Paravertebral block's effect on analgesia and inflammation in advanced gastric cancer patients undergoing transarterial chemoembolization and microwave ablation.

BACKGROUND: Transarterial chemoembolization (TACE) combined with microwave ablation (MWA) is an effective treatment strategy for patients with advanced gastric cancer and liver metastasis. However, it may cause severe postoperative pain and inflammatory responses. The paravertebral block (PVB) is a regional anesthetic technique that provides analgesia to the thoracic and abdominal regions. AIM: To evaluate the effect of PVB on postoperative analgesia and inflammatory response in patients undergoing TACE combined with MWA for advanced gastric cancer and liver metastasis. METHODS: Sixty patients were randomly divided into PVB and control groups. The PVB group received ultrasound-guided PVB with 0.375% ropivacaine preoperatively, whereas the control group received intravenous analgesia with sufentanil. The primary outcome was the visual analog scale (VAS) score for pain at 6 h, 12 h, 24 h, and 48 h after the procedure. Secondary outcomes were the dose of sufentanil used, incidence of adverse events, and levels of inflammatory markers (white blood cell count, neutrophil percentage, C-reactive protein, and procalcitonin) before and after the procedure. RESULTS: The PVB group had significantly lower VAS scores at 6 h, 12 h, 24 h, and 48 h after the procedure compared with the control group (P < 0.05). The PVB group also had a significantly lower consumption of sufentanil and a lower incidence of nausea, vomiting, and respiratory depression than did the control group (P < 0.05). Compared with the control group, the PVB group had significantly lower levels of inflammatory markers 24 h and 48 h after the procedure (P < 0.05). CONCLUSION: PVB can effectively reduce postoperative pain and inflammatory responses and improve postoperative comfort and recovery in patients with advanced gastric cancer and liver metastasis treated with TACE combined with MWA.

Predictive value of multiple imaging predictive models for spread through air spaces of lung adenocarcinoma: A systematic review and network meta­analysis.

Spread Through Air Spaces (STAS) is involved in lung adenocarcinoma (LUAD) recurrence, where cancer cells spread into adjacent lung tissue, impacting surgical planning and prognosis assessment. Radiomics-based models show promise in predicting STAS preoperatively, enhancing surgical precision and prognostic evaluations. The present study performed network meta-analysis to assess the predictive efficacy of imaging models for STAS in LUAD. Data were systematically sourced from PubMed, Embase, Scopus, Wiley and Web of Science, according to the Cochrane Handbook for Systematic Reviews of Interventions) and A Measurement Tool to Assess systematic Reviews 2. Using Stata software v17.0 for meta-analysis, surface under the cumulative ranking area (SUCRA) was applied to identify the most effective diagnostic method. Quality assessments were performed using Cochrane Collaboration's risk-of-bias tool and publication bias was assessed using Deeks' funnel plot. The analysis encompassed 14 articles, involving 3,734 patients, and assessed 17 predictive models for STAS in LUAD. According to comprehensive analysis of SUCRA, the machine learning (ML)_Peri_tumour model had the highest accuracy (56.5), the Features_computed tomography (CT) model had the highest sensitivity (51.9) and the positron emission tomography (pet)_CT model had the highest specificity (53.9). ML_Peri_tumour model had the highest predictive performance. The accuracy was as follows: ML_Peri_tumour vs. Features_CT [relative risk (RR)=1.14; 95% confidence interval (CI), 0.99-1.32]; ML_Peri_tumour vs. ML_Tumour (RR=1.04; 95% CI, 0.83-1.30) and ML_Peri_tumour vs. pet_CT (RR=1.04; 95% CI, 0.84-1.29). Comparative analyses revealed heightened predictive accuracy of the ML_Peri_tumour compared with other models. Nonetheless, the field of radiological feature analysis for STAS prediction remains nascent, necessitating improvements in technical reproducibility and comprehensive model evaluation.

The correlation between tumor radiological features and spread through air spaces in peripheral stage IA lung adenocarcinoma: a propensity score-matched analysis.

