Nociception related biomolecules in the adult human saliva: A scoping review with additional quantitative focus on cortisol.

Nociception related salivary biomolecules can be useful patients who are not able to self-report pain. We present the existing evidence on this topic using the PRISMA-ScR guidelines and a more focused analysis of cortisol change after cold pain induction using the direction of effect analysis combined with risk of bias analysis using ROBINS-I. Five data bases were searched systematically for articles on adults with acute pain secondary to disease, injury, or experimentally induced pain. Forty three articles met the inclusion criteria for the general review and 11 of these were included in the cortisol-cold pain analysis. Salivary melatonin, kallikreins, pro-inflammatory cytokines, soluable TNF-α receptor II, secretory IgA, testosterone, salivary α-amylase (sAA) and, most commonly, cortisol have been studied in relation to acute pain. There is greatest information about cortisol and sAA which both rise after cold pain when compared with other modalities. Where participants have been subjected to both pain and stress, stress is consistently a more reliable predictor of salivary biomarker change than pain. There remain considerable challenges in identifying biomarkers that can be used in clinical practice to guide the measurement of nociception and treatment of pain. Standardization of methodology and researchers' greater awareness of the factors that affect salivary biomolecule concentrations are needed to improve our understanding of this field towards creating a clinically relevant body of evidence.

Association of previous stillbirth with subsequent perinatal outcomes: a systematic review and meta-analysis of cohort studies.

OBJECTIVE: We conducted a systematic review and meta-analysis to examine the relationship between stillbirth and various perinatal outcomes in subsequent pregnancy. DATA SOURCES: PubMed, the Cochrane Library, Embase, Web of Science, and CNKI databases were searched up to July 2023. STUDY ELIGIBILITY CRITERIA: Cohort studies that reported the association between stillbirth and perinatal outcomes in subsequent pregnancies were included. METHODS: We conducted this systematic review and meta-analysis in accordance with the PRISMA guidelines. Statistical analysis was performed using R and Stata software. We used random-effects models to pool each outcome of interest. We performed a meta-regression analysis to explore the potential heterogeneity. The certainty (quality) of evidence assessment was performed using the GRADE approach. RESULTS: Nineteen cohort studies were included, involving 4,855,153 participants. From these studies, we identified 28,322 individuals with previous stillbirths who met the eligibility criteria. After adjusting for confounders, evidence of low to moderate certainty indicated that compared with women with previous live births, women with previous stillbirths had higher risks of recurrent stillbirth (odds ratio, 2.68; 95% confidence interval, 2.01-3.56), preterm birth (odds ratio, 3.15; 95% confidence interval, 2.07-4.80), neonatal death (odds ratio, 4.24; 95% confidence interval, 2.65-6.79), small for gestational age/intrauterine growth restriction (odds ratio, 1.3; 95% confidence interval, 1.0-1.8), low birthweight (odds ratio, 3.32; 95% confidence interval, 1.46-7.52), placental abruption (odds ratio, 3.01; 95% confidence interval, 1.01-8.98), instrumental delivery (odds ratio, 2.29; 95% confidence interval, 1.68-3.11), labor induction (odds ratio, 4.09; 95% confidence interval, 1.88-8.88), cesarean delivery (odds ratio, 2.38; 95% confidence interval, 1.20-4.73), elective cesarean delivery (odds ratio, 2.42; 95% confidence interval, 1.82-3.23), and emergency cesarean delivery (odds ratio, 2.35; 95% confidence interval, 1.81-3.06) in subsequent pregnancies, but had a lower rate of spontaneous labor (odds ratio, 0.22; 95% confidence interval, 0.13-0.36). However, there was no association between previous stillbirth and preeclampsia (odds ratio, 1.72; 95% confidence interval, 0.63-4.70) in subsequent pregnancies. CONCLUSION: Our systematic review and meta-analysis provide a more comprehensive understanding of adverse pregnancy outcomes associated with previous stillbirth. These findings could be used to inform counseling for couples who are considering pregnancy after a previous stillbirth.

Effect of PFOA exposure on diminished ovarian reserve and its metabolism.

