[Efficacy and safety of different nerve block methods for the treatment of pudendal neuralgia].

Objective: To identify efficacy and safety of pudendal nerve block in tubing through the third posterior sacral foramen for the treatment of pudendal neuralgia (PN). Methods: A retrospective study with 222 PN patients was conducted in the Department of Pain Management of Beijing Tsinghua Changgung Hospital from January 2020 to April 2023. These patients were divided into two groups based on their treatment methods: pudendal nerve block in tubing through the third posterior sacral foramen (observation group, n=101) and ultrasound-guided pudendal nerve block (control group, n=121). Primary outcome measure was the 90-day postoperative pain relief rate. Secondary outcome measures included visual analog scale (VAS) at 1, 7, 14, 30 and 90 d after surgery, the incidence of tramadol uses after surgery, postoperative self-rating anxiety scale (SAS) scores and the incidence of adverse events. Factors that influenced pain relief within 90 days after surgery were analyzed by using binary logistic regression analysis. Results: Observation group included 34 males and 67 females, aged (49.8±16.0) years old. Control group included 38 males and 83 females, aged (43.7±14.0) years old. The 90-day postoperative pain relief rate of the observation group patients was 38.6% (39/101), which was higher than the 24.0% (29/121) of the control group patients (P=0.018). Both the observation group and the control group showed an interaction effect of time and group after treatment for VAS scores (both P<0.05). In intra-group comparison, the VAS scores at 1, 7, 14, 30 and 90 d after treatment in both groups were lower than those before treatment (all P<0.05). In inter-group comparison, the differences of the VAS scores were not statistically significant in the observation group compared with those in the control group at 1, 7, 14, 30 and 90 d after surgery (all P>0.05). The SAS score of the observation group at 90 d after surgery was 51.5±6.2, which was lower than the 53.4±5.8 of the control group (P=0.022). There was no statistically significant difference in the incidence of postoperative tramadol uses and adverse events between the two groups (both P>0.05). Pudendal nerve block in tubing through the third posterior sacral foramen was a protective factor for pain postoperative relief in PN patients at 90 d after surgery (OR=1.92, 95%CI: 1.05-3.48, P=0.033). Conclusion: Pudendal nerve block in tubing through the third posterior sacral foramen is a safe and effective minimally invasive treatment. It has a higher postoperative pain relief rate within 90 d after surgery, without increasing the uses of postoperative rescue analgesics and the incidence of adverse events.

MiR-650 inhibits the progression of glioma by targeting FAM83F.

OBJECTIVE: The aim of this study was to explore whether miR-650 could inhibit the proliferation of glioma by regulating FAM83F and to investigate the specific role of miR-650 in glioma occurrence. PATIENTS AND METHODS: The expression of FAM83F in tumor or para-cancerous tissues of 24 glioma patients was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Meanwhile, FAM83F expression in 6 glioma cell lines (LN229, U87, U251, LN308, SNB19 and H4) was also detected. Subsequently, the proliferation of glioma cells transfected with miR-650 mimics was evaluated by cell counting kit-8 (CCK-8) and EDU (5-ethynyl-2'-deoxyuridine) assay, respectively. In addition, Luciferase reporter gene assay and rescue experiment were applied to verify the relationship between miR-650 and FAM83F. RESULTS: MiR-650 expression in glioma tissues was significantly decreased, while the expression of FAM83F was remarkably upregulated. This indicated that the level of miR-650 was negatively correlated with that of FAM83F. Similar results were obtained in glioma cells. We then transfected miR-650 mimics into LN229 and U251 cells, and found that the expression of miR-650 was significantly upregulated. Meanwhile, the viability of cells significantly decreased. In addition, the interaction between miR-650 and FAM83F was verified by Luciferase reporter gene assay. Rescue experiments showed that miR-650 could inhibit cell proliferation by targeting FAM83F. CONCLUSIONS: MiR-650 was lowly expressed in glioma tissues, which could promote cell proliferation through up-regulating the expression of FAM83F.

[Efficacy of staging surgery in pulmonary atresia with intact ventricular septum].

