HNRNPC mediates lymphatic metastasis of cervical cancer through m6A-dependent alternative splicing of FOXM1.

Cervical cancer (CCa) patients with lymph node (LN) metastasis face poor prognoses and have limited treatment options. Aberrant N6-methyladenosine (m6A) modification of RNAs are known to promote tumor metastasis, but their role in CCa remains unclear. Our study reveals that HNRNPC, an alternative splicing (AS) factor and m6A reader, increases tumor-related variants through m6A-dependent manner, thereby promoting lymphatic metastasis in CCa. We found that HNRNPC overexpression correlates with lymphatic metastasis and poorer prognoses in CCa patients. Functionally, knocking down HNRNPC markedly inhibited the migration and invasion of several CCa cell lines, while supplementing HNRNPC restored the malignant phenotypes of these cells. Mechanistically, HNRNPC regulates exon skipping of FOXM1 by binding to its m6A-modified motif. Mutating the m6A site on FOXM1 weakened the interaction between HNRNPC and FOXM1 pre-RNA, leading to a reduction in the metastasis-related FOXM1-S variant. In conclusion, our findings demonstrate that m6A-dependent alternative splicing mediated by HNRNPC is essential for lymphatic metastasis in CCa, potentially providing novel clinical markers and therapeutic strategies for patients with advanced CCa.

HTR1B regulates mitochondrial homeostasis and mitophagy by activating the ERK/ MAPK signalling pathway during human embryonic arrest.

Background: Previous studies have shown that serotonin and its receptors are widely distributed in mammalian reproductive tisssues and play an important role in embryonic development. However, the specific effects of the serotonergic system on embryonic arrest (EA) and the underlying mechanism require further investigation. Methods: Chorionic villi were collected from patients with EA and healthy pregnant women. Western blotting (WB) and immunohistochemistry (IHC) were used to detect serotonin receptor 1B (HTR1B) levels and evaluate mitochondrial function. Additionally, HTR-8/SVneo cells were transfected with an HTR1B overexpression plasmid. Quantitative real-time polymerase chain reaction(qRT-PCR), Cell Counting Kit-8 (CCK-8), and wound healing assays were utilized to evaluate mitophagy level, cell proliferation and cell migration, respectively. Results: We discovered elevated HTR1B levels in the chorionic villi of the patients with EA compared to controls. Concurrently, we observed enhanced levels of nucleus-encoded proteins including mitofilin, succinate dehydrogenase complex subunit A (SDHA), and cytochrome c oxidase subunit 4 (COXIV), along with the mitochondrial fusion protein optic atrophy 1(OPA1), fission proteins mitochondrial fission protein 1(FIS1) and mitochondrial fission factor (MFF) in the EA group. Additionally, there was an excessive mitophagy levels in EA group. Furthermore, a notable activation of mitogen-activated protein kinase (MAPK) signaling pathway proteins including extracellular regulating kinase (ERK), c-Jun N-terminal kinase (JNK), and P38 was observed in the EA group. By overexpressing HTR1B in HTR-8/SVneo cells, we observed a significant reduction in cell proliferation and migration. HTR1B overexpression also caused an increase in levels of SDHA and FIS1, as well as an upregulation of mitophagy. Notably, the ERK inhibitor U0126 effectively mitigated these effects. Conclusion: These findings show that HTR1B influences mitochondrial homeostasis, promoting excessive mitophagy and impairing cell proliferation and migration by activating the MAPK signalling pathway during post-implantation EA. Therefore, HTR1B may serve as a potential therapeutic target for patients with EA.

Predicting tall-cell subtype of papillary thyroid carcinomas independently with preoperative multimodal ultrasound.

