Enhanced Recovery Protocol Versus Conventional Care in Patients Undergoing Esophagectomy for Cancer: Advantages in Clinical and Patient-Reported Outcomes.

BACKGROUND: This study was designed to compare the clinical and patient-reported outcomes (PROs) between the enhanced recovery after surgery (ERAS) protocol and conventional care in patients undergoing esophagectomy for cancer, which have not previously been compared. METHODS: This single-center retrospective study included prospective PRO data from August 2019 to June 2021. Clinical outcomes included perioperative complications and postoperative length of stay (PLOS). Patient-reported outcomes were assessed by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30) and esophagus-specific module (QLQ-OES18) preoperatively to 6 months postoperatively. Mixed-effects models were used to longitudinally compare quality of life (QOL) scores between the two modes. RESULTS: Patients undergoing conventional care and ERAS were analyzed (n = 348 and 109, respectively). The ERAS group had fewer overall complications, pneumonia, arrhythmia, and a shorter PLOS than the conventional group, and outperformed the conventional group in five functional QLQ-C30 domains and five symptom QLQ-OES18 domains, including less dysphagia (p < 0.0001), trouble talking (p = 0.0006), and better eating (p < 0.0001). These advantages persisted for 3 months postoperatively. For the cervical circular stapled anastomosis, the initial domains and duration of benefit were reduced in the ERAS group. CONCLUSIONS: The ERAS protocol has significant advantages over conventional care in terms of clinical outcomes, lowering postoperative symptom burden, and improving functional QOL in patients who have undergone esophagectomy. Selection of the optimal technique for cervical anastomosis is a key operative component of ERAS that maintains the symptom domains and duration of the advantages of PROs.

Effect of small follicles on clinical pregnancy and multiple pregnancy rates in intrauterine insemination: a cohort study.

STUDY QUESTION: What is the effect of small follicles on clinical pregnancy and multiple pregnancy rates in women undergoing IUI with ovarian stimulation (IUI-OS)? SUMMARY ANSWER: The presence of ≥2 small follicles with a diameter of 10-12 or 12-14 mm was associated with an increased chance of clinical pregnancy and the presence of any 12-14 mm or larger follicles, but not smaller follicles, was statistically significantly associated with an increased risk for multiple pregnancy. WHAT IS KNOWN ALREADY: IUI-OS is widely used as the first-line treatment for unexplained or mild male factor infertility. However, IUI is associated with the risk of multiple pregnancy. While the positive association between the number of follicles ≥14 mm and the chance of pregnancy and the risk of multiple pregnancy is known, the impact of smaller follicles is uncertain. STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study that included women undergoing IUI cycles from January 2007 to May 2021 in one assisted reproduction center. PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied the impact of the number and size of follicles on trigger day on clinical pregnancy and multiple pregnancy rates. Generalized estimation equation regression models were used to compute unadjusted and adjusted odds ratios and 95% CI in all women and only women who achieved clinical pregnancy separately. The chance of clinical pregnancy and multiple pregnancy for different numbers of small follicles in cycles with one >18-mm follicle was calculated using marginal effects estimate. MAIN RESULTS AND THE ROLE OF CHANCE: This cohort included 12 933 IUI cycles in 7504 women. The overall clinical pregnancy rate was 16.1% (2081/12 933), with a multiple pregnancy rate of 10.5% (218/2081). In the adjusted analysis, the chance of clinical pregnancy increased significantly with the increase in the number of follicles with the diameter of 14-16, 16-18, and 18-20 mm. As for 10-12 mm [adjusted odds ratio (aOR) 1.22, 95% CI 1.02-1.46] and 12-14 mm (aOR 1.29, 95% CI 1.07-1.56) follicles, only groups with ≥2 follicles of those sizes showed significantly increased chance of clinical pregnancy. In cycles that led to pregnancy, follicles with the diameter of 12-14 mm were associated with an increased risk of multiple pregnancy (aOR 1.73, 95% CI 1.19-2.53 for one such follicle; aOR 2.27, 95% CI 1.44-3.56 for ≥2 such follicles), while 10- to 12-mm follicles were not significantly associated with multiple pregnancy (aOR 1.18, 95% CI 0.72-1.95 for ≥2 such follicles). The associations of multiple pregnancy were similar when including all cycles. LIMITATIONS, REASONS FOR CAUTION: This was a retrospective observational study from a single center. The records of follicle diameter in our center were of a 2-mm interval which limited our ability to analyze the size of follicle as a continuous variable. Also, the number of cycles with a high number of small follicles was still limited which impeded more detailed analysis on the ≥2 follicles subgroup. Similarly, the value of some parts of the marginal probability estimation for multiple pregnancy versus pregnancy according to size and number of follicles was also limited by the low sample size of certain combinations. WIDER IMPLICATIONS OF THE FINDINGS: Follicles larger than 10 mm, especially those ≥12 mm, may need to be clearly recorded during transvaginal ultrasound surveillance and their potential effects on both pregnancy and multiple pregnancy can be discussed with couples undergoing IUI. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China (Grant numbers 82201912, 82371651, and 82071615) and Shanghai Sailing Program (21YF1423200). B.W.M. is supported by an NHMRC Investigator grant (GNT1176437). B.W.M. reports consultancy for ObsEva and Merck and travel support from Merck. B.W.M. has received research funding from Ferring and Merck. The authors declare no other competing interests. TRIAL REGISTRATION NUMBER: N/A.