Owing to its difficulty in degrading and ease of accumulation in the body, perfluorooctanoic acid (PFOA) has a detrimental effect on reproduction. This study aimed to examine the effect of PFOA concentration in follicular fluid during ovulation stimulation on embryo quality and the impact of PFOA exposure on the metabolic components of follicular fluid. This was a single-center prospective study that included 25 patients with diminished ovarian reserve (DOR), 25 with normal ovarian reserve (NOR), and 25 with polycystic ovary syndrome (PCOS). Follicular fluid samples were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry. We demonstrated that the PFOA levels of follicular fluid in the DOR group were higher than those in the NOR group and PCOS group (P < 0.05). PFOA concentration in the PCOS group was negatively correlated with high-quality embryos (P < 0.05). To gain more insight into the impact of PFOA on the metabolic composition of follicular fluid, we classified the DOR group based on the PFOA concentration, for which metabolomic analysis was performed. In the high-concentration PFOA group, there was an increase and a decrease in three and nine metabolites, respectively, compared to that in the low-concentration group. These results suggest that PFOA may alter the metabolic composition of follicular fluid, thus, affecting ovarian reserve function.

Endometrial compaction after human chorionic gonadotrophin administration reduces ectopic pregnancy rate following fresh embryo transfer in vitro fertilization/intracytoplasmic sperm injection cycles in patients with non-thin endometrium: a retrospective cohort study.

BACKGROUND: This study aims to study whether the change of endometrial thickness between the day of human chorionic gonadotrophin (HCG) administration and the day of embryo transfer (ET) has any effect on ectopic pregnancy (EP) rate following fresh in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles. METHODS: This study retrospectively analyzed 3134 patients who underwent fresh IVF/ICSI ET, including 3022 intrauterine, 112 ectopic cycles. Multiple logistic regression analysis and stratified analysis were used to study the effect of endometrial compaction after HCG administration on EP in patients with non-thin endometrium after adjusting for confounding factors. RESULTS: After adjusting for confounders, multiple logistic regression analysis found that the risk of EP in the compaction group was significantly lower than that in the non-compaction group (OR = 0.49; 95% CI: 0.31-0.78; P = 0.0023). The results of the stratified analysis demonstrated the EP rate in patients with an endometrial thickness ≥ 8 mm on the day of ET; the compaction group significantly reduced the incidence of EP (OR = 0.49; 95% CI: 0.31-0.79; P = 0.0036). In patients with an endometrial thickness ≥ 8 mm on the day of ET, the incidence of EP had no statistical significance in two group (OR = 1.02; 95% CI: 0.18-5.88; P = 9790). CONCLUSION(S): In patients with non-thin endometrium, endometrial thickness compaction from the day of HCG to the ET day reduced the risk of EP significantly.

Progestin-primed ovarian stimulation protocol with or without clomiphene citrate for poor ovarian responders: a retrospective cohort study.

OBJECTIVE: To explore the efficacy of progestin-primed ovarian stimulation (PPOS) combined with clomiphene citrate (CC) versus PPOS protocol used alone on cycle characteristics and pregnancy outcomes for women with the poor ovarian response (POR). METHODS: We performed a retrospective cohort study and a total of 578 POR patients who underwent IVF/ICSI cycles were collected and divided into Group A (HMG 300 IU/d + MPA 10 mg/d) and Group B (HMG 300 IU/d + MPA 10 mg/d + CC 50 mg/d). The primary outcome measure was the number of oocytes retrieved, other outcome measures were cycle characteristics and clinical pregnancy rate. RESULTS: The baseline information between the two groups were not statistically significant (P > 0.05). Compared with Group A, Group B had a lower total dose of human menopausal gonadotrophin (HMG) (2998.63 ± 1051.09 vs. 3399.18 ± 820.75, P < 0.001) and the duration of stimulation (10.21 ± 3.56 vs. 11.27 ± 2.56, P < 0.001). Serum luteinizing hormone level was higher in Group B on human chorionic gonadotrophin injection day (P < 0.001). The number of oocyte for retrieval, maturation, and fertilization were significantly lower in Group B than that in Group A (P < 0.001). However, the oocyte retrieval rate, maturation rate, fertilization rate, and viable embryo rate showed no statistical difference in the two groups (P > 0.05). After adjusting for confounders, the clinical pregnancy rate (OR 1.286; 95% CI 0.671-2.470) and live birth rate (OR 1.390; 95% CI 0.478-3.990) were comparable between the two groups. CONCLUSIONS: PPOS protocol combined with CC reduces the total dose of HMG and the duration of stimulation, and can also achieve similar oocyte yields and clinical pregnancy rate compared with the PPOS protocol used alone in poor ovarian responders.

