Clinical Effect of Uterosacral and Cardinal Ligament Fixation versus Sacrospinous Ligament Fixation of Vaginal Vault Prolapse: A Retrospective Analysis.

Objective: This study aimed at comparing sacrospinous ligament fixation (SSLF) with uterosacral and cardinal ligament fixation (USCLF) concerning complications and outcomes in patients with pelvic organ prolapse (POP). Methods: A retrospective analysis was performed on the clinical data of patients with POP stage III or above uterine prolapse treated at Wenzhou People's Hospital from January 2013 to December 2019. Patients were divided into two groups: USCLF group and SSLF group. The perioperative indicators, postoperative complications, pelvic organ prolapse quantification (POP-Q), Pelvic Floor Distress Inventory-20 (PFDI-20), and POP/Urinary Incontinence Sexual Questionnaire-12 (PISQ-12) scores of the groups were analyzed and compared. Results: (1) The operative time and intraoperative blood loss in the USCLF group were lower than those in the SSLF group, with statistical significance (p < 0.05). (2) The incidence of postoperative buttock pain in the SSLF group was 10.7% (6/56), higher than that in the USCLF group (0/56) (Fisher's exact test, p = 0.027). (3) At one year of follow-up, significant improvement in Aa, Ba, C, Ap, and Bp values was observed in both groups (p < 0.05). The values of the Aa and Ba sites in the USCLF group were lower than those in the SSLF group one year after surgery (p < 0.05). (4) The PFDI-20 and PISQ-12 scores of the groups one year after surgery were lower than those before surgery (p < 0.05). Conclusion: Uterosacral and cardinal ligament suture fixation leads to less bleeding and better postoperative quality of life than preoperative and may be better than SSLF at preventing the recurrence of anterior wall prolapse after surgery.

Photosynthetic compensation of non-leaf organ stems of the invasive species Sphagneticola trilobata (L.) Pruski at low temperature.

Biological invasion is a hot topic in ecological research. Most studies on the physiological mechanisms of plants focus on leaves, but few studies focus on stems. To study the tolerance of invasive plant (Sphagneticola trilobata L.) to low temperature, relevant physiological indicators (including anthocyanin and chlorophyll) in different organs (leaves and stems) were analyzed, using a native species (Sphagneticola calendulacea L.) as the control. The results showed that, upon exposure to low temperature for 15 days, the stems of two Sphagneticola species were markedly reddened, their anthocyanin content increased, chlorophyll and chlorophyll fluorescence parameters decreased, and the accumulation of reactive oxygen species in the stem increased. The percentage increases of antioxidants and total antioxidant capacities in stems were significantly higher in S. trilobata than in S. calendulacea. This showed that S. trilobata had higher cold tolerance in stems while leaves were opposite. To further verify the higher cold tolerance of the stem of S. trilobata, a defoliation experiment was designed. We found that the defoliated stem of S. trilobata reduced anthocyanin accumulation and increased chlorophyll content, while alleviating membrane lipid damage and electrical conductivity, and the defoliated stem still showed an increase in stem diameter and biomass under low temperature. The discovery of the physiological and adaptive mechanisms of the stem of S. trilobata to low temperature will provide a theoretical basis for explaining how S. trilobata maintains its annual growth in South China. This is of great significance for predicting the future spread of cloned and propagated invasive plants.

miR-218 suppresses the growth of hepatocellular carcinoma by inhibiting the expression of proto-oncogene Bmi-1.

PURPOSE: To identify microRNAs (miRNAs) directly regulating the proto-oncogene Bmi-1 expression in the development of hepatocellular carcinoma (HCC) and to explore the underlying molecular mechanisms. METHODS: Four HCC cell lines, including HepG2, Bel7404, Huh7, and PLC5, the normal hepatocellular cell line MIHA, and 30 HCC biopsies were included in this study. Potential miRNAs, which interact with Bmi-1 and are involved in the development of HCC were identified through bioinformatic analyses. The expression of miRNA and Bmi-1 in HCC cell lines and HCC tissues was analyzed using fluorescence protein analysis, real-time quantitative PCR (RT-qPCR), and Western blotting. RESULTS: Bioinformatic analysis suggested that miR-218 is a potential miRNA regulating Bmi-1 expression. Fluorescence protein analysis, RT-qPCR, and Western blotting confirmed the direct interaction between miR-218 and Bmi-1. In addition, increased expression of Bmi-1 was detected in HCC cell lines and HCC tissues. In most HCC tissues, the expression of miR-218 was decreased and was associated with increased expression of Bmi-1. CONCLUSION: miR-p218 downregulates the expression of the proto-oncogene Bmi-1 in HCC, and it may be an effective target for the treatment of this disease.