BACKGROUND: The consolidation tumor ratio (CTR) is a predictor of invasiveness in peripheral T1N0M0 lung adenocarcinoma. However, its association with spread through air spaces (STAS) remains largely unexplored. We aimed to explore the correlation between the CTR of primary tumors and STAS in peripheral T1N0M0 lung adenocarcinoma. METHODS: We collected data from patients who underwent surgery for malignant lung neoplasms between January and November 2022. Univariate and multivariate analyses following propensity-score matching with sex, age, BMI, were performed to identify the independent risk factors for STAS. The incidence of STAS was compared based on pulmonary nodule type. A smooth fitting curve between CTR and STAS was produced by the generalized additive model (GAM) and a multiple regression model was established using CTR and STAS to determine the dose-response relationship and calculate the odds ratio (OR) and 95% confidence interval (CI). RESULTS: 17 (14.5%) were diagnosed with STAS. The univariate analysis demonstrated that the history of the diabetes, size of solid components, spiculation, pleural indentation, pulmonary nodule type, consolidation/tumor ratio of the primary tumor were statistically significant between the STAS-positive and STAS-negative groups following propensity-score matching(p = 0.047, 0.049, 0.030, 0.006, 0.026, and < 0.001, respectively), and multivariate analysis showed that the pleural indentation was independent risk factors for STAS (with p-value and 95% CI of 0.043, (8.543-68.222)). Moreover, the incidence of STAS in the partially solid nodule was significantly different from that in the solid nodule and ground-glass nodule (Pearson Chi-Square = 7.49, p = 0.024). Finally, the smooth fitting curve showed that CTR tended to be linearly associated with STAS by GAM, and the multivariate regression model based on CTR showed an OR value of 1.24 and a p-value of 0.015. CONCLUSIONS: In peripheral stage IA lung adenocarcinoma, the risk of STAS was increased with the solid component of the primary tumor. The pleural indentation of the primary tumor could be used as a predictor in evaluating the risk of the STAS.

Integrative pharmacology reveals the mechanisms of Erzhi pills, A traditional Chinese formulation, stimulating melanogenesis.

ETHNOPHARMACOLOGICAL RELEVANCE: Erzhi pills (EZP), a traditional Chinese medicine formula prescribed for the treatment of vitiligo, has shown promising efficacy. However, the oral bioactive components and mechanisms underlying the promotion of melanogenesis by EZP remain unclear. AIM OF THE STUDY: This study aimed to investigate the pharmacological basis and mechanism of EZP in promoting melanogenesis. MATERIALS AND METHODS: UHPLC-TOF-MS analysis was used to identify absorbed phytochemicals in serum after oral administration of EZP. Network pharmacology methods were used to predict potential targets and pathways involved in the melanogenic activity of EZP, resulting in the construction of a "compound-target-pathway" network. Zebrafish and B16F10 cells were used to evaluate the effects of EZP on tyrosinase activity and melanin content. Western blot and ELISA analyses were used to validate the effects of EZP on melanogenesis-related proteins, including MITF, TYR, CREB, p-CREB, and cAMP. RESULTS: UHPLC-TOF-MS analysis identified 36 compounds derived from EZP in serum samples. Network pharmacology predictions revealed 89 target proteins associated with the identified compounds and closely related to vitiligo. GO and KEGG analyses indicated the involvement of the cAMP/PKA signaling pathway in the promotion of melanogenesis by EZP. Experimental results showed that EZP increased tyrosinase activity and melanin content in zebrafish and B16F10 cells without inducing toxicity. Western blot and ELISA results suggested that the melanogenic effect of EZP may be related to the activation of the cAMP/PKA signaling pathway. These results confirm the feasibility of combining serum pharmacological and network pharmacological approaches. CONCLUSIONS: EZP have the potential to increase tyrosinase activity and melanin content in zebrafish and cells possibly through activation of the cAMP/PKA pathway.

Development and validation of the thyroid cancer self-perceived discrimination scale to identify patients at high risk for psychological problems.

