Inhibition of the P38 MAPK/NLRP3 pathway mitigates cognitive dysfunction and mood alterations in aged mice after abdominal surgery plus sevoflurane.

BACKGROUND: Cognitive dysfunction, encompassing perioperative psychological distress and cognitive impairment, is a prevalent postoperative complication within the elderly population, and in severe cases, it may lead to dementia. Building upon our prior research that unveiled a connection between postoperative mood fluctuations and cognitive dysfunction with the phosphorylation of P38, this present investigation aims to delve deeper into the involvement of the P38 MAPK/NLRP3 pathway in perioperative neurocognitive disorders (PND) in an abdominal exploratory laparotomy (AEL) aged mice model. METHODS: C57BL/6 mice (male, 18-month-old) underwent AEL with 3 % anesthesia. Then, inhibitors targeting P38 MAPK (SB202190, 1 mg/kg) and GSK3ß (TWS119, 10 mg/kg) were administered multiple times daily for 7 days post-surgery. The NLRP3-cKO AEL and WT AEL groups only underwent the AEL procedure. Behavioral assessments, including the open field test (OFT), novel object recognition (NOR), force swimming test (FST), and fear conditioning (FC), were initiated on postoperative day 14. Additionally, mice designated for neuroelectrophysiological monitoring had electrodes implanted on day 14 before surgery and underwent novel object recognition while their local field potential (LFP) was concurrently recorded on postoperative day 14. Lastly, after they were euthanasized, pathological analysis and western blot were performed. RESULTS: SB202190, TWS119, and astrocyte-conditional knockout NLRP3 all ameliorated the cognitive impairment behaviors induced by AEL in mice and increased mean theta power during novel location exploration. However, it is worth noting that SB202190 may exacerbate postoperative depressive and anxiety-like behaviors in mice, while TWS119 may induce impulsive behaviors. CONCLUSIONS: Our study suggests that anesthesia and surgical procedures induce alterations in mood and cognition, which may be intricately linked to the P38 MAPK/NLRP3 pathway.

A novel trauma induced urethral stricture in rat model.

Urethral stricture (US) is a longstanding disease, while there has not existed a suitable animal model to mimic the condition. We aimed to establish a trauma-induced US animal model to simulate this clinical scenario. A total of 30 rats were equally distributed into two groups, sham and US group. All rats were anesthetized with isoflurane and undergone cystostomy. In the US group, a 2 mm incision was made in the urethra and sutured to induce US. The sham group only make a skin incision on the ventral side of the anterior urethra. 4 weeks later, ultrasound and cystourethrography were performed to evaluate the degree of urethral stricture, pathological examinations were carried out to evaluate the degree of fibrosis. Urodynamic evaluation and mechanical tissue testing were performed to evaluate the bladder function and urethral tissue stiffness. The results showed that the urethral mucosa was disrupted and urethral lumen was stenosed in the US group. Additionally, the US group showed elevated bladder pressure, prolonged micturition intervals and increased tissue stiffness. In conclusion, the rat urethral stricture model induced by trauma provides a closer representation of the real clinical scenario. This model will significantly contribute to advancing research on the mechanisms underlying traumatic urethral stricture.

First report of 'Candidatus Phytoplasma asteris' associated with witches'-broom and plexus bud disease of Cerasus serrula in China.