[Effects of Bushen Wenyang Huayu Recipe on Expressions of HIF-1α, PHD2, and VHL in Endometriosis Rats with Shen Yang Deficiency Blood Stasis Syndrome].

OBJECTIVE: To observe the effect of Bushen Wenyang Huayu Recipe (BWHR) on hypoxia inducible factor-1α (HIF-1α), proline hydroxylase2 (PHD2), von Hippel Lindau disease (VHL) suppressor gene expressions in endometriosis (EM) rats with Shen yang deficiency blood stasis syndrome (SYDBSS), and to explore the pathogenesis of EM and the mechanism of BWHR for treating EM. METHODS: Totally 50 SD rats were randomly divided into five groups, i.e., the blank control group, the sham-operation group, the model group, the Chinese medicine (CM) group, and the Western medicine (WM) group, 10 in each group. Rats in the blank control group and the sham-operation group were fed routinely. Rats in the rest 3 groups received 30-day "extended refrigerator freezing and ice water immersion" and combined with " autotransplantation" to establish EM rat model with SYDBSS. One Milliliter BWHR at 3.33 g/mL was administered to rats in the CM group by gastrogavage. Gestrinone at the daily dose of 0. 5 mg/kg was administered to rats in the WM group by gastrogavage. Equal volume of normal saline was administered to rats in the model group, the blank control group, and the sham-operation group. The size and morphology of ectopic foci in rats were observed after 4 weeks of medication. Expressions of serum CA125, plasma cyclic adenosine monophosphate (cAMP), and plasma cyclic guanosine monophosphate (cGMP) were detected by radioimmunoassay. Morphological changes of eutopic endometrium and ectopic tissue were observed under the optical microscope by HE staining. Protein expressions and contents of HIF-lα, PHD2, and VHL were detected by immunohistochemical SABC method and Western blot. mRNA expressions of HIF-1α, PHD2, and VHL were detected by RT-PCR. RESULTS: The ectopic foci grew significantly in the model group. Their volumes were obviously contracted after treated by CM and WM. Compared with the blank control group and the sham-operation group, serum CA125 and plasma cGMP obviously increased, cAMP obviously decreased (P < 0.05); expressions and contents of HIF-1α mRNA and protein all decreased (P < 0.05); mRNA and protein expressions and contents of PHD2 and VHL all decreased in the model group (P < 0.05). Compared with model group, levels of CA125 and cGMP obviously decreased; cAMP levels obviously increased, expressions and contents of HIF-1α mRNA and protein all increased, mRNA and protein expressions and contents of PHD2 and VHL all increased in the WM group and the CM group (P < 0.05). Compared with the CM group, PHD2 protein contents were higher in the WM group (P < 0.05). HIF-1α was negatively correlated with PHD2 (r = -0.799, P = 0.00). HIF-1α was negatively correlated with VHL (r = -0. 625, P = 0.003). CONCLUSIONS: BWHR could effectively treat EM. Its mechanism might be associated with reducing contents of HIF-1α, serum CA125, and plasma cGMP, and up-regulating expressions of PHD2, VHL, and cAMP.

Association between admission pan-immune-inflammation value and short-term mortality in septic patients: a retrospective cohort study.

Pan-Immune-Inflammation Value (PIV) has recently received more attention as a novel indicator of inflammation. We aimed to evaluate the association between PIV and prognosis in septic patients. Data were extracted from the Medical Information Mart for Intensive Care IV database. The primary and secondary outcomes were 28-day and 90-day mortality. The association between PIV and outcomes was assessed by Kaplan-Meier curves, Cox regression analysis, restricted cubic spline curves and subgroup analysis. A total of 11,331 septic patients were included. Kaplan-Meier curves showed that septic patients with higher PIV had lower 28-day survival rate. In multivariable Cox regression analysis, log2-PIV was positively associated with the risk of 28-day mortality [HR (95% CI) 1.06 (1.03, 1.09), P < 0.001]. The relationship between log2-PIV and 28-day mortality was non-linear with a predicted inflection point at 8. To the right of the inflection point, high log2-PIV was associated with an increased 28-day mortality risk [HR (95% CI) 1.13 (1.09, 1.18), P < 0.001]. However, to the left of this point, this association was non-significant [HR (95% CI) 1.01 (0.94, 1.08), P = 0.791]. Similar results were found for 90-day mortality. Our study showed a non-linear relationship between PIV and 28-day and 90-day mortality risk in septic patients.

