Adrenal cortical carcinoma in children: a clinicopathological analysis of 25 cases / 中华病理学杂志

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of adrenal cortical carcinoma (ACC) in children. Methods: Twenty-five children with ACC diagnosed in the Department of Pathology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from March 2014 to August 2022 were retrospectively analyzed. The related literature was reviewed. Results: A total of 25 children with ACC were collected, including 11 males and 14 females, with a male to female ratio of 1.0∶1.3. The patient ages ranged from 8 months to 14 years (median, 4 years). Eighteen cases with clinical data had functional tumors (18/22, 81.8%) presenting with virilization or precocious puberty (15/18), symptoms related to hypercortisolism (8/18) or endocrine symptoms mixed with both (5/18), while 3 cases (3/22, 13.6%) had unknown clinical data. The clinical manifestations of four patients with nonfunctional tumors were an abdominal mass and/or abdominal pain, walking instability and others. Grossly, the average maximum diameter of the tumor was 9.4 cm. Most of the tumors were nodular and partially encapsuled. The cut surfaces were gray or gray brown, soft with hemorrhage. Histologically, the tumor cells were diffusely distributed, separated by a vascular-rich network. The tumor cells were large, with distinct nucleoli, abundant eosinophilic or clear cytoplasm, and round or oval nuclei. The mitotic index was high, and atypical mitoses were common. Necrosis, calcification, capsule invasion or/and venous invasion were present. In some cases, the tumor invaded the surrounding soft tissues or kidneys. Immunohistochemically, the tumor cells were diffusely positive for syn and SF1 and focally positive for α-inhibin, Melan A and Calretinin, but negative for CgA. Ki-67 proliferation index ranged from 2%-90%. TP53 gene status was examined in 7 cases, in which mutations were detected in 4 cases. Follow-up data was obtained in 21 patients, among whom 18 received chemotherapy and 3 received radiotherapy. Distant metastasis occurred in 13 patients. Median progression-free survival (PFS) was 11.2 months and median overall survival (OS) was 54.7 months. Patients aged less than 5 years had a better prognosis for OS (P<0.05) than the older ones (≥5 years), but a similar PFS (P>0.05). Male patients and Ki-67 proliferation index <15% had a better prognosis tendency for OS, but there was no statistically significant difference (P>0.05). Conclusions: ACC in children is a rare, often functional tumor associated with Li-Fraumeni genetic syndrome and has a poor prognosis. Diagnosis and differential diagnosis require a combination of morphological, phenotypic and clinical analysis.

Association between telomere length in the DNA of peripheral blood leukocytes and the propofol dose in anesthesia induction: an observational study

Abstract Introduction: Propofol is a widely used anesthetic and its dose is closely related to aging. Telomere length (TL) is a unique heritable trait, and emerging as a biomarker of aging, health and disease. Telomerase RNA component (TERC) plays an important role in maintaining TL. We proposed a hypothesis that propofol dose in general anesthesia can be predicted by measuring TL before operation, which greatly reduced the risk of anesthesia, especially the elderly. Methods: The association between the propofol dose in anesthesia induction and: TL in the DNA of peripheral blood leukocytes; body weight; sex; difference of the Bispectral Index (BIS) before and after anesthesia induction in patients was evaluated by multivariable linear regression analyses. The mutation at the 5'end or 3'end of TERC was detected. We recruited 100 patients of elective surgery. Results: We found that propofol dose in anesthesia induction was clearly correlated significantly with TL (r = 0.78, p < 0.001), body weight (r = 0.84, p = 0.004), sex (r = 0.83, p= 0.84, p = 0.004), sex (r = 0.83, p = 0.004), and difference of BIS before and after anesthesia induction (r = 0.85, p = 0.029). By comparing the absolute values of standardized regression coefficients (0.58, 0.21, 0.19, and 0.12) of the four variables, it can be seen that TL contributes the most to the propofol dose in anesthesia induction. However, the mutation at the 5' end or 3' end of TERC was not found. Conclusions: These findings provide preliminary evidence that the propofol dose in anesthesia induction was clearly correlated with genetically determined TL. TL may be a promising predictor of the propofol dose, which is beneficial to improve the safety of anesthesia and reduce perioperative complications.