Up-regulation of MSH6 is associated with temozolomide resistance in human glioblastoma.

The impact of DNA mismatch repair (MMR) on resistance to temozolomide (TMZ) therapy in patients with glioblastoma (GBM) is recently reported but the mechanisms are not understood. We aim to analyze the correlation between MMR function and the acquired TMZ resistance in GBM using both relevant clinical samples and TMZ resistant cells. First we found increased expression of MSH6, one of key components of MMR, in recurrent GBM patients' samples who underwent TMZ chemotherapy, comparing with those matched samples collected at the time of diagnosis. Using the cellular models of acquired resistance to TMZ, we further confirmed the up-regulation of MSH6 in TMZ resistant cells. Moreover, a TCGA dataset contains a large cohort of GBM clinical samples with or without TMZ treatment reinforced the increased expression of MSH6 and other MMR genes after long-term TMZ chemotherapy, which may resulted in MMR dysfunction and acquired TMZ resistance. Our results suggest that increased expression of MSH6, or other MMR, may be a new mechanism contributing to the acquired resistance during TMZ therapy; and may serve as an indicator to the resistance in GBM.

Perfluorooctane sulfonate (PFOS) induces apoptosis and autophagy by inhibition of PI3K/AKT/mTOR pathway in human granulosa cell line KGN.

Perfluorooctane sulfonate (PFOS) is recognized as an environmental endocrine disruptor with widespread use in industrial manufacturing and daily life, contributing to various public health concerns. However, the precise impacts of PFOS on the ovary and its regulatory mechanisms remain unclear. This study aims to delineate the ovarian toxicity of PFOS and scrutinize its effects on apoptosis and autophagy through modulation of the PI3K/AKT/mTOR pathway in the human granulosa cell line (KGN). Cell viability, assessed via the Cell Counting Kit-8 (CCK8), revealed a dose-dependent reduction in cell viability upon PFOS exposure. Flow cytometry analysis demonstrated an elevated proportion of apoptotic cells following PFOS treatment. Western blot analyses unveiled increased expression of Bax, Cyt c, cleaved caspase-9, and LC3-II/I, coupled with decreased expression of Bcl-2 and p62. Transmission electron microscopy (TEM) observations illustrated a heightened number of autophagosomes induced by PFOS. Molecular docking investigations, in conjunction with Western blot experiments, substantiated PFOS's significant inhibition of the PI3K/AKT/mTOR signaling pathway. These findings collectively underscore that PFOS induces apoptosis and autophagy in KGN cells through modulation of the PI3K/AKT/mTOR pathway, providing experimental evidence for PFOS-induced ovarian toxicity and elucidating the underlying regulatory mechanisms in KGN cells.

The prognosis of patients with primary pulmonary mucosa-associated lymphoid tissue lymphoma: Treated with surgery or chemotherapy?

OBJECTIVES: The goal of this project was to evaluate the effect of surgical treatment and the long-term survival of patients with staged IE/IIE pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: From January 2004 to December 2018, we retrospectively analysed 96 patients diagnosed with low-stage primary pulmonary MALT lymphoma according to the modified Ann Arbor staging system (IE/IIE). We compared the outcomes of different treatment modalities for staged IE/IIE MALT lymphoma. Progression-free survival (PFS) and overall survival were estimated using Kaplan-Meier curves, and the differences were compared using the log-rank test. The Cox proportional hazards model was used in this study. RESULTS: The median PFS time of low-staged MALT lymphomas was 118 months. The overall survival and PFS of the radical surgery group and the biopsy + chemotherapy group suggested no significant difference (P = 0.63, P = 0.65). Patients positive for Blc-2 and Ki-67 suffered from a compromised PFS (P = 0.023, P = 0.006). The Cox adjusted proportional hazards model analysis suggested that surgical procedures were not protective factors for patients with low-staged (IE/IIE) pulmonary MALT lymphoma, whereas being positive for Blc-2 and Ki-67 was a risk factor for patients with low-staged pulmonary MALT lymphoma (hazard ratio: 9.567; P = 0.044; hazard ratio: 6.042, P = 0.049). CONCLUSIONS: Our findings suggested that for staged IE/IIE pulmonary MALT lymphoma, radical surgical resection did not provide a survival benefit compared with chemotherapy after biopsy. Thus, radical surgery may be avoided unless biopsy is necessary for a diagnosis that requires sublobar resection. For those lesions that were Blc-2- or Ki-67-positive, compromised survival may be suggested.

