Objective: To explore the neuroprotective effects of the Shaoyao Gancao decoction (SGD) against excitatory damage in PC12 cells and the role of the Src-NR2-nNOS pathway mediation by SGD in regulating γ-aminobutyric acid (GABA)-glutamate (Glu) homeostasis. Methods: N-Methyl-d-aspartic acid (NMDA) was used to establish a PC12 cell excitability injury model. To investigate the neuroprotective effect of SGD, a cell counting kit-8 (CCK-8) assay was used to determine PC12 cell viability, Annexin V/Propidium Iodide (Annexin V/PI) double staining was used to determine PC12 cell apoptosis, and Ca2+ concentration was observed using laser confocal microscopy. GABA receptor agonists and antagonists were used to analyze the neuroprotective interactions between γ-aminobutyric acid (GABA) and NMDA receptors. Additionally, molecular biology techniques were used to determine mRNA and protein expression in the Src-NR2-nNOS pathway. We analyzed the correlations between the regulatory sites of GABA and NMDA interactions, excitatory neurotoxicity, and brain damage at the molecular level. Results: NMDA excitotoxic injury manifested as a significant decrease in cell activity, increased apoptosis and caspase-3 protein expression, and a significant increase in intracellular Ca2+ concentration. Administration of SGD, a GABAA receptor agonist (muscimol), or a GABAB receptor agonist (baclofen) decreased intracellular Ca2+ concentrations, attenuated apoptosis, and reversed NMDA-induced upregulation of caspase-3, Src, NMDAR2A, NMDAR2B, and nNOS. Unexpectedly, a GABAA receptor antagonist (bicuculline) and a GABAB receptor antagonist (saclofen) failed to significantly increase excitatory neurotoxicity. Conclusions Taken together, these results not only provide an experimental basis for SGD administration in the clinical treatment of central nervous system injury diseases, but also suggest that the Src-NR2A-nNOS pathway may be a valuable target in excitotoxicity treatment.

Objective We aimed to study the protective effect of total glucosides of paeony (TGP) on chemical liver injury with pattern of liver yin deficiency in rats and determine whether it exerts these effects through the phosphoinositide 3-kinase(PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway.Methods Forty male Sprague-Dawley rats were randomly divided into the following four groups: (i) the blank group, (ii) the model group, (iii) the Yiguan Jian group, and (iv) the TGP group (10 rats per group). For 6 weeks, rats in all groups except for the blank group were injected intraperitoneally with 20％ carbon tetrachloride olive oil solution and were given thyroid tablets (30mg/kg) by gavage in order to establish the model of chemical liver injury with pattern of liver yin deficiency. During the modeling period, rats in the blank and model groups were gavaged daily with distilled water, while rats in the Yiguan Jian group and the TGP group were gavaged with 635mg/kg of Yiguan Jian decoction and 50mg/kg of TGP suspension, respectively. During the administration period, the body weight and rectal temperature of rats were measured every 2 weeks. After the administration, 24-hour food intake, 24-hour water intake, and moisture capacity in tongue surface were recorded. Serum cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and interleukin-1 receptor antagonist (IL-1Ra) contents were measured by ELISA and the cAMP/cGMP ratio was calculated. Changes in the serum levels of alanine aminotransferase (ALT), alanine transaminase (AST), gamma-glutamyl transpeptidase (γ-GT), alkaline phosphatase (ALP), total bilirubin (TBIL), and total bile acids (TBA) were detected using colorimetric method. Masson staining was performed to observe the degree of liver fibrosis and to calculate the relative collagen area. Real-time PCR and Western blotting were conducted to determine the PI3K, AKT, and mTOR mRNA and protein expression levels in rat liver.Results Compared with the blank group, rats in the model group had a lower body weight at weeks 2, 4, and 6, a higher rectal temperature at weeks 2, 4, and 6, and a higher 24-hour food intake; the cAMP level was elevated, the cGMP level was decreased, and the cAMP/cGMP ratio was elevated; the contents of IL-1, IL-6, and TNF-α were elevated, and the contents of IL-10 and IL-1Ra were decreased; ALT, AST, γ-GT, ALP, TBIL, and TBA levels were elevated; the percentage of collagen area in the liver was increased; and the mRNA and protein phosphorylation levels of PI3K, AKT, and mTOR were elevated ( P<0.05). Compared with the model group, rats in the TGP group showed a decrease in rectal temperature at weeks 2, 4, and 6, a decrease in 24-hour food intake and water intake, and an increase in the moisture capacity in tongue surface; rats in the Yiguan Jian and TGP groups showed a decrease in cAMP, an increase in cGMP, and a decrease in the cAMP/cGMP, the contents of IL-1, IL-6, and TNF-α were decreased and the content of IL-10 was increased, the percentage of collagen area in the liver was decreased; ALT, AST, γ-GT, ALP, and TBIL levels were decreased in the TGP group, and PI3K, AKT, and mTOR were downregulated at the mRNA and protein levels(P<0.05).Conclusion TGP has a good protective effect on chemical liver injury with pattern of liver yin deficiency in rats. TGP may regulate the balance of yin and yang by inhibiting the PI3K/AKT/mTOR pathway, reducing the secretion of pro-inflammatory cytokines, and increasing the release of anti-inflammatory cytokines.

