Protective effects of total saponins from Panax japonicus against high-fat diet-induced testicular Sertoli cell junction damage in mice / 南方医科大学学报

OBJECTIVE@#To investigate the protective effects of total saponins from Panax japonicus (TSPJ) against high-fat dietinduced testicular Sertoli cell junction damage in mice.@*METHODS@#Forty male C57BL/6J mice were randomized into normal diet group, high-fat diet group, and low-dose (25 mg/kg) and high-dose (75 mg/kg) TSPJ treatment groups (n=10). The mice in the normal diet group were fed a normal diet, while the mice in the other groups were fed a high-fat diet. After TSPJ treatment via intragastric administration for 5 months, the testes and epididymis of the mice were collected for measurement of weight, testicular and epididymal indices and sperm parameters. HE staining was used for histological evaluation of the testicular tissues and measurement of seminiferous tubule diameter and seminiferous epithelium height. The expression levels of ZO-1, occludin, claudin11, N-cadherin, E-cadherin and β-catenin in Sertoli cells were detected with Western blot, and the localization and expression levels of ZO-1 and β-catenin in the testicular tissues were detected with immunofluorescence assay. The protein expressions of LC3B, p-AKT and p-mTOR in testicular Sertoli cells were detected using double immunofluorescence assay.@*RESULTS@#Treatment with TSPJ significantly improved high-fat diet-induced testicular dysfunction by reducing body weight (P < 0.001), increasing testicular and epididymal indices (P < 0.05), and improving sperm concentration and sperm viability (P < 0.05). TSPJ ameliorated testicular pathologies and increased seminiferous epithelium height of the mice with high-fat diet feeding (P < 0.05) without affecting the seminiferous tubule diameter. TSPJ significantly increased the expression levels of ZO-1, occludin, N-cadherin, E-cadherin and β-catenin (P < 0.05) but did not affect claudin11 expression in the testicular tissues. Immunofluorescence assay showed that TSPJ significantly increased ZO-1 and β-catenin expression in the testicular tissues (P < 0.001), downregulated LC3B expression and upregulated p-AKT and p-mTOR expressions in testicular Sertoli cells.@*CONCLUSION@#TSPJ alleviates high-fat diet-induced damages of testicular Sertoli cell junctions and spermatogenesis possibly by activating the AKT/mTOR signaling pathway and inhibiting autophagy of testicular Sertoli cells.

Role and possible mechanism of estrogen receptor α down-regulation leading to damage of TM4 Sertoli cell connectivity in mice / 中国药理学通报

Aim To investigate the role of autophagy in the dysfunction of testicular TM4 cell junction induced by ERα down-regulation. Methods TM4 cells were treated with different concentrations of E R a inhibitor ICI182780 (ICI), and the proliferative activity of TM4 cells was detected by CCK-8 method. The number and morphological changes of TM4 cells were observed by light microscope. The levels of E R a, junction function related proteins and autophagy marker proteins were detected by Western blot. The expression and localization of Cx43 were detected by immunofluorescence staining. The cells were treated with chloroquine (CQ) and ICI for 24 h. The expression levels of autophagy and junction function related proteins were detected by Western blot. Results When ICI concentration was 50 nmol • L ~ or above, the cell viability decreased significantly. The increase of cell vacuoles in ICI group was observed by light microscope. Compared with normal control group, the protein expression levels of E R a, ZO-1, occludin, claudin-11, p-catenin and Cx43 in ICI groups significantly dropped, while the expression levels of N-cadherin and E-cadherin had no significant changes; LC3 II significantly rose, while p62 expression significantly fell. The results of immunofluorescence showed that the fluorescence expression of Cx43 in ICI group decreased significantly, but the position of CX43 did not change significantly. Compared with ICI group, the expression levels of LC3 II, p62, Cx43, ZO-1 and β-Catenin significantly increased. Conclusions The down-regulation of E R a leads to damage of TM4 cell junction function, which may be related to the activation of autophagy.