Quercetin activates autophagy to protect rats ovarian granulosa cells from H2O2-induced aging and injury.

Autophagy is closely related to the aging of various organ systems, including ovaries. Quercetin has a variety of biological activities, including potential regulation of autophagy. However, whether quercetin-regulated autophagy activity affects the process of ovarian aging and injury has not been clarified yet. This study explores whether quercetin can resist H2O2-induced aging and injury of granulosa cells by regulating autophagy and its related molecular mechanisms in vitro experiments. The cell viability, endocrine function, cell aging, and apoptosis were detected to evaluate the effects of quercetin and autophagy regulators like 3-methyladenine and rapamycin. The levels of autophagy markers Atg5, Atg12, Atg16L, Lc3B II/I, and Beclin1 were determined by Western blot to assess the effects of quercetin, 3-methyladenine and rapamycin on autophagy. Our results showed quercetin resisted H2O2-induced granulosa cell aging and injury by activating protective autophagy. The treatment of 3-methyladenine and rapamycin confirmed the protective function of autophagy in H2O2-induced granulosa cells. 3-methyladenine treatment inhibited the expression of autophagy markers Atg5, Atg12, Atg16L, Lc3B II/I, and Beclin1 and abolished the positive effects on cell viability, estradiol secretion, and cell apoptosis activated by quercetin. In conclusion, quercetin activates autophagy by upregulating the expression of autophagy-related proteins to resist H2O2-induced aging and injury, which is crucial for stabilizing the function of granulosa cells under oxidative injury conditions and delaying aging. This study may explain the protective effects of quercetin on ovarian aging and injury from the perspective of regulating autophagy.

Surgery for bronchiectasis-destroyed lung: feasibility of video-assisted thoracoscopic surgery, and surgical outcomes.

OBJECTIVES: To provide the experience of surgical treatment for bronchiectasis-destroyed lung (BDL) and evaluate the feasibility of video-assisted thoracoscopic surgery (VATS). METHODS: BDL patients underwent surgical treatment between January 2013 and June 2018 were included. Logistic regression was performed to assess factors for major complications, and Cox's regression was performed to assess factors affected symptomatic outcome. RESULTS: Totally, 143 patients were treated by VATS (n = 64) and thoracotomy (n = 79). Nine (14.1%) cases scheduled for VATS were converted to thoracotomy for dense adhesions (n = 6) and frozen hilum (n = 3). The VATS group had a median chest tube duration, hospitalization and a time of returning to full activity of 4 days, 5 days and 1.5 months, respectively. Major complications occurred in 28 (19.6%) of all patients, 50.0% after pneumonectomy and 13.4% after lobectomy/extensive lobectomy. Multivariable analysis identified pneumonectomy [odds ratio, 3.64; 95% confidence interval (CI), 1.18-11.21] as a significant predictor for major complications. Overall, 141 (98.6%) patients benefitted from surgery (completely asymptomatic, n = 109; acceptable alleviation, n = 32). Thirty-four patients experienced relapse of the disease, including 13 with productive cough, 11 with haemoptysis and 10 with recurrent infections. Pseudomonas aeruginosa infection [hazard ratio (HR), 3.07; 95% CI, 1.38-6.83] and extent of remanent bronchiectatic areas (HR, 1.03; 95% CI, 1.00-1.05) were independent risk factors for shorter relapse free interval. CONCLUSIONS: VATS for BDL is feasible in well-selected patients. Pneumonectomy increased the risk of postoperative major complications. Removing all BDL lesions contributed to satisfactory prognosis.

Establishment of a prediction model for the impact of endometrial thickness on the day of embryo transfer on ectopic pregnancy in frozen-thawed embryo transfer cycle.