Objective: To develop a Thyroid Cancer Self-Perceived Discrimination Scale (TCSPDS) to identify patients at high risk for psychological problems and to test its reliability, validity and acceptability. Methods: Using classical test theory, a total of 176 thyroid cancer patients from November 2021 to October 2022 were recruited to develop the TCSPDS. Item analysis was used to improve the preliminary TCSPDS. Exploratory factor analysis (EFA), confirmatory factor analysis (CFA) and structural equation model (SEM) were used to test the construct validity of the final TCSPDS. Pearson correlation coefficient was used to analyze the validity coefficient between TCSPDS and EORTC QLQ-C30 to test the criterion-related validity (CRV) of the final TCSPDS. The internal consistency coefficient (Cronbach's alpha coefficient), split half reliability (Spearman-Brown coefficient) and test-retest reliability were used to verify the reliability of the final TCSPDS. The questionnaire completion time and effective response rate were used to validate the acceptability of the final TCSPDS. Results: The TCSPDS consisted of 20 items and was divided into 3 subscales: 8 items for stigma, 6 items for self-deprecation, and 6 items for social avoidance. The TCSPDS had good validity (χ2/df=1.971, RMSEA=0.074, GFI=0.921, CFI= 0.930, IFI=0.932, TLI=0.901, Validity coefficient=0.767), reliability (Cronbach's alpha=0.867, Spearman-Brown coefficient=0.828, test-retest reliability coefficient=0.981) and acceptability [average completion time (15.01 ± 1.348 minutes) and an effective response rate of 95.14%]. Patients with higher TCSPDS scores reported a lower quality of life (P<0.05). Conclusion: The TCSPDS could be used for early identification and assessment of the level of self-perceived discrimination in patients with thyroid cancer, which may provide a scientific basis for health education, social support and psychosocial oncology services in the future, especially in Southwest China.

[Effects of Fusobacterium nucleus derived outer membrane vesicles on claudin-4 expression in oral epithelial cells].

PURPOSE: To investigate the effect of outer membrane vesicles (OMVs) secreted by Fusobacterium nucleatum (F.n) on Claudin-4 of human oral keratinocytes (HOK) and oral epithelial barrier function. METHODS: Fusobacterium nucleatum was cultured under anaerobic conditions. The OMVs were extracted by dialysis and characterized by nanosight and transmission electron microscopy (TEM). HOK were stimulated with OMVs at different mass concentrations(0-100 µg/mL) for 12 h, and stimulated with 100 µg/mL OMVs for 6 h and 12 h respectively. The expression of Claudin-4 at gene and protein level was analyzed by RT-qPCR and Western blotting. Inverted fluorescence microscope was used to observe co-localization of HOK and OMVs and localization and distribution of Claudin-4 protein. Human oral epithelial barrier was constructed by Transwell apical chamber. Transepithelial electrical resistance(TER) of barrier was measured with a transmembrane resistance measuring instrument(EVOM2), and the permeability of the barrier was evaluated by transmittance of fluorescein isothiocyanate-dextran(FD-4). Statistical analysis was performed with GraphPad Prism 8.0 software package. RESULTS: Compared with the control group, the expression of Claudin-4 at protein and gene level in the HOK of OMVs stimulated group was significantly reduced (P＜0.05), and immunofluorescence showed that the continuity of Claudin-4 fluorescence among cells was destroyed. OMVs stimulation decreased TER value of oral epithelial barrier(P＜0.05) and increased the transmittance of FD-4(P＜0.05). CONCLUSIONS: OMVs derived from Fusobacterium nucleatum may damage oral mucosal epithelial barrier function through inhibiting the expression of Claudin-4.

Sarcoidosis with the livedo reticularis-like appearance.

Sarcoidosis is a multisystem inflammatory disease manifesting as noncaseating epithelioid cell granulomas. 25 to 30% of individuals with systemic sarcoidosis show variable cutaneous manifestations. A 59-year-old female was seen with reticular purplish-red nodules and plaques on the legs for three months. A skin biopsy of the livedo area revealed non-caseating epithelioid cell granulomas surrounding blood vessels in the dermis. She was diagnosed with sarcoidosis livedo, and cutaneous lesions subsided with oral prednisone. Sarcoidosis livedo (SL) assumes a uncommon livedo reticularis-like presentation. This is the first Chinese patient with SL, and more patients are needed to unveil the unique characters of SL.

Excitatory Effects of Astrocytic Hydrogen Sulfide on the Electrical Activity of Oxytocin Neurons in the Supraoptic Nucleus.

