Using "Age and Total-PSA" as the Main Indicators: The Results of Taizhou Integrated Prostate Screening (No 2).

The aim of the study was to analyze population-based prostate cancer (PCa) screening and the incidence of PCa among males ≥50 years of age residing in the Luqiao district of Taizhou, China. From October to December 2020, male residents ≥50 years of age were screened for serum total prostate-specific antigen (total-PSA). If t-PSA re-test levels persisted above 4 µg/L, subjects underwent further noninvasive examinations, including digital rectal examination or multiparameter magnetic resonance imaging (mpMRI) of the prostate. Subjects underwent prostate biopsy of pathological tissue based on t-PSA and mpMRI results. A total of 3524 (49.1%) residents participated in this PCa screening study. In total, 285 (8.1%) subjects exhibited t-PSA levels ≥4.0 µg/L and 112 (3.2%) underwent noninvasive examinations. Forty-two (1.2%) residents underwent prostate biopsy, of which 16 (0.45%) were diagnosed with PCa. Of those diagnosed with PCa, three (19%) had localized PCa (cT1-cT2N0M0), six (37%) had locally advanced PCa (cT3a- cT4N0-1M0), and seven (44%) had advanced metastatic PCa (M1). Unfortunately, 3477 (48.5%) residents did not participate in the study, mainly due to lack of awareness of PCa based on feedback from local health centers. Age and t-PSA were used as primary screening indicators and, when further combined with mpMRI and prostate biopsy, confirmed the diagnosis of PCa among participating residents. Although this was a relatively economical and convenient screening method, education and knowledge should be further enhanced to increase the participation rate in PCa screening programs.

Design and Implementation of Taizhou Integrated Prostate Screening.

A community-based prostate cancer screening program was conducted to assess the morbidity and associated factors for prostate cancer among the subpopulation of men aged ≥50 years in Taizhou, China. Taizhou Integrated Prostate Screening (TIPS) is a large, observational, population-based study of prostate cancer screening data based on serum prostate-specific antigen (PSA) concentrations. A pilot census of all male residents aged 50 years or older was conducted in Luqiao District, one of the field sites of the TIPS cohort in the city of Taizhou, Zhejiang. The interviewer-administered questionnaire evaluated demographic characteristics and environmental exposure factors. A total of 1,806 out of 3,516 participants completed the questionnaire. The overall prevalence of PSA ≥4 ng/mL was 11.5%, and included participants at low risk (9.2%), moderate risk (1.7%), and high risk (0.6%). Participants aged 60-69, 70-79, and ≥80 years had a 2.7-fold, 4.2-fold, and 6.5-fold higher risk of elevated PSA, respectively, in comparison with those aged 50 to 59 years (p < .001). Eighteen patients were diagnosed with prostate cancer, of whom 11 (61.1%) underwent radical surgery. This community-based PSA screening program indicated the results for early detection of prostate cancer among men aged ≥50 years. Early screening and appropriate clinical therapy for the management of prostate cancer are essential in this subpopulation.

Antibody response to SARS-CoV-2 vaccines among hospitalized patients in China: a case-control study.

A lack of confidence on the vaccination drive hinders the management of the COVID-19 pandemic. We aimed to assess the antibody response to the SARS-CoV-2 vaccine among hospitalized patients in China. This case-control study was based on SARS-CoV-2 sero-surveillance during hospitalization. From April to June 2021, hospitalized patients without documented COVID-19 infection from the Department of Urology were routinely assayed for anti-SARS-CoV-2 antibodies. The SARS-CoV-2 vaccination history of each participant was obtained from their vaccination records. Of the 405 participants, there were 37 seropositive participants (case group) and 368 seronegative participants (control group); 68 participants (16.8%) had received the inactivated SARS-CoV-2 vaccine, including 54 who received the Sinovac-CoronaVac vaccine and 14 received the Sinopharm vaccine. All seropositive participants who had received one or two doses of the SARS-CoV-2 vaccine were assessed for at least 16 days, while 31 (8.4%) of 368 seronegative controls who had received the vaccine were tested for 1-94 days. The overall seroconversion rate was 54.4% (37/68) in the vaccinated participants who received the inactivated SARS-CoV-2 vaccine. The odds ratio (OR) and confidence interval (CI) for seropositivity was 6.20 (95% CI: 2.05-18.71) in those received full vaccination with two doses versus those partially vaccinated participants with one dose after adjusting for sex and age. These findings imply that the inactivated SARS-CoV-2 vaccine could have a protective antibody response.