Internal Structural Connections in the Popliteus Tendon Complex with Posterior Cruciate Ligament and Clinical Implications / Conexiones Estructurales Internas en el Complejo Tendón Poplíteo con Ligamento Cruzado Posterior e Implicaciones Clínicas

SUMMARY: At present, the anatomical relationship the mid-portion of popliteus tendon complex (PTC) and the surrounding tissues is still unclear, especially its relationship to the posterior cruciate ligament (PCL). It affected the anatomical reconstruction of the posterolateral complex (PLC) injury. A total of 30 cases of the adult human knee joint fixed with formalin were used. Sagittal sections were made in 14 knee joints by the P45 plastination technique and dissection of 16 cases of knee joints. The P45 section revealed that the popliteus muscle fascia ran superiorly over the posterior edge of the tibial intercondylar eminence, and turned forward to be integrated into the PCL. Laterally, near the posterior edge of the lateral tibial plateau, the popliteus tendon penetrates through the articular capsule (AC), where two dense fibrous bundles were given off upwards by the popliteus tendon: one was the ventral fiber bundle, which ran superiorly over the posterior edge of the tibial plateau and then moved forwards to connect with the lateral meniscus; the dorsal fibers bundle ascended directly and participated in the AC. Meanwhile, the popliteus muscle dissection showed that at the posterior edge of the platform of the lateral condyle of the tibia, at the tendon-muscle transition, the PTC and AC were anchored to PCL.

En la actualidad, la relación anatómica entre la porción media del complejo tendinoso poplíteo (CTP) y los tejidos circundantes aún no está clara, especialmente su relación con el ligamento cruzado posterior (LCP). Esto afecta la reconstrucción anatómica de la lesión del complejo posterolateral (LCP). Se utilizaron un total de 30 casos de articulaciones de rodillas humanas de individuos adultos fijadas con formalina. Se realizaron cortes sagitales en 14 articulaciones de rodilla mediante la técnica de plastinación P45 y disección de 16 casos de articulaciones de rodilla. La sección P45 reveló que la fascia del músculo poplíteo discurría superiormente sobre el margen posterior de la eminencia intercondílea tibial y giraba hacia delante para integrarse en el LCP. Lateralmente, cerca del margen posterior de la platillo tibial lateral, el tendón poplíteo penetra a través de la cápsula articular (CA), donde el tendón poplíteo desprendió hacia arriba dos haces fibrosos densos: uno era el haz de fibras ventral, que corría superiormente sobre el margen posterior de la meseta tibial y luego se movió hacia adelante para conectar con el menisco lateral; el haz de fibras dorsales ascendía directamente y participaba en la CA. Por su parte, la disección del músculo poplíteo mostró que en el margen posterior del platillo del cóndilo lateral de la tibia, en la transición tendón-músculo, el CTP y el AC estaban anclados al LCP.

Detailed anatomy of the corpora-glans ligament via the P45 plastination method / Anatomía detallada de los ligamentos cuerpo cavernoso-glande mediante el método de plastinación P45

SUMMARY: The corporo-glans ligament is the ligament connecting the corpus cavernosum and the glans of the penis. The anatomical description of the corporo-glans ligaments shape is still uncertain, this knowledge affects penile reconstructive procedures. The anatomy of the corporo-glans ligament was analyzed and recorded via observing sagittal sections of 10 different penile P45 plastination sections. According to the P45 plastination sections, the corporo-glans junction displayed a fibrous tissue band connecting the distal ends of the two corpus cavernous (CC) with the glans penis (GP). The fibrous band was a round-obtuse shape and ran deep into the glans of the penis and occupied about 2/3 of the whole GP. The original end was laid in a socket embedded in the GP. The density of the fibers of the ligament at the original end close to the tunica albuginea was less than that of the other parts. The fibers originating from the tunica albuginea, directly extended to the blind end of the two CC, covering the distal end of the two CC.

El ligamento cuerpo cavernoso-glande es el ligamento que conecta el cuerpo cavernoso y el glande del pene. La descripción anatómica de la forma de los ligamentos cuerpo cavernoso -glande aún es incierta; este conocimiento afecta los procedimientos reconstructivos del pene. La anatomía del ligamento cuerpo cavernoso-glande se analizó y registró mediante la observación de 10 secciones sagitales diferentes del pene a través de plastinación P45. Según las secciones de plastinación, la unión cuerpo-glande mostraba una banda de tejido fibroso que conectaba los extremos distales de los dos cuerpos cavernosos con el glande del pene. La banda fibrosa tenía una forma redonda y obtusa y se adentraba profundamente en el glande del pene ocupando alrededor de 2/3 de él. En su origen se coloca en un espacio profundo en el glande del pene. La densidad de las fibras del ligamento cuerpo cavernoso-glande en su origen cercano a la túnica albugínea era menor que el de las otras partes. Las fibras que se originan en la túnica albugínea, se extienden directamente hasta el extremo ciego de los dos cuerpos cavernosos, cubriendo el extremo distal de estos.