Cherry blossoms (Cerasus serrula) are native to the temperate zone around the Himalayas in the northern hemisphere, mainly distributed in the west and southwest of China, including Yunnan, Sichuan and Tibet. Cherry has high ornamental, edible and medicinal value. In August 2022, we observed that Cherry trees exhibited witches' broom and plexus bud in Kunming City, Yunan Province, China. The symptoms consisted of many small branches with little leaves at the top of branches, stipule lobation, and clustered adventitious buds that are tumor-like on the branches that usually cannot sprout normally. As disease intensity increased, the branches dried up from the top to the bottom till the death of the whole plant. We named this disease C. serrula witches' broom disease (CsWB). We found CsWB in the areas of Panlong, Guandu, Xishan Districts in Kunming, where more than 17% of the plants we surveyed were infected. We collected 60 samples from across the three districts. These included 15 symptomatic and 5 asymptomatic plants per district. The lateral stem tissues were observed under a scanning electron microscope (Hitachi S-3000N). The nearly spherical bodies were found in the phloem cells of symptomatic plants. Total DNA extraction was conducted from 0.1 g tissue using the CTAB method (Porebski et al. 1997), ddH2O was used as the negative control, and Dodonaea viscose plants with witches' broom symptoms were used as the positive control. The nested PCR was used to amplify the 16S rRNA gene (Lee et al. 1993; Schneider et al. 1993) and PCR amplicon of 1.2 kb were amplified (GenBank accessions: OQ408098; OQ408099; OQ408100). The direct PCR specific to the ribosomal protein (rp) gene yielded amplicons of approximately 1.2 kb with primer pair rp(I)F1A and rp(I)R1A (Lee et a. 2003) (GenBank accessions: OQ410969; OQ410970; OQ410971). The fragment from 33 symptomatic samples was consistent with the positive control, and absent for asymptomatic samples, suggesting an association of phytoplasma with the disease. A BLAST analysis of the 16S rRNA sequences of CsWB phytoplasma showed that it has a 99.76% similarity with Trema laevigata witches' broom phytoplasma (GenBank accession MG755412). The rp sequence shared 99.75% identity with Cinnamomum camphora witches' broom phytoplasma (GenBank accession OP649594). An analysis with iPhyClassifier showed that the virtual RFLP pattern derived from the 16S rDNA sequence shares 99.3% similarity with that of the 'Ca. Phytoplasma asteris' reference strain (GenBank accession: M30790), and the virtual RFLP pattern derived from the fragment is identical (similarity coefficient 1.00) to the reference pattern of 16Sr group I, subgroup B (GenBank accession: AP006628). Thus, CsWB phytoplasma is identified as 'Ca. Phytoplasma asteris'-related strain belonging to sub-group 16SrI-B. The phylogenetic tree was constructed based on 16S rRNA gene and rp gene sequences by using MEGA version 6.0 (Tamura et al. 2013) with neighbor-joining (NJ) method and bootstrap support was estimated with 1000 replicates. The result indicated that the CsWB phytoplasma formed a subclade in 16SrI-B and rpI-B respectively. In addition, the clean 1-year-old C. serrula were tested positive for the phytoplasma using the nested PCR 30 days after being grafted with naturally infected twigs with CsWB symptoms. To the best of our knowledge, Cherry blossoms is a new host of 'Ca. Phytoplasma asteris'-related strains in China. The newly emerged disease is a threat to the ornamental value of cherry blossoms and the production of wood quality.

Anesthesia Analysis of Compound Lidocaine Cream Alone in Adult Male Device-Assisted Circumcision.

OBJECTIVE: to evaluate the anesthetic effect among adult male patients with the single use of compound lidocaine cream in device-assisted circumcision, hoping to provide an anesthetic method for the simplification of the surgical process. METHODS: Male adult patients undergoing device-assisted circumcision through prepuce local anesthesia using lidocaine cream in Xiangya Hospital of Central South University from December 2020 to August 2021 were selected. According to different age groups and different surgical procedures, the anesthetic effect of compound lidocaine cream was analyzed considering the aspects of anesthetic cost, anesthetic time, anesthetic duration, anesthetic effect, anesthetic side effects and anesthetic satisfaction. RESULTS: In the study, 99.1% of 649 patients needed only 1 application of compound lidocaine cream to complete the operation. The time taken for anesthesia was short; the whole anesthesia process only required approximately 2-5 min. However, for patients with severe phimosis, the time to complete the anesthesia procedure was correspondingly longer. The pain degree caused by anesthesia was low, and the patients with a pain score of ≤3 points accounted for 96.7%. The anesthetic effect lasted for a sufficiently long period, and the time of algesia recovery from local anesthesia was almost 1 h after surgery. The anesthesia effect was sufficient, and patients with an intraoperative pain score of ≤3 accounted for 98.7%, which could meet the surgical requirements. There were few side effects of the anesthesia. The overwhelming majority of patients were pleased with the anesthesia, and 98.9% of patients had an anesthesia satisfaction score of ≥7. CONCLUSION: The compound lidocaine cream, as a local anesthetic, is safe and effective for most adult male device-assisted circumcisions. More useful information needs to be corroborated by more advanced evidence, especially for severe phimosis.

Vasectomy reversal in China during the recent decade: insights from a multicenter retrospective investigation.