OBJECTIVES: This study aimed to explore the differences between tall-cell subtype of papillary thyroid carcinoma (TCPTC) and classical papillary thyroid carcinoma (cPTC) using multimodal ultrasound, and identify independent risk factors for TCPTC to compensate the deficiency of preoperative cytological and molecular diagnosis on PTC subtypes. METHODS: Forty-six TCPTC patients and 92 cPTC patients were included. Each patient received grey-scale ultrasound, colour Dopplor flow imaging (CDFI) and shear-wave elastography (SWE) preoperatively. Clinicopathologic information, grey-scale ultrasound features, CDFI features and SWE features of 98 lesions were compared using univariate analysis to find out predictors of TCPTC, based on which, a predictive model was built to differentiate TCPTC from cPTC and validated with 40 patients. RESULTS: Univariate and multivariate analyses identified that extra-thyroidal extension (odds ratio [OR], 15.12; 95% CI, 2.26-115.44), aspect ratio (≥0.91) (OR, 29.34; 95% CI, 1.29-26.23), and maximum diameter ≥14.6 mm (OR, 20.79; 95% CI, 3.87-111.47) were the independent risk factors for TCPTC. Logistic regression equation: P = 1/1+ExpΣ[-5.099 + 3.004 × (if size ≥14.6 mm) + 2.957 × (if aspect ratio ≥ 0.91) + 2.819 × (if extra-thyroidal extension). The prediction model had a good discrimination performance for TCPTC: the area under the receiver-operator-characteristic curve, sensitivity, and specificity were 0.928, 0.848, and 0.954 in cohort 1, and the corresponding values in cohort 2 were 0.943, 0.923, and 0.926, respectively. CONCLUSION: Ultrasound has the potential for differential diagnosis of TCPTC from cPTC. A prediction model based on ultrasound characteristics (extra-thyroidal extension, aspect ratio ≥0.91, and maximum diameter ≥14.6 mm) was useful in predicting TCPTC. ADVANCES IN KNOWLEDGE: Multimodal ultrasound prediction of TCPTC was a supplement to preoperative cytological diagnosis and molecular diagnosis of PTC subtypes.

Structurally diverse phthalides from fibrous roots of Ligusticum chuanxiong Hort. and their biological activities.

Falonolide A (1) and B (2), two novel polyyne hybrid phthalides resulting from unprecedented carbon skeleton polymerized by Z-ligustilide and falcarindiol, along with six new related phthalides (3-8), were isolated from Ligusticum chuanxiong Hort. Their structures were elucidated by spectroscopic analysis, computer-assisted structure elucidation (CASE) analysis, DP4+ probability analysis and electronic circular dichroism (ECD) calculations. A plausible biosynthetic pathway for 1-8 was proposed, and the production mechanism of 2 was revealed by density functional theory (DFT) method. Compounds 4 and 6 exhibited significant vasodilatory activity with EC50 of 8.00 ± 0.86 and 6.92 ± 1.02 µM, respectively. Compound 4 also displayed significant inhibitory effect of NO production with EC50 value of 8.82 ± 0.30 µM. Based on the established compounds library, structure-activity relationship analysis of phthalides was explored to provide insights into the drug development of vasodilators and anti-flammatory.

Ganoderma lucidum-Derived Meroterpenoids Show Anti-Inflammatory Activity In Vitro.

Ganoderma lucidum, known as the "herb of spiritual potency", is used for the treatment and prevention of various diseases, but the responsible constituents for its therapeutic effects are largely unknown. For the purpose of obtaining insight into the chemical and biological profiling of meroterpenoids in G. lucidum, various chromatographic approaches were utilized for the title fungus. As a result, six undescribed meroterpenoids, chizhienes A-F (1-6), containing two pairs of enantiomers (4 and 5), were isolated. Their structures were identified using spectroscopic and computational methods. In addition, the anti-inflammatory activities of all the isolates were evaluated by Western blot analysis in LPS-induced macrophage cells (RAW264.7), showing that 1 and 3 could dose dependently inhibit iNOS but not COX-2 expression. Further, 1 and 3 were found to inhibit nitric oxide (NO) production using the Greiss reagent test. The current study will aid in enriching the structural and biological diversity of Ganoderma-derived meroterpenoids.

Minor ergosteroids and a 19-nor labdane-type diterpenoid with anti-inflammatory effects from Ganoderma lucidum.