Comparison of pingyangmycin fibrin glue composite and pingyangmycin dexamethasone composite in the treatment of pharyngolaryngeal venous malformation / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze and compare the efficacy and safety of pingyangmycin fibrin glue composite (PFG) and pingyangmycin dexamethasone composite (PD) in the treatment of pharyngolaryngeal venous malformation (VM). Methods: The clinical data of 98 patients with pharyngolaryngeal VM who underwent sclerotherapy with pingyangmycin composite in the First Affiliated Hospital of Sun Yat-sen University from June 2013 to November 2022 were retrospectively analyzed. According to their treatment, patients were divided into PFG group (n=34) and PD group (n=64), among those patients there were 54 males and 44 females, aged 1-77(37.06±18.86)years. The lesion size, total treatment times and adverse events were recorded before and after treatment. And the efficacy was divided into three grades: recovery, effective and invalid. According to the length of VM, all patients were divided into three subgroups, to compare the differences in efficacy and treatment times between each two groups.And finally the adverse events and their treatments were analyzed. SPSS 25.0 software was used for statistical analysis. Results: The efficacy of PFG group was 94.11%(32/34), the recovery rate was 85.29%(29/34).And the efficacy of PD group was 93.75%(60/64), the recovery rate was 64.06%(41/64). No serious adverse eventst occurred in subgroup comparison, there was no statistical difference between the two groups in efficacy and the times of treatments when the length was≤3 cm (Zefficacy=1.04, ttreatment times=2.18, P>0.05); when the length was 3-5 cm, there was no significant efficacy difference between the two groups(Zefficacy=1.17, P>0.05), but the treatment times of PFG were less (ttreatment times=4.87, P<0.01); when the length≥5 cm, efficacy of PFG was significantly better than PD (Zefficacy=2.94, P<0.01), and had fewer treatments times (ttreatment times=2.16, P<0.01). There were no serious adverse events in either group during treatment and follow-up. Conclusion: Both PFG and PD are safe and effective composite sclerotherapy agent for the treatment of laryngeal VM, but PFG has a higher cure rate and fewer treatment times for massive lesions.

Research progress in epigenetic pharmacological effects of rhein / 中国中药杂志

Rhein, which is one of the main active components of Rheum palmatum, has a range of pharmacological activities such as the regulation of the metabolism of glucose and lipids, anti-inflammatory, anti-tumor, anti-fibrosis, etc. Epigenetics refers to the heritable variation of gene expression without altering the DNA sequence. It is involved in the emergence and development of inflammation, renal fibrosis, diabetes, cancer, atherosclerosis, and other diseases, thus becoming a new strategy for the treatment of many di-seases. A series of studies have shown that epigenetic modification may be a common molecular mechanism of various pharmacological effects of rhein. This paper summarized the effects of rhein on the regulation of epigenetic modification and its underlying mechanisms, which involve the regulation of DNA methylation, protein acetylation, and RNA methylation, so as to provide a basis for the development and application of rhein.

Protective effect of Liujing Toutong Tablets on rats with permanent cerebral ischemia via NF-κB signaling pathway / 中国中药杂志