Objective:To evaluate the indications, surgical skills and clinic outcomes of abdominal minimal incision sacrocolpopexy (AMISC) for treatment of advanced pelvic organ prolapse (POP).Methods:The retrospective study analyzed 30 women with advanced POP who underwent AMISC between June 2016 and October 2019, including 9 cases of recurrent prolapse and 10 cases of vault prolapse. AMISC was especially applicable to: (1) patients with several medical complications who was unable to tolerate general anesthesia or laparoscopic surgery, but able to tolerate combined spinal-epidural anesthesia and open surgery; (2) other abdominal procedures were indicated to perform with AMISC simultaneously, such as myomectomy, subtotal hysterectomy etc, the specimens were easy to get out of the abdominal cavity and morcellation was avoided; (3) surgeons preferring open surgery to laparoscopic surgery or skilled in open surgery; (4) patients with prior pelvic operations, presenting severe abdominal and pelvic adhesions. Objective outcomes were assessed by pelvic organ prolapse quantification (POP-Q) system. Subjective outcome were assessed by pelvic floor distress inventory-short form 20 (PFDI-20), pelvic floor impact questionnaire-short form (PFIQ-7) and patient global impression of improvement (PGI-I).Results:All patients with 1-3 medical complications were successfully performed with AMISC without stopping procedure, enlarging the incision or changing to other procedure, the operation duration was (110±19) minutes. The mean time of follow-up was (33.5±12.4) months (range: 8-49 months). The postoperative points of Aa, Ba, C, Ap, Bp reduced significantly and point C improved from (2.33±2.50) cm to (-7.54±1.18) cm after AMISC ( P<0.01). The objective cure rates were both 100% (30/30) in apex and posterior compartment, while 97% (29/30) in anterior compartment. Postoperative scores of PFDI-20 and PFIQ-7 were all significant decreased (all P<0.01). About PGI-I, 29 patients chose “significant improvement”, subjective satisfaction was 97% (29/30). Anterior sacral plexus hemorrhage occurred in 2 cases (7%, 2/30). There was no intestinal obstruction or injury of bladder, bowel and ureter intra- and postoperation. Two cases (7%, 2/30) had mesh exposure. Conclusion:AMISC is a safety, convenient, minimal traumatic and durable procedure for apical prolapse with short learning curve in the most of cases.

