Nonlinear correlation between serum vitamin D levels and the incidence of endometrial polyps in infertile women.

STUDY QUESTION: Are serum vitamin D levels associated with the incidence of endometrial polyps (EPs) in infertile patients? SUMMARY ANSWER: Serum 25(OH)D levels were nonlinearly correlated with the incidence of EPs in infertile women. WHAT IS KNOWN ALREADY: EPs are a common condition that may affect the receptivity of the endometrium in women of reproductive age. Vitamin D regulates cell proliferation and differentiation, apoptosis, angiogenesis, anti-inflammation, and immunomodulation, in addition to its well-known functions in balancing calcium and phosphorus. Previous studies have shown that vitamin D concentrations are associated with reproductive outcomes, and that low vitamin D levels are associated with the incidence of colorectal polyps and nasal polyps. There is little evidence regarding the relationship between EPs and serum vitamin D levels. STUDY DESIGN, SIZE, DURATION: We conducted a cross-sectional study using data from Guangdong Women and Children Hospital from January 2019 to October 2023, enrolling 3107 patients. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 3107 infertile patients who underwent hysteroscopy were included in this study; 642 patients had endometrial polyps and 2465 had a normal uterine cavity. Hysteroscopy findings included risk of EPs, polyp size, percentage of multiple polyps, and incidence of chronic endometritis (CE). Serum vitamin D were assessed by measuring total 25(OH)D using chemiluminescence. According to international guideline recommendations for vitamin D deficiency, patients were divided into two groups: the <50 nmol/l group and the ≥50 nmol/l group. Univariable and multivariable logistic regression models, stratified analyses, and smooth curve fitting were used to examine the relationship between serum 25(OH)D levels and risk of EPs. MAIN RESULTS AND THE ROLE OF CHANCE: Of all patients, 23.8% (740/3107) were vitamin D deficient (<50 nmol/l). The incidence of EPs was significantly higher in the 25(OH)D < 50 nmol/l group than in the ≥50 nmol/l group (24.9% vs 19.3%; P = 0.001). However, there were no differences in polyp size, proportion of multiple polyps, and presence of CE between the two groups. After controlling for confounders, 25(OH)D ≥ 50 nmol/l (compared with <50 nmol/l) was negatively associated with risk of EPs (adjusted OR, 0.733; 95% CI, 0.598-0.898). Other variables that had an impact on polyp incidence included BMI, type of infertility, CA125, and CD138-positive plasma cells. In addition, a linear regression model between age and serum 25(OH)D levels showed a positive linear association. Subgroup analyses were performed for different age groups, and the risk of EPs was significantly higher in the 25(OH)D < 50 nmol/l group than in the ≥50 nmol/l group, both in the younger subgroup (23.8% vs 19.1%) and in the older subgroup (28.0% vs 19.9%). The smooth curve fitting model showed a nonlinear correlation between 25(OH)D levels and risk of EPs (nonlinear P-value = 0.020), with an optimal threshold of 51.8 nmol/l for 25(OH)D levels. Moreover, subgroup smooth curve fitting models showed a nonlinear correlation between 25(OH)D levels and polyp risk in patients aged <35 years (nonlinear P-value = 0.010), whereas a linear correlation between 25(OH)D levels and polyp risk was found in patients aged ≥35 years (nonlinear P-value = 0.682). LIMITATIONS, REASONS FOR CAUTION: Caution should be exercised in interpreting our findings as this is a correlational study and causality cannot be inferred from our results. In addition, because of strict inclusion and exclusion criteria, our results may not be generalizable to unselected populations, including premenopausal women or women of other races. WIDER IMPLICATIONS OF THE FINDINGS: This study demonstrated for the first time that vitamin D deficiency is an independent risk factor for the incidence of EPs in infertile patients. Identifying modifiable risk factors (e.g. vitamin D deficiency) can help in the development of new strategies for treating polyps or to protect against polyp development. Further clinical intervention trials and laboratory studies are needed to evaluate the effect of vitamin D on the development of EPs and to elucidate the mechanisms. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the National Natural Science Foundation of China (82101718) and Natural Science Foundation of Guangdong Province, China (2022A1515010776). No competing interest was involved in this study. TRIAL REGISTRATION NUMBER: N/A.

