into berberine group and placebo groups after operation, 20 rabbits in each group. The berberine group received intra-articular injection of 100 μmol/L berberine 0.3 ml every week for 6 weeks. In placebo group, the same dose of 0.9% sodium chloride injection was injected into the left knee joint cavity every week for 6 weeks. Another 20 12-month-old male rabbits, weighing (2.68±0.18) kg, underwent sham operation on the left knee joint without intra-articular injection intervention (sham operation group). On the last day of the sixth week after operation, three groups of animals were sacrificed to obtain knee joint specimens. The femoral medial condyle samples were obtained for histological evaluation of cartilage and subchondral bone, Mankin scoring system was used to evaluate articular cartilage structure. Image-Pro Plus(IPP) software was used to evaluate subchondral bone plate bone volume(BV), bone volume/total volume(BV/TV), trabecular circumference(TC), mean trabecular thickness (Tb.Th). Real-time quantitative reverse transcription polymerization Enzyme chain reaction(reverse transcription-polymerase chain reaction, RT-PCR) was used to detect the mRNA expression levels of OPG and RANKL in subchondral bone tissue at 6 weeks after operation.@*RESULTS@#The cartilage structure evaluation showed that the surface of cartilage tissue in the sham operation group was smooth and flat, and the safranin coloration was full in the full thickness of the cartilage;the cartilage tissue in the berberine group showed uneven surface layer, and the staining of safranin O was mildly decreased;the surface layer fibrosis was seen in placebo group, Safranin O faded significantly. The Mankin score in the berberine group was lower than that in placebo group(P<0.01), but higher than that in sham operation group(P<0.01). The structural evaluation of subchondral bone plate showed that the trabecular bone in sham-operated group was densely arranged;after berberine intervention, the trabeculae were closely arranged;the subchondral bone trabeculae in placebo group were relatively sparse, and the distance between trabeculae was wider. Subchondral bone plate IPP software evaluation showed that BV, BV/TV, TC, Tb.Th in berberine group were higher than those in placebo group(P<0.01), BV, BV/TV, TC, Tb.Th in berberine group were higher than those in placebo group(P<0.01), while lower than the sham operation group (P<0.01). PCR test results showed that the expression of OPG mRNA in the berberine group was significantly higher than that in placebo group(P<0.01), and OPG mRNA in the berberine group was lower than that in sham operation group (P<0.01). There was no significant difference in mRNA expression of RANKL among three groups(P>0.05);the ratio of OPG/RANKL in berberine group was higher than that in placebo group(P<0.01), but lower than that in sham operation group(P<0.01).@*CONCLUSION@#Intra-articular injection of berberine can effectively inhibit the resorption of subchondral bone in the early stage of OA and delay the development of the disease. The specific mechanism may be that berberine maintains the balance of OPG/RANKL system by up-regulating the expression of OPG gene in subchondral bone.

Clinical observation of chiropractic manipulation in the treatment of degenerative scoliosis / 中国骨伤

OBJECTIVE@#To observe clinical efficacy of chiropractic manipulation in the treatment of degenerative scoliosis (DS).@*METHODS@#From June 2017 to September 2019, 120 patients with degenerative scoliosis were randomly divided into treatment group (60 cases) and control group(60 cases). The patients in treatment group were treated with chiropractic manipulation once every other day for 4 weeks. The patients in control group were treated with eperisone hydrochloride tablets combined with thoracolumbar orthopedic(TSLO)brace, oral eperisone hydrochloride tablets 50 mg three times a day, wearing TSLO brace for not less than 8 hours a day. The course of treatment was 4 weeks. After the patients were selected into the group, visual analogue scale (VAS) and Oswestry Disability Index (ODI) were recorded before treatment, 1, 2, 3, 4 weeks after treatment and 1 month after treatment. The full length X-ray of the spine was taken before and 4 weeks after treatment, and the scoliosis Cobb angle, sagittal vertical axis (SVA) and lumbar lordosis (LL) were measured and compared. The adverse reactions during the treatment were recorded.@*RESULTS@#There were significant differences in VAS and ODI between two groups at each time point after treatment (P<0.001), VAS and ODI at 2 weeks after treatment (PVAS=0.025, PODI=0.032) and 3 weeks after treatment(PVAS=0.040, PODI=0.044) in treatment group were significantly different from those in control group, but there was no significant difference in VAS and ODI at other time points between treatment group and control group (P>0.05). There was significant difference in Cobb angle between treatment group(P=0.010) and control group(P=0.017) after treatment, but there was no significant difference in LL and SVA between treatment group and control group. There was no significant difference in Cobb angle, LL and SVA between two groups before and after treatment. During the treatment, there were 4 mild adverse reactions in the control group and no adverse reactions in the treatment group.@*CONCLUSION@#Chiropractic manipulation can effectively relieve pain and improve lumbar function in patients with degenerative scoliosis. The onset of action is faster than that oral eperisone hydrochloride tablets combined with TSLO brace, and it has better safety and can improve Cobb angle of patients with degenerative scoliosis.