Choledocholithiasis characteristics with periampullary diverticulum and endoscopic retrograde cholangiopancreatography procedures: Comparison between two centers from Lanzhou and Kyoto.

BACKGROUND: Most of study regarding periampullary diverticulum (PAD) impact on endoscopic retrograde cholangiopancreatography (ERCP) therapy for choledocholithiasis based on data from one endoscopy center and lacked to compare the clinical characteristic of choledocholithiasis with PAD from different geographical patients. AIM: To compare the choledocholithiasis clinical characteristics between two regional endoscopy centers and analyze impacts of clinical characteristics on ERCP methods for choledocholithiasis patients with PAD. METHODS: Patients seen in two endoscopy centers (The First Hospital of Lanzhou University, Lanzhou, Gansu Province, China, and Kyoto Second Red Cross Hospital, Kyoto, Japan) underwent ERCP treatment for the first time between January 2012 and December 2017. The characteristics of choledocholithiasis with PAD were compared between the two centers, and their ERCP procedures and therapeutic outcomes were analyzed. RESULTS: A total of 829 out of 3608 patients in the Lanzhou center and 241 out of 1198 in the Kyoto center had choledocholithiasis with PAD. Lots of clinical characteristics were significantly different between the two centers. The common bile duct (CBD) diameter was wider, choledocholithiasis size was lager and multiple CBD stones were more in the Lanzhou center patients than those in the Kyoto center patients (14.8 ± 5.2 mm vs 11.6 ± 4.2 mm, 12.2 ± 6.5 mm vs 8.2 ± 5.3 mm, 45.3% vs 20.3%, P < 0.001 for all). In addition, concomitant diseases, such as acute cholangitis, gallbladder stones, obstructive jaundice, cholecystectomy, and acute pancreatitis, were significantly different between the two centers (P = 0.03 to < 0.001). In the Lanzhou center, CBD diameter and choledocholithiasis size were lower, and multiple CBD stones and acute cholangitis were less in non-PAD patients than those in PAD patients (13.4 ± 5.1 mm vs 14.8 ± 5.2 mm, 10.3 ± 5.4 mm vs 12.2 ± 6.5, 39% vs 45.3%, 13.9% vs 18.5%, P = 0.002 to < 0.001). But all these characteristics were not significantly different in the Kyoto center. The proportions of endoscopic sphincterotomy (EST), endoscopic balloon dilatation (EPBD), and EST+EPBD were 50.5%, 1.7%, and 42.5% in the Lanzhou center and 90.0%, 0.0%, and 0.4% in the Kyoto center, respectively. However, the overall post-ERCP complication rate was not significantly different between the two centers (8.9% in the Lanzhou and 5.8% in the Kyoto. P = 0.12). In the Lanzhou center, the difficulty rate in removing CBD stones in PAD was higher than in non-PAD group (35.3% vs 26.0%, P < 0.001). But the rate was no significant difference between the two groups in Kyoto center. The residual rates of choledocholithiasis were not significantly different between the two groups in both centers. Post-ERCP complications occurred in 8.9% of the PAD patients and 8.1% of the non-PAD patients in the Lanzhou Center, and it occurred in 5.8% in PAD patients and 10.0% in non-PAD patients in the Kyoto center, all P > 0.05. CONCLUSION: Many clinical characteristics of choledocholithiasis patients with PAD were significantly different between the Lanzhou and Kyoto centers. The patients had larger and multiple stones, wider CBD diameter, and more possibility of acute cholangitis and obstructive jaundice in the Lanzhou center than those in the Kyoto center. The ERCP procedures to manage native duodenal papilla were different depending on the different clinical characteristics while the overall post-ERCP complications were not significantly different between the two centers. The stone residual rate and post-ERCP complications were not significantly different between choledocholithiasis patients with PAD and without PAD in each center.

