Synthesis and antibacterial activities of phosphonate derivatives containing aminothiazoloxime fragment / 药学学报

Based on the principle of molecular hybridization, fifteen compounds were designed and synthesized through the combination of aminothiazoloxime and phosphonate fragment. The results showed that these compounds had better inhibitory effects on the tested bacteria. In particular, the activities of compounds Ⅲf and Ⅲi against S. aureus, E. coli, methicillin-resistant S. aureus (MRSA) and fluoroquinolone-resistant E. coli (FREC) were the most significant, the minimal inhibitory concentration (MIC) of Ⅲf was 1, 8, 4, 16 μg·mL-1 respectively, and the MIC of Ⅲi was 4, 4, 16, 8 μg·mL-1 respectively, which were slightly lower than that of the control drug oxacillin, and their anti-E. coli, MRSA and FREC activities were superior to that of the control drug oxacillin. Their activities to S. aureus were close to that of oxacillin, and to E. coli, MRSA and FREC were superior to that of oxacillin, which is worthy of further study.

Detection rate and clinical characteristics of vulvar squamous intraepithelial lesion / 中华妇产科杂志

Objective:To explore the detection rate, clinical characteristics of vulvar squamous intraepithelial lesion (SIL).Methods:Women diagnosed with vulvar high-grade squamous intraepithelial lesions (HSIL) through colposcopy-guided biopsy from January 1, 2018 to August 31, 2022 in Obstetrics and Gynecology Hospital of Fudan University were included in a 1∶1 ratio with patients diagnosed with vulvar low-grade squamous intraepithelial lesions (LSIL) during the same period. Clinical characteristics including human papillomavirus (HPV) infection rate, genotype, cytology result, colposcopy impression, and lesion location were retrospectively analyzed.Results:(1) The proportion of vulvar SIL detected by colposcopy-guided biopsy increased annually from 2018 to 2022, with rates of 1.64% (740/45 057), 2.34% (1 110/47 402), 2.68% (1 108/41 335), 3.26% (1 536/47 078), 3.31% (667/20 155), with an average rate of 2.57% (5 161/201 027). (2) A total of 1 096 cases of vulvar HSIL and 1 096 cases of vulvar LSIL were included. The overall infection rate of HPV was 92.7% (1 993/2 150), with higher infection rate in vulvar HSIL patients than that in vulvar LSIL patients [96.0% (1 012/1 054) vs 89.5% (981/1 096); χ2=33.62, P<0.001]. Among vulvar HSIL patients, the common HPV genotype from high to low were HPV 16 (66.7%), HPV 52 (14.3%), and HPV 58 (10.0%). For vulvar LSIL patients, the most common HPV genotype were respectively HPV 16 (24.9%), HPV 6 (20.1%) and HPV 52 (17.1%). The overall sensitivity rate of cytology was 53.6%, with no significance difference between vulvar LSIL and HSIL groups (54.3% vs 52.9%; χ2=0.40, P=0.526). The accuracy of colposcopy impression for vulvar HSIL was lower than that for vulvar LSIL [40.2% (163/405) vs 81.7% (380/465); χ2=158.72, P<0.001]. About 57.3% (1 257/2 192) of the patients had concomitant cervical and vaginal lesions, with a higher rate in vulvar HSIL group than that in vulvar LSIL group [62.6% (686/1 096) vs 52.1% (571/1 096); χ2=24.67, P<0.001]. Unifocal lesion was the main type, with no significance difference between vulvar LSIL and HSIL groups [81.4% (381/468) vs 82.5% (386/468); χ2=0.18, P=0.671]. The most common lesion locations were the posterior commissure, followed by labia minora, vaginal vestibule, labia majora, perianal and clitoris. Conclusions:The detection rate of vulvar SIL under colposcopy is about 3%, and the infection rate of HPV is 92.7%. Vulvar SIL, especially vulvar HSIL, is likely to cause concomitant cervical and vaginal lesions. The accuracy of colposcopy in diagnosing vulvar HSIL is low. Therefore a comprehensive and careful examination of the vulva is necessary and suspicious vulvar lesions should be undergone colposcopy-guided biopsy for diagnosis.