Spirulina platensis aqueous extracts ameliorate colonic mucosal damage and modulate gut microbiota disorder in mice with ulcerative colitis by inhibiting inflammation and oxidative stress / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Ulcerative colitis (UC) is a chronic and recurrent inflammatory bowel disease (IBD) that has become a major gastroenterologic problem during recent decades. Numerous complicating factors are involved in UC development such as oxidative stress, inflammation, and microbiota disorder. These factors exacerbate damage to the intestinal mucosal barrier. Spirulina platensis is a commercial alga with various biological activity that is widely used as a functional ingredient in food and beverage products. However, there have been few studies on the treatment of UC using S. platensis aqueous extracts (SP), and the underlying mechanism of action of SP against UC has not yet been elucidated. Herein, we aimed to investigate the modulatory effect of SP on microbiota disorders in UC mice and clarify the underlying mechanisms by which SP alleviates damage to the intestinal mucosal barrier. Dextran sulfate sodium (DSS) was used to establish a normal human colonic epithelial cell (NCM460) injury model and UC animal model. The mitochondrial membrane potential assay 3-‍‍(4,5-dimethylthiazol-2-yl)-2,‍5-diphenyltetrazolium bromide (MTT) and staining with Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) and Hoechst 33258 were carried out to determine the effects of SP on the NCM460 cell injury model. Moreover, hematoxylin and eosin (H&E) staining, transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qPCR), western blot, and 16S ribosomal DNA (rDNA) sequencing were used to explore the effects and underlying mechanisms of action of SP on UC in C57BL/6 mice. In vitro studies showed that SP alleviated DSS-induced NCM460 cell injury. SP also significantly reduced the excessive generation of intracellular reactive oxygen species (ROS) and prevented mitochondrial membrane potential reduction after DSS challenge. In vivo studies indicated that SP administration could alleviate the severity of DSS-induced colonic mucosal damage compared with the control group. Inhibition of inflammation and oxidative stress was associated with increases in the activity of antioxidant enzymes and the expression of tight junction proteins (TJs) post-SP treatment. SP improved gut microbiota disorder mainly by increasing antioxidant enzyme activity and the expression of TJs in the colon. Our findings demonstrate that the protective effect of SP against UC is based on its inhibition of pro-inflammatory cytokine overproduction, inhibition of DSS-induced ROS production, and enhanced expression of antioxidant enzymes and TJs in the colonic mucosal barrier.

The function of auditory cortex in the elderly using functional near-infrared spectroscopy technology / 中华耳鼻咽喉头颈外科杂志