To date, there is little information about the demography of vasectomy reversal (VR) patients or the factors currently influencing VR effectiveness in China, especially after the universal two-child policy was released in 2015. In this research, demographic data and perioperative medical records of VR patients were extracted from seven major hospitals in different provinces or municipalities of China. Meanwhile, a telephone survey of the patients was conducted to collect follow-up information. Eventually, 448 VR cases from the past 13 years were included. The results were analyzed by stratified comparison to investigate factors that can influence postoperative vas deferens patency and pregnancy rate. Appropriately statistical methods were used, and all of the protocols were approved by the Ethics Committees of the institutes in this research. The results showed that the annual operation volume of VR quadrupled after the two-child policy was implemented. Nonmicrosurgery and a long duration of vasectomy were significantly associated with a lower patency rate. A follow-up survey showed that the general postoperative pregnancy rate was 27.2%. For female partners over the age of 35 years, the postoperative pregnancy rate showed a more severe decline, but only 35.5% of them had been given a fertility examination before their husbands' VR surgery. Our work revealed that more patients in China have been demanding VR in recent years. High-quality microsurgery and a short duration of vasectomy are crucial for restoring patency by VR. Clinical andrologists should perform a preoperative fertility evaluation of the patients' female partners.

Incidence and risk factors of in-hospital venous thromboembolism in non-oncological urological inpatients: A single center experience.

Objective: To determine incidence and risk factors for venous thromboembolism (VTE) development of in-hospital VTE in urological inpatients who underwent non-oncological surgery in a tertiary hospital in China. Methods: Consecutive 1453 inpatients who were admitted to a non-oncological urological ward in the tertiary hospital from January 1, 2018 to December 31, 2018 were enrolled in the study, and the VTE events were diagnosed by ultrasound or computed tomographic pulmonary angiography. Patients' occurrence of VTE and characteristics which may contribute to the development of VTE were collected and analyzed as incidence and risk factors. Results: The incidence of VTE in non-oncological urological inpatients is 2.3%. In our cohort, patients who experienced previous VTE (adjusted odds ratios [aOR] 14.272, 95% CI 3.620-56.275), taking anticoagulants or antiplatelet agents before admission (aOR 10.181, 95% CI 2.453-42.256), D-dimer (max) ≥1 µg/mL (aOR 22.456, 95% CI 6.468-77.967), lower extremity swelling (aOR 10.264, 95% CI 2.242-46.994), chest symptoms (aOR 79.182, 95% CI 7.132-879.076), operation time of more than or equal to 180 min (aOR 10.690, 95% CI 1.356-84.300), and Caprini score (max) of more than or equal to 5 (aOR 34.241, 95% CI 1.831-640.235) were considered as risk factors for VTE. Conclusion: In this study, we found that the incidence of VTE in non-oncological surgery was about 2.3%, which was higher than some previous studies. Risk factors could be used for early detection and diagnosis of VTE.

Decreased pancreatic leakage rate in the application of a measurable variable-diameter pancreatic duct catheter in laparoscopic pancreaticoduodenectomy.

Background: Pancreatic leakage remains one of the most serious complications after laparoscopic pancreaticoduodenectomy (LPD). At present, most medical centers use local materials for the common pancreatic duct catheters required for pancreaticoenterostomy. However, there is a lack of a measurable and variable-diameter pancreatic duct catheter. Recently, a measurable variable-diameter pancreatic duct catheter was developed to remedy the limitation of the common pancreatic duct catheters. This study sought to evaluate its preventive effect on pancreatic leakage in LPD. Methods: A total of 202 patients who underwent LPD using the Hong's single-stitch method from January 2021 to April 2022 were included in the study. Patients were divided into the 2 groups: the variable-diameter group (n=111) and the normal group (n=91) according to the application of different pancreatic duct catheters. Patient characteristics and perioperative data, including operation time, pancreatic fistula rate, postoperative bleeding rate and postoperative length of stay in the two groups were collected and analyzed. The Chi-square test was used to compare the differences between the groups in relation to the categorical variables. Results: Among the 202 patients, there were 123 males and 79 females, with an average age of 58.79±7.89 years (range, 15-79 years), and an average body mass index (BMI) of 23.55±4.25 kg/m2. There were no statistically significant differences between the variable-diameter group and the normal group in terms of age, sex, BMI, operation time, intraoperative blood loss, preoperative bilirubin, and pancreatic texture (P>0.05). The pancreatic fistula rate (2.70% vs. 9.89%) and postoperative median length of stay (15 vs. 16 days) of the variable-diameter group was significantly lower than that of the normal group. Conclusions: The measurable variable-diameter pancreatic duct catheter could decrease the pancreatic fistula rate and postoperative median length of stay in the application of laparoscopic duodenectomy.