Simultaneously quantitative analysis of 35 components in gualoupi injection using hydrophilic interaction liquid chromatography tandem mass spectrometry / 药学学报

A hydrophilic interaction chromatography tandem mass spectrometry method was developed for simultaneous quantification of 35 components in gualoupi injection. The analytes were separated with an ACQUITY XBridge Amide column using 20 mmol·L-1 ammonium formate aqueous solution (pH 3.0) as mobile phase A and 20 mmol·L-1 ammonium formate (pH 3.0)∶acetonitrile (1∶9) as mobile phase B for gradient elution. Mass spectrometry with dynamic multiple reaction monitoring and external standard method were used for quantitative analysis. A total of 35 components were determined in 10 batches of gualoupi injection. The results showed that the 35 compounds had a good linear relationship within their respective concentration ranges with the correlation coefficients (R2 > 0.998 0), the recoveries ranged from 76.6% to 118.5%. The results showed that γ-aminobutyric acid, trigonelline, alanine, threonine, homoserine, citrulline, and leucine were abundant in gualoupi injection, while nicotinamide, methylsuccinic acid, cytosine and choline account for a low percentege. The present study provides an important reference for elucidation of the effective material basis and the improvement of quality standard of gualoupi injection.

Comparative study of next generation sequencing and immunohistochemistry on molecular classification of endometrial carcinoma / 中华病理学杂志

Objective: To investigate the differences in molecular classification of endometrial carcinoma (EC) between various technical methods and to explore molecular classification schemes suitable for Chinese population. Methods: The study used a comprehensive scheme of next generation sequencing (NGS) and immunohistochemistry for molecular classification of 254 EC cases that were obtained at Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China from April 2021 to March 2022. According to the recommended threshold of Sanger sequencing which was approximate-20% variant allele fraction (VAF), NGS data were extracted to simulate the results of Sanger sequencing. Results: The 254 EC patients had a mean age of 51 years (range, 24 to 89 years). Combination of POLE (9-14 exons), TP53 total exons and microsatellite instability (MSI) detection was a better single scheme than NGS alone, while combination of MSI fragment analysis and conventional immunohistochemistry was the best solution and seemed best aligned with TCGA data and recent studies. POLE ultramuted type, mismatch repair defect type, TP53 mutant type and non-specific molecular characteristic type accounted for 11.4% (29/254), 31.5% (80/254), 22.4% (57/254) and 34.6% (88/254) of the cases, respectively. If Sanger sequencing was adopted for POLE and TP53 detection, the frequencies of these EC types were 9.1% (23/254), 31.5% (80/254), 12.9% (33/254) and 46.6% (118/254), respectively, with greatly increasing non-specific molecular characteristics cases. If POLE was detected by Sanger sequencing and others by immunohistochemistry, they were 9.1% (23/254), 42.2% (92/218), 13.8% (35/254) and 40.9% (105/254), respectively, with increasing the false positive rates of the mismatch repair defect group. Conclusions: Small and medium-sized NGS panels with MSI detection is a better solution than NGS alone. Sanger sequencing is currently available for POLE mutation detection, which is not sensitive enough for TP53 mutation detection, and seems equivalent to the efficiency of TP53 by immunohistochemistry. Further optimization of small and medium-sized NGS panels covering MSI detection and POLE and TP53 full exons may be the best choice for the future to meet national conditions.

On the application effect of mobile augmented reality technology in the teaching of neuroanatomy / 中华医学教育探索杂志

Objective:To explore the application of mobile augmented reality (mAR) technology in the teaching of neuroanatomy, and to observe its effect on students' academic performance and cognitive load.Methods:By collecting and designing various neuroanatomy multimedia teaching resources (graphics, animations and videos), using augmented reality (AR) marker-based image recognition technology, the multimedia resources were placed at the tags in the traditional book pages to make the books interactive. And various multimedia resources were combined with traditional printed books through mobile devices. Forty students were randomized into the experimental group or the control group. The experimental group was taught with mAR multimedia materials, and the control group adopted traditional teaching methods. After a 6-hour course was completed, all students had a unified test, and the academic performance test and the PAAS(platform-as-a-service) cognitive load scale were used for data collection and analysis. The variance analyses (MANOVA and ANOVA) were used for significance testing.Results:One-way MANOVA test was used to determine the learning effect of mAR on academic performance and cognitive load. The results showed that there was a significant difference between the experimental group and the control group ( P<0.05). The univariate ANOVA test found that the experimental group students who learned neuroanatomy through mAR had better test scores than the control group students. In addition, compared with the control group students, the cognitive load of students in experimental group was significantly reduced, with statistical significance (all P<0.05). Conclusion:Through the teaching practice, we found that using mAR to learn neuroanatomy helps students improve their academic performance while reducing their cognitive load.