Impact of different progesterone timings on live birth rates for blastocyst frozen embryo transfer cycles.

RESEARCH QUESTION: Do different timings of progesterone administration for day 5 and day 6 blastocysts affect the live birth rate (LBR) of artificial frozen embryo transfer (FET) cycles? DESIGN: This retrospective cohort study included 1362 patients who underwent artificial FET cycles. The effects of 6 and 7 days of progesterone administration prior to blastocyst transfer on clinical outcomes were compared in day 5 and day 6 blastocysts. Univariable and multivariable regression analyses were undertaken. RESULTS: In all patients, LBR was comparable between the two groups (51.8% versus 47.9%, P = 0.165). For day 6 blastocysts, after adjusting for confounders, the 7-day progesterone regimen resulted in a significantly higher LBR (44.8% versus 36.4%, P = 0.039, adjusted OR = 1.494, 95% CI 1.060-2.106) and lower pregnancy loss rate (15.4% versus 25.2%, P = 0.031, adjusted OR = 0.472, 95% CI 0.260-0.856) compared with the 6-day progesterone regimen. For day 5 blastocysts, there were no significant differences in pregnancy outcomes between the two regimens, but the rate of low birthweight was higher with the 7-day progesterone regimen than with the 6-day progesterone regimen (13.9% versus 6.7%, P = 0.032). CONCLUSIONS: In all blastocyst analyses, no difference in LBR was found between the 6- and 7-day progesterone regimens in artificial FET cycles. For day 6 blastocysts, LBR was significantly higher with the 7-day progesterone regimen than with the 6-day progesterone regimen, whereas for day 5 blastocysts, pregnancy outcomes were comparable between the two regimens.

Toward the efficient direct regeneration of spent cathode materials through the effect of residual sodium ions analysis.

Recycling spent lithium-ion batteries is an important means for promoting sustainability within the energy industry. In this study, the effects of residual sodium on the regeneration process and the performance of spent LiNi0.5Co0.2Mn0.3O2 were explored. An appropriate amount of residual sodium was found to improve the properties of the regenerated material, with the best cycle performance and rate performance at a residual sodium of 3 mol %. The first-cycle and 100-cycle discharge capacities were 136.4 mA h g-1 and 120 mA h g-1, respectively, with a capacity retention rate of 87.98% after 100 cycles at a rate of 1 C. The electrochemical performance of the regenerated cathode materials was improved because sodium occupied the lithium sites in the crystal structure, providing a channel for lithium deintercalation. These results indicate that the residual sodium ions should be monitored in appropriate quantities to improve the efficiency of recycling spent lithium-ion batteries.

Experiment and simulation of flexible CNT/SA/PDMS electromagnetic shielding composite.

Flexible electromagnetic shielding composites have a great potential for wide range applications. In this study, two flexible composites were produced by plating Ni nanoparticles on carbon nanotubes (CNTs) or infiltrating carbon nanofibers/polydimethylsiloxane (CNF/PDMS) polymer into CNT/sodium alginate (CNT/SA) sponge skeleton (CNT/SA/CNF/PDMS composites). The composites are tested under the X band in the frequency range of 8.2 - 12.4 GHz, the electromagnetic interference shielding effectiveness (EMI-SE) values of the above two composites are almost as twice as that of CNT/SA/PDMS composite at a same CNT loading. Introducing nano-sized Ni particles on CNT improved the microwave absorption capacity of the composite, while adding CNF on the PDMS matrix enhanced the conductivity of these composites. Under 10% strain, both flexible composites show stable conductivity. Simulation and calculation results shown that increasing the cladding rate of Ni nanoparticles on the surface of CNT, reducing the average size of Ni particles, and increasing the loading of CNF in PDMS matrix can significantly improve conductivity and then EMI performance of the materials. All of these could benefit for the design of flexible electromagnetic shielding composites.

Gestational PM2.5 exposure may increase the risk of small for gestational age through maternal blood pressure and hemoglobin: A mediation analysis based on a prospective cohort in China, 2014-2018.