Pulmonary embolism following urological non-oncological surgery: The clinical features, management, and long-term follow-up outcome from a tertiary hospital of China.

Objective: To evaluate the clinical features, treatment, and outcomes of pulmonary embolism (PE) after urological non-oncological surgery in a tertiary hospital of China. Methods: A total of eight patients who suffered from PE after urological non-oncological surgery from 2016 to 2019 were recruited to the study. Clinical data such as symptoms, vital signs, electrocardiogram, echocardiography, and computed tomographic pulmonary arteriography (CTPA) were reviewed. In addition, the management and long-term follow-up outcome of PE were reported. Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire was applied for five patients to evaluate health-related quality of life after PE. Results: All patients survived during their hospitalization, and five patients were contacted during follow-up. Five of the eight patients were anticoagulated regularly until the re-examination results of CTPA and lower extremities ultrasound were normal. The period of anticoagulant sustained at least one month for each patient. The long-term follow-up outcomes showed that PE had little impact on the patients' quality of life. Conclusions: The study demonstrated that the prognosis of PE patients was not as terrible as feared when treated immediately in the ward. Early diagnosis and treatment of PE is vital for prognosis. However, further verifications based on the results of large studies are still needed.

Establishment of Prediction Models for Venous Thromboembolism in Non-Oncological Urological Inpatients - A Single-Center Experience.

Purpose: Venous thromboembolism (VTE) comprises deep venous thrombosis (DVT) and pulmonary embolism (PE), which can lead to death. VTE is an insidious disease with no specific symptoms and overlooked readily. We aimed to establish prediction models for VTE in non-oncological urological inpatients to aid urologists to better identify VTE patients. Patients and Methods: A retrospective analysis of 1453 inpatients was carried out. The risk factors for VTE had been clarified in our previous study. A stepwise regression method was used to screen the relevant influencing factors for VTE and construct a logistic regression prediction model to predict VTE. To validate the accuracy of the model, data from 291 patients from another cohort were used for external validation. Results: A total of 1453 inpatients were enrolled. Five potential risk factors (previous VTE; treatment with anticoagulants or anti-platelet agents before hospital admission; D-dimer ≥0.89 µg/mL; lower-extremity swelling; chest symptoms) were selected by multivariable analysis with p < 0.05. These five risk factors were used to build a logistic regression prediction model. When p < 0.1 in the multivariable logistic regression model, two additional risk factors were added: Caprini score ≥5 and complications, and all seven risk factors were used to build another prediction model. Internal verification showed the cutoff values, sensitivity, and specificity of the two models to be 0.02474, 0.941, 0.816 (model 1) and 0.03824, 0.941, and 0.820 (model 2), respectively. Both models had good predictive ability, but prediction accuracy was 43.0% for both when using the data of the additional 291 inpatients in the two models. Conclusion: Two novel prediction models were built to predict VTE in non-oncological urological inpatients. This is a new method for VTE screening, and internal validation showed a good performance. External validation results were suboptimal but may provide clues for subsequent VTE screening.

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Recturethral fistula (RUF) is a kind of serious complication that mainly happened during the treatment of prostate cancer. It has become one of the most difficult diseases to treat in urology because of its special anatomical location, complicated condition, and the varied prognosis. At present, the main treatment methods for RUF are conservative treatment such as application of antibiotics and indwelling catheters, etc. and surgical treatment such as transperineal approach, transsphincter approach, transanal approach, transabdominal approach, etc. However, there is no explicit treatment protocol for RUF. What's more, the etiology of RUF has changed greatly in recent years. Summarizing the advantages and disadvantages of different RUF's treatment methods and their prognosis will be helpful for the decision of clinical treatment.

Incidence and Risk Factors of Venous Thromboembolism in Patients After Transurethral Resection of the Prostate (TURP).