Uterine infusion strategies for infertile patients with recurrent implantation failure: a systematic review and network meta-analysis.

BACKGROUND: Intra-uterine infusion treatments were reported to be beneficial to embryo implantation and pregnancy outcomes, and considered as potential therapies for infertile patients with recurrent implantation failure (RIF). Nevertheless, their efficiencies were controversial and there lack of consensus on which intrauterine treatment is the most effective. METHODS: All prospective trials (in Chinese or English) were searched in Databases PubMed, Cochrane, Web of Science, and CNKI from July 2013 to July 2023. We included studies that investigated various uterine infusions, including chorionic gonadotropin, granulocyte colony-stimulating factor, monocytes, platelet-rich plasma, etc. during IVF treatment and reported subsequent pregnancy outcomes. RESULTS: We finally included 56 researches, including 40 randomized controlled trials, 14 non-randomized controlled trials, and 3 prospective cohort studies. This study included a total of 11 uterine perfusion methods: Placebo, Human Chorionic Gonadotropin (HCG), Granulocyte Colony-Stimulating Factor (G-CSF), platelet-rich plasma (PRP), Peripheral Blood Mononuclear Cell (PBMC), Growth hormone (GH), dexamethasone (DEX), Embryo culture supernatant (ESC), PRP combined with G-CSF (PRP + G-CSF), RPR combined with subcutaneous injection of G-CSF (RPR + G-CSFsc), G-CSF combined with subcutaneous injection of AXaIU (G-CSF + AXaIUsc). Intrauterine infusion of HCG, PBMC, G-CSF, and PRP significantly improves pregnancy outcomes in patients with repeated implantation failure compared with blank controls or placebo, and PRP improved the clinical pregnancy and live birth most. GH and ESC infusion might improve the pregnancy outcomes, but uterine infusion of DEX was shown with high miscarriage. The combination therapy did not show a significant advantage over the mono-therapy. CONCLUSIONS: Intrauterine infusion of HCG, PBMC, G-CSF, and PRP are promising strategies for improving pregnancy outcomes for infertile patients with recurrent implantation failure. Among these treatments, PRP may be the best. More researches are required to explore the effect of drug combinations and less commonly used drugs as well. TRIAL REGISTRATION: Our study was registered in PROSPERO and the ID was CRD42023467188.

Coordinate-Free and Low-Order Scaling Machine Learning Model for Atomic Partial Charge Prediction for Any Size of Molecules.