Objective: To assess the feasibility and efficacy of a staged invasive treatment strategy for the treatment of pulmonary atresia with intact ventricular septum, in the first stage using a catheter-based stent placement, second-stage surgery, and three-stage atrial septal occlusion. Methods: Totally 19 children with pulmonary atresia with intact ventricular septum were enrolled at Department of Cardiovascular Surgery, the Children's Hospital of Zhejiang University School of Medicine from January 2009 to December 2017, including 11 male and 8 female patients. The age was (13.8±7.7) days (ranging from 3 to 35 days). The weight was (3.4±0.5) kg (ranging from 2.8 to 4.1 kg). Among them, there were 13 cases of type Ⅱ and 6 cases of type Ⅲ. Regular follow-up visits for patients with stage Ⅰ arterial duct stenting after 1, 3, and 6 months; and routine follow-ups for 1, 3, and 6 months after stage Ⅱ surgery.The t test was used to compare the oxygen saturation between pre-operation and post-operation. Results: All 19 patients underwent arterial catheterization. The preoperative peripheral oxygen saturation was (64.4±5.3)%, while increased to (86.0±3.0)% after operation (t=16.353, P=0.000). One patient died during follow-up and 2 patients lost follow-up. One patient received stent balloon dilatation due to oxygen saturation decrease.Twelve patients completed the second-stage surgery and 1 case died after surgery. The rest were alive, including 2 cases of double-ventricular correction and 9 cases of semi-ventricular treatment in one room; 2 cases had completed three-stage atrial septal occlusion. Conclusions: Stage Ⅰ arterial duct stent, stage Ⅱ surgery, and stage Ⅲ atrial septal occlusion to treat pulmonary atresia with intact ventricular septum in children is feasible and effective. The method can be used as the important treatment direction for pulmonary atresia with intact ventricular septum.

Tacrolimus protects vascular endothelial cells from injuries caused by Ox-LDL by regulating endoplasmic reticulum stress.

OBJECTIVE: To study the protective effect of tacrolimus on endothelial cells under the action of oxidized low-density lipoprotein (Ox-LDL), and to explore the mechanism of tacrolimus in protecting endothelial cells. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVEC) were used and they were divided into the blank group, tacrolimus group, ox-LDL injury group, and tacrolimus + ox-LDL (tacrolimus treatment) group, for treatment. The cell viability was detected via methyl thiazolyl tetrazolium (MTT) assay; the cytotoxic response was detected via lactate dehydrogenase (LDH) release assay, and the proportion of apoptotic cells was detected via flow cytometry. Moreover, the releases of superoxide dismutase (SOD), reactive oxygen species (ROS), were detected, and the expression levels of apoptosis-related molecules, and the endoplasmic reticulum stress (ERS)-related molecules were detected via polymerase chain reaction (PCR) and Western blotting. RESULTS: Ox-LDL could significantly reduce the viability of endothelial cells, increase the cytotoxicity and induce the apoptosis, while tacrolimus could effectively reduce such a toxic effect in a dose-dependent manner (p<0.05). Also, tacrolimus could significantly reduce the oxidative stress response of cells caused by ox-LDL and the expressions of ERS-related proteins, and protect the cells from oxidative stress injury (p<0.05). CONCLUSIONS: Tacrolimus regulates ERS of endothelial cells to reduce ox-LDL-induced injuries.

Redox control of ß2-glycoprotein I-von Willebrand factor interaction by thioredoxin-1.

BACKGROUND: ß(2) -Glycoprotein I (ß(2) GPI) is an abundant plasma protein that is closely linked to blood clotting, as it interacts with various protein and cellular components of the coagulation system. However, the role of ß(2) GPI in thrombus formation is unknown. We have recently shown that ß(2) GPI is susceptible to reduction by the thiol oxidoreductases thioredoxin-1 and protein disulfide isomerase, and that reduction of ß(2) GPI can take place on the platelet surface. METHODS: ß(2) GPI, reduced by thioredoxin-1, was labeled with the selective sulfhydryl probe N(a)-(3-maleimidylpropionyl)biocytin and subjected to mass spectrometry to identify the specific cysteines involved in the thiol exchange reaction. Binding assays were used to examine the affinity of reduced ß(2) GPI for von Willebrand factor (VWF) and the effect of reduced ß2GPI on glycoprotein (GP)Ibα binding to VWF. Platelet adhesion to ristocetin-activated VWF was studied in the presence of reduced ß(2) GPI. RESULTS: We demonstrate that the Cys288-Cys326 disulfide in domain V of ß(2) GPI is the predominant disulfide reduced by thioredoxin-1. Reduced ß(2) GPI in vitro displays increased binding to VWF that is dependent on disulfide bond formation. ß(2) GPI reduced by thioredoxin-1, in comparison with non-reduced ß(2) GPI, leads to increased binding of GPIbα to VWF and increased platelet adhesion to activated VWF. CONCLUSIONS: Given the importance of thiol oxidoreductases in thrombus formation, we provide preliminary evidence that the thiol-dependent interaction of ß(2) GPI with VWF may contribute to the redox regulation of platelet adhesion.

In vivo modulation of angiogenesis by beta 2 glycoprotein I.