OBJECTIVE: Venous thromboembolism (VTE) in patients following transurethral resection of the prostate (TURP) has been overlooked for many years. This research was aimed to investigate the incidence and risk factors of VTE in patients after TURP. METHODS: A total of 451 patients who underwent TURP between January 2017 and December 2020 were retrospectively analyzed. Clinical data of the patients were collected, such as basic demographic data, prostate volume, creatinine values, hemoglobin values, surgery duration, Caprini score, international prostate symptom score (IPSS), quality of life (QOL) score, plasma D-dimer levels, and so on. Univariate analysis and multivariate logistic regression were performed to identify the potential risk factors of VTE. Venous ultrasonography of lower extremities was performed routinely to detect VTE for patients after TURP. RESULTS: In total, 36 (8%) out of the 451 patients suffered from VTE. A total of 12 (2.7%) patients were confirmed with deep venous thrombosis (DVT). Two patients (0.4%) were identified with pulmonary embolism (PE). Twenty-two (4.9%) patients were suffered from superficial venous thrombosis. Furthermore, according to the results of multivariate stepwise logistic regression analysis, having a history of VTE (adjusted odds ratio [aOR] = 10.980, 95% CI = 2.265-53.223), complicated with postoperative bladder hematoma (aOR = 6.302, 95% CI = 2.265-17.532), D-dimer >1.25 mg/L (aOR = 4.402, 95% CI = 1.798-10.774), and age >65 (aOR = 3.106, 95% CI = 1.084-8.893) were independent risk factors of VTE after TURP. In addition, the nomogram prediction model is a useful auxiliary prevention tool of VTE. CONCLUSION: The incidence of VTE is severely underestimated in patients following TURP. A lot of asymptomatic VTEs have been overlooked. Early detection and diagnosis of VTE are essential. Nevertheless, further verifications based on the results of large-scaled studies are still needed.

Application value of D-dimer testing and Caprini risk assessment model (RAM) to predict venous thromboembolism (VTE) in Chinese non-oncological urological inpatients: a retrospective study from a tertiary hospital.

BACKGROUND: The Caprini risk assessment model (RAM) and D-dimer testing have been widely used in the prediction of venous thromboembolism (VTE). However, the clinical significance of these testing options are limited in non-oncological urological inpatients because of the low specificity. METHODS: This retrospective study included 1,453 patients who were admitted to the non-oncological unit of the Department of Urology, Xiangya Hospital, Central South University, from January 2018 to December 2018. The highest score of Caprini RAM and the highest D-dimer level were collected in this retrospective study. Ultrasound examinations of the lower extremities or computed tomographic pulmonary arteriography (CTPA) were applied to patients who were suspected of having VTE, if necessary. RESULTS: A total of 1,453 patients were collected in this study, which included 34 VTE and 1,419 non-VTE patients. The threshold of D-dimer was 0.89 µg/mL, according to the receiver operating characteristic (ROC) curve, with a sensitivity of 82.4%, a specificity of 83.3%, and a negative predictive value (NPV) of 99.5%. The cut-off of the Caprini RAM was 5, with a sensitivity of 76.5%, a specificity of 58.7%, and an NPV of 99.0%. The area under the curve (AUC) was higher for D-dimer (0.86) than for the Caprini score (0.73). CONCLUSIONS: The application of 0.89 µg/mL and a score of 5 as cut-offs for D-dimer testing and Caprini RAM, respectively, could safely decrease the proportion of Chinese non-oncological urological inpatients who needed to undergo further examinations. These new findings may enhance the application value of D-dimer testing and Caprini RAM for Chinese non-oncological urological inpatients.

Inhibition of eNOS by L-NAME resulting in rat hind limb developmental defects through PFKFB3 mediated angiogenetic pathway.