Prevalence and frequencies of human papilloma virus types in adenocarcinoma in situ of the uterine cervix / 中华病理学杂志

Objective: To examine the prevalence and frequencies of human papillomavirus (HPV) genotypes in cervical adenocarcinoma in situ (AIS). Methods: The cases of cervical AIS with concurrent tests of cytology and HPV typing from January 2007 to February 2020 in the Obstetrics and Gynecology Hospital of Fudan University were collected and analyzed. Results: A total of 478 cases of cervical AIS were obtained. The average age of the patients was 39.4 years (range, 19-81 years). The largest age group was 30-39 years (44.8%), followed by 40-49 years (34.7%). Among the 478 patients, 355 underwent high-risk HPV (hrHPV) testing and had a hrHPV-positive rate of 93.8%. Of the 355 patients, 277 also underwent HPV typing and were mostly positive for either or both HPV16 and HPV18 (93.1%), with 55.6% positive for HPV18 and 48.7% positive for HPV16. Among the 478 cases, 266 cases (55.6%) were diagnosed with both AIS and squamous intraepithelial lesion (SIL), while 212 cases (44.4%) were diagnosed with only AIS. Patients infected with HPV16 in the AIS and SIL group significantly outnumbered those in the AIS alone group (P<0.05). Moreover, the rate of positive cytology was 55.9% (167/299 cases), while that of negative cytology was 44.1% (132/299). Among the 109 patients with negative cytology results and co-tested hrHPV, there were 101 HPV-positive cases (92.7%), of which 88 cases were subject to HPV typing and showed an HPV16/18 positive rate of 94.3% (83/88 cases). Conclusions: The combination of HPV typing and cytological screening can maximize the detection rate of cervical AIS, and should continue to be utilized, ideally on a larger scale, in the future.

Major progress in tumor accumulation and penetration of nanomedicine / 药学学报

Nanomedicine has great potential in cancer therapy, but the complex tumor microenvironment greatly prevents nanomedicine from being effectively delivered into tumor in vivo. It has been widely accepted that the encapsulated drugs in the nanoparticles have to go through five major cascading steps, including blood circulation, accumulation in tumor, penetration into the depth of tumor tissue, internalization by tumor cells and then intracellular drug release, before they can exert the anti-tumor efficacy. Among the five steps, drug accumulation in tumor and penetration in the depth of tumor have been the two major issues undermines the antitumor efficacy of nanomedicine. This paper summarizes the new major progress in improving the tumor accumulation and penetration of nanomedicine, especially the technologies that appeared or developed in the last five years.

Risk stratified management of cervical adenocarcinoma in situ based on cone margin state / 中华妇产科杂志

Objective:To investigate the hierarchical management scheme of cervical adenocarcinoma in situ (AIS) based on cervical conization margin state.Methods:All medical records of 249 patients diagnosed as AIS by loop electrosurgical excision procedure (LEEP) conization from Jan. 2010 to Dec. 2015 in Obstetrics and Gynecology Hospital of Fudan University were retrospectively reviewed, to explore the relationship between the status of the resection margin and the residual lesion after LEEP, and the multivariate logistic regression method was used to analyze the related factors that affect the residual lesion after LEEP in cervical AIS patients.Results:(1) The age of 249 cervical AIS patients was (40±8) years old (range: 23-71 years old). Of the 249 patients, 19 (7.6%, 19/249) had residual lesions; 69 cases were pathologically diagnosed as AIS after LEEP, and the residual lesion rate was 13.0% (9/69), which was significantly higher than that of AIS + high-grade squamous intraepithelial lesion [5.6% (10/180); χ2=3.968, P=0.046]; 33 cases were multifocal lesions, the residual rate of lesions was 21.2% (7/33), which was significantly higher than that of single focal lesions patients [5.6% (12/216); χ2=7.858, P=0.005]; 181 patients underwent endocervical curettage (ECC) before surgery, the residual rate of lesions in ECC-positive patients was 14.0% (14/100) , significantly higher than that of ECC-negative patients [4.9% (4/81); χ2=4.103, P=0.043]. (2) Among 249 cases of AIS patients, the positive rate of resection margins after LEEP was 35.3% (88/249); the residual rate of lesions in patients with positive resection margins (14.8%, 13/88) was significantly higher than those with negative margins [3.8%(6/156); χ2=9.355, P=0.002]. The age of patients underwent total hysterectomy after LEEP was (43±7) years old, which was significantly higher than that of patients who did not undergo total hysterectomy [(37±8) years old; t=6.518, P<0.01].Among the patients underwent total hysterectomy after LEEP, 3 cases (2.0%, 3/152) had fertility requirements, while 38 cases (39.2%, 38/97) did not underwent total hysterectomy, the difference between the two groups was statistically significant ( χ2=59.579, P<0.01). Among the 152 patients who underwent total hysterectomy after LEEP, the residual rate of lesions was 11.8% (18/152); the residual rate of lesions in patients with positive resection margins was significantly higher than that of patients with negative resection margins [18.8% (12/64) vs 7.0% (6/86); χ2=4.861, P=0.028]. The median follow-up time of 97 patients who did not undergo total hysterectomy after LEEP was 32 months (range: 4-70 months). During the follow-up period, 3 cases of cervical AIS recurrence (3.1%, 3/97) and were followed by hysterectomy,no invasive adenocarcinoma were seen. (3) Multivariate logistic regression analysis showed that the positive resection margin ( OR=4.098, 95% CI: 1.235-13.595, P=0.021), multifocal lesions ( OR=5.464, 95% CI: 1.494-19.981, P=0.010) were independent risk factors that affected the residual lesions in patients with cervical AIS after LEEP. Conclusions:The cervical AIS patients after LEEP conization suggested be stratified by cone margin state as the first-line stratified index, age and fertility needs as the second-line stratified management index. The individualized management plan should be developed based on comprehensive assessment of high-risk factors of residual lesions.