BACKGROUND: Maternal gestational PM2.5 exposure was associated with small for gestational age (SGA). Identifying potential mediating factors may help design preventive strategies to reduce this risk. OBJECTIVE: This study aimed to explore the roles of maternal blood pressure and hemoglobin may play in the PM2.5 exposure and SGA relationship among 117,162 births in 16 counties across China during 2014-2018. METHODS: Daily PM2.5 concentration was collected from China National Environmental Monitoring Center. According to maternal residency during pregnancy, the PM2.5 exposure for each trimester and the whole pregnancy was assessed using an inverse-distance weighting approach. Repeated measurements of maternal blood pressure and hemoglobin during pregnancy were collected for each woman. We estimated the total effect of gestational PM2.5 exposure on SGA, and further tested the mediation effects of maternal blood pressure and hemoglobin concentration during pregnancy. RESULTS: Of 117,162 included mother-infant pairs, 11,361 (9.7 %) were SGA. The odds ratios of SGA associated with PM2.5 exposure (per 10 µg/m3 increase) in the second trimester and the whole pregnancy were 1.023 (95 % CI: 1.009, 1.037) and 1.024 (1.001, 1.048), respectively. We identified the independent mediating effect of blood pressure and hemoglobin in the second and third trimesters, with the proportion of mediation ranging from 1.64 % to 5.78 % and 2.40 % to 8.70 %, respectively. When considering the mediators jointly, we found a stronger mediating effect with a proportion of mediation ranging from 3.93 % to 13.69 %. DISCUSSION: Increases in maternal blood pressure and hemoglobin in the second and third trimesters can independently and jointly mediate the effects of gestational PM2.5 exposure on SGA. Monitoring and managing maternal blood pressure and hemoglobin during prenatal care may constitute a promising avenue to reducing SGA risk associated with gestational PM2.5 exposure.

Circadian rhythm genes mediate fenvalerate-induced inhibition of testosterone synthesis in mouse Leydig cells.

Fenvalerate (Fen), a widely used pesticide, is known to impair male reproductive functions by mechanisms that remain to be elucidated. Recent studies indicated that circadian clock genes may play an important role in successful male reproduction. The aim of this study was to determine the effects of Fen on circadian clock genes involved in the biosynthesis of testosterone using TM3 cells derived from mouse Leydig cells. Data demonstrated that the circadian rhythm of testosterone synthesis in TM3 cells was disturbed following Fen treatment as evidenced by changes in the circadian rhythmicity of core clock genes (Bmal1, Rev-erbα, Rorα). Further, the observed altered rhythms were accompanied by increased intracellular Ca2+ levels and modified steroidogenic acute regulatory (StAR) mRNA expression. Thus, data suggested that Fen inhibits testosterone synthesis via pathways involving intracellular Ca2+ and clock genes (Bmal1, Rev-Erbα, Rorα) as well as StAR mRNA expression in TM3 cells.

Preimplantation genetic testing for complex chromosomal rearrangements: clinical outcomes and potential risk factors.

Objective: Complex chromosome rearrangements (CCR) are rare structural abnormalities involving at least three breakpoints, categorized into three types based on their structure: type A (three-way rearrangements), type B (double two-way translocations), and type C (exceptional CCR). However, thus far, limited data exists on preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR) in CCR carriers. This study aims to evaluate the clinical outcomes and influencing factors of PGT-SR in couples with CCR. Methods: Fifteen couples with unique CCR recruited from 793 couples following PGT-SR between January 2017 and May 2023. In addition, a total of 54 CCR cases, 39 previously reported as well as 15 newly added, were included in the analysis of factors associate with normal/balanced embryos. Results: A total of 100 blastocysts were biopsied and analyzed in 15 CCR couples after 17 PGT-SR cycles, with 16.0% being euploid, 78.0% aneuploid and 6.0% mosaic. 11 normal/balanced embryos and one mosaic embryo were transferred, resulting in eight live births. Furthermore, based on the combined data from 54 CCR carriers, the proportion of normal/balanced embryos was 10.8%, with a significant decrease observed among female carriers compared to male heterozygotes (6.5% vs. 15.5%, p = 0.002). Type B exhibited the lowest rate of euploid embryos at only 6.7%, followed by type A at 11.6% and type C at 14.0%, although the differences were not significant (p = 0.182). After completing the multivariate generalized estimating equation (GEE) analysis, type B (p = 0.014) and female carrier (p = 0.002) were identified as independent risk factors for fewer euploid embryos. Conclusion: The occurrence of balanced CCR in patients with reproductive abnormalities may be more frequent than we expected. Despite the proportion of normal/balanced embryos being significantly low, which can be influenced by CCR type and carrier's sex, PGT-SR may improve the reproductive outcomes among CCR cases. These findings can optimize the clinical management and genetic counseling of CCR carriers seeking assisted reproductive technology (ART).