Circular RNA Circ-0002570 Accelerates Cancer Progression by Regulating VCAN via MiR-587 in Gastric Cancer.

BACKGROUND: Circular RNAs (circRNAs) are closely associated with the occurrences and progress of gastric cancer (GC). We aimed to delve into the function and pathological mechanism of Circular RNA-0002570 (circ-0002570) in GC progression. METHODS: CircRNAs differentially expressed in GC were screened using bioinformatics technology. The expression of circ-0002570 was detected in GC specimens and cells via qRT-PCR, and the prognostic values of circ-0002570 were determined. The functional roles of circ-0002570 on proliferation, migration, and invasion in GC cells were explored in vitro and in vivo. Interaction of circ-0002570, miR-587, and VCAN was confirmed by dual-luciferase reporter assays, Western blotting, and rescue experiments. RESULTS: Circ-0002570 expression was distinctly increased in GC tissues compared to adjacent normal specimens, and GC patients with higher circ-0002570 expressions displayed a short survival. Functionally, knockdown of circ-0002570 resulted in the inhibition of cell proliferation, migration, and invasion, and suppressed tumor growth in vivo. Mechanistically, miR-587 was sponged by circ-0002570. VCAN expression in NSCLC was directly inhibited by miR-587. Overexpression of circ-0002570 prevented VCAN from miR-587-mediated degradation and thus facilitated GC progression. CONCLUSION: The circ-0002570-miR-587-VCAN regulatory pathway promoted the progression of GC. Our findings provided potential new targets for the diagnosis and therapy of GC.

Effect of Helicobacter Pylori on Plasma Metabolic Phenotype in Patients With Gastric Cancer.

BACKGROUND: Although Helicobacter pylori (Hp) as high risk factor for gastric cancer have been investigated from human trial, present data is inadequate to explain the effect of Hp on the changes of metabolic phenotype of gastric cancer in different stages. PURPOSE: Herein, plasma of human superficial gastritis (Hp negative and positive), early gastric cancer and advanced gastric cancer analyzed by UPLC-HDMS metabolomics can not only reveal metabolic phenotype changes in patients with gastric cancer of different degrees (30 Hp negative, 30 Hp positive, 20 early gastric cancer patients, and 10 advanced gastric cancer patients), but also auxiliarily diagnose gastric cancer. RESULTS: Combined with multivariate statistical analysis, the results represented biomarkers different from Hp negative, Hp positive, and the alterations of metabolic phenotype of gastric cancer patients. Forty-three metabolites are involved in amino acid metabolism, and lipid and fatty acid metabolism pathways in the process of cancer occurrence, especially 2 biomarkers glycerophosphocholine and neopterin, were screened in this study. Neopterin was consistently increased with gastric cancer progression and glycerophosphocholine tended to consistently decrease from Hp negative to advanced gastric cancer. CONCLUSION: This method could be used for the development of rapid targeted methods for biomarker identification and a potential diagnosis of gastric cancer.

Questionnaire Survey on the Current Situation and Experience in Prevention and Control Measures at Urology Clinics During the COVID-19 Epidemic in China.

COVID-19, the coronavirus disease 2019; SARS-CoV-2, the coronavirus 2; ACE2, angiotensin converting enzyme 2; S protein, spiked glycoprotein; TMPRSS2, transmembrane serine protease 2; WHO, World Health Organization. Purpose: Although the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2, has been viably controlled in China, a new normal in healthcare strategies has become standard in China and worldwide. We conducted a questionnaire study to disseminate the experience from China in terms of urology outpatient prevention and control measures under standardized prevention policies against COVID-19. Participants and Methods: From May 3, 2020 to June 25, 2020, we conducted an anonymous cross-sectional questionnaire study, focused on the status of and experiences with outpatient urology prevention and control measures during the COVID-19 pandemic. The targeted respondents were urologists in mainland China, covering all levels of hospitals and clinics. Results: A total of 216 (97%) valid responses were collected. We found that 183 (85%) respondents were from outside of Hubei province in China. One-hundred-and-fifty-eight (73%) respondents believed that SARS-CoV-2 could be detected in urine, and that protection against urine exposure was needed. Over 80% of respondents recommended WeChat application or similar online video meetings for virtual outpatient consultations. The suggested flowcharts and recommendations to prevent new cases were easy to understand and approved by most physicians, which could provide reference for outpatient prevention and control. We still need to make adequate preparations under the new normal of the COVID-19 Epidemic, especially for those suspected of being infected. Conclusions: Although the scientific validation of the questionnaire is limited, it provides a first snapshot of the experiences relating to the prevention and control measures in urology clinics in China, and can inform future policies in this field.