Effects of propofol on inflammatory response and activation of p38 MAPK signaling pathway in rats with ventilator-induced lung injury

ABSTRACT Purpose: To investigate the effects of propofol on inflammatory response and activation of p38 mitogen-activated protein kinase (MAPK) signaling pathway in rats with ventilator-associated lung injury (VALI). Methods: Thirty-six Sprague Dawley (SD) rats were divided into control, VALI and VALI+propofol groups. The VALI group received the mechanical ventilation for 2 h. The VALI+propofol group received the mechanical ventilation for 2 h, which was accompanied by intravenous injection of propofol with dose of 8 mg·kg-1·h-1. At the end, the mean arterial pressure (MAP) and blood gas indexes were measured, and the lung wet/dry mass ratio (W/D) and biochemical indexes of lung tissue and bronchoalveolar lavage fluid (BALF) were determined. Results: Compared with VALI group, in VALI+propofol group the blood pH, partial pressure of oxygen, partial pressure of carbon dioxide and MAP were increased, the lung W/D, lung tissue myeloperoxidase activity and total protein concentration, white blood cell count, and tumor necrosis factor α, interleukin 1β and interleukin 6 levels in BALF were decreased, and the p-p38 MAPK protein expression level and phosphorylated p38 MAPK (p-p38 MAPK)/p38 MAPK ratio were decreased. Conclusions: Propofol treatment may alleviate the VALI in rats by reducing the inflammatory response and inhibiting the activation of p38 MAPK signaling pathway.

Rhynchophylline nanosuspensions sustained-release tablets: Preparation, optimization and release evaluation in vitro / 中草药

Objective: To prepare the rhynchophylline nanosuspensions and lyophilized powder, and study its sustained-release tablets. Methods: Rhynchophylline nanosuspensions were prepared by microprecipitation combined with high pressure homogenization method, and the particle size and zeta potential were determined. Scanning electron microscopy (SEM) was employed to observe the appearances of nanosuspensions. Nanosuspensions were prepared into lyophilized powder using lactose as freeze-dried protectors. HPMC (hydroxypropyl methyl cellulose) was used as hydrophilic matrix to prepare the sustained-release tablets. Single factor investigation and orthogonal experiments were employed to optimize the formulation of rhynchophylline nanosuspensions sustained-release tablets, and the model fitting was also been studied. Results: The particle size and zeta potential of rhynchophylline nanosuspensions were (153.7 ± 4.9) nm and (-18.54 ± 1.32) mV, respectively. The appearances of rhynchophylline nanosuspensions were spherical or nearly spherical. After orthogonal optimization, the cumulative release rate of rhynchophylline nanosuspensions sustained-release tablets was 92.53% in 12 h. The optimized formulation of hydrogel matrix sustained-release tablets was better accorded with Higuchi model: ln(1-Mt/M∞)=0.286 0 t1/2-0.069 0 (r=0.992 4). The drug release from hydrogel matrix sustained-release tablets were controlled by diffusion and degradation. Conclusion: The obtained rhynchophylline nanosuspensions has small particle size. The prepared hydrogel matrix sustained-release tablets can control the release of rhynchophylline nanosuspensions in a slow characteristic.