Objective: This study aims to investigate the factors affecting the ectopic pregnancy (EP) rate in the frozen-thawed embryo transfer (FET) cycle. Methods: This study retrospectively analyzed 5606 FET cycles, including 5496 cycles resulting in intrauterine pregnancy and 110 cycles resulting in EP. Smooth curve fitting and piece-wise linear regression were utilized to evaluate a non-linear association between endometrial thickness (EMT) and EP. Multiple logistic regression analysis was used to study the effect of EMT on the embryo transfer (ET) day and other indexes on EP rate after adjusting for confounding factors. A nomographic prediction model was employed to predict EP occurrence. The predictive efficacy of the model was assessed using the area under the receiver operating characteristic (ROC) curve (AUC), utilizing the bootstrap sampling method for internal validation. Results: After accounting for the confounding factors, the segmented linear regression analysis indicated that the EMT inflection point was 9 mm; the EP rate significantly decreased by 28% with each additional millimeter of EMT up to 9 mm (odds ratio (OR) = 0.72; 95% confidence interval (CI), 0.53-0.99; P = 0.0412) while insignificantly decreased when the EMT was greater than 9 mm (OR = 0.91; 95% CI, 0.76-1.08; P = 0.2487). Multivariate logistic regression analysis revealed that after adjusting for confounders, EP risk significantly increased in the number of previous EPs ≥ 1 (OR = 2.29; 95% CI, 1.26-4.16; P = 0.0064) and tubal factor infertility (OR = 3.86; 95% CI, 2.06-7.24; P < 0.0001). Conversely, EP risk was significantly reduced by the increased EMT (OR = 0.84; 95% CI, 0.74-0.96; P = 0.0078) and the blastocyst transfer (OR = 0.45; 95% CI, 0.27-0.76; P = 0.0027). These variables were used as independent variables in a nomogram prediction model, resulting in an AUC of 0.685. The nomination models were internally verified using self-sampling (bootstrap sampling resampling times = 500). This validation yielded an AUC of 0.689, with a sensitivity of 0.6915 and a specificity of 0.5790. The internal validation indicated minimal fluctuations in the AUC, signifying a relatively stable model. Conclusion: Undergoing EMT on the day of ET poses a separate EP risk in the FET cycle; to mitigate the EP incidence, the EMT should exceed 9 mm before ET. Furthermore, previous EPs and tubal factor infertility were additional factors independently increasing EP risk. Furthermore, implementing blastocyst transfer demonstrated that EP incidence was significantly reduced. Utilizing a nomogram predicting system enables EP risk evaluation before ET for individual patients, establishing a basis for devising clinical strategies for ET.

Neoadjuvant therapy does not increase postoperative morbidity of sleeve lobectomy in locally advanced non-small cell lung cancer.

OBJECTIVES: To evaluate the feasibility and safety of sleeve lobectomy after neoadjuvant therapy by assessing the postoperative morbidity. METHODS: Patients who underwent sleeve lobectomy for non-small cell lung cancer (NSCLC) were retrospectively analyzed from January 2018 to December 2021. A total of 613 patients were enrolled, including 124 patients who received previous neoadjuvant therapy and 489 patients who did not. Propensity score matching was adopted to create a balanced cohort consisting of 97 paired cases. Patient demographics and perioperative outcomes were compared between the 2 groups, and logistic regression analysis was used to identify risk factors for postoperative complications. RESULTS: In the entire cohort, univariable logistic regression analysis showed that smoking history (odds ratio [OR], 1.501; 95% confidence interval [CI], 1.011-2.229, P = .044), open thoracotomy (OR, 1.748; 95% CI, 1.178-2.593, P = .006), and operation time more than 150 minutes (OR, 1.548; 95% CI, 1.029-2.328, P = .036) were risk factors for postoperative complications, and multivariable logistic regression analysis showed open thoracotomy was an independent risk factor (OR, 1.765; 95% CI, 1.178-2.643, P = .006). In the balanced cohort, the neoadjuvant group had a lower proportion of double-sleeve resections (3.1% vs 11.3%, P = .035) and longer postoperative chest tube drainage (6.67 ± 3.81 vs 5.13 ± 3.74 days, P < .001). However, no significant differences were observed in postoperative morbidity between the 2 groups (25.8% vs 24.7%, P = .869). The complete pathologic response of chemoimmunotherapy was significantly superior to chemotherapy alone (28.2% vs 4.1%, P < .001), and no significant differences were noted in postoperative morbidity in different neoadjuvant therapy modalities. CONCLUSIONS: After neoadjuvant therapy, sleeve lobectomy can be safely performed with no increased postoperative morbidity.

Chest tube-free video-assisted thoracoscopic surgery secured by quantitative air leak monitoring: a case series.