L-arginine/NOS/NO signaling pathway plays a critical role in controlling variety of vascular diseases. However, whether NOS inhibition by L-NAME suppresses late embryonic development is undefined. The aim of this study is to determine whether NOS inhibition by L-NAME is critical for late embryonic rat hind limb development. The pregnant rat at E13.5 administrated L-NAME by consecutive intraperitoneal injection. The embryos been harvested from E16.5 to E 20.5. Hematoxylin and Eosin Staining, Immunofluorescence and Immunohistochemistry performed to determine hind limb Vasculogenesis, HUVEC culture, Adenoviral PFKFB3 infection, Real time PCR and western blot were performed to determine whether L-arginine/NOS/NO pathway controlling late embryonic hind limb development through PFKFB3 mediated angiogenetic pathway. NOS inhibition by L-NAME resulting in late embryonic hind limb developmental defects characterized by severe hemorrhage. The in vivo studies showed that NOS inhibition strongly suppressed hind limb angiogenetic remodeling by impairing differentiation of endothelial cells and smooth muscle cells, and extracellular matrix synthesis. For underlie mechanism, our studies indicated that L-NAME treatment dramatically suppresses PFKFB3 expression in hematopoietic progenitor cells, tubulogenetic endothelial cells and smooth muscle cells. Knockdown of PFKFB3 dramatically inhibits the expression of angiogenetic genes, as well as tubulogenesis and extracellular matrix related genes. Taken together, our data in this study demonstrated that L-arginine-eNOS-NO pathway is important for rat hind limb development during late embryonic stage. This could be both a useful animal model and a promising therapeutic treatment for defects of late embryonic developmental hind limbs.

Relationships Between Eating Behaviors and Hand Grip Strength Among Chinese Adults: A Population-Based Cross-Sectional Study.

PURPOSE: Poor eating behaviors are associated with imbalances in energy and food intake, which may directly or indirectly contribute to muscle strength loss. This study aimed to investigate the association between eating behaviors and hand grip strength in Chinese adults. MATERIALS AND METHODS: We designed and conducted a cross-sectional study of 2009 Chinese individuals aged 25-65 years in 2017. Eating behaviors, including breakfast consumption, snacking after dinner, and eating rate, were assessed using a self-administered questionnaire. Hand grip strength was assessed using a digital grip dynamometer. Age, sex, BMI, physical activity, educational level, occupation, living status, sleep duration, smoking and drinking status, hypertension, diabetes, and depressive symptoms were used as confounding factors. RESULTS: After final adjustments for confounding factors, grip strength was measured as 35.2 (95% confidence interval [CI]: 34.7-35.8), 36.0 (95% CI: 35.6-36.4), and 36.9 (95% CI: 36.6-37.3) for those who skipped, occasionally ate, and regularly ate breakfast, respectively (p for trend <0.001). Those who always, sometimes, and seldom snacked after dinner (p for trend <0.001) reported the following grip strength: 34.7 (95% CI: 34.0-35.3), 36.2 (95% CI: 35.8-36.6), and 36.9 (95% CI: 36.6-37.2), respectively. Significant associations were not found between eating rate and grip strength. CONCLUSION: This study showed that higher frequency of breakfast consumption and lower frequency of snacking after dinner were associated with higher grip strength in Chinese adults. Therefore, eating behaviors may be involved in muscle function.

Andrographolide promotes skeletal muscle regeneration after acute injury through epigenetic modulation.

Myopathy is a muscle disease in which muscle fibers do not function properly, and eventually cause severe diseases, such as muscular dystrophy. The properly regeneration of skeletal muscle plays a pivotal role to maintain the muscle function after muscle injury. The aim of this study is to determine whether andrographolide plays an effect role on regulating skeletal muscle regeneration. Mouse satellite cells, C2C12 cells and Cardiotoxin (CTX) intramuscular injection induced acute skeletal muscle injury model were used to evaluate whether andrographolide is essential for skeletal muscle regeneration. The underling mechanism detected using immunohistochemistry stain, western blot, real time PCR. Andrographolide promotes mouse skeletal muscle regeneration. In cardiotoxin induced skeletal muscle injury model, andrographolide treatment enhanced myotube generation and promoted myotube fusion. Andrographolide treatment dramatically increased expression of myotube differentiation related genes, including Desmin, MyoD, MyoG, Myomaker, Tnni2, Dmd, Myoz1 and Myoz3. For the mechanism studies, we observed that andrographolide treatment significantly promoted histone modification, such as H3K4Me2, H3K4Me3 and H3K36Me2, both in vivo and in vitro. Treatment with DZNep, a Lysine methyltransferase EZH2 inhibitor, significantly attenuated andrographolide-induced expression of Myf5, Myomaker, Skeletal muscle α-actin, MyoD and MyoG. Taken together, our data in this study demonstrate andrographolide epigenetically drives differentiation and fusion of myotube, eventually promotes skeletal muscle regeneration. This should be a therapeutic treatment for skeletal muscle regeneration after muscle damage.