The atomic partial charge is of great importance in many fields, such as chemistry and drug-target recognition. However, conventional quantum-based computing of atomic charges is relatively slow, limiting further applications of atomic charge analysis. With the help of machine learning methods, various kinds of models appear to speed up atomic charge calculations. However, there are still some concerning problems. Some models based on geometric coordinates require high-accuracy geometry optimization as a preprocess, while other models have a limitation on the size of input molecules that narrow the applications of the model. Here, we propose a machine learning atomic charge model based on a message-passing featurizer. This preprocessing featurizer can quickly extract atomic environment information from a molecule according to the connectivity inside the molecule. The resulting descriptor can be used with a neural network to quickly predict the atomic partial charge. The model is able to automatically adapt to any size of molecule while remaining efficient and achieves a root-mean-square error in the Hirshfeld charge prediction of 0.018e, with an overall time complexity of O(n2). Thus, this model could enlarge the range of applications of atomic partial charge to more fields and cases.

Longitudinal patient-reported outcomes after minimally invasive McKeown esophagectomy for patients with esophageal squamous cell carcinoma.

PURPOSE: Surgery for esophageal squamous cell carcinoma (ESCC) is characterized by a poor prognosis and high complication rate, resulting in a heavy symptom burden and poor health-related quality of life (QOL). We evaluated longitudinal patient-reported outcomes (PROs) to analyze the correlations between symptoms and QOL and their changing characteristics during postoperative rehabilitation. METHODS: We investigated patients with ESCC who underwent minimally invasive McKeown esophagectomy at Sichuan Cancer Hospital between April 2019 and December 2019. Longitudinal data of the clinical characteristics and PROs were collected. The MD Anderson Symptom Inventory and European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires were used to assess symptoms and QOL and compare the trajectories of PROs during the investigation. RESULTS: A total of 244 patients with ESCC were enrolled in this study. Regarding QOL, role and emotional functions returned to baseline at 1 month after surgery, and cognitive and social functions returned to baseline at 3 months after surgery. However, physical function and global QOL did not return to baseline at 1 year after surgery. At 7 days and 1, 3, 6, and 12 months after surgery, the main symptoms of the patients were negatively correlated with physical, role, emotional, cognitive, and social functions and the overall health status (P < 0.05). CONCLUSION: Patients with ESCC experience reduced health-related QOL and persisting symptoms after minimally invasive McKeown esophagectomy, but a recovery trend was observed within 1 month. The long-term QOL after esophagectomy is acceptable.

Anti-tumor necrosis factor-α therapy may not be safe during pregnancy in women with inflammatory bowel disease: an updated meta-analysis and systematic review.

BACKGROUND: Inflammatory Bowel Disease (IBD) affects reproductive-aged women. Active disease can lead to decreased fertility. Although the vast majority of international guidelines recommend for the continuation of anti-TNF-α during pregnancy, recent studies have raised concerns about the safety of anti-tumor necrosis factor-α (TNF-α) therapy during pregnancy, both for patients and for physicians. METHODS: Studies that evaluate the safety of anti-TNF-α therapy in pregnant women with IBD were identified using bibliographical searches. An updated meta-analysis was performed for pregnancy outcomes, such as live birth, abortion, still birth, preterm birth, low birth weight, congenital abnormalities, and neonatal infection. Odds ratio (OR) with 95% confidence interval (CI) are reported. Data on disease activity, timing of anti-TNF-α therapy were collected for further analysis. RESULTS: Overall, 11 studies were screened from on-line databases and international meeting abstracts. An increased risk of abortion (OR, 1.33; 95% CI, 1.02-1.74; P = 0.04) and preterm birth (OR, 1.16; 95% CI, 1.05-1.28; P = 0.004), and a decreased risk of live birth (OR, 0.83; 95% CI, 0.74-0.94; P = 0.002]) were found in the anti-TNF-α therapy group compared with the control group (no use of anti-TNF-α therapy). The subgroup analyses based on the disease activity showed there is no significant association between the use of anti-TNF-α therapy during pregnancy on adverse pregnancy outcomes of abortion, preterm birth, and live birth. The rates of still birth, low birth weight, and congenital abnormalities in the anti-TNF-α therapy group were not significantly different from those in the control group. CONCLUSIONS: Anti-TNF-α therapy does not increase the risks of still birth, low birth weight, and congenital abnormalities; however it may be assicated with increased risks of abortion and preterm birth, which are accompanied by a lower rate of live birth. Although these findings may be confounding by potential disease activity, they offer some opposite viewpoints with biologic agent use. Therefore, more studies are required to further confirm the safety of anti-TNF-α therapy in pregnancy with IBD.