Effects of high-fat diet on testicular germ cell apoptosis in mice through endoplasmic reticulum stress / 中国药理学通报

Aim To study the effects of high-fat diet on testicular germ cell apoptosis in mice through endoplasmic reticulum stress. Methods C57BL/6J male mice were assigned into normal group and high-fat diet group randomly, with six mice in each group. The mice in normal group or high-fat diet group were fed with regular or high-fat diet continuously for five months. The mice were weighed, anesthetized, and euthanized to collect testicular and epididymal tissue for analysis. The testicular tissue was weighed and their indices were calculated. Epididymal tissue was collected for semen analysis. The morphological alterations of testicular tissue were observed using hematoxylin-eosin ( HE ) staining. The apoptosis of germ cells was detected by TUNEL staining and the apoptotic indices were calculated. The expression levels of apoptosis and endoplasmic reticulum stress-related proteins in testicular tissue were detected by Western blot. The protein expression and localization of GRP78 in testicular tissue were further detected by immunofluorescence. Results The results showed that compared to the normal group, the high-fat diet group had a significant increase in body weight, a significant decrease in testicular index, sperm concentration, and sperm vability, loose arrangement of germ cells, significant thinning of the seminiferous epithelium, no significant change in the diameter of seminiferous tubules, a significant increase in germ cell apoptosis , with an increased apoptosis index, and significant increase in expression of Bax and cleaved-caspase-12,and a significant decrease in Bcl-2 protein expression. The expression levels of GRP78 , p-IREl, XBP1, and ATF6a proteins were significantly up-regulated, while p-PERK, p-eIF2a, ATF4 protein expression showed no significant changes. Immunofluorescence results further showed a significant increase in the expression of GRP78 protein in the testicular tissue,with no significant changes in the expression location. Conclusions High-fat diet can induce the apoptosis of mouse testicular germ cells, and the mechanism may be related to the activation of endoplasmic reticulum stress IRE1 and ATF6 signaling pathway.

Meta-analysis and trial sequential analysis of Qingjin Huatan Decoction for treating community-acquired pneumonia in elderly / 中国中药杂志

To systematically evaluate the clinical efficacy and safety of modified Qingjin Huatan Decoction in the treatment of community-acquired pneumonia in the elderly, and provide evidence-based reference for the clinical application of this prescription. Randomized controlled trials of Qingjin Huatan Decoction in the treatment of community-acquired pneumonia in the elderly were collected by searching PubMed, EMbase, Cochrane Library, CNKI, China Biomedical Literature database, VIP database and WanFang database. Outcome indicators included clinical effective rate, inflammation index, symptom improvement time, chest radiograph improvement time, hospitalization time and adverse reactions. RevMan 5.3 and Stata/IC 15.1 software were used for Meta-analysis; TSA 0.9.5.10 Beta software was used for trial sequential analysis, and GRADE profiler 3.6 was used for grade evidence quality evaluation. Thirteen studies were included finally, including 1 058 patients, 536 patients in the experimental group and 522 patients in the control group.Meta-analysis showed that, the clinical effective rate of the experimental group was significantly higher than that of the control group(RR=1.16, 95%CI[1.10, 1.21], P<0.000 01); fever time(MD=-1.32, 95%CI[-1.93,-0.71], P<0.000 1), cough time(MD=-1.95, 95%CI[-2.69,-1.21), P<0.000 01), time to rale disappearance(MD=-1.55, 95%CI[-2.37,-0.73], P=0.000 2), time to chest radiograph improvement(MD=-1.72, 95%CI[-2.98,-0.46], P=0.007), and hospitalization time(MD=-3.16, 95%CI[-4.58,-1.74], P<0.000 01) in the experimental group were significantly shorter than those in the control group. The improvement in CRP(WMD=-3.44,95%CI[-4.50,-2.38],P<0.001), WBC(WMD=-2.04,95%CI[-3.31,-0.78],P<0.01), IL-6(WMD=-4.27,95%CI[-4.62,-3.92],P<0.001), and TNF-α(WMD=-0.47,95%CI[-0.55,-0.39], P<0.001) of the experimental group was significantly better than that of the control group. There was no significant difference in PCT improvement between the two groups(WMD=-0.63, 95%CI[-1.65, 0.40], P=0.23). No serious adverse reactions occurred in both groups. Sequential analysis of the trial showed that in the studies with cumulative inclusion of clinical effective rate, the data passed the traditional threshold and TSA threshold, further confirming its clinical efficacy. GRADE evaluation showed that the evidence level was low to extremely low. Western medicine treatment combined with Qingjin Huatan Decoction may improve clinical efficiency in the treatment of community-acquired pneumonia in the elderly, improve clinical symptoms faster, reduce CRP, WBC and other inflammatory indicators, and shorten hospital stay. The level of evidence obtained in this study is low, which needs to be further verified by high-quality multi-center, randomized controlled trials.