Objective: Functional near-infrared spectroscopy (fNIRS) was used to study the effect of aging on the neuroimaging characteristics of cerebral cortex in the process of speech perception. Method: Thirty-four adults with normal hearing were recruited from March 2021 to June 2021, including 17 in the young group, with 6 males, 11 females, age (32.1±5.0) years, age range 20-39 years. and 17 in the elderly group, with 6 males, 11 females, age (63.2±2.8) years, age range 60-70 years. The test material was the sentence table of the Mandarin Hearing Test in Noise (MHINT). The task state block experiment design was adopted, and the temporal lobe, Broca's area, Wernicke's area, motor cortex were used as regions of interest. Objective brain imaging technology (fNIRS) combined with subjective psychophysical testing method was used to analyze the activation area and degree of cerebral cortex related to auditory speech perception in the elderly and young people under different listening conditions (quiet, signal-to-noise ratio of 10 dB, 5 dB, 0 dB, -5 dB). SPSS 23 software was used for statistical analysis. Result: The activation area and degree of activation in the elderly group were lower than those in the young group under each task condition; The number of activation channels in the young group were significantly more than those in the old group, and the number of activation channels in the left hemisphere were more than those in the right hemisphere, but there was no difference in the number of activation channels. There were more channels affected by age in the left hemisphere than in the right hemisphere. The activation degree of the young group when the signal-to-noise ratio was 0 dB was significantly higher than that of other signal-to-noise ratio conditions (P<0.05), but there was no significant difference in the old group under the five conditions (P>0.05). The speech recognition score of the young group was higher than that of the old group under all conditions. When the quiet and signal-to-noise ratio was 10 dB, the correct score of the two groups was equal or close to 100%. With the gradual decrease of signal-to-noise ratio, there was a significant difference between the two groups when the signal-to-noise ratio was 5 dB. The speech recognition accuracy of the young group decreased significantly when the signal-to-noise ratio was 0 dB, while that of the old group decreased significantly when the signal-to-noise ratio was 5 dB. Conclusions: With the increase of age, the speech perception in noisy environment and the activity of cerebral cortex gradually deteriorate, and the speech dominance hemisphere (left hemisphere) will be significantly affected by aging. The overall activation area and activation degree of the elderly under different speech tasks are lower than those of the young.

Analysis on prevalence and epidemic risk of animal plague in different ecological plague foci in Inner Mongolia Autonomous Region / 中华预防医学杂志

The risk of plague epidemics and relapse of various types of plague foci persists in Inner Mongolia Autonomous Region. For Marmota sibirica plague foci, the animal plague has not been found but antibody has been detected positive. Nowadays, Marmota sibirica has been increasing in population and distribution in China. In bordering countries Mongolia and Russia, the animal plague has been continuously prevalent. For Spermophilus dauricus plague foci, the animal plague has been taken place now and then. Compared to the above foci, the animal plague is most prevalent in Meriones unguiculatus plague foci and frequently spread to humans. Due to higher strain virulence and historical disaster in Marmota sibirica plague foci and Spermophilus dauricus plague foci, plague prevention and control should be strengthened on these foci. In addition to routine surveillance, epidemic dynamics need to be further monitored in these two foci, in order to prevent their relapse and spread to humans.

Prognostic value of postoperative adjuvant chemotherapy in patients with cervical and upper thoracic esophageal squamous cell carcinoma / 中国胸心血管外科临床杂志

@#Objective    To explore whether surgery combined with adjuvant chemotherapy can bring survival benefits to patients with cervical and upper thoracic esophageal squamous cell carcinoma (ESCC). Methods    The clinical data of patients with cervical and upper thoracic ESCC who underwent R0 resection and neck anastomosis in our department from 2006 to 2010 were retrospectively analyzed. Patients received neoadjuvant therapy or adjuvant radiotherapy were excluded. The adjuvant chemotherapy group was given a combination of taxanes and platinum based chemotherapy after surgery; the surgery alone group did not receive adjuvant chemotherapy. The Kaplan-Meier method was used to analyze the survival difference between the adjuvant chemotherapy group and the surgery alone group. Results    A total of 181 patients were enrolled, including 141 (77.9%) males and 40 (22.1%) females, with an average age of 61.0±8.2 years (80 patients aged≤61 years, 101 patients aged>61 years). There were 70 (38.7%) patients of cervical ESCC, and 111 (61.3%) patients of upper thoracic ESCC. Eighty-seven (48.1%) patients underwent postoperative adjuvant chemotherapy, and 94 (51.9%) patients underwent surgery alone, and the basic clinical characteristics were well balanced between the two groups (P>0.05). The median survival time of patients in the adjuvant chemotherapy group and the surgery alone group was 31.93 months and 26.07 months, and the 5-year survival rate was 35.0% and 32.0%, respectively (P=0.227). There was no statistical difference in median survival time between the cervical ESCC and upper thoracic ESCC group (31.83 months vs. 29.76 months, P=0.763). For cervical ESCC patients, the median survival time was 45.07 months in the adjuvant chemotherapy group and 14.70 months in the surgery alone group (P=0.074). Further analysis showed that the median survival time of lymph node negative group was 32.53 months, and the lymph node positive group was 24.57 months (P=0.356). The median survival time was 30.43 months in the lymph-node positive group with adjuvant chemotherapy and 17.77 months in the lymph-node positive group with surgery alone. The survival curve showed a trend of difference, but the difference was not statistically significant (P=0.557). Conclusion    There is no statistical difference in the long-term survival of cervical and upper thoracic ESCC patients after R0 resection. Postoperative adjuvant chemotherapy may have survival benefits for patients with cervical ESCC and upper ESCC with postoperative positive lymph nodes, but the differences are not statistically significant in this setting.