A chemical investigation on the fruiting bodies of Ganoderma lucidum led to the isolation and identification of five undescribed ergosteroids including two des-D-steroids (3 and 4) and one rare 6/6/7/5-fused carbon skeletal ergosterol (5) along with one 19-nor labdane-type diterpenoid (6). Their structures including their absolute configurations, were assigned by spectroscopic methods, ECD calculations, and X-ray diffraction analysis. In addition, the anti-inflammatory activities of all the isolates were evaluated. The results indicated that compound 1 can significantly down-regulate the protein expression of iNOS and COX-2 at 20 µM in LPS- stimulated RAW264.7 cells.

Observation of the therapeutic effect of Tongyuan needling combined with jingyu herb-separated moxibustion on recurrent implantation failure of kidney deficiency and blood stasis. / "é€šå ƒé’ˆæ³•"联合精玉药灸治疗肾虚血瘀型反复种植失败疗效观察.

OBJECTIVES: To observe the therapeutic effect of Tongyuan needling combined with jingyu herb-separated moxibustion on the patients with recurrent implantation failure (RIF) of kidney deficiency and blood stasis undergoing frozen embryo transfer of the conventional hormone replacement therapy cycle. METHODS: Sixty RIF of kidney deficiency and blood stasis patients who planned for frozen embryo transfer were randomly divided into a combined treatment group (30 cases) and a western medication group (30 cases). In the western medication group, the conventional hormone replacement therapy was performed for endometrial preparation during transfer cycle. On the basis of treatment as the western medication group, in the combined treatment group, Tongyuan needling combined with jingyu herb-separated moxibustion was adopted. Regarding tongyuan needling, the acupoint prescription for Tongdu Tiaoshen (promoting the governor vessel and regulating the spirit, e.g. Dazhui [GV 14], Ganshu [BL 18], Shenshu [BL 23] and back-shu points) and that for Yinqi Guiguan (conducting qi back to the primary, e.g. Zhongwan [CV 12], Qihai [CV 6], Guanyuan [CV 4] and front-mu points) were selected. Acupuncture was delivered at these two prescriptions alternatively each time. After acupuncture, the herb-separated moxibustion (in which, the herbal powder was prepared with the modified Yangjing Zhongyu decoction for cultivating the kidney essence and promoting pregnancy) was operated at Shenque (CV 8). This combined therapy was delivered once every two days, 3 sessions a week till the day of embryo transfer. The pregnancy outcomes (positive rate of human chorionic gonadotropin [ß-HCG] and clinical pregnancy rate) were compared between the two groups, as well as the TCM syndrome score, serum estradiol (E2) and progesterone (P) levels, endometrial thickness and type, endometrial blood flow index (pulsatility index [PI], resistance index [RI]) before and after treatment. RESULTS: After treatment, the clinical pregnancy rate of the combined treatment group was 40.0% (12/30), higher than that of the western medication group (16.7%, 5/30, P<0.05); and the difference in the positive rate of ß-HCG was not significant statistically between the two groups (P>0.05). After treatment, the serum levels of E2 and P were elevated (P<0.05), the endometrial thickness was thickened (P<0.05); the scores of TCM syndrome, and the levels of PI and RI were reduced (P<0.05) when compared with those before treatment in the two groups. The proportion of type A endometrium increased compared with that before treatment in the combined treatment group (P<0.05). Except the levels of E2 and P, the above indexes in the combined treatment group were superior to the western medication group (P<0.05). CONCLUSIONS: On the basis of frozen embryo transfer of conventional hormone replacement cycle, the intervention of Tongyuan needling combined with jingyu herb-separated moxibustion can effectively relieve the clinical symptoms, increase the endometrial blood flow and its thickness, and improve the endometrial receptivity, thereby ameliorate pregnancy outcomes in RIF patients of kidney deficiency and blood stasis.

Six new diterpenoids from the resins of Populus euphratica and their anti-inflammatory activities.

Six new diterpenoids, identified as two abietane derivatives, euphraticanoids J and K (1 and 2), two pimarane derivatives, euphraticanoids L and M (3 and 4), and two 9,10-seco-abietane derivatives, euphraticanoids N and O (5 and 6) were isolated from Populus euphratica resins. Their structures including absolute configurations were characterized using spectroscopic, quantum chemical NMR, and ECD calculation methods. The anti-inflammatory activity of the compounds was tested and the results revealed that compounds 4 and 6 inhibited the production of iNOS and COX-2 in a dose-dependent manner in lipopolysaccharide (LPS)-induced RAW 264.7 cells.