Estimation of couple fecundity in the general population and the association with monthly time-varying ambient particulate matter exposure in low- and middle-income countries: A population-based multi-center epidemiological study.

BACKGROUND: Declining total fertility rates have been observed in low- and middle-income countries (LMICs). However, it remains unclear if this trend is related to a reduction in fecundity of general population. Research evidence on contributing factors to fecundity reduction is also limited. We aimed to first estimate couple fecundity in LMICs and then investigate its association with ambient particulate matter (PM) exposure. METHODS: Using the information from Demographic and Health Surveys between 2003 and 2019, we estimated median time to pregnancy (TTP) and infertility prevalence across 30 LMICs, by employing a current duration approach. Individual PM (PM1, PM2.5, and PM10) exposure during the period of 'at risk' of pregnancy was assessed by months. An accelerated failure model was used to elucidate the association between monthly time-varying PM exposure and TTP. Subsequently, we estimated the prolonged TTP attributable to PM exposures above the World Health Organization (WHO)'s recommended air quality level in 2021. RESULTS: Within the study regions, median TTP ranged from 6.90 (95 % CI 6.02-7.87) months in Latin America & Caribbean to 10.29 (95 % CI 9.28-11.36) months in East Asia & Pacific, with corresponding infertility prevalence varying from 33 % (95 % CI 29 %-36 %) to 44 % (95 % CI 41 %-48 %). Our estimations indicated that TTP was 1.08 (95 % CI: 0.99-1.18), 1.12 (95 % CI 1.06-1.19), and 1.05 (95 % CI 1.03-1.07) times longer for every 10 µg/m3 increment in PM1, PM2.5, and PM10, respectively. The prolonged TTP attributable to PM exposures surpassing the WHO guideline ranged from 0.11 to 2.81 months across the studied regions. DISCUSSION: Ambient particulate matter is identified as a potential contributing factor to impaired fecundity in general population of LMICs. The findings underscore the importance of coordinated efforts to control ambient air pollution to mitigate the risk of fecundity reduction among the general population.

Olgotrelvir as a Single-Agent Treatment of Nonhospitalized Patients with Covid-19.

BACKGROUND: Olgotrelvir is an oral antiviral with dual mechanisms of action targeting severe acute respiratory syndrome coronavirus 2 main protease (i.e., Mpro) and human cathepsin L. It has potential to serve as a single-agent treatment of coronavirus disease 2019 (Covid-19). METHODS: We conducted a phase 3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of olgotrelvir in 1212 nonhospitalized adult participants with mild to moderate Covid-19, irrespective of risk factors, who were randomly assigned to receive orally either 600 mg of olgotrelvir or placebo twice daily for 5 days. The primary and key secondary end points were time to sustained recovery of a panel of 11 Covid-19-related symptoms and the viral ribonucleic acid (RNA) load. The safety end point was incidence of treatment-emergent adverse events. RESULTS: The baseline characteristics of 1212 participants were similar in the two groups. In the modified intention-to-treat population (567 patients in the placebo group and 558 in the olgotrelvir group), the median time to symptom recovery was 205 hours in the olgotrelvir group versus 264 hours in the placebo group (hazard ratio, 1.29; 95% confidence interval [CI], 1.13 to 1.46; P<0.001). The least squares mean (95% CI) changes of viral RNA load from baseline were -2.20 (-2.59 to -1.81) log10 copies/ml in olgotrelvir-treated participants and -1.40 (-1.79 to -1.01) in participants receiving placebo at day 4. Skin rash (3.3%) and nausea (1.5%) were more frequent in the olgotrelvir group than in the placebo group; there were no treatment-related serious adverse events, and no deaths were reported. CONCLUSIONS: Olgotrelvir as a single-agent treatment significantly improved symptom recovery. Adverse effects were not dose limiting. (Funded by Sorrento Therapeutics, a parent company of ACEA Therapeutics; ClinicalTrials.gov number, NCT05716425.).