Tanshinone II A attenuates vascular remodeling through klf4 mediated smooth muscle cell phenotypic switching.

The aim of this study is to investigate the therapeutic role of Tanshinone II A, a key integrant from salvia miltiorrhiza, against pathological vascular remodeling. Completed ligation of mouse left common carotid arteries animal model and rat smooth muscle cells used to investigate the role of Tanshinone II A in regulating pathological vascular remodeling through hematoxylin and eosin staining, immunohistochemistry staining, immunofluorescence staining, adenovirus infection, real time PCR and western blotting. Our data demonstrated that Tanshinone II A treatment suppresses vascular injury-induced neointima formation. In vitro studies on rat smooth muscle cell indicated that Tanshinone II A treatment attenuates PDGF-BB induced cell growth, and promotes smooth muscle cell differentiated marker genes expression that induced by rapamycin treatment. Tanshinone II A treatment significant inhibits rat smooth muscle cell proliferation and migration. Tanshinone II A promotes KLF4 expression during smooth muscle phenotypic switching. Overexpression of KLF4 exacerbates Tanshinone II A mediated smooth muscle cell growth inhibition. Tanshinone II A plays a pivotal role in regulating pathological vascular remodeling through KLF4 mediated smooth muscle cell phenotypic switching. This study demonstrated that Tanshinone II A is a potential therapeutic agent for vascular diseases.

Expression of MMP-2 in residual VX2 liver tumor after transcatheter arterial embolization combined with portal venous embolization in an animal model.

OBJECTIVE: This study aimed to analyze the effects of transcatheter arterial embolization (TAE) combined with portal venous embolization (PVE) on the expression of MMP-2 in residual VX2 liver tumor tissues, liver function and non-embolic lobe regeneration. METHODS: A total of 72 rabbits were randomly divided into Sham, TAE, PVE and TAE â€‹+ â€‹PVE groups (n â€‹= â€‹18/group). The tissue samples from each group were taken at 6 â€‹h, 3 days and 7 days after interventional operation, respectively. MMP-2 expression was detected by immunohistochemistry, Real-time PCR, and Western-blotting. The main indicators (such as AST, ATL, and TBIL) of liver function and the volume of non-embolized hepatic lobes were measured in each group after operation. One-way ANOVA and Kruskal-wallis method were used for statistical analysis. RESULTS: The expression of MMP-2 mRNA and protein remained the highest in the Sham group, and the expression of MMP-2 mRNA and protein in TAE, PVE and TAE â€‹+ â€‹PVE groups were successively increased, and the expression of MMP-2 in TAE â€‹+ â€‹PVE group was always significantly higher than TAE group. The AST and ALT levels in each group on day 7 after operation showed a significant declination, and all groups have recovered to the preoperative baseline level and TBIL has a slight fluctuation in each group after operation with no statistical difference. On day 7 after operation, the increasing volume of non-embolized liver lobes in TAE â€‹+ â€‹PVE group showed a more significant effect than those in PVE group, but there was no statistical significance (37.62 â€‹± â€‹1.54 â€‹ml VS 36.18 â€‹± â€‹1.15 â€‹ml, P â€‹= â€‹0.881), and its volume was significantly higher than those in the sham group (27.03 â€‹± â€‹1.11 â€‹ml). CONCLUSION: TAE â€‹+ â€‹PVE is considered to be an efficient and safe approach for treating rabbit VX2 liver transplantation tumor, but the expression of MMP-2 increased fastest after TAE â€‹+ â€‹PVE, which might promote tumor cell invasion and metastasis.

Andrographolide attenuates imbalance of gastric vascular homeostasis induced by ethanol through glycolysis pathway.