Clinical significance of different periampullary diverticulum classifications for endoscopic retrograde cholangiopancreatography cannulation.

BACKGROUND: Different types of periampullary diverticulum (PAD) may differentially affect the success of endoscopic retrograde cholangiopancreatography (ERCP) cannulation, but the clinical significance of the two current PAD classifications for cannulation is limited. AIM: To verify the clinical value of our newly proposed PAD classification. METHODS: A new PAD classification (Li-Tanaka classification) was proposed at our center. All PAD patients with native papillae who underwent ERCP from January 2012 to December 2017 were classified according to three classification systems, and the effects of various types of PAD on ERCP cannulation were compared. RESULTS: A total of 3564 patients with native papillae were enrolled, including 967 (27.13%) PAD patients and 2597 (72.87%) non-PAD patients. In the Li-Tanaka classification, type I PAD patients exhibited the highest difficult cannulation rate (23.1%, P = 0.01), and type II and IV patients had the highest cannulation success rates (99.4% in type II and 99.3% in type IV, P < 0.001). In a multivariable-adjusted logistic model, the overall successful cannulation rate in PAD patients was higher than that in non-PAD patients [odds ratio (OR) = 1.87, 95% confidence interval (CI): 1.04-3037, P = 0.037]. In addition, compared to the non-PAD group, the difficulty of cannulation in the type I PAD group according to the Li-Tanaka classification was greater (OR = 2.04, 95%CI: 1.13-3.68, P = 0.004), and the successful cannulation rate was lower (OR = 0.27, 95%CI: 0.11-0.66, P < 0.001), while it was higher in the type II PAD group (OR = 4.44, 95%CI: 1.61-12.29, P < 0.01). CONCLUSION: Among the three PAD classifications, the Li-Tanaka classification has an obvious clinical advantage for ERCP cannulation, and it is helpful for evaluating potentially difficult and successful cannulation cases among different types of PAD patients.

miRNA-215-5p suppresses the aggressiveness of breast cancer cells by targeting Sox9.

Several studies have shown that miR-215-5p acts as a tumor suppressor in certain cancers, but its role in the progression and metastasis of breast carcinoma remains incompletely understood. Herein, we prove that miR-215-5p is substantially down-expressed in breast carcinoma as compared with nontumor tissue. Up-regulation of miR-215-5p inhibits the aggressive abilities of breast carcinoma cells in vitro. We performed luciferase reporter tests to show that SRY-Box 9 (Sox9) is the target of miR-215-5p; as predicted, Sox9 depletion replicates the suppressive effects of miR-215-5p on breast carcinoma cells, and overexpression of Sox9 rescues the effects of miR-215-5p on breast cancer cell progression. In addition, a xenograft model assay was used to reveal that miR-215-5p inhibits breast cancer cell growth and metastatic potential in vivo. Overall, these results imply that miRNA-215-5p suppresses the aggressiveness of breast cancer cells through targeting Sox9.

Plasma microRNAs as potential new biomarkers for early detection of early gastric cancer.