Lysyl oxidase and hypoxia-inducible factor 1α: biomarkers of gastric cancer.

BACKGROUND: Gastric cancer (GC) is one of the main causes of cancer mortality worldwide. Recent studies on tumor microenvironments have shown that tumor metabolism exerts a vital role in cancer progression. AIM: To investigate whether lysyl oxidase (LOX) and hypoxia-inducible factor 1α (HIF1α) are prognostic and predictive biomarkers in GC. METHODS: A total of 80 tissue and blood samples were collected from 140 patients admitted to our hospital between August 2008 and March 2012. Immunohistochemical staining was performed to measure the expression of LOX and HIF1α in tumor and adjacent tissues collected from patients with GC. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis was used to detect the mRNA expression levels of LOX and HIF1α in patients with GC. In addition, single-factor analysis was applied to analyze the relationship between LOX, HIF1α and prognosis of GC. RESULTS: Immunohistochemical staining suggested that the expression levels of LOX and HIF1α increased in tumor tissues from patients with GC. QRT-PCR analysis indicated that mRNA expression of LOX and HIF1α was also upregulated in tumor tissues, which was in accordance with the above results. We also detected expression of these two genes in blood samples. The expression level of LOX and HIF1α was higher in patients with GC than in healthy controls. Additional analysis showed that the expression level of LOX and HIF1α was related to the clinicopathological characteristics of GC. Expression of LOX and HIF1α increased with the number of lymph node metastases , deeper infiltration depth and later tumor-node-metastasis stages. Single-factor analysis showed that high expression of LOX and HIF1α led to poor prognosis of patients with GC. CONCLUSION: LOX and HIF1α can be used as prognostic and predictive biomarkers for GC.

Clinical efficacy of pelvic autologous tissue reconstruction in treating pelvic organ prolapse in 36 patients.

This study aims to search for a new, economic, convenient, and low recurrence rate operation for the surgical management of pelvic organ prolapse (POP). The clinical value of the operation for treating POP was determined through retrospective case series. The new operation was called, pelvic autologous tissue reconstruction.Women with symptomatic uterine prolapse, who required surgery, were recruited. A total of 97 women [stage III to IV, according to POP quantification (POP-Q) staging] were collected from January 2010 to December 2016. Among these women, 61 women underwent a traditional operation (TO, vaginal hysterectomy and vaginal anterior and posterior wall repair), while the remaining women underwent pelvic autologous tissue reconstruction.First, there was no statistically significant difference in intraoperative blood loss, indwelling urethral catheter time, in-hospital time, and the time of passage of gas through the anus between the pelvic autologous reconstruction (PAR) and TO groups (P > .05). The average operation time in the PAR group was significantly longer than that in the TO group (P < .05). Second, ultrasonic parameters before and after the operation between the 2 groups were compared. The postoperative rotation angle of the urethra (UR), posterior vesicourethral angle (PVA), and bladder neck descent (BND) significantly decreased in the PAR group (P < .05). There was no statistically significant difference in UR between before and 12 months after surgery in the TO group (P > .05). Furthermore, BND increased in the TO group at 12 months after the operation, compared with that at 3 months after the operation (P < .05). There was no significant difference in PVA and UR before the surgery and at 3 and 12 months after the surgery between the 2 groups (P > .05). In addition, BND was significantly smaller in the PAR group than in the TO group at 3 and 12 months after the surgery (P < .05). Third, there was no statistically significant difference in PFIQ-7 and PISG-12 in both groups after surgery.The stability of the pelvic floor structure was better in the PAR group than in the TO group. Furthermore, PAR is better for preventing the occurrence of pelvic floor prolapse and stress urinary incontinence after surgery.

Knockdown of IRF3 inhibits extracellular matrix expression in keloid fibroblasts.

Keloid is a pathologic fibro-proliferative disorder and is characterized by hyper-proliferation of fibroblasts and excess extracellular matrix (ECM) deposition. Interferon regulatory factor 3 (IRF3) is a member of the interferon-regulatory factor (IRF) family and has been shown to play a critical modulator in the progression of fibrosis. However, the function of IRF3 in dermal fibrosis remains unclear. Thus, in this study, we investigated the effects of IRF3 on keloid-derived fibroblasts (KFs) proliferation and ECM expression, and explored the underlying mechanism. Our results indicated that the expression of IRF3 was highly expressed in human keloid tissues. Down-regulation of IRF3 significantly inhibited KF proliferation and the expression of type I collagen and α-smooth muscle actin (α-SMA), as well as suppressed the expression of TGF-ß receptor I and II in TGF-ß1-stimulated KFs. Furthermore, down-regulation of IRF3 suppressed the phosphorylation levels of Smad2 and Smad3 in human KFs induced by TGF-ß1. Taken together, our data showed that down-regulation of IRF3 inhibited the proliferation and ECM expression in KFs via suppressing the TGF-ß1/Smad signaling pathway. Thus, our findings suggest that IRF3 may represent a promising target for treatment of the keloid disease.