This study investigated the neuroprotective effects and underlying mechanism of Liujing Toutong Tablets(LJTT) on a rat model of permanent middle cerebral artery occlusion(pMCAO). The pMCAO model was established using the suture method. Eighty-four male SPF-grade SD rats were randomly divided into a sham operation group, a model group, a nimodipine group(0.020 g·kg~(-1)), and high-, medium-, and low-dose LJTT groups(2.8, 1.4, and 0.7 g·kg~(-1)). The Longa score, adhesive removal test and laser speckle contrast imaging technique were used to evaluate the degree of neurological functional impairment and changes in local cerebral blood flow. The survival and mortality of rats in each group were recorded daily. After seven days of continuous administration following the model induction, the rats in each group were euthanized, and brain tissue and blood samples were collected for corresponding parameter measurements. Nissl staining was used to examine pathological changes in brain tissue neurons. The levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), IL-1β, vascular endothelial growth factor(VEGF), calcitonin gene-related peptide(CGRP), beta-endorphin(β-EP), and endogenous nitric oxide(NO) in rat serum were measured using specific assay kits. The entropy weight method was used to analyze the weights of various indicators. The protein expression levels of nuclear factor kappa-B(NF-κB), inhibitor kappaB alpha(IκBα), phosphorylated IκBα(p-IκBα), and phosphorylated inhibitor of NF-κB kinase alpha(p-IKKα) in brain tissue were determined using Western blot. Immunohistochemistry was used to detect the protein expression of chemokine-like factor 1(CKLF1) and C-C chemokine receptor 5(CCR5) in rat brain tissue. Compared with the sham operation group, the model group showed significantly higher neurological functional impairment scores, prolonged adhesive removal time, decreased cerebral blood flow, increased neuronal damage, reduced survival rate, significantly increased levels of TNF-α, IL-1β, IL-6, CGRP, and NO in serum, significantly decreased levels of VEGF and β-EP, significantly increased expression levels of NF-κB p65, p-IκBα/IκBα, and p-IKKα in rat brain tissue, and significantly upregulated protein expression of CKLF1 and CCR5. Compared with the model group, the high-dose LJTT group significantly improved the neurological functional score of pMCAO rats after oral administration for 7 days. LJTT at all doses significantly reduced adhesive removal time and restored cerebral blood flow. The high-and medium-dose LJTT groups significantly improved neuronal damage. The LJTT groups at all doses showed reduced levels of TNF-α, IL-1β, IL-6, CGRP, and NO in rat serum, increased VEGF and β-EP levels, and significantly decreased expression levels of NF-κB p65, p-IκBα/IκBα, p-IKKα, and CCR5 protein in rat brain tissue. The entropy weight analysis revealed that CGRP and β-EP were significantly affected during the model induction, and LJTT exhibited a strong effect in reducing the release of inflammatory factors such as TNF-α and IL-1β. LJTT may exert a neuroprotective effect on rats with permanent cerebral ischemia by reducing neuroinflammatory damage, and its mechanism may be related to the inhibition of the NF-κB signaling pathway and the regulation of the CKLF1/CCR5 axis. Additionally, LJTT may exert certain analgesic effects by reducing CGRP and NO levels and increasing β-EP levels.

Mining Novel Anti-Nocardia Drug Targets Based on Pan-genomics and Subtractive Proteomics / 中山大学学报(医学科学版)

ObjectiveNocardia is an apathogen that causes opportunistic infections in humans and has a global distribution. In recent years， resistance of Nocardia to commonly used drugs have been observed， highlighting the urgent need for the identification of new drug targets and the development of novel antimicrobial agents against Nocardia. MethodsThirty-one complete genome sequences of Nocardia strains were retrieved from the GenBank database. Pan-genomic analysis was performed using BPGA， and drug target candidates were screened using subtractive proteomics. Homology modeling was employed to predict the 3D structures of target proteins， and potential drugs targeting these proteins were predicted using DrugBank. Molecular docking techniques were utilized to validate the binding activity between the drugs and target proteins. ResultsThe pan-genomic analysis of the 31 Nocardia strains revealed 1 421 core proteins. Fifteen candidate drug target proteins were identified through subtractive proteomics analysis. Among them， the physicochemical properties of the OG1493 protein （such as amino acid count， molecular weight， isoelectric point， grand average of hydropathicity， fat index，and instability index Ⅱ） were found to be most suitable for a drug target protein. Using the DrugBank database， seven compounds， namely Adenosine-5'-Rp-Alpha-Thio-Triphosphate， alpha，beta-Methyleneadenosine 5'-triphosphate， Phosphoaminophosphonic Acid-Adenylate Ester ，Radicicol，2-Hydroxyestradiol， p-Coumaric acid， and Ethylmercurithiosalicylic acid were identified as potential compounds capable of exerting anti-Nocardia effects by targeting this protein. Molecular docking results indicated a strong binding affinity between the target protein and these compounds. The experimental result showed that that Radicicol could be a potential antibacterial drug targeting this particular protein. ConclusionPan-genomic analysis and subtractive proteomics are valuable approaches for mining novel anti-Nocardia drug targets.