BACKGROUND: Early gastric cancer (EGC), compared with advanced gastric cancer (AGC), has a higher 5-year survival rate. However, due to the lack of typical symptoms and the difficulty in diagnosing EGC, no effective biomarkers exist for the detection of EGC, and gastroscopy is the only detection method. AIM: To provide new biomarkers with high specificity and sensitivity through analyzed the differentially expressed microRNAs (miRNAs) in EGC and AGC and compared them with those in benign gastritis (BG). METHODS: We examined the differentially expressed miRNAs in the plasma of 30 patients with EGC, AGC, and BG by miRNA chip analysis. Then, we analyzed and selected the significantly different miRNAs using bioinformatics. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) confirmed the relative transcription level of these miRNAs in another 122 patients, including patients with EGC, AGC, Helicobacter pylori (H. pylori)-negative gastritis (Control-1), and H. pylori-positive atrophic gastritis (Control-2). To establish a diagnostic model for the detection of plasma miRNA in EGC, we chose miRNAs that can be used to determine EGC and AGC from Control-1 and Control-2 and miRNAs in EGC from all other groups. RESULTS: Among the expression profiles of the miRNA chips in the three groups in the discovery set, of 117 aberrantly expressed miRNAs, 30 confirmed target prediction, whereas 14 were included as potential miRNAs. The RT-qPCR results showed that 14 potential miRNAs expression profiles in the two groups exhibited no differences in terms of H. pylori-negative gastritis (Control-1) and H. pylori-positive atrophic gastritis (Control-2). Hence, these two groups were incorporated into the Control group. A combination of four types of miRNAs, miR-7641, miR-425-5p, miR-1180-3p and miR-122-5p, were used to effectively distinguish the Cancer group (EGC + AGC) from the Control group [area under the curve (AUC) = 0.799, 95% confidence interval (CI): 0.691-0.908, P < 0.001]. Additionally, miR-425-5p, miR-24-3p, miR-1180-3p and miR-122-5p were utilized to distinguish EGC from the Control group (AUC = 0.829, 95%CI: 0.657-1.000, P = 0.001). Moreover, the miR-24-3p expression level in EGC was lower than that in the AGC (AUC = 0.782, 95%CI: 0.571-0.993, P = 0.029), and the miR-4632-5p expression level in EGC was significantly higher than that in AGC (AUC = 0.791, 95%CI: 0.574-1.000, P = 0.024). CONCLUSION: The differentially expressed circulatory plasma miR-425-5p, miR-1180-3p, miR-122-5p, miR-24-3p and miR-4632-5p can be regarded as a new potential biomarker panel for the diagnosis of EGC. The prediction and early diagnosis of EGC can be considerably facilitated by combining gastroscopy with the use of these miRNA biomarkers, thereby optimizing the strategy for effective detection of EGC. Nevertheless, larger-scale human experiments are still required to confirm our findings.

A passive microfluidic device for continuous microparticle enrichment.

A passive microfluidic device is reported for continuous microparticle enrichment. The microparticle is enriched based on the inertial effect in a microchannel with contracting-expanding structures on one side where microparticles/cells are subjected to the inertial lift force and the momentum-change-induced inertial force induced by highly curved streamlines. Under the combined effect of the two forces, yeast cells and microparticles of different sizes were continuously focused in the present device over a range of Reynolds numbers from 16.7 to 125. ∼68% of the particle-free liquid was separated from the sample at Re = 66.7, and ∼18 µL particle-free liquid was fast obtained within 10 s. Results also showed that the geometry of the contracting-expanding structure significantly influenced the lateral migration of the particle. Structures with a large angle induced strong inertial effect and weak disturbance effect of vortex on the particle, both of which enhanced the microparticle enrichment in microchannel. With simple structure, small footprint (18 × 0.35 mm), easy operation and cell-friendly property, the present device has great potential in biomedical applications, such as the enrichment of cells and the fast extraction of plasma from blood for disease diagnose and therapy.

Malignant infiltrating intraductal papillary mucinous neoplasm with internal fistula: one case report and clinical practice.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is a rare tumor that originates in the pancreatic duct. The diagnosis of benign, borderline or malignant to IPMN is significant in terms of making an appropriate treatment plan and prognosis. This article summarizes our clinical experience of a case report and discussion by literature review. Methods and case report: A 73 year old male patient was admitted for an occupying lesion of the pancreas. The magnetic resonance cholangiopancreatography (MRCP) scan considered IPMN, endoscopic retrograde cholangiopancreatography (ERCP) also confirmed diagnosis of IPMN. Both the biliary and pancreatic duct stents were replaced, but we did not obtain any evidence by cytological evaluation. One month later, ERCP and intraductal ultrasonography (IDUS) showed infiltrating growth of the tumor. Endoscopic ultrasonography guided fine-needle aspiration was performed at the same time, and pathological diagnosis was suggested as borderline IPMN. RESULTS: In the absence of pathological support, the patient presented with the clinical diagnosis of infiltrating intraductal papillary mucinous adenocarcinoma (IPMC) and was recommended for surgery. However, the patient and his family refused surgery, and were discharged. Subsequently, the patient died 6.5 months (197 days) following first diagnosis. CONCLUSIONS: Currently, the definition and classification of IPMN is done by specification, although there remain some difficulties in diagnosing its subtypes. For diagnostic purposes, CT, MRCP, ERCP, IDUS, EUS and EUS-FNA can all be applied. Cytological negative pathology might not completely rule out malignancy, and would still require further examination and follow-up.