Different kinds of factors contribute to gastric ulcer development which characterized by damaging gastric mucosal layer. However, gastric vascular homeostasis is not well defined and whether andrographolide has a protective function is largely unknown. The goal of this study is to investigate the potential function roles and underlying mechanism by which andrographolide regulates gastric vascular homeostasis in vivo and in vitro. Gastric ulcer animal model induced on andrographolide pretreated C57/BL6 mouse by ethanol intragastric administration. Hematoxylin and Eosin Stain, Masson's trichrome stain and Immunohistochemistry stain performed to observe gastric vascular homeostasis, which associated hemorrhage, extracellular matrix deposition and macrophage infiltration. The activity of vascular endothelial cells were associated with the proliferation and migration, which were detected using cell counting, MTS, and wound scratch healing assay. The underlying endothelial glycolytic mechanism investigated in vivo and in vitro. Andrographolide pretreatment dramatically attenuates ethanol intragastric administration induced imbalance of gastric vascular homeostasis which characterized by severe hemorrhage, increase extracellular matrix deposition and augment macrophage infiltration. Andrographolide treatment conspicuous inhibits HUVEC-C activity characterized by suppressing proliferation and migration of endothelial cells. Mechanically, andrographolide treatment significant suppresses the expression of glycolytic genes, especially decrease PFKFB3 expression. The treatment with PFKFB3 inhibitor, 3-PO, exacerbates the inhibitory function of andrographolide on vascular endothelial cell proliferation and migration. Those data Suggests that andrographolide contributes to maintain gastric vascular homeostasis, at least partially, by inhibiting PFKFB3 mediated glycolysis pathway. Andrographolide plays a crucial role in maintaining gastric vascular homeostasis during gastric ulcer development through regulating vascular endothelial cell glycolytic pathway.

Elaphroporia ailaoshanensis gen. et sp. nov. in Polyporales (Basidiomycota).

A new poroid wood-inhabiting fungal genus, Elaphroporia, typified by E. ailaoshanensissp. nov., is proposed based on a combination of morphological features and molecular evidence. The genus is characterised by an annual growth habit, resupinate basidiocarps, becoming rigid and light-weight up on drying, a monomitic hyphal system with thick-walled generative hyphae bearing both clamp connections and simple septa, slightly amyloid, CB+ and ellipsoid, hyaline, thin-walled, smooth and IKI-, CB- basidiospores. Sequences of ITS and LSU nrRNA gene regions of the studied samples were generated, and phylogenetic analyses were performed with maximum likelihood, maximum parsimony and bayesian inference methods. The phylogenetic analysis based on molecular data of ITS+nLSU sequences showed that Elaphroporia belonged to the residual polyporoid clade and was closely related to Junghuhnia crustacea. Further investigation was obtained for more representative taxa in the Meruliaceae based on ITS+nLSU sequences, in which the result demonstrated that the genus Elaphroporia formed a monophyletic lineage with a strong support (100 % BS, 100 % BP, 1.00 BPP) and then grouped with Flaviporus and Steccherinum.

Periostin promotes migration, proliferation, and differentiation of human periodontal ligament mesenchymal stem cells.

OVERVIEW: Periostin (POSTN) is critical to bone and dental tissue morphogenesis, postnatal development, and maintenance; however, its roles in tissue repair and regeneration mediated by human periodontal ligament mesenchymal stem cells (PDLSCs) remain unclear. The present study was designed to evaluate the effects of POSTN on hPDLSCs in vitro. MATERIALS AND METHODS: hPDLSCs were isolated and characterized by their expression of the cell surface markers CD44, CD90, CD105, CD34, and CD45. Next, 100 ng/mL recombinant human POSTN protein (rhPOSTN) was used to stimulate the hPDLSCs. Lentiviral POSTN shRNA was used to knockdown POSTN. The cell counting kit-8 (CCK8) and scratch assay were used to analyze cell proliferation and migration, respectively. Osteogenic differentiation was investigated using an alkaline phosphatase (ALP) activity assay, alizarin staining, and quantitative calcium analysis and related genes/protein expression assays. RESULTS: Isolated hPDLSCs were positive for CD44, CD90, and CD105 and negative for CD34 and CD45. In addition, 100 ng/mL rhPOSTN significantly accelerated scratch closure, and POSTN-knockdown cells presented slower closure at 24 h and 48 h. Furthermore, the integrin inhibitor Cilengitide depressed the scratch closure that was enhanced by POSTN at 24 h. The CCK8 assay showed that 100 ng/mL rhPOSTN promoted hPDLSC proliferation. Moreover, 100 ng/mL rhPOSTN increased the expression of RUNX2, OSX, OPN, OCN, and VEGF and enhanced ALP activity and mineralization. POSTN silencing decreased the expression of RUNX2, OSX, OPN, OCN, and VEGF and inhibited ALP activity and mineralization. CONCLUSIONS: POSTN accelerated the migration, proliferation, and osteogenic differentiation of hPDLSCs.