Preparation of disulfiram naonosuspensions and their anti-tumor efficacy in vitro and in vivo / 药学学报

Disulfiram (DSF) is a traditional anti-alcohol drug, but it was recently found that DSF has strong inhibitory effect on the growth of a variety of cancer cells. However, its clinical application is greatly limited due to its poor solubility, instability in gastrointestinal tract and short plasma half-life. In this study, DSF is fabricated into nanosuspensions with the aim of trying to solve these problems. DSF nanosuspensions (DSF-NSps) were prepared by the anti-solvent precipitation method under ultrasonication, and the suitable stabilizer was screened according to the size, polydispersity index (PDI), and zeta potential of the resultant nanosuspensions, along with their particle size change during the storage at room temperature. The particle size, PDI, and zeta potential of DSF-NSps were determined using dynamic light scattering method, while the morphology of DSF-NSps was observed by transmission electronic microscope (TEM). The stability of DSF-NSps in media was examined according to their particle size change in different physiological media. The concentration of DSF was measured by HPLC assay. The in vitro drug release was evaluated on basis of dialysis. MTT assay was employed to evaluate the in vitro cytotoxicity of DSF-NSps against cancer cell lines. The 4T1 tumor-bearing mouse model was used to evaluate the in vivo therapeutic efficacy of DSF-NSps. All the animal experiments were acquired according to the Regulations for Animal Experiments and Guidelines for Ethical as defined by Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College. As a result, the combinational use of soyabean lecithin (SPC) and D-alpha tocopherol acid polyethyene glycol succinate (TPGS) was determined to best stabilize DSF-NSps when the ratio of DSF-SPC-TPGS was 24∶20∶4 (weight ratio), with small particle size and good storage stability. The resultant DSF-NSps showed a regular spherical morphology and drug loading content of (45.36 ± 2.09) %, with average particle size of 175.00 ± 0.75 nm, PDI of 0.24 ± 0.07 and zeta potential of -14.3 mV. DSF-NSps displayed good particle size stability in a variety of biological media including phosphate buffer saline, normal saline, 5% glucose, artificial gastric fluid, artificial intestinal fluid and plasma, which would meet the demand of both intravenous and oral administration. The in vitro study demonstrated that nano-encapsulation greatly increased the stability of DSF in aqueous media, DSF-NSps exhibited sustained release of the encapsulated drug and significantly inhibited 4T1 cells compared to free DSF (IC50, 1.07 vs 5.53 μg·mL-1, P<0.01). DSF-NSps showed a good dose-response relationship on the 4T1 tumor-bearing mice with the tumor inhibition rates at the three doses being 80.22%, 75.14% and 66.10%, all higher than that of paclitaxel injections (55.01%, P<0.05). The in vivo biodistribution study displayed that DSF-NSps were mainly distributed into liver, spleen and tumor. In sum, disulfiram nanoparticles could be expected to provide an effective anti-cancer drug for the treatment of breast cancer.

Analysis of recurrence and its influencing factors in patients with cervical HSIL within 24 months after LEEP / 中华妇产科杂志

Objective To analyze clinical outcome of high grade squamous intraepithelial lesion (HSIL) within 24 months after loop electrosurgical excision procedure (LEEP),and to explore risk factors of recurrent cervical HSIL,the risk of progress into cervical cancer and methods of follow-up.Methods This retrospective study was carried out on 1 005 patients who underwent LEEP,diagnosing with HSIL after LEEP from January 2011 to December 2013 at Obstetrics and Gynecology Hospital Affiliated to Fudan University to confer the difference between non-recurrent group and recurrent group 24 months after the LEEP conization.Patients were followed with ThinPrep cytologic test (TCT),high risk HPV (HR-HPV) test,colposcopy guided biopsy.Results A total of 1 005 cases were enrolled in this study with HSIL in the LEEP specimen,no residual HSIL in the 6-month follow up,and have follow up records in 24 months after LEEP.HSIL recurred in 5 cases,microinvasive carcinoma in 1 case,low grade squamous intraepithelial lesion (LSIL) in 17 cases at 12 months follow-up.HSIL recurred in 8 cases,LSIL in 11 cases,adenocarcinoma in situ in 1 case,and invasive cervical carcinoma in 1 case in Ⅰ b1 stage at 24 months after LEEP.The recurrence rate was 1.3％ (13/1 005),and the progression rate was 0.3％ (3/1 005).There was no significant difference in age,length,circumference and width of LEEP between recurrent and non-recurrent patients (P ＞ 0.05).The recurrence rate was highest in the endocervical positive margin group with 3/16,which was higher than ectocervical positive margin and negative margin (P＜0.01,P=0.040,respectively).The recurrence rate of endocervical positive margin group and fibrous interstitial positive margin group showed no significant difference (P=0.320).There was no significant difference between ectocervical positive margin and negative margin [2.8％ (2/72) vs 0.7％ (6/882),P=0.117].Postoperative cytological examination combined with HR-HPV detection has a high sensitive and high negative predictor value of HSIL recurrence with both 100.0％.Multivariate logistic regression analysis showed that positive endocervical positive margin,abnormal follow-up cytological examination and positive HR-HPV after LEEP were independent factors affecting recurrence of HSIL patients after LEEP (P＜0.05).Conclusions Age,length,circumference and width of LEEP have no effect on recurrence within 24 months after HSIL.The high risk factors for HSIL recurrence within 24 months after LEEP in HSIL patients include:positive HPV,abnormal cytology,and positive endocervical positive margin.Colposcopy biopsy and endocervical curettage have important role in diagnosing HSIL recurrence and progression.