A multiparametric clinic-ultrasomics nomogram for predicting extremity soft-tissue tumor malignancy: a combined retrospective and prospective bicentric study.

OBJECTIVE: We aimed at building and testing a multiparametric clinic-ultrasomics nomogram for prediction of malignant extremity soft-tissue tumors (ESTTs). MATERIALS AND METHODS: This combined retrospective and prospective bicentric study assessed the performance of the multiparametric clinic-ultrasomics nomogram to predict the malignancy of ESTTs, when compared with a conventional clinic-radiologic nomogram. A dataset of grayscale ultrasound (US), color Doppler flow imaging (CDFI), and elastography images for 209 ESTTs were retrospectively enrolled from one hospital, and divided into the training and validation cohorts. A multiparametric ultrasomics signature was built based on multimodal ultrasomic features extracted from the grayscale US, CDFI, and elastography images of ESTTs in the training cohort. Another conventional radiologic score was built based on multimodal US features as interpreted by two experienced radiologists. Two nomograms that integrated clinical risk factors and the multiparameter ultrasomics signature or conventional radiologic score were respectively developed. Performance of the two nomograms was validated in the retrospective validation cohort, and tested in a prospective dataset of 51 ESTTs from the second hospital. RESULTS: The multiparametric ultrasomics signature was built based on seven grayscale ultrasomic features, three CDFI ultrasomic features, and one elastography ultrasomic feature. The conventional radiologic score was built based on five multimodal US characteristics. Predictive performance of the multiparametric clinic-ultrasomics nomogram was superior to that of the conventional clinic-radiologic nomogram in the training (area under the receiver operating characteristic curve [AUC] 0.970 vs. 0.890, p = 0.006), validation (AUC: 0.946 vs. 0.828, p = 0.047) and test (AUC: 0.934 vs. 0.842, p = 0.040) cohorts, respectively. Decision curve analysis of combined training, validation and test cohorts revealed that the multiparametric clinic-ultrasomics nomogram had a higher overall net benefit than the conventional clinic-radiologic model. CONCLUSION: The multiparametric clinic-ultrasomics nomogram can accurately predict the malignancy of ESTTs.

Predicting malignancy in thyroid nodules based on conventional ultrasound and elastography: the value of predictive models in a multi-center study.

BACKGROUND: This study aimed to establish predictive models based on features of Conventional Ultrasound (CUS) and elastography in a multi-center study to determine appropriate preoperative diagnosis of malignancy in thyroid nodules with different risk stratification based on 2017 Thyroid Imaging Reporting and Data System by the American College of Radiology (ACR TI-RADS) guidelines. METHODS: Five hundred forty-eight thyroid nodules from three centers pathologically confirmed by the cytology or histology were retrospectively enrolled in the study, which were examined by CUS and elastography before fine needle aspiration (FNA) and surgery. Characteristics of CUS of thyroid nodules were reviewed according to 2017 ACR TI-RADS. Binary logistic regression analysis was used to develop the prediction models based on the different risk stratification of CUS features and elastography which were statistically significant. Values of predictive models were evaluated regarding the discrimination and calibration. RESULTS: Binary logistic regression showed that patients' age, taller-than-wider, lobulated or irregular boundary, extra-thyroid extension, microcalcification and the elastic parameter of Virtual touch tissue imaging quantification (VTIQ) max were independent predictors for thyroid malignancy (p < 0.05) in the ACR model and showed the area under the curve (AUC) in training (0.912) and validation cohort (internal and external: 0.877 vs 0.935). Predictive models showed predictors in ACR TR4 and TR5 for malignancy and diagnostic performance of AUC in training, internal and external validation cohort respectively: the VTIQ max (p < 0.001) with AUC of 0.809 vs 0.842 vs 0.705 and the age, taller than wide, VTIQ max variables with AUC of 0.859 vs 0.830 vs 0.906 in validation cohort. All predictive models have better calibration capabilities (p > 0.05). CONCLUSIONS: Predictive models combined CUS and elastography features would aid clinicians to make appropriate preoperative diagnosis of thyroid nodules among different risk stratification. The elastography parameter of VTIQ max has the priority in distinguishing thyroid malignancy with moderately suspicious (ACR TR4).