INTRODUCTION: In the regulation of oxytocin (OT) neuronal activity, hydrogen sulfide (H2S), a gaseous neurotransmitter, likely exerts an excitatory role. This role is associated with increased expression of astrocytic cystathionine-ß-synthase (CBS), the key enzyme for H2S synthesis. However, it remains unclear whether H2S is mainly produced in astrocytes and contributes to the autoregulation of OT neurons. METHODS: In hypothalamic slices of male rats, OT and H2S-associated drug effects were observed on the firing activity and spontaneous excitatory postsynaptic currents (sEPSCs) of putative OT neurons in the supraoptic nucleus (SON) in whole-cell patch-clamp recording. Expression of glial fibrillary acidic protein (GFAP) in the SON was analyzed in Western blots. In addition, changes in the length of rat pups' hypothalamic astrocytic processes were observed in primary cultures. RESULTS: In brain slices, OT significantly increased the firing rate of OT neurons, which was simulated by CBS allosteric agonist S-adenosyl-L-methionine (SAM) and H2S slow-releasing donor GYY4137 but blocked by CBS inhibitor aminooxyacetic acid (AOAA). L-α-aminoadipic acid (a gliotoxin) blocked SAM-evoked excitation. OT and SAM also increased the frequency and amplitude of sEPSCs; the effect of OT was blocked by AOAA. Both OT and GYY4137 reduced GFAP expression in the SON. Morphologically, OT or GYY4137 time-dependently reduced the length of astrocytic processes in primary cultures. CONCLUSIONS: These findings indicate that the auto-excitatory effect of OT on OT neurons is mediated by H2S from astrocytes at least partially and astrocytic H2S can elicit retraction of astrocytic processes that subsequently increase OT neuronal excitability.

Semi-quantitative and quantitative dynamic contrast-enhanced (DCE) MRI parameters as prostate cancer imaging biomarkers for biologically targeted radiation therapy.

BACKGROUND: Biologically targeted radiation therapy treatment planning requires voxel-wise characterisation of tumours. Dynamic contrast enhanced (DCE) DCE MRI has shown promise in defining voxel-level biological characteristics. In this study we consider the relative value of qualitative, semi-quantitative and quantitative assessment of DCE MRI compared with diffusion weighted imaging (DWI) and T2-weighted (T2w) imaging to detect prostate cancer at the voxel level. METHODS: Seventy prostate cancer patients had multiparametric MRI prior to radical prostatectomy, including T2w, DWI and DCE MRI. Apparent Diffusion Coefficient (ADC) maps were computed from DWI, and semi-quantitative and quantitative parameters computed from DCE MRI. Tumour location and grade were validated with co-registered whole mount histology. Kolmogorov-Smirnov tests were applied to determine whether MRI parameters in tumour and benign voxels were significantly different. Cohen's d was computed to quantify the most promising biomarkers. The Parker and Weinmann Arterial Input Functions (AIF) were compared for their ability to best discriminate between tumour and benign tissue. Classifier models were used to determine whether DCE MRI parameters improved tumour detection versus ADC and T2w alone. RESULTS: All MRI parameters had significantly different data distributions in tumour and benign voxels. For low grade tumours, semi-quantitative DCE MRI parameter time-to-peak (TTP) was the most discriminating and outperformed ADC. For high grade tumours, ADC was the most discriminating followed by DCE MRI parameters Ktrans, the initial rate of enhancement (IRE), then TTP. Quantitative parameters utilising the Parker AIF better distinguished tumour and benign voxel values than the Weinmann AIF. Classifier models including DCE parameters versus T2w and ADC alone, gave detection accuracies of 78% versus 58% for low grade tumours and 85% versus 72% for high grade tumours. CONCLUSIONS: Incorporating DCE MRI parameters with DWI and T2w gives improved accuracy for tumour detection at a voxel level. DCE MRI parameters should be used to spatially characterise tumour biology for biologically targeted radiation therapy treatment planning.

[Correlation between low expression of Hsp90 protein in keratinocytes and the number of small extracellular vesicles and its potential clinical significance].