Ilizarov technique in treatment of Gustilo type Ⅲ B and C of large tibia bone defect combined with soft tissue defect / 局解手术学杂志

Objective To investigate the efficacy of Ilizarov technique in treatment of Gustilo type Ⅲ B and C of large tibia bone defect combined with soft tissue defect. Methods Thirty cases with large tibia bone defect combined with soft tissue defect in our hospital from January 2016 to December 2018 were selected including 25 cases with type Ⅲ B and 5 cases with type Ⅲ C,who were all open tibia fractures and treated with Ilizarov technique. Results All patients were followed up for 10 to 18 months with an average of 15 months. The bone defects were reconstructed, the difference between the length of the affected limb and the healthy side was less than 2 cm. The fracture was healed and the wound was closed. One case was with paralysis of common peroneal nerve and recoveried after 3 months. Twenty-two cases recovered without extra surgery, five cases restored with skin graft and three cases covered the wound by rotating skin flap. Conclusion Ilizarov technique is one of effective ways to treat Gustilo Ⅲ type B and type C of large defect combined with soft tissue defect.

Relationship between various histological status of margins of LEEP and residual HSIL or worse at hysterectomy following conization / 中华妇产科杂志

Objective To investigate the relationship between various loop electrosurgical excision procedure (LEEP) margin status and residual high grade squamous intraepithelial lesion (HSIL) or worse at hysterectomy following conization. Methods The relevant clinicopathological data were collected in the Obstetrics and Gynecology Hospital, Fudan University from Jan. 2014 to Dec. 2015, including 947 cases who underwent hysterectomy within 6 months of LEEP. The residual HSIL or worse at hysterectomy were analyzed among the groups. (1) Clear margins, involved margins, and without 1 mm negative margins. (2) Only one positive margin, two positive margins and three positive margins. (3) A positive margin of internal ostium of cervix, of external ostium of cervix and of the basement. Results (1) The histological evaluation of the uterine specimens showed residual HSIL or worse in 234 cases (24.7％, 234/947). The proportion of residual lesions was 7.3％ (21/286) in population with clear margins, 33.2％ (211/635) with involved margins, 7.7％ (2/26) without 1 mm negative margins, respectively. The positive margins group had significant difference at the aspect of residual rate in contrast to the negative margins group and the without 1 mm negative margins group (P<0.01). Further studies conclusively showed that the proportion of residual lesions was very similar between the negative margins group and the without 1 mm negative margins group (P>0.05). (2) The involved margins were interpretable in 621 cases. This was detected in 25.3％(111/438) patients with only one positive margin, 47.4％(74/156) with two positive margins and 77.8％(21/27) among three positive margins, respectively (P<0.01). (3) Furthermore, there were 418 cases only one positive margin was definite, and the proportion of residual lesions was 31.0％(62/200) in population with a positive margin of internal ostium of cervix, 18.2％(31/170) of external ostium of cervix and 33.3％(16/48) of the basement. The residual rates were higher in the endocervical and basal margin groups than that in the ectocervical margin group, and the differences were significant (P<0.05). Conclusions The risk of residual HSIL or worse is significantly greater with involved margins at hysterectomy following LEEP. Both the positive endocervical and basal margin are excellent predictors of residual diseases, while the without 1 mm negative margin may be not. Clinicians should avoid treating it as positive margin and prevent overtreatment.

Consistency of diagnosis between cervical cytology and colposcopic biopsy diagnosis / 中华病理学杂志

Objective@#To identify underlying reasons for discrepant cases of positive cytology but negative histology.@*Methods@#Cases with positive cytology and negative histology from 2008 to 2016 were retrieved from Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University. Low grade squamous intraepithelial lesion or higher grade lesions were considered as positive cytology test in the study. Consecutive follow-up biopsies and as well as sites of biopsy were documented for analysis.@*Results@#Overall positive rate of biopsy followed positive cytology was 74.3%(8 990/12 097). Of the negative biopsies, 675 cases were followed-up with multiple biopsy. Two-hundred and eighty-seven cases (42.5%, 287/675) were confirmed to have lesions. Comparing with those with initial positive biopsiews, patients of the latter group were significantly older and had other specimen types including vaginal biopsy, cone biopsy and hysterectomy. The final histological diagnoses were well correlated with cytological results (Kappa=0.505, P<0.01).@*Conclusions@#Qualified cervical cytology is complimentary to histological diagnosis. Clinicians should not ignore the positive cytological result prior to a normal histological diagnosis. In contradictory cases, repeated colposcopy and biopsy at extended anatomic sites may reveal additional lesions.