Added value of shear-wave elastography in the prediction of extracapsular extension and seminal vesicle invasion before radical prostatectomy.

The purpose of this study was to analyze the value of transrectal shear-wave elastography (SWE) in combination with multivariable tools for predicting adverse pathological features before radical prostatectomy (RP). Preoperative clinicopathological variables, multiparametric magnetic resonance imaging (mp-MRI) manifestations, and the maximum elastic value of the prostate (Emax) on SWE were retrospectively collected. The accuracy of SWE for predicting adverse pathological features was evaluated based on postoperative pathology, and parameters with statistical significance were selected. The diagnostic performance of various models, including preoperative clinicopathological variables (model 1), preoperative clinicopathological variables + mp-MRI (model 2), and preoperative clinicopathological variables + mp-MRI + SWE (model 3), was evaluated with area under the receiver operator characteristic curve (AUC) analysis. Emax was significantly higher in prostate cancer with extracapsular extension (ECE) or seminal vesicle invasion (SVI) with both P < 0.001. The optimal cutoff Emax values for ECE and SVI were 60.45 kPa and 81.55 kPa, respectively. Inclusion of mp-MRI and SWE improved discrimination by clinical models for ECE (model 2 vs model 1, P = 0.031; model 3 vs model 1, P = 0.002; model 3 vs model 2, P = 0.018) and SVI (model 2 vs model 1, P = 0.147; model 3 vs model 1, P = 0.037; model 3 vs model 2, P = 0.134). SWE is valuable for identifying patients at high risk of adverse pathology.

Knockdown of tankyrase 1 inhibits the progression of gastric adenocarcinoma via regulating human telomerase reverse transcriptase and telomeric repeat binding factor 1.

Background: Gastric cancer is one of the most lethal cancers. Aberrant expression levels of genes are frequently associated with cell immortalization and the occurrence of tumors. In this study, we aimed to investigate the role of tankyrase 1 (TANK1) in gastric adenocarcinoma and clarify the underlying mechanism. Methods: The messenger RNA (mRNA) levels of TANK1, human telomerase reverse transcriptase (h-TERT), and telomeric repeat binding factor 1 (TRF1) in clinical specimens and SGC-7901 cells were measured via real-time quantitative polymerase chain reaction (RT-qPCR). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and immunohistochemistry (IHC) assays were utilized to observe the cell apoptosis as well as Ki67 and h-TERT expression in tumor-bearing models. The effects of TANK1 antisense oligonucleotides (TANK1 ASODN) on viability and apoptosis of SGC 7901 cells were evaluated by cell counting kit-8 and flow cytometry analysis. Results: We found that TANK1 and h-TERT were both increased in gastric adenocarcinoma, while TRF1 was decreased. Tumor-bearing models demonstrated that TANK1 ASODN appeared to be effective in inhibiting tumor growth and decreasing the expression of h-TERT. Additionally, TANK1 ASODN inhibited the viability and promoted apoptosis of SGC-7901 cells. Moreover, the mRNA levels of h-TERT and TRF1 were modulated by TANK1 ASODN. Conclusions: This study revealed that TANK1 ASODN inhibits the proliferation and induced the apoptosis of gastric adenocarcinoma cells via manipulating the expression levels of h-TERT and TRF1.

Populusene A, an Anti-inflammatory Diterpenoid with a Bicyclo[8,4,1]pentadecane Scaffold from Populus euphratica Resins.

Populusene A (1), an unprecedented carbon skeleton featuring a bicyclo[8.4.1]pentadecane nucleus and a bridgehead double bond (anti-Bredt system), and populusin A (2), a cembrane-type diterpenoid possessing an uncommon dioxatricyclo[6.6.1.12,5]hexadecane scaffold, were isolated from the exudates of Populus euphratica. Their structures were elucidated by spectroscopic, computational, and crystallographic methods. A plausible biosynthetic route for 1 and 2 was proposed. Compounds 1 and 2 were found to significantly inhibit the production of TNF-α and IL-6 and the expression of iNOS, COX-2, and p-NF-κB at 125 nM in RAW264.7 cells.

miR-149 contributes to resistance of 5-FU in gastric cancer via targeting TREM2 and regulating ß-catenin pathway.