Vacuum-assisted venous drainage in adult open-heart surgery: A randomized controlled trial / 中国胸心血管外科临床杂志

@#Objective    To analyze the safety and efficacy of vacuum-assisted venous drainage (VAVD) in cardiac surgery under cardiopulmonary bypass (CPB). Methods    A total of 180 patients from 3 centers between November 17, 2017 and October 1, 2018 were enrolled and randomly assigned to a VAVD group and a gravity drainage (GD) group by 1∶1 ratio. During the open-heart surgery under CPB, the VAVD group completely relied on VAVD, and the GD group used conventional GD. The primary endpoint was arterial flow before CPB, 15 min after aortic cross-clamping and rewarming to 36 °C of nasopharyngeal temperature. The secondary endpoints included hematocrit, hemoglobin concentration, blood product transfusion, etc. The safety endpoint was free hemoglobin concentration, etc. Results    The full analysis set contained 175 patients, 87 in the VAVD group and 88 in the GD group. Patients in the VAVD group were aged 52.8±12.0 years, and males accounted for 55.2%; patients in the GD group were aged 51.4±12.1 years, and males accounted for 59.1%. The demographic characteristics between the two groups were not statistically different. Compared to the GD group, the VAVD group could provide comparable arterial flow in CPB [average of 3 time points, 2.37±0.22 L/(min·m2) vs. 2.41±0.25 L/(min·m2), P=0.271], while not elevating free hemoglobin concentration. Conclusion    VAVD can provide enough venous drainage, while not elevating free hemoglobin concentration or damaging blood.

Bioinformatics analysis of differentially expressed genes associated with chronic schistosomiasis japonica-induced hepatic fibrosis / 中国血吸虫病防治杂志

Objective To screen differentially expressed genes (DEGs) associated with chronic schistosomiasis japonica-induced hepatic fibrosis and analyze their functions. Methods The dataset of gene expression profiles of patients with chronic schistosomiasis japonica-induced hepatic fibrosis was downloaded from the Gene Expression Omnibus (GEO) database, and DEGs were screened using R package. The biological functions of DEGs were characterized using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. In addition, the protein-protein interaction (PPI) network of DEGs was created to screen the hub genes. Results A total of 62 DEGs were identified, including 12 down-regulated genes and 50 up-regulated genes. GO enrichment analysis showed that DEGs were mainly enriched in 116 biological processes, including fatty acid, sulfur compound, acyl-coenzyme A and thioester metabolism; 19 cellular components, including mitochondrial matrix, outer mitochondrial membrane and organelle outer membrane; and 7 molecular functions, including insulin-like growth factor binding and oxidoreductase activity. KEGG pathway enrichment analysis that the DEGs were significantly enriched in phosphatidylinositol-3-kinase/serine/threonine protein kinase (PI3K/Akt), mitogen-activated protein kinase (MAPK), calcium metabolism and cyclic adenosine monophosphate (cAMP) signaling. PPI network analysis identified six hub genes involved in the development of chronic schistosomiasis japonica-induced hepatic fibrosis, including ACACA, ACSL1, GPAM, THRSP, PLIN1 and DGAT2, and ACSL1, ACACA and PLIN1 were the top 3 hub genes. Conclusions ACSL1, ACACA and PLIN1 may be the hub genes associated with the development of chronic schistosomiasis japonica-induced hepatic fibrosis, and abnormal lipid metabolism mediated by these DEGs may play an important role in the development of chronic schistosomiasis japonica-induced hepatic fibrosis.