Background: Although chest tube-omitted video-assisted thoracoscopic surgery (VATS) has been proven to be safe and efficacious, its universal application is precluded by a varying morbidity rate due to a lack of standardization. Since digital chest drainage has already shown improved accuracy and consistency in the management of postoperative air leak, we incorporated it in the strategy of intraoperative chest tube withdrawal, aiming to achieve better results. Methods: We collected the clinical data of 114 consecutive patients who underwent elective uniportal VATS pulmonary wedge resection at the Shanghai Pulmonary Hospital from May 2021 to February 2022. Their chest tubes were withdrawn intraoperatively after an air-tightness test facilitated by digital drainage: the end flow rate had to be kept ≤30 mL/min for >15 s at the setting of -8 cmH2O suctioning. The recordings and patterns of the air suctioning process were documented and analyzed as potential standards of chest tube withdrawal. Results: The mean age of the patients was 49.7±11.7 years. The mean size of the nodules was 1.0±0.2 cm. The location of the nodules encompassed all lobes, and 90 (78.9%) patients received preoperative localization. The postoperative morbidity and mortality rates were 7.0% and 0%, respectively. Six patients had clinically overt pneumothorax and two patients had postoperative bleeding that required intervention. All of the patients recovered on conservative treatment except for one case of pneumothorax that required additional tube thoracostomy. The median length of postoperative stay was 2 days; and the median time of suctioning, peak flow rate, and end flow rate were 126 s, 210 mL/min, and 0 mL/min, respectively. The median numeric rating scale for pain was 1 on postoperative day (POD) 1 and 0 on the day of discharge. Conclusions: Chest tube-free VATS assisted by digital drainage is feasible with minimal morbidity. Its strength of quantitative air leak monitoring produces important measurements for the prediction of postoperative pneumothorax and future standardization of the procedure.

Prognostic factors and role of postoperative radiotherapy in surgically resected thymomas.

Objective: To investigate the prognostic factors in and role of postoperative radiotherapy (PORT) for surgically resected thymomas. Methods: A total of 1540 patients with pathologically confirmed thymomas undergoing resection between 2000 and 2018 were identified retrospectively from the SEER (Surveillance, Epidemiology, and End Results) database. Tumors were restaged as local (limited to thymus), regional (invasion to mediastinal fat and other neighboring structures), or distant stage. Disease-specific survival (DSS) and overall survival (OS) were estimated by the Kaplan-Meier method and the log-rank test. Adjusted hazard ratios (HRs) with 95% CIs were calculated by Cox proportional hazards modeling. Results: Tumor stage and histology were independent predictors of both DSS (regional: HR, 3.711; 95% CI, 2.006-6.864; distant: HR, 7.920; 95% CI, 4.061-15.446; type B2/B3: HR, 1.435; 95% CI, 1.008-2.044) and OS (regional: HR, 1.461; 95% CI, 1.139-1.875; distant: HR, 2.551; 95% CI, 1.855-3.509; type B2/B3: HR, 1.409; 95% CI, 1.153-1.723). For patients with regional stage and type B2/B3 thymomas, PORT was associated with better DSS after thymectomy/thymomectomy (HR, 0.268; 95% CI, 0.099-0.727), but the association was not significant after extended thymectomy (HR, 1.514; 95% CI, 0.516-4.44). Among patients with lymph node metastases, those who received PORT (HR, 0.372; 95% CI, 0.146-0.949), chemotherapy (HR, 0.843; 95% CI, 0.303-2.346), or both (HR, 0.296, 95% CI, 0.071-1.236) had a better OS. Conclusions: The extent of invasion and tumor histology were independent predictors of worse survival following surgical resection of thymoma. Patients with regional invasion and type B2/B3 thymoma who undergo thymectomy/thymomectomy may benefit from PORT, while patients with nodal metastases may benefit from multimodal therapy, including PORT and chemotherapy.

Determination of tryptophan and its indole metabolites in follicular fluid of women with diminished ovarian reserve.

Tryptophan (TRP) and its indole metabolites exhibit numerous biological effects, especially their antioxidant properties. This study used untargeted metabolomics in conjunction with targeted metabolomics to investigate the differential expression of tryptophan and its indole metabolites in follicular fluid (FF) of diminished ovarian reserve (DOR) and normal ovarian reserve (NOR) populations. This study included patients with DOR (n = 50) and females with NOR (n = 35) who received in vitro fertilization and embryo transfer. Untargeted metabolomics suggests that diminished ovarian reserve affects the metabolic profile of FF, TRP and indole metabolites were significantly down-regulated in the DOR group. Targeted metabolomics quantification revealed that the levels of TRP, IPA and IAA in the FF of the DOR group were significantly lower than those of the NOR group (P < 0.01). The concentration of TRP in FF is positively correlated with the available embryo rate in NOR females. These results provide data support to explore the pathogenesis of DOR and to look for new biomarkers and ovarian protectors. Additionally, alterations in TRP and its indole metabolites in FF may indirectly reflect the interaction between intestinal flora and the follicular microenvironment.