Objective To evaluate the indications and clinic outcomes of vaginal high uterosacral ligament suspension (HUS) for treatment of recurrent advanced pelvic organ prolapse (POP). Methods This retrospective study analyzed 42 women with recurrent advanced POP who were referred to Fourth Medical Center of PLA General Hospital and underwent transvaginal HUS between November 2005 and January 2018. Primary surgeries included 30 vaginal colporrhaphy, 5 Manchester operation, 5 transvaginal mesh repair,2 sacrospinous ligament fixation.The median time for recurrence from primary pelvic floor repair surgery was 9 months, including 14 cases (33%, 14/42)≤3 months (median time was 2 months) and 25 cases (67%, 28/42) longer than 3 months (median time was 18 months).The rate of recurrent prolapse in stageⅢorⅣ was 79% (33 cases), 45% (19 cases) and 17%(7 cases) in anterior, apical and posterior compartment respectively. Results Transvaginal high bilateral uterosacral ligaments were identified and used for successful vaginal vault suspension after vaginal hysterectomy and residual cervical resection in all 42 consecutive patients. The cases of transvaginal mesh used in anterior wall and posterior wall were 25 (60%, 25/42) and 3 (7%, 3/42) respectively. There was no major intra-and postoperative complications,such as ureter and other pelvic organ injury. The median time of follow-up was 5.3 years after transvaginal HUS. The points of pelvic organ prolapse quantification system reduced significantly and point C improved from+0.3 cm to-8.2 cm after reoperation (P<0.01). The objective cure rate were 100% (42/42) both in apex and posterior compartment,while 93% (39/42) in anterior compartment. None had reoperation or pessary usage for recurrence of prolapse. Conclusion Transvaginal HUS with vaginal wall repair could be as a safety, cost-effective, minimal traumatic and durable procedure for recurrent POP in the most of cases.

Objective To assess the five?year effect of the transvaginal high uterosacral ligament suspension (HUS) with or without additional concomitant native?tissue anterior and (or) posterior repair in women suffering from middle compartment defect. Methods A retrospective review of records identified 79 women who underwent transvaginal HUS with or without additional concomitant native?tissue anterior and (or) posterior repair from January 2007 to January 2018 in Fourth Medical Center, General Hospital of People′s Liberation Army. The middle compartment defects were predominant in these patients with point C no less than point Ba or Bp if accompanied with anterior or posterior vaginal wall prolapse. Follow?up visits were performed 2,6 and 12 months after surgery and then annually. Anatomic results of pelvic organ prolapse (POP) was established by pelvic examination using pelvic organ prolapse quantitation system (POP?Q) staging. Funtional results were obtained by patient global impression of improvement (PGI?I) scale in POP, pelvic floor distress inventory?short form 20 (PFDI?20) and pelvic floor impact questionnaire short form (PFIQ?7). Surgical success required the fulfillment of all 3 criteria: (1) anterior or posterior vaginal wall prolapsed leading edge of 0 cm or less and apex of 1/2 total vaginal length or less; (2) the absence of POP symptoms as reported on the PFDI?20 question No.3 ("Do you usually have a bulge or something falling out that you can see or feel in your vaginal area?"); and (3) no prolapse reoperations or pessary use during the study period. Results Of 79 women, 51(65%, 51/79) women completed the five?year follow?up during the study period. The median follow?up time was 5.2 years (2.8-8.3 years). The overall surgery success rate was 86% (44/51) according to above all 3 criteria. Prolapse recurrence rates were isolated anterior 8% (4/51), isolated apical 0, isolated posterior 2% (1/51) and multiple compartments 4% (2/51). Seven women (14%,7/51) developed anterior or posterior prolapse beyond the hymen with the leading edge≤1 cm. No apical prolapsed occurred. None of recurrent women underwent retreatment,including either surgery or pessary usage at last follow?up. The subjective satisfaction rate was 90% (46/51). There was a 1% (1/79) rate of intraoperative ureteral kinking and 3% (2/79) rate of postoperative morbidity. Conclusions The transvaginal HUS for middle compartment defect offers good long?term anatomical results with excellent vault suspension. With additional concomitant native?tissue anterior and (or) posterior repair, it will be a reconstructive surgery for the majority of moderate?to?severe POP. It is minimal traumatic and worthy of being popularized for clinical application.