Beta 2 glycoprotein I (ß2GPI) is the major auto antigen in the antiphospholipid syndrome but also interacts with fibrinolytic and angiogenic proteins. The aim of this study was to examine the angiogenic potential of ß2GPI in vivo in ß2GPI deficient mice utilizing angiogenic assays. ß2GPI deficient mice show increased microvessel formation in comparison to ß2GPI replete controls when injected with growth factor free-matrigel implants. However, microvessel formation in matrigel plugs of ß2GPI deficient mice was less than in ß2GPI replete mice when basic fibroblast growth factor (bFGF) was included in the matrigel. Hemoglobin content was higher in vascular endothelial growth factor (VEGF) containing-matrigel plugs in the ß2GPI deficient mouse demonstrating that the lack of ß2GPI led to increased extravasation by VEGF. Melanoma B16F10 tumour growth was enhanced in ß2GPI deficient mice. Melanoma microvessel density was increased in ß2GPI deficient mice but the proliferation rate of tumour cells (determined by Ki67 immunohistochemistry) was unaffected by the presence or absence of ß2GPI. Subcutaneous delivery of native human ß2GPI by the ALZET osmotic pump did not affect melanoma tumour growth in ß2GPI deficient mice. We conclude that the in vivo unopposed action of ß2GPI is anti-angiogenic however this function is modified in the presence of a strong angiogenic stimulus into stabilization of vessel formation. Although the presence of ß2GPI attenuates vessel sprouting in certain tumours, no survival benefit is conferred to tumour bearing animals. This does not preclude the potential benefit of modified or fragments of ß2GPI in anti-angiogenesis research.

Mast cells/basophils in the peripheral blood of allergic individuals who are HIV-1 susceptible due to their surface expression of CD4 and the chemokine receptors CCR3, CCR5, and CXCR4.

A population of metachromatic cells with mast cell (MC) and basophil features was identified recently in the peripheral blood of patients with several allergic disorders. This study now shows that these metachromatic cells express on their surface the high-affinity IgE receptor (FcepsilonRI), CD4, and the chemokine receptors CCR3, CCR5, and CXCR4, but not the T-cell surface protein CD3 and the monocyte/macrophage surface protein CD68. This population of MCs/basophils can be maintained ex vivo for at least 2 weeks, and a comparable population of cells can be generated in vitro from nongranulated hematopoietic CD3(-)/CD4(+)/CD117(-) progenitors. Both populations of MCs/basophils are susceptible to an M-tropic strain of human immunodeficiency virus 1 (HIV-1). Finally, many patients with acquired immunodeficiency syndrome have HIV-1-infected MCs/basophils in their peripheral blood. Although it is well known that HIV-1 can infect CD4(+) T cells and monocytes, this finding is the first example of a human MC or basophil shown to be susceptible to the retrovirus. (Blood. 2001;97:3484-3490)

Genetic influences on type I collagen synthesis and degradation: further evidence for genetic regulation of bone turnover.

Circulating osteocalcin, a marker of bone formation, is under strong genetic influence, and this effect is related to the genetic influence on bone density. To examine genetic influences on bone turnover further, other markers of bone formation (serum carboxyterminal propeptide of type I procollagen, PICP), bone resorption (serum pyridinoline cross-linked carboxyterminal telopeptide of type I collagen, ICTP), and nonosseous connective tissue synthesis (serum aminoterminal propeptide of type III procollagen, PIIINP) were studied in 82 female twin pairs: 42 monozygotic (MZ) and 40 dizygotic (DZ) twin pairs (mean age, MZ; 48.4 yr; DZ; 45.6 yr). The intraclass correlation coefficients of MZ twin pairs, rMZ, for serum PICP (0.78) and serum ICTP (0.68) were significantly greater than the corresponding rDZ (0.31 and 0.36, respectively), but a genetic effect on serum PIIINP was not demonstrable. Within DZ twin pair differences in serum PICP predicted differences in lumbar spine bone density (r = -0.37); higher serum PICP levels indicating the twin with the lower lumbar spine bone density. Also within pair differences in serum ICTP and PICP predicted differences in bone density at the lumbar spine independent of serum osteocalcin. These data indicate that both synthesis and degradation of type I collagen are genetically determined and that this phenomenon is related to the genetic regulation of bone density.

Prediction of bone density from vitamin D receptor alleles.

Bone density achieved in early adulthood is the major determinant of risk of osteoporotic fracture. Up to 60% of women suffer osteoporotic fractures as a result of low bone density, which is under strong genetic control acting through effects on bone turnover. Here we show that common allelic variants in the gene encoding the vitamin D receptor can be used to predict differences in bone density, accounting for up to 75% of the total genetic effect on bone density in healthy individuals. The genotype associated with lower bone density was overrepresented in postmenopausal women with bone densities more than 2 standard deviations below values in young normal women. The molecular mechanisms by which bone density is regulated by the vitamin D receptor gene are not certain, although allelic differences in the 3' untranslated region may alter messenger RNA levels. These findings could open new avenues to the development and targeting of prophylactic interventions. It follows that other pathophysiological processes considered to be subject to complex multifactorial genetic regulation may also be modulated by a single gene with pleiotropic transcriptional actions.