Effect of Shugan Tiaoshen acupuncture combined with western medication on depression-insomnia comorbidity due to COVID-19 quarantine: a multi-central randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effect of Shugan Tiaoshen acupuncture (acupuncture for soothing the liver and regulating the mentality) combined with western medication on depression and sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, and investigate the potential mechanism from the perspective of cortical excitability.@*METHODS@#Sixty patients with depression-insomnia comorbidity due to COVID-19 quarantine were randomly divided into an acupuncture group and a sham-acupuncture group, 30 cases in each one. The patients of both groups were treated with oral administration of sertraline hydrochloride tablets. In the acupuncture group, Shugan Tiaoshen acupuncture was supplemented. Body acupuncture was applied to Yintang (GV 24+), Baihui (GV 20), Hegu (LI 4), Zhaohai (KI 6), Qihai (CV 6), etc. The intradermal needling was used at Xin (CO15), Gan (CO12) and Shen (CO10). In the sham-acupuncture group, the sham-acupuncture was given at the same points as the acupuncture group. The compensatory treatment was provided at the end of follow-up for the patients in the sham-acupuncture group. In both groups, the treatment was given once every two days, 3 times a week, for consecutive 8 weeks. The self-rating depression scale (SDS) and insomnia severity index (ISI) scores were compared between the two groups before and after treatment and 1 month after the end of treatment (follow-up) separately. The cortical excitability indexes (resting motor threshold [rMT], motor evoked potential amplitude [MEP-A], cortical resting period [CSP]) and the level of serum 5-hydroxytryptamine (5-HT) were measured before and after treatment in the two groups.@*RESULTS@#After treatment and in follow-up, SDS and ISI scores were decreased in both groups compared with those before treatment (P<0.05), and the scores in the acupuncture group were lower than those in the sham-acupuncture group (P<0.05), and the decrease range in the acupuncture group after treatment was larger than that in the sham-acupuncture group (P<0.05). After treatment, rMT was reduced (P<0.05), while MEP-A and CSP were increased (P<0.05) in the acupuncture group compared with that before treatment. The levels of serum 5-HT in both groups were increased compared with those before treatment (P<0.05). The rMT in the acupuncture group was lower than that in the sham-acupuncture group, while MEP-A and CSP, as well as the level of serum 5-HT were higher in the acupuncture group in comparison with the sham-acupuncture group (P<0.05).@*CONCLUSION@#Shugan Tiaoshen acupuncture combined with western medication can relieve depression and improve sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, which is probably related to rectifying the imbalanced excitatory and inhibitory neuronal functions.

Adjustment of X-ray angle intraoperation based on the anatomic shape of femoral neck section / 解剖学报

[Abstract] Objective To investigate the appropriate X-ray angle which image can represent total proximal of femur according to the anatomic shape of the femoral neck section. Methods The anatomic parameter of the femoral neck section was observed and measured. Found the femoral neck was contained with three main surfaces of anterior surface, posterosuperior surface and posteroinferior surface. A model of surface fluoroscopy has been made by covering aluminum foil papers on the three surfaces of femoral neck. Taking the midpoint of the femoral neck as the fluoroscopy center, the C-arm was rotated at an interval of 10° between 0° and 170°, and the three aluminum foil paper models were taken for X-ray projection respectively. The X-ray angle with the smallest image of aluminum foil paper was taken as the appropriate X-ray angle of the surface. A penetrating model of the femoral neck internal fixation was made of three Kirschner wires penetrating through the anterior, posterosuperior and posteroinferior surfaces of femoral neck. The images of the penetrating Kirschner wires were observed through the traditional anteroposterior, lateral view and the three appropriate X-ray angle views obtained from the above test. Results The length of the three main surfaces accounts for 80. 95% of the circumference of the femoral neck. The anterior surface coronal angle was 18°, the posterosuperior surface coronal angle was 65°, and the posteroinferior surface coronal angle was 165°. The Appropriate X-ray angle of the three surfaces were 20°, 70° and 170° respectively. In the images of the three appropriate X-ray angles, the penetrating Kirschner wires of anterior surface, posterosuperior surface and posteroinferior surface of the femoral neck could be clearly observed respectively, while the penetrating Kirschner wire could not be completely found in the traditional anteroposterior and lateral images. Conclusion Traditional anteroposterior and lateral fluoroscopy can not accurately display the three-dimensional structure of femoral neck. By increasing the appropriate X-ray angle of 20°, 70° and 170°, the reduction quality and bony violation from internal fixation implants on the anterior surface, posterosuperior surface and posteroinferior surface of the femoral neck could be observed respectively.