Objective To explore the clinical management and outcomes of polypropylene mesh and sling exposure after reconstructive pelvic surgery(RPS). Methods A total of 110 cases of mesh and sling exposure after RPS were analyzed, who admitted between Jan. 2002 and Oct. 2017 in First Affiliated Hospital of PLA General Hospital, in which 3 cases were referred from other hospitals. Mesh and sling exposures were identified in the outpatient clinic and categorized and managed according to International Continence Society and International Urogynecology Association(ICS-IUGA)classification about category, time and site(CTS)of mesh complication. Outpatient management included observation, topical estrogen use and mesh removal. Management in hospital included surgical removal of exposed mesh and repair of the resulting defects under the anesthesia. Seventy-four cases were managed in the outpatient setting, and 36 cases required inpatient management. Follow-up was consecutively performed from 1 month to 10 years. Objective outcome included the surgeon′s assessment of the healing state of the vaginal mucosa. Subjective outcome was evaluated with patient global impression of improvement questionnaire(PGI-I). Results One hundred and ten patients with mesh exposure were classified according to the different RPS underwent. There were 95 cases from transvaginal mesh surgery, 5 cases from anti-stress urinary incontinence sling surgery, and 10 cases from sacrocolpopxy. The outpatient group healed at an average of(3.0 ± 1.8)months. Of the 36 patients who required inpatient management, 21 cases healed completely at an average of 7 days after one surgery. The remaining 8 cases required either two or three times surgeries or conservative management. In the outpatient group, the PGI-I scale very much better was found in 65 cases(87.8％)and much better in 9 cases(12.2％). In the inpatient surgery group, the scale was very much better in 30 cases (83.3％), and much better in 6 cases(16.7％). Conclusions Among patients with mesh exposure after mesh-augmented RPS, 2/3 of patients with a CTS classification 1-3 could be managed in the office,and remaining 1/3 with CTS classification 4-6 need operation under anesthesia in hospital. If the mesh and sling exposure could be scientifically classified, according to the size, site and accompany symptoms, as well as pain, most of the mesh complications after explosure could be resolved. Using the pelvic floor repair and polypropylene mesh sling, the majority of the patients could get a better outcome, without affecting the effect of the original operation.

OBJECTIVE:To improve community pharmaceutical care so as to promote the rational drug use of community resi-dent and improve the quality of life. METHODS:By analyzing the situation of community pharmaceutical care,the pharmaceutical care of community pharmacists was improved by changing pharmaceutical care mode,actively developing the propaganda of ratio-nal drug use,strengthening retraining of clinical pharmacists. RESULTS:With the help of Hongkou district quality control group, many hospitals of the district signed thepharmaceutical linkage assistance agreement. Through the efforts of Hongkou district quality control group and many hospitals,community pharmaceutical care was improved and the propaganda of rational drug use has achieved certain results. CONCLUSIONS:Through exploration and practice,the pharmaceutical care levels of community phar-macists have been improved and the rational drug use of community residents has been promoted.