Three initial diets for management of mild acute pancreatitis: a meta-analysis.

AIM: To compare non-liquid and clear-liquid diets, and to assess whether the latter is the optimal treatment for mild acute pancreatitis. METHODS: The Cochrane Library, PUBMED, EMBASE, EBM review databases, Science Citation Index Expanded, and several Chinese databases were searched up to March 2011. Randomized controlled trials (RCTs) that compared non-liquid with clear-liquid diets in patients with mild acute pancreatitis were included. A meta-analysis was performed using available evidence from RCTs. RESULTS: Three RCTs of adequate quality involving a total of 362 participants were included in the final analysis. Compared to liquid diet, non-liquid diet significantly decreased the length of hospitalization [mean difference (MD): 1.18, 95% CI: 0.82-1.55; P﹤0.00001] and total length of hospitalization (MD: 1.31, 95% CI: 0.45-2.17; P = 0.003). The subgroup analysis showed solid diet was more favorable than clear liquid diet in the length of hospitalization, with a pooled MD being -1.05 (95% CI: -1.43 to -0.66; P﹤0.00001). However, compared with clear liquid diet, both soft and solid diets did not show any significant differences for recurrence of pain after re-feeding, either alone [relative risk (RR): 0.95; 95% CI: 0.51-1.87; P = 0.88] and (RR: 1.22; 95% CI: 0.69-2.16; P = 0.49), respectively, or analyzed together as non-liquid diet (RR: 0.80; 95% CI: 0.47-1.36; P = 0.41). CONCLUSION: The non-liquid soft or solid diet did not increase pain recurrence after re-feeding, compared with the clear-liquid diet. The non-liquid diet reduced hospitalization.

[Preparation of podophyllotoxin nanostructured lipid carriers and its effects on immortalized human cervical epithelial cells with HPV infection in vitro].

OBJECTIVE: To study the effect of podophyllotoxin nanostructured lipid carriers (POD-NLC) on immortalized human cervical epithelial cells (H8) infected with HPV in vitro. METHODS: POD-NLC was prepared by emulsion evaporation method and characterized using transmission electron microscopy, Zetasizer analyzer and high-performance liquid chromatography (HPLC). H8 cells were treated with different concentrations (0.0001-1 µg/ml) of POD-NLC, free POD, or blank nanostructured lipid carriers (NLC), and the cell proliferation was assessed using MTT assay to evaluate the cytotoxic effects. The changes of cell morphology were observed using fluorescence microscopy, and the cell cycle changes and cell apoptosis were analyzed using flow cytometry. RESULTS: POD-NLC showed a spherical or elliptical shape with good stability in vitro. The average particle size of POD-NLC was 85.6∓10.25 nm, with a Zeta potential of 26.2∓4.1 mV and entrapment efficiency of POD of (88.56∓3.1)%. POD-NLC caused a significant inhibition of H8 cell proliferation in a concentration- and time-dependent manner. At an equivalent concentration, POD-NLC produced a stronger inhibitory effect on cell proliferation than POD. The inhibition rate of H8 cells after a 48-h exposure to POD-NLC and POD reached 95.8% and 65.6%, respectively, and at the highest concentration of 1 µg/ml, the IC(50) of POD-NLC and POD was 0.015 µg/ml and 0.13 µg/ml, respectively. Blank NLC did not obviously affect the proliferation of H8 cells. POD-NLC and POD both caused obvious increases in G(2)/M phase cell percentages and induced typical apoptotic changes of the cells, and their effects were comparable (P>0.05). CONCLUSION: Compared with POD, POD-NLC has more potent effect in inhibiting H8 cell proliferation and inducing cell apoptosis, suggesting its potential in the treatment of cervical HPV infection.