Successful medical drainage and surgical treatment for vertebral osteomyelitis and bilateral psoas abscess with gas formation caused by klebsiella pneumoniae in a diabetic patient

SUMMARY OBJECTIVE: We describe the case of a diabetic patient who developed vertebral osteomyelitis and bilateral psoas abscess with gas formation due to klebsiella pneumoniae. METHODS: A 64-year-old woman with a 4-year history of type-2 diabetes mellitus was admitted to the Emergency Department. The subject had a 2-day history of high-grade fever associated with chills and a 5-hour history of consciousness. She received empirical treatment with febrifuge, after which her fever decreased. RESULTS: Her fever recurred after an interval of three hours. A computed tomography scan of the abdomen revealed vertebral osteomyelitis and bilateral psoas muscle abscess with gas formation. Blood culture and purulent fluid described the growth of the Klebsiella pneumoniae. The patient received antibiotic therapy and bilateral drainage therapy after the drainage catheter was placed into the abscess cavity by CT-guidance. Due to the serious damage to the vertebral column and permanent pain, the patient underwent minimally invasive internal spinal fixation and recovered successfully. CONCLUSION: A case of vertebral osteomyelitis and bilateral psoas abscess with gas formation caused by Klebsiella pneumoniae in a diabetic patient. Antibiotic therapy, drainage, and minimally invasive internal spinal fixation were performed, which enabled a good outcome.

RESUMO OBJETIVO: Descrever o caso de uma paciente diabética que desenvolveu osteomielite vertebral e abcesso bilateral do psoas com formação de gás causada por klebsiella pneumoniae. MÉTODOS: Uma mulher de 64 anos de idade, com 4 anos de histórico de diabetes mellitus tipo 2, foi admitida no Serviço de Emergência. A paciente apresentava um quadro de dias de febre alta acompanhada de calafrios e um histórico de 5 horas de consciência. Ela recebeu tratamento empírico com antitérmico, após o qual a febre diminuiu. RESULTADOS: A febre retornou após um intervalo de três horas. Uma tomografia computadorizada do abdome revelou osteomielite vertebral e abcesso bilateral do músculo psoas com formação de gás. A cultura do sangue e o fluido purulento revelaram o crescimento de Klebsiella pneumoniae. A paciente recebeu antibióticos e terapia de drenagem bilateral após o cateter de drenagem ser posicionado na cavidade do abscesso com auxílio de TC. Devido a sérios danos à coluna vertebral e a dor permanente, a paciente foi submetida à fixação vertebral interna minimamente invasiva e recuperou-se com sucesso. CONCLUSÃO: Um caso de osteomielite vertebral e abscesso do psoas bilateral com a formação de gás causada por Klebsiella pneumoniae em uma paciente diabética. Antibioticoterapia, drenagem e fixação vertebral interna minimamente invasiva foram realizadas, o que permitiu um bom resultado.

In vivo imaging in tumor-bearing animals and pharmacokinetics of PEGylated liposomes modified with RGD cyclopeptide / 药学学报

The hydroxycamptothecin (HCPT) PEGylated liposomes (HCPT-LP) were modified with RGD cyclopeptide formed the tumor-targeting liposomes (HCPT-RGD-LP). HCPT-LP and HCPT-RGD-LP were injected intravenously with single dose of 5 mg x kg(-1) to rats. The drug concentration in plasma was determined and the pharmacokinetic behaviour was compared. The HCPT distribution in heart, liver, spleen, lung, kidney and plasma of mice was investigated following intravenous administration of HCPT-LP and HCPT injection. The nude mice implanted human hepatoma HepG2 cells were studied by in vivo imaging. The fluorescent probe was DiR and the nude mice were injected with DiR PEGylated liposomes (DiR-LP) and DiR-LP modified with RGD cyclopeptide (DiR-RGD-LP). The results showed that there was no significant difference (P > 0.05) of main pharmacokinetic parameters t1/2beta, CL, V(c), AUC(0-48 h), AUC(0-inifinity), MRT(0-48 h), MRT(0-infinity) between HCPT-RGD-LP and HCPT-LP. HCPT-LP had a remarkably better long-circulating effect than HCPT injection in mice and the concentration of HCPT was highest in liver. The DiR accumulation in tumors of DiR-RGD-LP was higher than that of DiR-LP by the visualized fluorescence of in vivo imaging. It indicated that such PEGylated liposomes modified with RGD cyclopeptide could improve the tumor targeting efficacy.