Drug resistance remains the unresolved obstacle for gastric cancer (GC) treatment. Recently more and more studies have shown that microRNAs are involved in cancer resistance and could apply to drug resistance therapy in tumors. The relationship between miR-149 and 5-fluorouracil (5-FU) resistance in GC remains unclear. Here we detected miR-149 expression in 5-FU resistance tumor tissues and cell lines, and found that miR-149 expression is upregulated in AGS/5-FU cells compared with AGS cells. Further experiments indicated that overexpression of miR-149 can alleviate 5-FU-induced apoptosis and proliferation inhibition by targeting TREM2. It was also confirmed that TREM2 regulated 5-FU resistance through ß-catenin pathway. Generally speaking, our results indicated that miR-149 contributes to resistance of 5-FU in gastric cancer via targeting TREM2 and regulating ß-catenin pathway.

Structurally diverse terpenoids with neuroprotective activities from the resins of Populus euphratica.

Five new terpenoids including one new abietane diterpenoid (1), one new aromadendrane diterpenoid (6), two new norsesquiterpenoids (8 and 9), and a new cembrane-derived diterpenoid (12), together with seven known compounds were isolated from Populus euphratica resins. The structures of these new compounds, including their absolute configurations, were characterized by spectroscopic and computational methods. All the compounds except 8 were test for their neuroprotective activities. The result revealed that compounds 1, 7, and 10-12 display neuroprotective activities in glutamate-induced SH-SY5Y cells in a concentration-dependent manner.

Neuroprotective Norsesquiterpenoids and Triterpenoids from Populus euphratica Resins.

Two new octanorlanostane-type triterpenes, euphraticanoids A and B (1 and 2), two new trinorsesquiterpenoids, euphraticanoids C and D (3 and 4), and eight known triterpenoids (5, 6, 8-13) along with one steroid (7) were isolated from Populus euphratica resins. The structures of these new compounds, including their absolute configurations, were characterized by spectrocsopic, chemical, and computational methods. Biological evaluation revealed that compounds 4, 7-9, 12, and 13 display neuroprotective activities in H2O2-induced HT-22 cells with 4, 8, and 9 occurring in a concentration-dependent manner and 7, 12, and 13 reaching the maximum effects at 20 µM. Meanwhile, the neuroprotective properties of all isolates were accessed using glutamate-induced SH-SY5Y cells and disclosed that compounds 3, 4, 8, and 9 could dose-dependently protect neural cell injury in a concentration range of 10-40 µM. Finally, a brief structure-activity relationship was briefly discussed.

Correction to: Suppressive effects of plumbagin on invasion and migration of breast cancer cells via the inhibition of STAT3 signaling and down-regulation of inflammatory cytokine expressions.

[This corrects the article DOI: 10.4248/BR201304007.].

[Efficacy of recombinant human thrombopoietin combined with high-dose dexamethasone in the treatment of refractory immune thrombocytopenia in children].

OBJECTIVE: To explore the efficacy and safety of recombinant human thrombopoietin (rhTPO) combined with high-dose dexamethasone (DXM) in the treatment of children with refractory immune thrombocytopenic purpura (ITP). METHODS: Fifty-eight ITP children who had failed first-line therapy were randomly divided into two groups: DXM treatment (n=27) and rhTPO + DXM treatment (n=31). The DXM treatment group received two continuous cycles of DXM treatment; in each cycle, patients received high-dose DXM (0.6 mg/kg daily) by intravenous drip for 4 days every 28 days. The rhTPO group received subcutaneous injection of rhTPO (300 U/kg daily) for 14 days additional to DXM treatment. The overall response rate (marked response rate + slight response rate) and adverse reactions were evaluated after 3, 7, and 14 days and 1, 2, and 3 months of treatment. RESULTS: After 7 and 14 days and 1 month of treatment, the rhTPO + DXM treatment group had a significantly higher marked response rate and a significantly higher overall response rate than the DXM treatment group (P<0.05). After 2 months of treatment, the rhTPO + DXM treatment group had a significantly higher overall response rate than the DXM group (P<0.05). One patient in the DXM treatment group had liver damage during the first week of treatment. There was no hypertension, fever, rash, allergy, or weakness in the two groups. CONCLUSIONS: rhTPO combined with high-dose DXM is an effective and safe approach for treating refractory ITP.