PURPOSE: To investigate the correlation between the level of heat shock protein 90(Hsp90) and the amount of small extracellular vesicles(sEVs) in keratinocytes. METHODS: Human keratinocytes(HaCaT) were cultured in vivo and divided into wild-type group, short hairpin RNA interference group (shRNA group, low expression of Hsp90), and 17-Allylamino-17-demethoxygeldanamycin group (17-AAG group, Hsp90 protein inhibitor). sEVs were isolated from culture system by ultracentrifugation, and their morphological characteristics were observed under transmission electron microscopy (TEM). Western blotting was applied to identify the biological characteristics of sEVs. The number of sEVs particles was detected by nanoparticle tracking analysis (NTA). GraphPad Prism8.0 software was used to analyze the difference in the number of sEVs among the groups by t test (non-parametric Mann-Whitney U test). RESULTS: HaCaT-derived sEVs, obtained by ultracentrifugation, were consistent with the criteria of morphological and biological identification. No expression of Hsp90 protein was detected in HaCaT-derived sEVs. When interfered with Hsp90-shRNA, the number of sEVs were significantly increased. On day 5, the sEVs number of shRNA-interfering group was (177.4±4.18)×108(n=3), while that of vector group was (82.34±4.83)×108(n=3), and the difference was statistically significant (P＜0.0001). After 5 days of inhibition with 17-AAG, the sEVs number of 17-AAG group was （652.5±26.73）×108(n=3) and that of control group was (262.22±5.44)×108(n=3), the difference was statistically significant (P＜0.000 1). CONCLUSIONS: Low expression of Hsp90 protein can promote the secretion of sEVs in HaCaT cells. sEVs may be involved in the transfer of molecules between epithelial cells and immune cells.

A Multi-Center, Randomized, Blind, Controlled Clinical Trial of the Safety and Efficacy of Micro Radio Frequency Therapy System for the Treatment of Overactive Bladder.

Purpose: The purpose of this study was to evaluate the efficacy and safety of low power micro radiofrequency (RF) therapy (µRFthera®) through urethra in the treatment of overactive bladders (OAB) through a prospective, single-blind, placebo-controlled, multi-center clinical protocol. Materials and Methods: One hundred and fourteen patients with refractory OAB were randomized at 2:1 ratio, treatment to control undergoing same procedures except only the micro-RF treatment group at turned "on" setting in energy. Bladder diaries recorded during the screening period (3 days before enrollment) and during follow-up period on week 1, 3, and 7, respectively. The patients in control could choose receiving an energized treatment during extension stage. Results: The treatment efficacy was 76.1%. There was 49.80% rate improvement compared to control (95%CL 32.48%, 67.13%). The crude rate ration (RR) was 2.89, 95% CI (1.67-5.01) with p < 0.001 in uni-variate analysis, while the RR became 2.94, 95% CI (1.67-5.16) with p < 0.001 after adjusted potential confounding factors in multi-variate analysis. Statistically significant improvements have been demonstrated in the frequency of urination, urgency, nocturia, and quality of life (QoL) scores. Conclusions: Micro RF therapy is safe and effective for the treatment of OAB. The main treatment-related complications were catheterization related complications. Clinical Trial Registration: Zhejiang Device Registration Certificate No. 202090909, www.chictr.org.cn, Clinical Trial Accession Number: ChiCTR2100050096.

The strong in vitro and vivo cytotoxicity of three new cobalt(II) complexes with 8-methoxyquinoline.

Three new cobalt(II) complexes, [Co(MQL)2Cl2] (CoCl), [Co(MQL)2Br2] (CoBr), and [Co(MQL)2I2] (CoI), bearing 8-methoxyquinoline (MQL) have been designed for the first time. MTT assays showed that CoCl, CoBr, and CoI exhibit much better antiproliferative activities than cisplatin toward cisplatin-resistant SK-OV-3/DDP and SK-OV-3 ovarian cancer cells, with IC50 values of as low as 0.32-5.49 µM. Further, CoCl and CoI can regulate autophagy-related proteins in SK-OV-3/DDP cells and, therefore, they can induce primarily autophagy-mediated cell apoptosis in the following order: CoCl > CoI. The different antiproliferative activities of the MQL complexes CoCl, CoBr, and CoI could be correlated with the lengths of their Co-X bonds, which adopted the following order: CoI > CoBr > CoCl. The 8-HOMQ complexes CoCl (ca. 60.1%) and CoI (ca. 48.8%) also showed potent in vivo anticancer effects after 15 days of treatment. In summary, the MQL ligand highly enhances the antiproliferative activities of cobalt(II) complexes in comparison to other previously reported 8-hydroxyquinoline metal complexes.