Effects of Gui Zhu Yi Kun formula on the P53/AMPK pathway of autophagy in granulosa cells of rats with polycystic ovary syndrome.

The aim of the present study was to investigate the molecular mechanism associated with the traditional Chinese medicine formula Gui Zhu Yi Kun formula (GZYKF), in the treatment of polycystic ovary syndrome (PCOS). In this study, granulosa cells (GCs) of rats with PCOS were cultured and treated with testosterone propionate (TP) alone or with serum from rats treated with different doses of GZYKF. The effect of TP on cell growth was assayed using the MTT method. Expression levels of Beclin-1, light chain (LC)3, mechanistic target of rapamycin (mTOR), tumor suppressor p53 (p53), adenosine monophosphate-activated protein kinase (AMPK), sestrin2 and tuberous sclerosis protein 1/2 were evaluated using quantitative polymerase chain reaction and western blotting. It was demonstrated that TP increased the expression of Beclin-1 and LC3, whereas GZYKF significantly decreased the TP-induced expression of Beclin-1 (P<0.01). Additionally, GCs treated with GZYKF exhibited significant increases in mTOR, phosphorylated mTOR and AMPKα expression levels, and significant reductions in p53 and sestrin2 expression levels were observed. In conclusion, the findings of the present study suggest that a reduction in ovarian GCs in rats with PCOS may be associated with GC autophagy. Furthermore, the effects of GZYKF in mediating the p53/AMPK pathway may inhibit GC autophagy, which suggests a possible novel mechanism underlying the treatment of PCOS with GZYKF.

[Expression of Rictor and mTOR in colorectal cancer and their clinical significance].

OBJECTIVE: To explore the expression of Rictor and mTOR in the colorectal cancer and their clinical significance. METHODS: The expression levels of Rictor and mTOR in HCT116, SW480, LoVo and HCoEpiC cells were detected by indirect immunofluorescence and Western blotting. Sixty-two paraffin-embedded surgical specimens of colorectal cancer tissue and adjacent tissues were examined for Rictor expression using immunohistochemistry. The association of the expression levels of Rictor protein with the clinicopathologic features and the overall survival of the patients was analyzed. RESULTS: The expression level of Rictor was significantly higher in colorectal cancer tissues than in the adjacent tissues (P<0.05). The expression levels of Rictor and mTOR in the colon cancer cell lines were higher than those in human normal colon epithelial cell line HCoEpiC. The expression of Rictor was correlated with Dukes stage and lymphatic metastasis of the tumors but not with other clinicopathological parameter (P>0.05). Patients with Rictor expression had a lower overall survival rate than those without Rictor expression. CONCLUSION: Rictor overexpression is associated with the carcinogenesis and progression of colorectal cancer and can be an independent indicator for evaluating the prognosis of colorectal cancer patients.

Gap junction composed of connexin43 modulates 5­fluorouracil, oxaliplatin and irinotecan resistance on colorectal cancers.

Chemotherapy is one of the most commonly used therapeutic strategies for metastatic colon cancer. However, the development of resistance to chemotherapeutic agents limits their application in clinical use. The underlying mechanisms of this resistance development require further elucidation. The current study investigated the effects of connexin43 (Cx43) gap junctions on 5­fluorouracil (5­FU), oxaliplatin and irinotecan in colon cancer cells. Three different methods were used to manipulate Cx43 gap junction function: i) Cell culture at different densities; ii) pretreatment with a Cx43 specific inhibitor or enhancer; and iii) Cx43 gene knock­down. Results indicated that the cell toxicity of 5­FU, oxaliplatin and irinotecan was cell density­dependent, which was mediated by gap junctions. Downregulation of Cx43 gap junction functioning attenuated 5­FU, oxaliplatin and irinotecan toxicity in colon cancer cells, which was increased in cells treated with a Cx43 gap junction function enhancer. Thus, the results of the present study suggest that resistance to 5­FU, oxaliplatin and irinotecan in colon cancer cells was relative to Cx43 expression loss as cancer developed, which may indicate a novel basis for therapeutic strategy development to combat drug resistance in numerous cell types, in addition to colon cancer cells.