Gas-phase alkyl and N-alkylamino cation affinities of anionic alpha-oxygen nucleophiles (H n XO-; X = N, P, As, O, S, Se, F, Cl, Br; n = 0-2): a theoretical G2(+)M study.

In this work, we studied anionic alpha-oxygen nucleophiles in which there was an atom of with one or more unshared lone-pair electrons from groups 15-17 and periods 2-4 of the periodic table positioned adjacent to the negative attacking-oxygen (i.e., H n XO-; X = N, P, As, O, S, Se, F, Cl, Br; n = 0-2); these nucleophiles were termed "alpha-agents." Specifically, we investigated the gas-phase simple alkyl cation affinities (ACAs) and the simple N-alkylamino cation affinities (NAAMCAs) of these alpha-agents theoretically via the modified G2(+)M method. Our calculations indicate that the O-C bond of CH3OXH n is somewhat similar to that of iPrOXH n (n = 0, 1, 2; X = N, P, As, O, S, Se, F, Cl, Br). Also, steric repulsion is an important influence on these cation affinities. It appears that the kinetic gas-phase alpha effect in the SN2 reactions of interest cannot be explained by the thermodynamic proton affinity or the affinity (SuA) of the anionic or neutral nucleophile (Nu) for the substrate cation, as the gas-phase ACA (NAAMCA) was found to be linearly correlated with the PA for the alpha-agents, similar to the previously reported linear correlation of the gas-phase ACA (NAAMCA) with the PA for normal nucleophiles.

Can radical parametrectomy be omitted in occult cervical cancer after extrafascial hysterectomy?

BACKGROUND: Occult invasive cervical cancer discovered after simple hysterectomy is not common, radical parametrectomy (RP) is a preferred option for young women. However, the morbidity of RP was high. The aim of our study is to assess the incidence of parametrial involvement in patients who underwent radical parametrectomy for occult cervical cancer or radical hysterectomy for early-stage cervical cancer and to suggest an algorithm for the triage of patients with occult cervical cancer to avoid RP. METHODS: A total of 13 patients with occult cervical cancer who had undergone RP with an upper vaginectomy and pelvic lymphadenectomy were included in this retrospective study. Data on the clinicopathologic characteristics of the cases were collected. The published literature was also reviewed, and low risk factors for parametrial involvement in early-stage cervical cancer were analyzed. RESULTS: Of the 13 patients, 9 had a stage IB1 lesion, and 4 had a stage IA2 lesion. There were four patients with grade 1 disease, seven with grade 2 disease, and two with grade 3 disease. The median age of the entire patients was 41 years. The most common indication for extrafascial hysterectomy was cervical intraepithelial neoplasia 3. Three patients had visible lesions measuring 10-30 mm, in diameter and ten patients had cervical stromal invasions with depths ranging from 4 to 9 mm; only one patient had more than 50% stromal invasion, and four patients had lymph-vascular space invasion (LVSI). Perioperative complications included intraoperative bowel injury, blood transfusion, vesico-vaginal fistula, and ileus (1 case for each). Postoperative pathologic examination results did not show residual disease or parametrial involvement. One patient with positive lymph nodes received concurrent radiation therapy. Only one patient experienced recurrence. CONCLUSIONS: Perioperative complications following RP were common, whereas the incidence of parametrial involvement was very low among selected early-stage cervical cancer patients. Based on these results, we thought that patients with very low-risk parametrial involvement(tumor size ≤ 2 cm, no LVSI, less than 50% stromal invasion, negative lymph nodes) may benefit from omitting RP. Further prospective data are warranted.