Management of oral leukoplakia by ablative fractional laser-assisted photodynamic therapy: A 3-year retrospective study of 48 patients.

OBJECTIVES: This study aimed to review the results of oral leucoplakia (OL) using ablative fractional laser-assisted photodynamic therapy (AFL-PDT) and to further evaluate the risk factors for recurrence and malignant transformation. MATERIALS AND METHODS: Forty-eight patients diagnosed with OL using histopathology were enrolled in this study. All patients received one session of AFL-PDT. Therapeutic efficacy was evaluated 1 month posttreatment. Follow-up was scheduled every 3 months in the first year and every 6 months thereafter. RESULTS: An overall positive response rate of 87.5% (42/48) was achieved, including 62.5% (30/48) complete responses and 25.0% (12/48) partial responses. During the 3-year follow-up period, the recurrence and malignant transformation rates were 37.5% (18/48) and 8.3% (4/48), respectively. Lesions on gingiva/palate seemed to be associated with recurrence (p < 0.001; odds ratio [OR]: 1.64, 95% confidence interval [CI]: 1.13-2.37). The severity of epithelial dysplasia (p = 0.02; OR: 2.93, 95% CI: 1.96-4.42) and recurrence (p = 0.016; OR: 3.14, 95% CI: 2.04-4.84) were associated with a predisposition to malignant transformation. CONCLUSIONS: AFL-PDT is an effective management of OL, but requires close follow-up. OL lesions on the gingiva/palate are predisposed to recurrence. OLs that recur with moderate/severe epithelial dysplasia have a higher risk of transforming into oral squamous cell carcinoma.

Astrocytic Hydrogen Sulfide Regulates Supraoptic Cellular Activity in the Adaptive Response of Lactating Rats to Chronic Social Stress.

Maternal social stress among breastfeeding women can be adapted in chronic process. However, neuroendocrine mechanisms underlying such adaptation remain to be identified. Here, we report the effects of 2 hr/day unfamiliar male rat invasion (UMI) stress on maternal behaviors in lactating rats during postpartum day 8 (UMI8) to postpartum day 12 (UMI12). Rat dams at UMI8 presented signs of maternal anxiety, depression, and attacks toward male intruder. These changes partially reversed at UMI12 except the sign of anxiety. In the supraoptic nucleus (SON), UMI12 but not UMI8 significantly increased the expression of c-Fos and phosphorylated extracellular signal-regulated protein kinase 1/2. At UMI8 but not UMI12, length of glial fibrillary acidic protein (GFAP, astrocytic cytoskeletal element) filaments around oxytocin (OT) neurons was significantly longer than that of their controls; the amount of GFAP fragments at UMI12 was significantly less than that at UMI8. Expression of cystathionine ß-synthase (CBS, enzyme for H2S synthesis) at UMI12 was significantly higher than that at UMI8. CBS expression did not change significantly in the somatic zone of the SON but decreased significantly at the ventral glia lamina at UMI8. In brain slices of the SON, aminooxyacetate (a CBS blocker) significantly increased the expression of GFAP proteins that were molecularly associated with CBS. Aminooxyacetate also reduced the firing rate of OT neurons whereas Na2S, a donor of H2S, increased it. The adaptation during chronic social stress is possibly attributable to the increased production of H2S by astrocytes and the subsequent retraction of astrocytic processes around OT neurons.

Protective Mechanism of Luteinizing Hormone and Follicle-Stimulating Hormone Against Nicotine-Induced Damage of Mouse Early Folliculogenesis.