Identification and treatment of persistent small airway dysfunction in paediatric patients with asthma: a retrospective cohort study.

BACKGROUND: Asthma is a common respiratory disease. In asthma, the small airways have more intensive inflammation and prominent airway remodelling, compared to the central airways. We aimed to investigate the predictive value of risk factors and the fractional concentration of exhaled nitric oxide (FeNO) for persistent small airway dysfunction (p-SAD), and compare the effects of different treatment modalities. METHODS: This retrospective cohort study included 248 children with asthma (aged 4-11 years). Binary logistic regression was used to analyse the risk factors for p-SAD. Correlations among FEV1/FVC, small airway function parameters, and FeNO levels in patients with asthma were analysed using Spearman's rank correlation. The receiver operating characteristic curve and the Delong test were used to analyse the predictive value of FeNO for p-SAD. Differences in the treatment effects of inhaled corticosteroids (ICS) and ICS with a long-acting beta-agonist (ICS/LABA) on p-SAD were analysed using Fisher's exact test. RESULTS: Asthmatic children with older age of receiving the regular treatment (OR 1.782, 95% CI 1.082-2.935), with younger age at the time of onset of suspected asthma symptoms (OR 0.602, 95% CI 0.365-0.993), with longer duration of using ICS or ICS/LABA (OR 1.642, 95% CI 1.170-2.305) and with worse asthma control (OR 3.893, 95% CI 1.699-8.922) had increased risk for p-SAD. Significant negative correlations of small airway function parameters with FeNO at a 200 mL/s flow rate (FeNO200), and the concentration of nitric oxide in the alveolar or acinar region (CaNO) were observed. The areas under the curve of FeNO200 (cut-off:10.5ppb), CaNO (cut-off:5.1ppb), and FeNO200 combined with CaNO were 0.743, 0.697, and 0.750, respectively, for asthma with p-SAD. After using ICS or ICS/LABA, switching to ICS/LABA was easier than continuing with ICS to improve small airway dysfunction (SAD) in the 8th month. CONCLUSIONS: Paediatric asthma with p-SAD is associated with older age at receiving regular treatment, younger age at the time of onset of suspected asthma symptoms, longer duration of using ICS or ICS/LABA, worse asthma control, and higher FeNO200 and CaNO levels, all of which can be combined with small airway function indicators to distinguish p-SAD from asthma. ICS/LABA improves SAD better than ICS alone.

Graphene/Cholesteric Liquid-Crystal-Based Electro-Driven Thermochromic Light Modulators toward Wide-Gamut Dynamic Light Color-Tuning-Related Applications.

Light filters are ubiquitous in projection and display techniques, illumination engineering, image sensing, photography, etc., while those enabling wide-gamut dynamic light color tuning are still lacking. Herein, by combining the electro-heating capability of graphene and unique optical properties (thermochromism and circular dichroism) of small-molecule-weight cholesteric liquid crystal (ChLC), a brand-new thermochromic light modulator is constructed as actively tunable color filter. Transparent graphene/glass hybrid with reasonably high conductivity serves both as a high-performance heater for actuating the thermochromism of temperature-responsive ChLC and as neutral light attenuator for brightness control. Thanks to the temperature- and polarization-dependent spectral properties of the ChLC, widely tunable hue and saturation properties of transmission light color are achieved, respectively. Several intriguing applications, e.g., color-variable smart windows for backlight color tuning and color-variable filters for photography, are also demonstrated. This work hereby provides new paradigms for promoting the applications of graphene/ChLC-based light modulators in next-generation light-management-related scenarios.