Identifying the critical windows and joint effects of temperature and PM2.5 exposure on small for gestational age.

The potential critical windows for extreme ambient temperature, air pollution exposure and small for gestational age (SGA) are still unclear, and no study has explored their joint effects on SGA. In a national multi-center prospective cohort, we included 179,761 pairs of mother-infant from 16 counties of 8 provinces in China during 2014-2018. Daily averaged temperature and PM2.5 concentration were matched to the maternal residential address to estimate personal exposure. Extreme temperature exposures were categorized by a series of percentile in each meteorological and geographic division for the entire pregnancy, each trimester and gestational week (GA-week). Generalized linear mixed models (GLMMs) and distributed lag nonlinear models (DLNMs) were used to estimate the whole pregnancy-, trimester-specific, and weekly-specific associations of extreme temperature and PM2.5 exposures with SGA. Combined effects were evaluated with the relative excess risk due to interaction (RERI) and proportion attributable to interaction (AP). We observed that by referring to temperature at the 41st - 50th percentile, heat (>90th percentile) exposure during 13th - 29th GA-weeks was associated with SGA; odds ratio (OR) and 95 % confidence intervals (CI) was 1.16 (1.06, 1.28). For cold (<=10th percentile), inverse associations were observed during the 1st - 8th GA-weeks. PM2.5 exposure during the 2nd - 5th and 19th - 27th GA-weeks was associated with SGA, with the strongest association in the 2nd GA-week (OR = 1.0017, 95 %CI: 1.0001, 1.0034, for a 10 µg/m3 increase). No interactive effects between ambient temperature and PM2.5 on SGA were observed. Our findings suggest the weekly susceptibility windows for heat and PM2.5 exposure were primarily the gestational weeks within the 2nd trimester, therefore, corresponding protective measures should be conveyed to pregnant women during routine prenatal visits to reduce exposures.

The mediation of the placenta on the association between maternal ambient temperature exposure and birth weight.

Studies have indicated that exposure to low and high temperatures during pregnancy negatively affects fetal development. The placenta plays vital functions in fetal development and could also be impacted by suboptimal temperatures. However, whether the placenta mediates the association between suboptimal temperature and birth weight is unknown. Our study aims to evaluate the association between ambient temperature and birth weight as well as the mediation effect of the placenta. A prospective birth cohort study was conducted during 2017-2020 in Guangzhou, China (n = 3349 participants). We defined extreme temperature exposure during the whole pregnancy by using different thresholds, including low temperatures (< 25th, < 15th, < 10th, < 5th percentiles), and high temperatures (> 75th, > 85th, > 90th, > 95th percentiles). Three different approaches (generalized linear model, inverse probability weighting, and doubly robust model) were applied to estimate the effects of low/high temperatures on birth weight and placental indicators, including placental weight, placental volume, and placental-to-birth weight ratio (PFR), respectively. We observed that both low and high ambient temperatures during the whole pregnancy were associated with lower birth weight and negative changes in placental indicators. The estimated lower mean birth weight ranged from -158 g (95 % CI: -192 g, -123 g) to -363 g (95 % CI: -424 g, -301 g) for low temperatures and from -97 g (95 % CI: -135 g, -59 g) to -664 g (95 % CI: -742 g, -585 g) for high temperatures. In mediation analyses, placental weight mediated 28.79 % to 40.47 % and 48.22 % to 54.38 % of the association of low and high temperatures with birth weight, respectively. The findings suggest that placental weight may mediate the association between ambient temperature exposure and birth weight.

Efficacy and safety of TCMs with anti-inflammatory effect in patients with rheumatoid arthritis: A network meta-analysis.