Previous studies have shown that nicotine could impair the germ cell cyst breakdown and the primordial follicle assembly by autophagy. In this paper, we discovered that luteinizing hormone (LH) and follicle-stimulating hormone (FSH) could counteract the damage caused by nicotine of mouse germ cell cyst breakdown. The neonatal mice were separately intraperitoneally injected with nicotine, nicotine plus LH, nicotine plus FSH, and saline (control) for 4 days. Compared with the nicotine group, the quality of oocytes and the number of follicles were remarkably increased in the nicotine plus LH group or nicotine plus FSH group. LH and FSH could alleviate nicotine-induced oocyte autophagy by different pathways. LH reduced the nicotine-induced autophagy by restoring the phosphorylation level of adenosine 5'-monophosphate-activated protein kinase α-1, while FSH by downregulating the phosphorylation level of Forkhead box class O 1. In addition, in a subsequent study of 6-week mice in different treated groups, we found that LH and FSH supplementation significantly improved normal maturation rates, fertilization rates, and embryo's developmental potential of oocytes in oocytes exposed to nicotine. Taken together, these results suggested that LH and FSH could counteract the damage caused by nicotine and finally ensure normal germ cell cyst breakdown and early embryo development.

Artificial intelligence and imaging biomarkers for prostate radiation therapy during and after treatment.

Magnetic resonance imaging (MRI) is increasingly used in the management of prostate cancer (PCa). Quantitative MRI (qMRI) parameters, derived from multi-parametric MRI, provide indirect measures of tumour characteristics such as cellularity, angiogenesis and hypoxia. Using Artificial Intelligence (AI), relevant information and patterns can be efficiently identified in these complex data to develop quantitative imaging biomarkers (QIBs) of tumour function and biology. Such QIBs have already demonstrated potential in the diagnosis and staging of PCa. In this review, we explore the role of these QIBs in monitoring treatment response during and after PCa radiotherapy (RT). Recurrence of PCa after RT is not uncommon, and early detection prior to development of metastases provides an opportunity for salvage treatments with curative intent. However, the current method of monitoring treatment response using prostate-specific antigen levels lacks specificity. QIBs, derived from qMRI and developed using AI techniques, can be used to monitor biological changes post-RT providing the potential for accurate and early diagnosis of recurrent disease.

Percutaneous Nephrolithotomy Can Reduce the Incidence of Sepsis Compared with Flexible Ureteroscopy in Treating Solitary Proximal Ureteral Stone Patients with Positive Urine Culture.

BACKGROUND: Sepsis is a potentially lethal complication for both flexible ureteroscopy (fURS) and percutaneous nephrolithotomy (PCNL). This study is aimed at comparing the sepsis rate after fURS and PCNL and the risk factors for sepsis in patients with solitary proximal ureteral stone. METHODS: We reviewed the data of patients with calculi between 10 mm to 20 mm who underwent fURS or PCNL surgery from Tongji Hospital's database. A total of 910 patients were eligible with 412 fURS cases and 498 PCNL cases. We used univariate analysis and multivariate logistic regression analysis to identify the risk factors for sepsis. Subgroup analysis was performed using logistic regression analysis. RESULTS: In the cohort, 27 (6.6%) and 19 (3.8%) patients developed sepsis after fURS and PCNL, respectively. Multivariate analysis shows that the risk factors for sepsis are fURS (OR = 3.160, P = 0.004), serum WBC ≥ 10,000 cells/µL (OR = 3.490, P = 0.008), albumin - globulin ratio < 1.2 (OR = 2.192, P = 0.029), positive urine culture (OR = 6.145, P < 0.001), and prolonged operation time (OR = 1.010, P = 0.046). Subgroup analysis was conducted using potential risk factors: stone size, serum WBC, urine culture, and albumin-globulin ratio (AGR). In subgroup of positive urine culture, patients were more likely to develop sepsis after fURS than PCNL. CONCLUSIONS: PCNL may be a better choice than fURS to reduce postoperative sepsis, especially for patients with positive urine culture.

Downregulation of SOX9 suppresses breast cancer cell proliferation and migration by regulating apoptosis and cell cycle arrest.