Synchronous mucinous metaplasia and neoplasia of the female genital tract / 中华病理学杂志

Objective@#To describe the clinicopathological features of synchronous mucinous metaplasia and neoplasia of the female genital tract (SMMN-FGT). @*Methods@#The sample consisted of 7 cases of SMMN-FGT recorded from November 2014 to September 2017 at Obstetrics and Gynecology Hospital, Fudan University.PAP method was used in immunohistochemistry.Clinical histories were retrieved and pathological slides were reviewed. @*Results@#The patients were 37 to 70 years old(mean 54 years old). All patients showed endometrial mucinous lesions associated with cervical lesions. Three cases were an admixture of minimal deviation adenocarcinoma(MDA) and gastrictype adenocarcinoma(GAS). Three cases were an admixture of lobular endocervical glandular hyperplasia (LEGH), atypical LEGH and focal gastrictype adenocarcinoma in situ, one of which had early invasive gastrictype adenocarcinoma.Endometrium showed a structure of LEGH in one patient with focal simple gastric mucinous metaplasia in her cervix. Gastric mucinous differentiation was found in unilateral fallopian tube in 6 patients. Ovarian mucinous lesions were found in 3 patients. p16 was negative staining in 6 cases and positive in 1 case. CK7 was diffusely positive in all lesions. CK20 and CDX2 were negative or only focally positive.The expression of MUC6 was strongly positive staining or focal staining. p53 in GAS and GAS in situ had mutant expression, but wild expression in MDA region. Patients were followed up for 2 to 34 months and no recurrence was found. @*Conclusions@#SMMN-FGT is a series of rare mucinous lesions involving multiple areas of the female genital tract, including benign or malignant lesions with gastric differentiation. It is not related to infection with high-risk human papilloma virus. When cervical gastrictype lesions are found, SMMN-FGT should be considered and should be differentiated from metastatic mucinous adenocarcinoma.

Study on matrix sustained release tablets of brucine solid lipid nanoparticles / 中草药

Objective To prepare brucine solid lipid nanoparticles (SLN) and its lyophilized powder, and then hydrogel matrix sustained-release tablets (HMST) of brucine SLN (SLN-HMST) were prepared. The factors that may influence drug release in vitro and release mechanism were also investigated in present study. Methods Based on single factor test, orthogonal test was designed to gain the optimum prescription. Zero-order, First-order and Higuchi models were used for the model fitting of drug release. Ritger-Pappas models were employed to study release mechanism of brucine SLN-HMST. Results Brucine SLN-HMST was better agreed with First-order kinetics model. The equation was ln(1-Mt/M∞) = -0.212 1 t + 0.106 4 (r = 0.992 3). The cumulative release could achieve 91.48% in 12 h. The sustained release features were obviously. The drug release from the tablets was controlled by diffusion and degradation of the matrix. Conclusion The prepared brucine SLN-HMST can deliver drug continually for 12 h with good reproducibility.

Two kinds of luteolin solid dispersion: Preparation, characterization, and pharmacokinetic behaviors in SD rats in vivo / 中草药

Objective To prepare luteolin solid dispersions (Lut-SD) and luteolin phospholipids complex solid dispersions (Lut-PC-SD), and compare the effects of two kinds of solid dispersions on the bioavailability in vivo. Methods PVP K30 was employed as carrier, and solvent evaporation method was used to prepare Lut-SD and Lut-PC-SD. Their existential state of luteolin in solid dispersions was analyzed by X-ray power diffraction (XRPD). The solubility and dissolution rate were also studied. SD rats in each group were administered intragastrically with Lut, Lut-SD, and Lut-PC-SD, respectively. Their blood samples were collected at different time intervals. Diosmetin was used as internal standard, the concentration of Lut in blood was analyzed by HPLC, and the main pharmacokinetic parameters were obtained. Results The results of XRPD indicated that Lut showed an amorphous state in Lut-SD and Lut-PC-SD. The solubility of Lut was enhanced from (61.09 ± 0.09) μg/mL to (365.33 ± 0.38) μg/mL and (401.14 ± 0.19) μg/mL by Lut-SD and Lut-PC-SD, repectively. The dissolution of Lut was also improved greatly by the two kinds of solid dispersions. Compared to Lut, the bioavailability of Lut-SD and Lut-PC-SD was enhanced to 150.10% and 204.52%, repectively. Conclusion Lut-SD and Lut-PC-SD both could enhance the bioavailability of Lut in SD rats notably. In addition, Lut-PC-SD could give a better effect.