High Moisture-Barrier Performance of Double-Layer Graphene Enabled by Conformal and Clean Transfer.

Graphene films that can theoretically block almost all molecules have emerged as promising candidate materials for moisture barrier films in the applications of organic photonic devices and gas storage. However, the current barrier performance of graphene films does not reach the ideal value. Here, we reveal that the interlayer distance of the large-area stacked multilayer graphene is the key factor that suppresses water permeation. We show that by minimizing the gap between the two monolayers, the water vapor transmission rate of double-layer graphene can be as low as 5 × 10-3 g/(m2 d) over an A4-sized region. The high barrier performance was achieved by the absence of interfacial contamination and conformal contact between graphene layers during layer-by-layer transfer. Our work reveals the moisture permeation mechanism through graphene layers, and with this approach, we can tailor the interlayer coupling of manually stacked two-dimensional materials for new physics and applications.

Impact of haemostasis methods during ovarian cystectomy on ovarian reserve: a pairwise and network meta-analysis.

BACKGROUND: Haemostasis during ovarian cystectomy is reported to damage the ovarian reserve, but the comparative impacts of three haemostasis methods (bipolar energy, suture and haemostatic sealant) on ovarian reserve in patients with ovarian cysts are not well known. METHODS: The Cochrane Library, PubMed and Web of Science databases were searched from the date of inception of the database to June 2022 for literature exploring the impact of haemostasis methods during ovarian cystectomy on ovarian reserve. A traditional meta-analysis was performed using Review Manager software. A network meta-analysis (NMA) was performed using Stata and GemTC software. RESULTS: The direct meta-analysis comparison indicated that the mean postoperative reduction of anti-Müllerian hormone (AMH) level was significantly higher in the electrocoagulation (bipolar) group than suture and haemostatic sealant group, both in the overall group and subgroup of women with ovarian endometrioma. In NMA, the reduction of postoperative AMH levels in the electrocoagulation (bipolar) group was higher than the suture group at 6 months with a statistical significance, and at 1, 3 and 12 months without a significant difference. The difference in the postoperative decrease of AMH level did not reach statistical significance between suture and sealant, coagulation and haemostatic sealant. The comprehensive ranking results revealed that suture treatment was, with the highest probability, beneficial to the protection of the ovarian reserve. CONCLUSIONS: There was insufficient research to detect the optimal haemostasis method for ovarian reserve preservation in ovarian cystectomy. Nevertheless, haemostasis by electrocoagulation (bipolar) should be avoided when possible, and the suture might be considered as the best choice.

Haemostasis during ovarian cystectomy is reported to damage the ovarian reserve, but the comparative impacts of three haemostasis methods (bipolar energy, suture and haemostatic sealant) on ovarian reserve in patients with ovarian cysts are not well known. The level of AMH is the most widely used surrogate for ovarian reserve. Our research compared the impact of three haemostasis methods (electrocoagulation, suture and haemostatic sealant) on changes in the levels of anti-Müllerian hormone at 1, 3, 6 and 12 month(s) after the operation. The outcomes revealed that there was insufficient research to detect the optimal haemostasis method for ovarian preservation in ovarian cystectomy. Nevertheless, haemostasis by electrocoagulation (bipolar) should be avoided when possible, and the suture might be considered as the best choice.

Assessing the Clinical Efficacy of Stereotactic Puncture in Combination with Postoperative Rehabilitation Training for Hypertensive Cerebral Hemorrhage.