Neurovascular coupling and central nervous system diseases / 中国药理学通报

Neurovascular coupling is the function of regulating blood flow of the central nervous system at the level of neurovascular units. The central nervous system diseases related to neurovascular coupling mainly include cerebrovascular diseases such as chronic cerebral ischemia and neurodegenerative diseases such as Alzheimer's disease,Parkinson's disease and Lewy body dementia. The main mechanism of neurovascular coupling dysfunction leading to the above diseases is cerebrovascular dysfunction or loss,which leads to serious damage to neuronal ischemia and affects its function. Therefore,this paper reviews the research status of neurovascular coupling and its related central nervous system diseases,in order to guide the follow-up research. The purpose of this paper is to provide a basis for the prevention,relief and treatment of central nervous system diseases related to neurovascular coupling through the mechanism of neurovascular coupling.

The protective effect of betelnut polyphenols on exercise-induced fatigue at high altitude and its network pharmacology in rats / 中国药理学通报

Aim: To explore the protective effect of betelnut polyphenols on high altitude exercise-induced fatigue in rats, and to select the main targets to carry out network pharmacology research to preliminarily explore its protective mechanism. Methods: We compared the protective effects of areca catechu polyphenols on high altitude exercise fatigue in rats in low, medium and high dose groups (400, 800, and 1600 mg·kg

The protective effect of catechin on acute high-altitude hypoxic injury / 中国药理学通报

Aim To study the protective effect of catechin on acute altitude injury in rats. Methods Rats were randomly divided into six groups: control group, altitude hypoxia model group, rhodiola capsule group, low -, middle-and high dose of catechin groups. After three days of preventive administration, animals were rushed to 4 010 m altitude. After five days of continuous administration, abdominal aortic blood of rats was collected for blood gas detection. Cardiac, brain and lung tissues were collected for HE staining to observe the pathological changes. MDA content, GSH content, NO content, SOD activity of myocardial, brain and lung tissues were detected, so were IL-6 and TNF-α content in serum. Results Compared with the control group, blood oxygen saturation of rats of altitud hypoxia model group was significantly reduced, while myocardial, brain and lung tissues were damaged to different degrees. MDA and NO content increased, while GSH content and SOD activity decreased. The serum inflammatory factors TNF-α and IL-6 levels were elevated significantly. After catechin treatment, blood oxygen saturation of hypoxia rats significantly increased (P < 0. 05). HE staining results showed that myocardial, brain and lung tissue injury was alleviated to some extent. MDA, NO, IL-6 and TNF-α content were down-regulated, while GSH content and SOD activity were up-regulated respectively. Conclusions Catechin can resist high altitude hypoxia and protect the main organs from hypoxia injury in rats acute exposed to altitude, which is related to alleviating oxidative stress and inflammation caused by acute hypoxia exposure.

Effect of a novel phosphodiesterase type 5 inhibitor,CPD1,on unilateral renal interstitial fibrosis caused by ureteric obstruction in mice / 中国药理学通报

Aim To investigate the effects of CPD1,a novel phosphodiesterase 5 inhibitor,on renal pathological phenotype and fibrotic protein expression in renal fibrosis model mice. Methods Male C57BL/6 J mice were divided into three groups randomly(sham group,UUO group and UUO+CPD1 group). Unilateral ureteric obstruction model was constructed by surgery,and CPD1(5 mg·kg-1·d-1)was administered by intragastric administration two hours after the modeling for seven days. HE and Sirius Red staining were used to observe the distribution of tissue structural lesions and fibrosis. Immunohistochemical staining and Western blot were used to detect the expression of fibronectin(FN),α-SMA,collagen-I and kidney injury molecule-1(Kim-1). Results Compared with sham operation group,the renal tubules of mice were dilated and accompanied by a large amount of inflammatory infiltration. Moreover,the expressions of FN,α-SMA,collagen-I and Kim-1 proteins increased significantly(P<0.05)in UUO group. CPD1 treatment improved the kidney structure and decreased the expression of collagen fibers. Furthermore,CPD1 inhibited the expression of FN,α-SMA,collagen-I and Kim-1 markedly(P<0.05). Conclusions Phosphodiesterase 5 inhibitor CPD1 alleviates the progression of renal fibrosis induced by unilateral ureteral obstruction through down-regulating ECM deposition in the extracellular matrix and expression of Kim-1. The specific mechanism remains to be further studied.