In vitro study of transdermal penetration and iontophoresis of hepatitis B vaccines through rat skin / 药学学报

In vitro percutaneous delivery of hepatitis B vaccines was investigated in order to assess the penetration of vaccine under passive diffusion and iontophoresis conditions. The study was carried out using Franz vertical diffusion cell through the hairless abdominal skin of Sprague-Dawley (SD) rats. Enzyme-linked immunosorbent assay (ELISA) was used to determine the cumulative amount of permeation and the retention amount of drug in skin. Passive diffusion alone resulted in less skin permeation and retention of hepatitis B vaccines, only (2.1 +/- 0.1) ng x cm(-2) and (2.3 +/- 0.1) ng x cm(-2) after 24 h when the initial concentration of vaccine in the donor compartment was 23 microg x mL(-1) and 46 microg x mL(-1), respectively. After removing the stratum corneum, the permeation and retention amount of hepatitis B vaccines increased to (383.7 +/- 86.2) ng x cm(-2) and (16.8 +/- 4.6) ng x cm(-2), respectively, 171.6-folds and 2.1-folds more than that from its intact skin with the drug loaded at 46 microg x mL(-1). Iontophoresis induced a significant increase of cumulative and retention amount of hepatitis B vaccines through the skin (P < 0.05). Application of iontophoresis significantly enhanced the permeation of hepatitis B vaccines (P < 0.05) by 2.7-folds and 6.6-folds for the intact skin, and by 1.6-folds and 1.8-folds for the tape-stripped skin with initial drug loading of 23 microg x mL(-1) and 46 microg x mL(-1), respectively. Iontophoresis also significantly increased the amount of drug retained in the skin. After applying iontophoresis for 6 h, the amount of skin retention was nearly the same as passive diffusion for 24 h both from intact skin [(16.8 +/- 4.6) ng x cm(-2) vs (13.3 +/- 5.4) ng x cm(-2)] (P > 0.05) and tape-stripped skin [(36.7 +/- 14.1) ng x cm(-2) vs (26.8 +/- 11.2) ng x cm(-2)] (P > 0.05). Overall, these findings revealed that the transportation efficiency of bioactive substance like hepatitis B vaccines may be improved by iontophoresis, which can be potentially used in the field of transcutaneous immunization.

The nasal development after one-staged correction of nose deformity and unilateral complete cleft lip in infancy / 中华整形外科杂志

<p><b>OBJECTIVE</b>To introduce one-staged correction of nasal deformity and unilateral complete cleft lip in infancy and to observe the nasal development after the operation.</p><p><b>METHODS</b>The unilateral complete cleft lip and nasal deformity were corrected in one stage in27 cases. They were followed up for several years. With post-operative photos, the anthropometric method was used to analyze the nasal development.</p><p><b>RESULTS</b>The long-term results were excellent in 10 cases, good in 14 cases, and poor in 3 cases.</p><p><b>CONCLUSIONS</b>Based on the anatomic findings of nasal blood supply, one-staged correction of nasal deformity and unilateral complete cleft lip in infancy can be performed with no obvious interference with nasal development. The secondary nasal deformity before school age can be alleviated or avoided.</p>

Spiral CT Diagnosis of Small Hepatocellular Carcinoma / 实用放射学杂志

Objective To study the CT features of small hepatocellular cancer.Methods 37 patients with small hepatocellular cancer proved histopathologically underwent spiral CT examinations including plain scans and contrast-enhanced scans.The arterial phase scan,the portal phase scan and delayed phase scan started at 25th second,70th second and 5th minute respectively after injecting the contrast medium with the high pressure syringe,the velocity was 2.5 ~3 ml/s,and the dose was 1.5 ml/kg.Results 73% (27/37) of tumors showed hyperdensity in arterial phase,65%(24/37) of tumors was hypodensity and 35% (13/37) had hyperdensity during portal phase,of which eight showed hypodensity in equilibrium phase.Conclusion Spiral CT can display the features of blood supply of small hepatocellular carcinoma that is of benefit in early diagnosis.

A clinical study of presurgical nasoalveolar molding in infants with complete cleft lip and palate / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To observe the clinical effect of presurgical nasoalveolar molding in infants with complete cleft lip and palate.</p><p><b>METHODS</b>Presurgical nasoalveolar molding was performed in 38 infants with cleft lip and palate (26 patients with unilateral cleft lip and palate, 12 patients with bilateral cleft lip and palate), aged between 5 and 30 days. The width of alveolar cleft was measured before and after the operation and the effect of treatment was assessed.</p><p><b>RESULTS</b>After 108 - 152 days of therapy, the average width of alveolar cleft decreased by 5.3 mm in 26 patients with unilateral cleft lip and palate. Nasal profile was improved in 76 percent of cases. In 12 patients with bilateral cleft lip and palate, the average width of left cleft decreased by 4.7 mm and that of the right decreased by 4.2 mm. The distance between right and left cleft increased by 5.1 mm. Nasal profile was improved in 66 percent of cases.</p><p><b>CONCLUSION</b>Presurgical nasoalveolar molding in complete cleft lip and palate can improve nasal profile and decrease the width of alveolar cleft.</p>