The number of metastatic lymph nodes is more predictive of prognosis than location-based N stage for nonsmall cell lung cancer: a retrospective cohort study.

BACKGROUND: The eighth edition of nodal classification is defined only by the anatomical location of metastatic lymph nodes and has limited prognostic discrimination power. The authors aimed to evaluate the prognostic significance and discriminatory capability of the number of metastatic lymph nodes (nN) in resected nonsmall cell lung cancer. MATERIALS AND METHODS: Patients with stage IA to IIIB resected nonsmall cell lung cancer between 1 January 2009 and 31 December 2013 were analyzed as a Chinese cohort. The optimal thresholds for the nN classification were determined by the X-tile. The receiver operating characteristic curve, net reclassification improvement and standardized net benefit calculated by decision curve analysis was estimated to quantify the nN classification's performance in prognostic stratification. External validation in the surveillance, epidemiology, and end results database was performed to test the robustness of the nN classification. RESULTS: Both cohorts showed a stepwise prognosis deterioration with increasing nN. One to three, four to six, and more than six were selected as optimal thresholds of nN classification in the Chinese cohort, which included 4432 patients, then validated in the SEER cohort ( n =28 022 patients). Multivariate Cox analysis showed the nN classification was an independent predictive factor for overall survival in both cohorts (Chinese cohort and SEER cohort: N 0 vs. N 1-3 , P <0.001; N 0 vs. N 3-6 , P <0.001; N 0 vs. N >6 , P <0.001). And prognostic discriminatory capability was improved in the nN classification compared with location-based N classification [5-year NRI score, 0.106 (95% CI: 0.049-0.132) and 5-year time-independent AUC, 0.593 (95% CI: 0.560-0.625) vs. 0.554 (95% CI: 0.520-0.588), P <0.001]. CONCLUSIONS: The nN classification tended to be a superior prognostic indicator than the location-based N classification. The number of metastatic lymph nodes should be considered in the future revision of the TNM system.

Modified slide tracheoplasty technique in the management of a long-segment tracheoesophageal fistula.

Post-tracheotomy tracheoesophageal fistula remains a challenge because it frequently involves a considerable length of the trachea. We report a case in which a modified slide tracheoplasty was successfully used to repair a long-segment, subglottic post-tracheotomy tracheoesophageal fistula. This technique not only shortened the length of the resected tracheal segment but also maintained the patency of the tracheal lumen.

Mesenchymal stem cell extracellular vesicles-derived microRNA-194-5p delays the development of intervertebral disc degeneration by targeting TRAF6.

OBJECTIVE: Mesenchymal stem cells-derived extracellular vesicles (MSCs-EVs) can improve intervertebral disc degeneration (IDD). Considering that, their concrete mechanisms from microRNA-194-5p/tumor receptor-associated factor 6 (miR-194-5p/TRAF6) axis in IDD ask for disclosure in a scientific way. METHODS: Nucleus pulposus (NP) cells and MSCs were obtained. EVs were isolated from the obtained MSCs and identified. miR-194-5p expression in MSC-EVs was altered by sequence transfection. Subsequently, MSCs-EVs were co-cultured with NP cells intervened by tumor necrosis factor α (TNF-α). NP cell proliferation and apoptosis, along with their osteogenic differentiation ability were evaluated. miR-194-5p and TRAF6 expression and their interaction were determined. RESULTS: In TNF-α-intervened NP cells, miR-194-5p was down-regulated and TRAF6 was up-regulated. Restoring miR-194-5p effectively enhanced proliferation and osteogenic differentiation, and reduced apoptosis of TNF-α-intervened NP cells. miR-194-5p-enriched MSCs-EVs protected TNF-α-intervened NP cells. miR-194-5p targeted TRAF6, TRAF6 overexpression exerted negatively for the growth of TNF-α-intervened NP cells, and could reduce the protective effects of miR-194-5p on TNF-α-intervened NP cells. CONCLUSION: It is elucidated that miR-194-5p derived from MSCs-EVs protects TNF-α-intervened NP cells through restricting TRAF6, replenishing a potential target for IDD treatment.