FKBP38 regulates apoptosis of dopaminergic neurons / 中国药理学通报

Aim To investigate the role of FKBP38 in inhibiting apoptosis in a rotenone-induced Parkinson's disease(PD)cell model. Methods In vivo experiments:MPTP-induced PD in vivo models were constructed,and the expressions of α-synuclein,TH and FKBP38 in brains of PD mice were detected. In vitro experiments:Dopaminergic neuron MN9D cells were stimulated with rotenone to construct an in vitro model of PD; Western blot was used to detect the expression levels of α-synuclein,TH,Tom20 and FKBP38 in PD in vitro model; FKBP38 lentivirus was transferred into MN9D cells to construct stable overexpression and FKBP38 knockdown cell lines; CCK-8 assay was used to detect the cell viability of FKBP38 overexpression and knockdown cells stimulated by rotenone; Western blot was used to detect anti-apoptotic protein Bcl-2 and apoptosis protein in PD cell model expression levels of Bax. Results The expression level of FKBP38 was significantly down-regulated in both in vitro and in vivo models of PD(P<0.01). Knockdown of FKBP38 aggravated the decline of dopaminergic neuron cell viability caused by rotenone(P<0.05),while overexpression of FKBP38 significantly ameliorated the decline of dopaminergic neuron cell viability caused by rotenone(P<0.05). Western blot results showed that overexpression of FKBP38 could significantly up-regulate the expression level of anti-apoptotic protein Bcl-2 and increase the ratio of Bcl-2/Bax in PD dopaminergic neurons(P<0.05). Conclusion In the PD cell model regulation of FKBP38 can improve the apoptosis of dopaminergic neurons.

Study on the protective effect of salidroside on memory impairment in mice under high altitude hypoxia / 中国药理学通报

Aim To explore the effect of salidroside on the learning and memory ability of mice under high altitude hypoxia. Methods Forty-eight C57BL/6J male mice were randomly divided into plain control group, plateau model group and salidroside group according to their body weight, with 16 mice in each group. The animals in each group were given prophylactic doses for three days and then rushed to a plateau with an altitude of 4 010 m. After one day of hypoxia exposure, Morris water maze was performed to test the learning and memory ability of mice; malondialdehyde(MDA), hydrogen peroxide(H

Effect of a novel phosphodiesterase type 5 inhibitor, CPD1, on carbon tetrachloride-induced liver fibrosis in mice / 中国药理学通报

Aim To investigate the effects of CPD1, a novel phosphodiesterase 5 inhibitor, on liver pathological phenotype and hepatic stellate cells (HSCs) activation in hepatic fibrosis model mice caused by carbon tetrachloride ( CCl

Effect of menthol, a transient receptor potential melastatin-8 channel activator, on pulmonary arterial hypertensive rats / 中国药理学通报

Aim To investigate the effects of menthol, a transient receptor potential melastatin-8 channel activator, on treating pulmonary arterial hypertension (PAH) in PAH model rats caused by monocrotaline (MCT). Methods Male Sprague-Dawley rats were divided into six groups randomly (control group, MCT group, MCT + menthol 1 mg • kg

Screening of key targets for diabetic cardiomyopathy based on transcriptomics and proteomics / 中国药理学通报

Aim To explore a potential new target for the prevention and treatment of diabetic cardiomyopathy ( DCM) in mice. Methods The myocardial proteomics of normal and diabetic mice was studied. The GEO database GSE161931 dataset was analyzed using R language with P < 0.05 and I log

Effects of plateau hypoxia on the pharmacokinetics and pharmacodynamics of atorvastatin calcium in hyperlipidemic rats / 中国药理学通报

Objective To study the effect of simulated high altitude hypoxia on the pharmacokinetics and pharmacodynamics of atorvastatin calcium in hyperlipidemia rats. Methods The wistar rats with hyperlipidemia induced by high-fat diet were divided into normoxia group and hypoxia group. Rats in the hypoxia group received a 14-day chronic hypoxia exposure at simulated an altitude of 5, 500 m. The two groups were given atorvastatin calcium(20 mg•kg