Background: Traditional Chinese medicines (TCMs), such as Tripterygium wilfordii Hook F (TwHF), Glycyrrhiza uralensis, Caulis sinomenii and others have anti-inflammatory effects. They are widely used in China to treat rheumatoid arthritis (RA), but proof of their use as an evidence-based medicine is little. The aim of this network meta-analysis (NMA) was to evaluate the efficacy and safety of TCMs. Methods: By searching online databases and using a manual retrieval method, randomized controlled trials (RCTs) that met specific selection criteria were included in the meta-analysis. The search included papers that were published between the establishment of the databases and November 10, 2022. Analyses were performed using Stata software (version 14) and Review Manager (version 5.3). Results: 61 papers with 6316 subjects were included in the current NMA. For ACR20, MTX plus SIN therapy (94.30%) may be a significant choice. For ACR50 and ACR70, MTX plus IGU therapy (95.10%, 75.90% respectively) performed better than other therapies. IGU plus SIN therapy (94.80%) may be the most promising way to reduce DAS-28, followed by MTX plus IGU therapy (92.80%) and TwHF plus IGU therapy (83.80%). In the analysis of the incidence of adverse events, MTX plus XF therapy (92.50%) had the least potential, while LEF therapy (22.10%) may cause more adverse events. At the same time, TwHF therapy, KX therapy, XF therapy and ZQFTN therapy were not inferior to MTX therapy. Conclusions: TCMs with anti-inflammatory effect were not inferior to MTX therapy in the treatment of RA patients. Combining with TCMs can improve the clinic efficacy and reduce the possibility of adverse events of DMARDs, which may be a promising regimen. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022313569.

Prognosis and Biological Function of miR-3195 in Non-Small Cell Lung Cancer.

PURPOSE: Lung cancer has the highest mortality and morbidity rates worldwide. Among the subtypes of lung cancer, non-small cell lung cancer (NSCLC) accounts for approximately 85% of cases. The present study evaluated the potential prognostic value and biological function of miR-3195 in NSCLC. PATIENTS AND METHODS: In total, 129 patients with NSCLC were enrolled in this study. The expression of miR-3195 expression in NSCLC tissues and cell lines was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan-Meier survival curve analysis and multivariate Cox regression analysis were used to elucidate the prognostic value of miR-3195. The Cell Counting Kit-8 (CCK-8) assay and Transwell cell migration experiments were carried out to explore the effective effect of miR-3195 on the biological behavior of NSCLC cells. RESULTS: The expression of miR-3195 was downregulated in NSCLC tissues and cell lines. Moreover, the decreased expression of miR-3195 was correlated with positive lymph node metastasis and high TNM stage. The overall survival of patients with low expression of miR-3195 was worse than those with high expression of miR-3195. Furthermore, miR-3195 was an independent prognostic indicator for overall survival in patients with NSCLC. Enhanced expression of miR-3195 restrained cell growth, migration, and invasion of NSCLC tumor cells, while attenuation of miR-3195 expression augmented cell proliferation activities, migration, and invasion potential. CONCLUSION: Our findings suggest that miR-3195 may be used as a prognostic biomarker for NSCLC and is likely to act as a tumor suppressor for NSCLC.

Modeling and characterization of the electrical conductivity on metal nanoparticles/carbon nanotube/polymer composites.

Flexible conductive films have good deformability and conductivity, and are expected to be used in flexible electronic devices. In this paper, four kinds of flexible conductive films were successfully prepared by compounding nano-sized metal (Ni, Cu, Au or AuCu alloy) particles to CNT surface and then dispersing to polydimethylsiloxane matrix. Experiment results show that the conductivity of these prepared films are almost two orders of magnitude higher than that of CNT/polydimethylsiloxane films with the same CNT loadings. A simulation model based on percolation network theory and Monte Carlo technology is introduced to study the influence of nanoparticles on the composite conductivity. Results confirmed that the introduction of nanoparticles effectively reduces the effective resistance of CNT and the tunnelling resistance at CNT junctions. The intrinsic conductivity and the length diameter ratio of CNT, the intrinsic conductivity, the size and the coverage ratio of nanoparticles are the core parameters affecting the conductivity of composite. Compared with CNT/polydimethylsiloxane films, the optimized theoretical conductivity of these nano-sized particles enhanced composites can be further improved.

The short-term outcomes of nonintubated anesthesia compared with intubated anesthesia in single-port video-assisted lung surgery in enhanced recovery after thoracic surgery: results from a single-center retrospective study.