Objective To assess the long-term effectiveness of the transvaginal high uterosacral ligament suspension (HUS) in women suffering from advanced pelvic organ prolapse (POP).Methods A retrospective review of records identified 118 women who underwent transvaginal HUS with or without additional concomitant anterior and (or) posterior repairs from June 2003 to August 2009 in the First Affiliated Hospital,General Hospital of People's Liberation Army.Of 118 women,104 women completed the follow-up during study period;these 104 women were analysed.Follow-up visits were performed 2,6 and 12 months after surgery and then annually.Anatomic results of POP was established by pelvic examination using pelvic organ prolapse quantitation system (POP-Q) staging.Funtional results were obtained by patient global impression of improvement (PGI-I),pelvic floor distress inventory-short form 20 (PFDI-20) and pelvic floor impact questionnaire short form (PFIQ-7).Surgical success required the fulfillment of all 3 criteria:(1) prolapse leading edge of 0 cm or less and apex of 1/2 total vaginal length or less;(2) the absence of pelvic organ prolapse symptoms as reported on the PFDI-20 question No.3 (Do you usually have a bulge or something falling out that you can see or feel in your vaginal area?);and (3) no prolapse reoperations or pessary use during the study period.Results The mean follow-up time was (9.1 ± 1.5) years.The overall surgery success rate was 91.3％ (95/104) according to above all 3 criteria.Prolapse recurrence rates were isolated anterior 6.7％ (7/104),isolated apical 0,isolated posterior 2.9％ (3/104) and multiple compartments 1.0％ (1/104).Five women (4.8％,5/104) developed bothersome vaginal bulge symptoms.None of recurrent women underwent retreatment,including either surgery or use of a pessary at last follow-up.The subjective satisfaction rate was 90.4％ (94/104).PFDI-20 and PFIQ-7 scores showed a statistically significant improvement from preoperative 72 and 65 points to postoperative 17 and 9 points respectively (all P＜0.01).There was a 2.9％ (3/104) rate of intraoperative ureteral kinking and 3.8％ (4/104) rate of postoperative morbidity.Conclusions The transvaginal HUS for vault prolapse offers good long-term anatomical results with excellent vault suspension.With additional concomitant anterior and (or) posterior repairs,it will be a reconstructive surgery for the majority of advanced POP.It is minimal traumatic and appropriate for different type of POP,especially for the eldly patients.It is worthy of being popularized for clinical application.

To study the potential molecular mechanism of tumor angiogenesis in its microenvironment, we investigated the effects of HepG2 conditioned medium on the proliferation of vascular endothelial cell and vascular angiogenesis in our laboratory. Human umbilical vein endothelial EA. hy926 cells were co-cultured with HepG2 conditioned medium in vitro. The proliferation and the tubulogenesis of EA. hy926 cells were detected by teramethylazo salt azole (MTT) and tube formation assay, respectively. The results showed that the survival rate of the EA. hy926 cells was significantly increased under the co-culture condition. HepG2 conditioned medium also enhanced the angiogenesis ability of EA. hy926 cells. In addition, the expressions of intracellular VEGF and extracellular VEGFR (Flk-1) were regulated upward in a time-dependent manner. In conclusion, the proliferation of vascular endothelial cells and Vascula angiogenesis were improved under the condition of indirect co-culture.
Carcinoma, Hepatocellular ; pathology ; Cell Proliferation ; Coculture Techniques ; Culture Media, Conditioned ; Endothelial Cells ; cytology ; Hep G2 Cells ; Human Umbilical Vein Endothelial Cells ; Humans ; Liver Neoplasms ; pathology ; Neovascularization, Pathologic ; Tumor Microenvironment ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism

Due to the good tumor-targeting and excellent biocompatibility, the drug-loading nanoparticles (NPs) has been widely applied in the diagnosis and treatment of cancer. However, after the NPs are recognized and internalized by cancer cells, the effects of NPs on cell migration behavior were unclear. In the present study, the self-assembly techniques (SAMs) was used to modify gold (Au) nanoparticles (Au NPs) with different chemical functional groups (CH3, OH, COOH and NH2) as model NPs. The dispersion of these groups in solution and the distribution in cells were studied by transmission electron microscope (TEM), respectively, and the proliferation was examined by MTT assay in vitro. The wound-healing and the Transwell assay were used to examine the effect of internalized Au-NPs on HepG2 cells migration. The results showed that different Au-NPs mainly distributed at the edge of the vesicle membrane and the gap between cells. The Au-NPs resulted in decreased cell viability in a concentration-depended manner. In addition, the results of wound-healing and Transwells assay indicated that the internalization of the NH2-NPs and OH-NPs would inhibit cell migration compared with those in the control group.
Carcinoma, Hepatocellular ; metabolism ; Cell Movement ; Cell Proliferation ; Cell Survival ; Gold ; Hep G2 Cells ; Humans ; Liver Neoplasms ; metabolism ; Metal Nanoparticles ; chemistry