Mechanism of Ferroptosis and Traditional Chinese Medicine Intervention on Neuronal Cell Ferroptosis After Stroke： A Review / 中国实验方剂学杂志

Stroke is a common cerebrovascular disease， characterized by high incidence， mortality and disability rate. Neuronal cells， the basic unit of the central nervous system， can be injured to varying degrees when stroke occurs. Neuronal cell injury after stroke is also the key cause leading to neurological dysfunction， affecting the prognosis and quality of life of patients. Therefore， reducing the neuronal cell injury and delaying the process of cell death are effective to decrease the nerve function injury in stroke patients and improve their prognosis， thus lowering the death and disability rate of stroke. Ferroptosis is a new form of cell death that has been widely concerned in recent years. Several studies have confirmed that there is ferroptosis in neuronal cells after stroke. Since ferroptosis is an adjustable form， its intervention can help regulate the injury and death of neuronal cells. Studies have shown that inhibiting ferroptosis plays a role in protecting neuronal cells. Traditional Chinese medicine （TCM）， with the multi-channel and multi-target treatment advantages， has been widely used in the whole stroke and has achieved good clinical efficacy. It might be a new direction taking TCM regulation of ferroptosis as the entry point for stroke treatment in the future. This review revealed the mechanism of ferroptosis， discussed the research status of TCM in intervening in neuronal cell ferroptosis， and provided reference for further improving the efficacy of TCM in stroke.

Investigation and analysis of smoking behaviour of civil servants in Minhang District, Shanghai / 环境与职业医学

Background The tobacco epidemic as one of the most serious public health problems in the world contributes great harm to human health. It is urgent to develop tobacco control strategy. Civil servants' behaviors as a role model for society have a great influence on the rest of society. Thus, it is important to promote tobacco control program on helping civil servants to quit smoking. Objective To understand the smoking and second-hand smoking exposures status, the awareness of knowledge of tobacco hazards, and the attitudes to tobacco control policies of civil servants in Minhang District, Shanghai. Furthermore, to explore the related strategies and measures for tobacco control, to provide a basis for the development and revision of relevant intervention measures and policies. Methods A total of 20 government agencies with newly installed smoking-free programs from 10 subdistricts and towns in Minhang District, including Xinzhuang, Wujing, Maqiao, Qibao, Meilong, Hongqiao, Zhuanqiao, Jiangchuan, Gumei, and Xinhong were selected as study sites.A questionnaire survey was conducted to investigate all civil servants (n=801) of selected agencies. The questionnaire included general characteristics, smoking and second-hand smoking exposure status, knowledge of tobacco hazard, and attitudes to tobacco control policies. Results A total of 794 civil servants returned valid questionnaires. The awareness rate of tobacco hazards in the smoking group was lower than that in the non-smoking group (P<0.05). Relatively high smoking rates were reported in those being male (17.08%), age ≥51 years old (25.61%), divorced or widowed (12.50%), technical secondary school or below education level (22.81%), having more than 10 years of working years (11.57%), being willing to dissuade indoor smoking (24.54%), having no punishment or warning measures for violation of smoking regulations in workplaces (18.37%), and having no dedicated smoking spot at home (15.38%). The results of multiple logistic regression analysis showed that age 31-40 years old (OR=3.446, 95%CI: 1.236-9.609) and to avoid confronting indoor smoking (OR=3.686, 95%CI: 1.041-13.049) were risk factors for smoking in civil servants. Conclusion Civil servants aged 31-40 years old who deliberately avoid confronting indoor smoking behaviors are the key intervention population of smoking control in Minhang District, Shanghai.