Double sternal elevation subxiphoid versus uniportal thoracoscopic thymectomy associated with superior clearance for stage I-II thymic epithelial tumors: Subxiphoid thymectomy compared with VATS.

OBJECTIVE: This study aimed to evaluate the therapeutic efficacy of thymectomy through a subxiphoid video-thoracoscopic approach with double elevation of the sternum compared with traditional intercostal uniportal video-assisted thoracic surgery for stage I-II thymic epithelial tumors (using the Masaoka-Koga staging system). METHOD: Patients with thymic tumors underwent resection through intercostal video-assisted thoracic surgery or subxiphoid video-thoracoscopic approach. Only those with pathologically confirmed thymic epithelial tumors were enrolled. Perioperative short-term/long-term outcomes were compared between 2 groups after propensity-score matching. RESULTS: A total of 141 patients diagnosed with thymic epithelial tumors and scheduled for minimally invasive surgery were included. In the intercostal video-assisted thoracic surgery group, the prevalence for conversion to open surgery was higher than in the subxiphoid video-thoracoscopic approach group for stage III thymic tumors (P = .019). After propensity-score matching for 122 patients undergoing video-assisted thoracic surgery, significantly larger resected specimens were found in the subxiphoid video-thoracoscopic approach group compared to the intercostal video-assisted thoracic surgery group (11.7 ± 3.8 vs 7.1 ± 2.7 cm, P < .001). The pain score on the first postoperative day (1.6 ± 0.6 vs 2.0 ± 0.7, P = .011) and the day of hospital discharge (1.2 ± 0.7 vs 1.6 ± 0.6, P = .017) in the subxiphoid video-thoracoscopic approach group were significantly lower. The operation time (168.4 ± 59.3 vs 92.5 ± 46.0 min, P < .001), chest tube drainage time (3.6 ± 1.2 vs 2.9 ± 0.9 days, P = .001), and hospital stay (3.7 ± 1.3 vs 2.9 ± 0.9 days, P = .004) were longer in the subxiphoid video-thoracoscopic approach group, with higher intraoperative blood loss (69.3 ± 61.0 vs 45.6 ± 42.5 mL, P = .045). No significant differences were found in the hospitalization cost, incidence of complications, or 3-year disease-free survival (96% vs 92%, P = .473) between the 2 groups. Four patients with stage III disease in the subxiphoid video-thoracoscopic approach group reached a 3-year disease-free survival of 75%. CONCLUSION: The subxiphoid video-thoracoscopic approach with double elevation of the sternum shows the potential for more extensive clearance of thymic tissue for thymic epithelial tumors compared to intercostal video-assisted thoracic surgery. Its inferior operation time and blood loss could be a trade-off for improved pain control and equivalent hospitalization cost, complications, and 3-year disease-free survival. The subxiphoid video-thoracoscopic approach may offer an advantage treatment for early-stage thymic epithelial tumors and may also be suitable for unexpected advanced thymic tumors identified intraoperatively.

An Immune-Related Genetic Feature Depicted the Heterogeneous Nature of Lung Adenocarcinoma and Squamous Cell Carcinoma and Their Distinctive Predicted Drug Responses.

One of the primary causes of global cancer-associated mortality is lung cancer (LC). Current improvements in the management of LC rely mainly on the advancement of patient stratification, both molecularly and clinically, to achieve the maximal therapeutic benefit, while most LC screening protocols remain underdeveloped. In this research, we first employed two algorithms (ESTIMATE and xCell) to calculate the immune/stromal infiltration scores. This helped identify the altered immune infiltration landscapes in lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC). Afterward, based on their immune-related characteristics, we successfully stratified the LUAD and LUSC into 2 and 3 clusters, respectively. Different from the conventional bioinformatic approaches that start from the investigation of differential expression of single genes, differentially enriched curated gene sets identified through gene set variation analyses (GSVA) were curated, and gene names were reconstructed afterward. Furthermore, weighted gene correlation network analyses (WGCNA) were used to reveal hub genes highly connected with the clustering process. Actual expression levels of critical hub genes among different clusters were compared and so were the functional pathways these genes enriched into. Lastly, a computational method was applied to predict and compare the responses of each cluster to primary therapeutic agents. The heterogeneity presented in our study, along with the drug responses expected for identified clusters, may shed light on future exploration of combination immunochemotherapy that facilitates the optimization of individualized therapy.