[Preparation of lidocaine nanoemulsion and its transdermal absorption by rat skin ex vivo].

OBJECTIVE: To prepare lidocaine nanoemulsion and investigate its transdermal delivery ability in vitro. METHODS: The optimal Km (surfactant/cosurfactant) value and the component proportion were determined by pseudoternary phase diagrams combined with Origin software analysis. The diameter and distribution range were detected by Zeta particle size analysis instrument, and the morphology of the nanoemulsion was observed by electron microscope. The permeation flux of lidocaine was determined in vitro using the modified Franz diffusion cell combined with HPLC, and the cumulative transdermal absorption amount and the apparent skin transdermal velocity were compared among nanoemulsion, gel and tincture containing 5% lidocaine. The permeation mode of lidocaine nanoemulsion was analyzed. RESULTS: The average drop size of lidocaine nanoemulsion was 29.8-/+14.4 nm, and 98% of the drop sizes ranged from 15.1 to 45.5 nm and 2% from 77.9 to 261.3 nm. The nanoemulsion drop showed a spherical morphology in a polydisperse system. The Kp value of the nanoemulsion (3.07-/+0.74 cm/h) was significantly higher than that of gel (1.27-/+0.35 cm/h) and tincture (0.97-/+0.18 cm/h), and the permeation rate of the nanoemulsion was 69.82-/+7.48 microg x cm(-2) x h(-1), which fitted the the Zero-order release dynamic procedure. CONCLUSIONS: The component proportion of lidocaine nanoemulsion can be conveniently obtained through pseudoternary phase diagrams and Origin software analysis, and the drop size, distribution, morphology and system type can be determined by Malvern Zetasizer combined with electron microscopy. The results also indicate that the nanoemulsion system with high permeation rate may provide a new promising means for local anesthesia.

[The histological changes of diabetic rats' skin and the effects on the percutaneous absorption of glucocorticoid].

To examine the histological changes of diabetic rats' skin and the effects on the percutaneous absorption of hydrocortisone (HC, a glucocorticoid), male Wistar rats were randomly divided into five groups: control group, diabetes one-week group (W1), two-week group (W2), three-week group (W3), and four-week group (W4), while each group contained 6 rats. Diabetes mellitus (DM) rat model was prepared with the method of streptozocin (STZ, 40 mg x kg(-1)) intraperitoneal injection. Abdominal skin was cut to carry out an in-vitro penetration experiment on an improved Franz diffusion cells, and phosphate buffer (PBS, pH 7.4) was used as receptor solution. The solution was analyzed with HPLC, and then the penetrating rate can be calculated. Meanwhile, rats' abdominal skins of different DM periods were HE stained and made into tissue slices to find if any histological changes occurred. The penetrating rate of control, W1, W2, W3, and W4 groups were 2.39 +/- 1.25, 3.22 +/- 1.72, 3.02 +/- 1.89, 3.63 +/- 2.02 and 5.00 +/- 3.36 microg x h(-1) x cm(-2), respectively. There was significant difference between the control and the W4 group (P < 0.05), but no significant differences were found between any other two groups (P > 0.05). The tissue slices showed that compared to the normal rats' skin, little change was observed in one-week DM rats' skin, but the skin of one-month DM rats' skin was observed thinner, and it became much thinner than that of rats with two-month diabetes, especially the epidermis. After making a rat into diabetic, the rats' skin goes through a pathological change, and this change is closely interrelated with the increase of the permeation of HC. Therefore, it is necessary to adjust the dose while some drug was applied on the skin in case of diabetes mellitus.

COX-2 inhibition improves immune system homeostasis and decreases liver damage in septic rats.