Background: Nonintubated anesthesia avoids invasive tracheal intubation operations and reduces trauma. in addition, it has advantages in lung surgery in some patients with poor lung function, in line with the concept of rapid recovery. However, few studies have discussed the clinical significance of Enhanced recovery after surgery (ERAS) combined with nonintubated anesthesia in single-port video-assisted thoracoscopic surgery (VATS). We conducted a retrospective study to examine the safety and availability of nonintubated anesthesia single-port video-assisted lung surgery (NI-SP-VALS) combined with ERAS programs in patients. Methods: This was a single-center retrospective study. All patients were preoperatively diagnosed with lung nodules and underwent NI-SP-VALS or intubated anesthesia SP-VALS (I-SP-VALS) combined with ERAS programs between July 2021 and March 2022. Short-term postoperative outcomes were compared in 2 cohorts. Results: In total, 272 patients were included. Among them, 91 patients received NI-SP-VALS combined with ERAS programs (observation group), and 181 underwent intubation anesthesia (control group). Baseline data were statistically different between the two groups, and 1:1 propensity score matching (PSM) matching was used. A total of 73 patients remained in each group after PSM, and baseline characteristics were not significantly different between the 2 cohorts. The time of hospital stay [4.00 (4.00-5.00) vs. 44.50 (0.00-5.75) d; P=0.029] and catheter stay [0.50 (0.20-2.00) vs. 2.00 (2.00-2.00) d; P<0.001] were significantly shorter, the white blood cell count (WBC) [9.45 (8.08-11.30) vs. 11 (8.50-12.80)/L; P=0.009] and the lowest SpO2 in operation [96.00 (94.00-97.50) vs. 97.00 (95.00-98.50); P=0.035] were also lower in the nonintubated group than those of the intubated group. No differences were observed in variables of intraoperation, other routine blood indexes, postoperative drainage, postoperative medicine use, postoperative symptoms, complications, hospitalization expenses, postoperative follow-up index, or self-assessment of anxiety. Conclusions: The data after PSM shows that compared with intubated anesthesia, NI-SP-VALS combined with ERAS programs is safe and effective. Nonintubated anesthesia promotes rapid recovery of patients and reduces postoperative inflammatory reactions. Hence, nonintubated anesthesia may conform to the idea of ERAS and has application value in thoracic surgery.

Microanatomic study of the vascular and duct system of the submandibular gland.

PURPOSE: Autologous microvascular submandibular gland (SMG) transfer is an effective treatment for severe keratoconjunctivitis sicca (KCS). However, epiphora (excessive tear secretion) may occur after the successful transfer of whole submandibular gland because tear secretion level is closely related to the size of the transferred gland. The aim of this study was to investigate the microanatomy of SMG to explore the possibility of partial SMG transfer to prevent postoperative epiphora. MATERIALS AND METHODS: Sixty intact and histologically normal human SMGs from patients with benign tumor of the mandible who underwent vascularized mandibular reconstruction and removal of the SMG for anastomosis of the blood vessels were included in the study. SMGs were perfused with methacrylate to form resin casts of blood vessels and ducts. The length and diameter of the blood vessels and ducts in the casts were measured using a sliding caliper. The numbers of lobules, distribution of arteries, veins, and ducts, as well as the relationship among them, were analyzed. RESULTS: The resin cast of the gland showed a treelike structure, with the vessels gradually dividing into multiple branches. The arteries, veins, and ducts run in parallel and were roughly divided into 3 levels: from the stem extending into the main branches (level I), into the narrower secondary branches (level II), and then the secondary branches subsequently divided into terminal branches (level III). The structures of the blood vessels and ducts were similar at each level in the lobules. In the vein casts, communicating vessels were found between the anterior facial vein and the concomitant vein of the facial artery. CONCLUSION: The characteristic treelike structure of the SMG vascular and ductal system may provide useful information for partial gland transfers.

Inhibition of Bcl-2 and Bcl-xL overcomes the resistance to the third-generation EGFR tyrosine kinase inhibitor osimertinib in non-small cell lung cancer.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated significant benefits to patients with non­small cell lung cancer (NSCLC) harboring EGFR­activating mutations; however, acquired resistance limits their long­term efficacy. Therefore, it remains an urgent requirement to discover the underlying mechanisms and investigate novel therapeutic strategies for overcoming the resistance to EGFR TKIs. The present study aimed to determine the mechanism underlying the resistance of NSCLC cells to osimertinib, a third­generation EGFR tyrosine kinase inhibitor, the osimertinib­resistant NSCLC cell sub­line HCC827/OR was established in the present study. It was found that the expression levels of Bcl­2 and Bcl­xL were significantly upregulated in resistant cells compared with sensitive cells. Furthermore, the suppression of Bcl­2 and Bcl­xL through small interfering RNA­mediated gene knockdown or using a small molecule specific inhibitor ABT­263 re­sensitized HCC827/OR cells to osimertinib treatment. Moreover, the combined treatment of HCC827/OR cells with ABT­263 and osimertinib enhanced the rate of cell apoptosis through the mitochondrial apoptotic pathway. Finally, ABT­263 was able to overcome the resistance of osimertinib in xenograft tumor models. In conclusion, these findings may provide an improved concept for the development of a novel combined therapeutic strategy for the treatment of NSCLC resistance to EGFR TKIs.