Preparation of annonaceous acetogenins nanosuspensions using poloxamer 188 as a stabilizer and their in vitro and in vivo investigation / 药学学报

Annonaceous acetogenins (ACGs) are effective part extracted and separated from Annona squamosa seeds, they have good antitumor activity against a variety of tumor cells. However, the solubility of ACGs is poor with serious toxic and side effects, which greatly limits their application in clinical practice. In this study poloxamer 188 (P188) was selected as a drug carrier or a stabilizer to prepare ACGs nanosuspensions (ACGs-NSps) using anti-solvent precipitation. The nanosuspensions were examined via dynamic light scattering (DLS) method to examine size of the nanosuspensions. Transmission electron microscopy was used to observe their morphology. HPLC assay was used to measure their drug loading content and the in vitro drug release. The stability of ACGs-NSps at room temperature, in various physiological media and plasma, and the hemolytic test and lyophilization were all investigated. MTT assay was performed to study the cytotoxocity of ACGs-NSps against four tumor cell lines. 4T1 bearing tumor model was used to assess their in vivo antitumor therapeutic efficacy. The obtained ACGs-NSps were spherical, the average particle size was 169.4±1.25 nm, the polydispersity index (PDI) value was 0.130±0.020, the zeta potential was -19.8 mV and the drug loading content was 48.18%. ACGs-NSps were stable at room temperature for at least 15 days. They could be lyophilized in the presence of 0.5% glucose and 2.0% P188. ACGs-NSps showed sustained in vitro drug release, and the cumulative drug release reached 80.82% within 144 hours. ACGs-NSps maintained their particle size in various physiological media, and plasma with no hemolysis and then met demands of both oral and intravenous administration. In contrast to free ACGs, ACGs-NSps displayed significantly higher cytotoxicity against 4T1 (IC50, 0.892±0.124 μg·mL-1 vs 2.495±0.108 μg·mL-1, P 50, 0.747±0.051 μg·mL-1 vs 2.204±0.064 μg·mL-1, P 50, 2.265±0.081 μg·mL-1 vs 4.159±0.071 μg·mL-1, P 50, 0.473±0.024 μg·mL-1 vs 1.196±0.022 μg·mL-1, P in vivo study demonstrated that the daily oral administration of ACGs-NSps (3 mg·kg-1) resulted in higher tumor inhibition rate compared to ACGs/oil solution (67.23% vs 53.11%), comparable to the intravenous injection of 0.5 mg·kg-1 ACGs-NSps every other day (70.34%). Nanosuspensions effectively solved the problem of ACGs insolubility and difficulty in drug delivery. Using P188, a pharmaceutic adjuvant approved by FDA for iv injection, the resultant ACGs-NSps appear promising as an anti-tumor drug that can be used in clinic.

Preparation of gambogic acid naonosuspensions and their anti-tumor efficacy / 药学学报

Gambogic acid (GA), the main active ingredient in gamboge, has been reported to have good anti-tumor activity with excellent selectivity. However, its clinical application is limited by the poor water solubility. GA nanosuspensions were designed in this study in order to solve this problem. GA nanosuspensions were prepared by microprecipitation method based on pH adjustment. Suitable stabilizer was screened according to the size and polydispersity index (PDI) of the resultant nanosuspensions. Dynamic light scattering method was used to measure the particle size and transmission electron microscopy was used to observe the morphology. The stability was studied in different medium. The drug release was evaluated using a dialysis method. MTT assay was used to assess their cytotoxicity in vitro against cancer cell line. Anti-tumor effect in vivo was investigated on H22-bearing mice. In result, Poloxamer (P188) was found to be a good stabilizer. The resultant GA nanosuspensions (GA-NSps) were 135.9 ±5.1 nm in diameter, with PDI value being 0.26 ±0.01 and the zeta potential being −35.1 ±1.36) mV. GA-NSps were nearly spherical. They were quite stable in various physiological media. GA-NSps exhibited a sustained drug release pattern, with the cumulative release reaching 90.26% within 312 h. In MTT assay, GA-NSps had a stronger cytotoxicity against HepG2 cells than the free drug (IC50, 0.851 8 μg·mL−1 vs 2.104 μg·mL−1, P vs 66.80%, P < 0.01). In summary, we prepared GA-NSps with high drug loading capacity, small particle size and good stability, and provided a solid basis for the effective dosage form of gambogic acid.