SRY-related high-mobility group box 9 (SOX9) is an important transcriptional factor that regulates diverse genes involved in development and stemness. Dysregulation of SOX9 encourages carcinogenesis in various types of cancer, including breast cancer. The present study aimed to explore the role of SOX9 in triple-negative breast cancer (TNBC). SOX9 expression was significantly upregulated in the TNBC MDA-MB-231, MDA-MB-436 and MDA-MB-468 cell lines compared with that in BT-549 cells. Based on a lentivirus assay, SOX9 inhibition in MDA-MB-231 and MDA-MB-436 cells suppressed cell proliferation and colony formation. Apoptosis was increased and the cell cycle was arrested at the G0/G1 phase in SOX9-knockdown cells. Transwell and wound-healing assays demonstrated that SOX9 inhibition decreased the migration and invasion of MDA-MB-231 and MDA-MB-436 cells. RNA sequencing identified that numerous genes were regulated by SOX9, including nucleophosmin, thioredoxin reductase 1, succinate dehydrogenase complex subunit D, nuclear receptor binding SET domain protein 2, eukaryotic translation initiation factor 4γ1 and glycogen phosphorylase L. Overall, the current study suggested that SOX9 acted as an oncogene in TNBC.

Management of pelvic organ prolapse of ruptured and extruded bladder from a rare complication of vaginal hysterectomy: a case presentation.

BACKGROUND: The prolapse of a ruptured and extruded bladder after vaginal hysterectomy is rare in clinical practice. We report the case of a significant mass that prolapsed from the vagina after a vaginal hysterectomy in a multiparous postmenopausal woman. CASE PRESENTATION: A 67-year old multiparous postmenopausal Chinese woman was found to have a significant mass extruding from the vagina after a vaginal hysterectomy. The mass was a ruptured and everted bladder, and the diagnosis was confirmed after physical and imaging examinations and urethral catheterization. The patient underwent an emergency operation for mass reduction, bladder repair, and partial colpocleisis under general anesthesia. She recovered without prolapse or urinary drainage complications after 35 months of follow-up. CONCLUSIONS: The present case serves as a guide for the management of patients with pelvic organ prolapse. The condition of patients should be carefully evaluated before surgery, and individualized operation should be performed. Careful postoperative follow-up is crucial for the timely exclusion of complications, especially in elderly patients with persistently increased abdominal pressure.

Key Roles of Cyclooxygenase 2-Protein Kinase A-Hyperpolarization-activated Cyclic Nucleotide-gated Channel 3 Pathway in the Regulation of Oxytocin Neuronal Activity in Lactating Rats with Intermittent Pup-Deprivation.

Suckling-evoked pulsatile release of oxytocin (OT) from the posterior pituitary plays a key role in breastfeeding, which relies on burst-like discharges of OT neurons. To explore cellular mechanisms regulating OT neuronal activity, using lactating rats with pup-deprivation (PD) during postpartum day 1-5, we observed the involvement of prostaglandin, cyclic AMP/protein kinase A (PKA) and hyperpolarization-activated cyclic nucleotide-gated channel 3 (HCN3) signaling pathway in OT neuronal activity. PD gradually reduced lactation efficiency. Intermittent PD (IPD) was largely reversed by intranasally-applied OT (IAO) but not by hypodermically-applied OT. IPD caused involution-like histological changes in the mammary glands, increased hypothalamic OT release but did not influence plasma OT concentrations. In the supraoptic nucleus, IPD increased OT receptor (OTR) expressions in OT neurons as well as Gαq subunit, Gß subunit and cyclooxygenase 2 (Cox-2). These effects except that on Gß subunit were reversed by IAO. Notably, IPD increased the expression of catalytic subunit of PKA in the SON, specifically in vasopressin neurons but not in OT neurons. In addition, IPD increased the expression of HCN3. IAO partially reversed these changes in the SON. Lastly, blocking HCN3 blocked excitation and burst firing in OT neurons-evoked by prostaglandin E2, a key mediator of OT-evoked burst firing; blocking Cox-2 or PKA reduced the molecular association between OTR and HCN3. Thus, there is a prostaglandin-cAMP/PKA-HCN3 pathway in the regulation of OT neuronal activity. PD disrupts lactation performance through uncoupling OTR and PKA-HCN3 signaling. The reversal effect of IAO highlights its therapeutic potential in PD-evoked hypogalactia.