Clinical and anatomic study on the ducts of the submandibular and sublingual glands.

PURPOSE: To investigate the relationship between the ducts of the submandibular gland (SMG) and sublingual gland (SLG) and discuss its clinical application relating to SMG radiologic examinations and transfer. MATERIALS AND METHODS: The microanatomy of the SMG and SLG was investigated by use of 30 adult cadavers through anatomic dissection by use of a microscope. The relationship between the SMG and SLG ducts was observed and recorded during operations of microvascular autologous SMG transfer in 63 cases of severe keratoconjunctivitis sicca. RESULTS: There were 3 patterns of SLG and SMG duct anatomic variation: 1) The SMG and SLG have their own respective ducts that secrete separately at the orifices of the ducts in the floor of the mouth. 2) The SLG has a major duct that joins the duct of the SMG. 3) The SLG only has many fine ducts (7-15) that secrete in the floor of the mouth. CONCLUSIONS: The anatomy of the ducts of the SMG and SLG is quite complicated. More attention should be paid to the anatomy of the ducts during surgery or imaging procedures related to the SMG.

Immunohistochemistry biomarker TP53 expression predicts the survival of thymomas.

BACKGROUND: Thymomas are rare malignancies. Thymectomy is the optimal therapy which could prolong the survival of patients. However, prognostic factors of thymomas are not clear. METHODS: Thymomas patients were enrolled from 2001 to 2016. Clinical and pathological prognostic factors of thymomas were evaluated by univariate and multivariate analyses. RESULTS: A total number of 98 patients was eligible for this study. All patients were received complete resection (CR). Diagnostic age [elder than the median 60 vs. younger than 60, hazard ratio (HR) =2.325, P=0.027], Masaoka stage (III vs. I, HR =10.756, P<0.001; IV vs. I, HR =6.558, P=0.014), and diabetes mellitus (DM) (with vs. without, HR =0.142, P=0.004) were independent prognostic factors for overall survival (OS). Immunohistochemistry (IHC) biomarker TP53 expression also influenced OS significantly (positive vs. negative, HR =5.157, P=0.018). Furthermore, age (elder than 60 vs. younger than 60, HR =2.980, P=0.022) was independent prognostic factors for recurrence free survival (RFS). CONCLUSIONS: We found that diagnostic age, clinical stages, DM, TP53 expression in IHC, and quality perioperative nursing are prognostic factors in thymomas.

PROTAC Bromodomain Inhibitor ARV-825 Displays Anti-Tumor Activity in Neuroblastoma by Repressing Expression of MYCN or c-Myc.

Neuroblastoma (NB) is one of the most common solid tumors in childhood. To date, targeting MYCN, a well-established driver gene in high-risk neuroblastoma, is still challenging. In recent years, inhibition of bromodomain and extra terminal (BET) proteins shows great potential in multiple of Myc-driven tumors. ARV-825 is a novel BET inhibitor using proteolysis-targeting chimera (PROTAC) technology which degrades target proteins by the proteasome. In this study, we investigated the effect of ARV-825 in neuroblastoma in vitro and in vivo. Our results showed that ARV-825 treatment robustly induced proliferative suppression, cell cycle arrest, and apoptosis in NB cells. Moreover, ARV-825 efficiently depleted BET protein expression, subsequently repressing the expression of MYCN or c-Myc. In the NB xenograft model, ARV-825 profoundly reduced tumor growth and led to the downregulation of BRD4 and MYCN expression in mice. Taken together, these findings provide evidence that PROTAC BET inhibitor is an efficient way to achieve MYCN/c-Myc manipulation, and ARV-825 can be used as a potential therapeutic strategy for the treatment of neuroblastoma.