OBJECTIVE: To evaluate cyclooxygenase-2 (COX-2) inhibition by NS-398 in septic rats with respect to immunologic derangements and hepatic damage. METHODS: Six sham rats (Sham), 24 rats that underwent experimentally induced sepsis using cecal ligation and puncture (CLP), and 24 rats that underwent induced sepsis after treatment with NS-398 (NS-398), were compared. Sham rats were immediately sacrificed. Six each of CLP and NS-398 animals were sacrificed at 3, 6, 12, and 24 h after induction of sepsis. From each rat was obtained liver for COX-2 mRNA copy number determination and blood for quantification of alanine transaminase (ALT), aspartate aminotransferase (AST), interleukin 10 (IL-10), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNFalpha) levels, and CD4:CD8 ratios. RESULT: Sham rats had a lower COX-2 mRNA copy number than NS-398 rats, which had a lower copy number than CLP rats. CLP and NS-938 rats had IL-10 and IL-6 levels above Sham levels. NS-938 rat IL-10 levels were greater and IL-6 levels less than those of CLP rats. For CLP rats, TNF production sharply declined and then increased above Sham levels; NS-398 rat TNF production was consistently mildly elevated above Sham levels. CD4:CD8 ratios sharply dropped over time; NS-398 showed a more modest decline. CLP rats showed unrelenting climbs in AST and ALT values; NS-398 rat levels peaked at 6 h and returned to normal after 12 h; the biochemical evidence of protection against septic liver damage was also seen morphologically, with ultrastructural and histologic normalization of nuclear appearances 12 h after sepsis induction with NS-398 pretreatment. CONCLUSION: Septic rats given the COX-2 inhibitor NS-398 showed amelioration of cytokine and cellular immunologic imbalances and decreased liver injury.

[Effects of podophyllotoxin solid lipid nanoparticles on proliferation and apoptosis of cervical carcinoma cells].

OBJECTIVE: To evaluate the anti-proliferative and apoptosis-inducing effect of podophyllotoxin solid lipid nanoparticles (PDP-SLN) in human cervical carcinoma cells in vitro. METHODS: Hela cells were treated with PDP and PDP-SLN at different concentrations (0.0005-5 micromol/L), and the proliferation of the cells was assessed using MTT assay and the apoptotic index was determined by flow cytometry. RESULTS: Both PDP and PDP-SLN showed obvious inhibitory effect on the cell proliferation in a dose- and time-dependent manner. At the same concentration, PDP-SLN produced stronger inhibitory effect on the cells than PDP, with IC50 24, 48, and 72 h after the cell exposure to PDP-SLN and PDP of 4.10, 0.65, 0.20 micromol/L and 9.2, 4.0, 1.3 micromol/L, respectively. Both PDP and PDP-SLN significantly induced the apoptosis of the Hela cell, and the apoptosis rates of the cells incubated in the presence of 0.5 micromol/L PDP-SLN reached 90.8% at 24 h and 94.2% at 72 h, significantly higher than the rate of cells incubated with PDP (64.1% at 24 h and 68.4% at 72 h, P<0.01). CONCLUSION: PDP-SLN can effectively suppress the proliferation and induce apoptosis of Hela cells in vitro.

[Treatment of recurrent condyloma acuminatum with solid lipid nanoparticle gel containing podophyllotoxin: a randomized double-blinded, controlled clinical trial].

OBJECTIVE: To observe the clinical efficacy and safety of podophyllotoxin delivered via solid lipid nanoparticle gel for topic treatment of recurrent condyloma acuminatum. METHODS: In a randomized double-blinded study, podophyllotoxin solid lipid nanoparticles gel and routine podophyllotoxin gel preparation was applied respectively for treatment of 97 volunteer patients with recurrent condyloma acuminatum. The therapeutic effect, condyloma acuminatum relapse following the treatment and adverse effect were evaluated. RESULTS: The wart clearance rate in the condyloma acuminatum patients in the first treatment course with podophyllotoxin solid lipid nanoparticle gel reached 97.1%, close to that with the routine preparation of 90.6%, but the nanoparticle preparation significantly reduced the recurrence rate and adverse effect (P<0.01). CONCLUSION: Podophyllotoxin delivered via solid lipid nanoparticle gel can effectively clear condyloma acuminatum and reduce its recurrence rate with only mild, tolerable adverse effect.