Objective: This study aims to investigate the clinical efficacy of stereotactic puncture for intracerebral hematoma removal, combined with postoperative individualized health education and rehabilitation training concerning hypertensive cerebral hemorrhage. We also assessed its impact on rebleeding prevention and neurological function recovery. Methods: A retrospective study was conducted, including 90 patients diagnosed with hypertensive cerebral hemorrhage in our hospital between March 2020 and June 2022. The inclusion criteria were patients with an episcleral hematoma volume exceeding 30 ml. The control group underwent minimally invasive removal using neuroendoscopy (45 patients), while the observation group received stereotactic puncture for intracerebral hematoma removal (45 patients). After surgery, both groups received individualized health education and rehabilitation training. The assessment included: (1) determination of clinical efficacy, (2) monitoring for rebleeding within 72 hours after surgery, (3) evaluation of daily living ability using the Barthel index, (4) assessment of motor function using the Fugl-Meyer Assessment (FMA) scale, and (5) monitoring for adverse reactions. Results: The observation group, which underwent stereotactic puncture for intracerebral hematoma removal combined with postoperative individualized health education and rehabilitation training, exhibited significantly better clinical efficacy, Barthel index scores, and FMA scores compared to the control group that underwent neuroendoscopic minimally invasive removal (P < .05). Notably, no complications were observed in either group, and there was no significant difference in the postoperative bleeding rate within 72 hours. Conclusions: The combined treatment approach of stereotactic puncture for intracerebral hematoma removal and postoperative individualized health education and rehabilitation training demonstrates promising therapeutic effects in managing hypertensive cerebral hemorrhage. This approach also contributes significantly to the rehabilitation of patients with hypertensive cerebral hemorrhage, warranting widespread clinical adoption.

GBAS Regulates the Proliferation and Metastasis of Ovarian Cancer Cells by Combining with eEF1A1.

BACKGROUND: The glioblastoma-amplified sequence (GBAS) is a newly identified gene that is amplified in approximately 40% of glioblastomas. This article probes into the expression, prognostic significance, and possible pathways of GBAS in ovarian cancer (OC). METHOD: Immunohistochemical methods were used to evaluate the expression level of GBAS in OC and its relationship with clinicopathological characteristics and prognosis. Glioblastoma-amplified sequence shRNA was designed to transfect into OC cell lines to silence GBAS expression, then detect the proliferation, apoptosis, and migration ability of the cell. Furthermore, an in vitro tumor formation experiment in mice was constructed to prove the effect of GBAS expression on the growth of OC in vivo. To further study the regulation mechanism of GBAS, we performed co-immunoprecipitation (Co-IP) and shotgun LC-MS mass spectrometry identification. RESULTS: Immunohistochemistry indicated that GBAS was markedly overexpressed in OC compared with normal ovarian tissue and was associated with lymph node metastasis. Inhibition of GBAS expression can significantly reduce OC cell proliferation, colony formation, promote cell apoptosis, and reduce the ability of cell migration and invasion. In vivo tumor formation experiments showed that the size and weight of tumors in mice after GBAS expression knockdown was significantly smaller. Glioblastoma-amplified sequence may be combined with elongation factor 1 alpha 1 (eEF1A1) to achieve its regulation in OC. Bioinformatics analysis data indicate that GBAS may be a key regulator of mitochondria-associated pathways, therefore controlling cancer progression. MicroRNA-27b, MicroRNA-23a, and MicroRNA-590 may directly targeting GBAS affects the biological behavior of OC cells. CONCLUSION: The glioblastoma-amplified sequence may regulate the proliferation and metastasis of OC cells by combining with eEF1A1.

Residual image recovery method based on the dual-camera design of a compressive hyperspectral imaging system.

Compressive hyperspectral imaging technology can quickly detect the encoded two-dimensional measurements and reconstruct the three-dimensional hyperspectral images offline, which is of great significance for object detection and analysis. To provide more information for reconstruction and improve the reconstruction quality, some of the latest compressive hyperspectral imaging systems adopt a dual-camera design. To utilize the information from additional camera more efficiently, this paper proposes a residual image recovery method. The proposed method takes advantage of the structural similarity between the image captured by the additional camera and the hyperspectral image, combining the measurements from the additional camera and coded aperture snapshot spectral imaging (CASSI) sensor to construct an estimated hyperspectral image. Then, the component of the estimated hyperspectral image is subtracted from the measurement of the CASSI sensor to obtain the residual data. The residual data is used to reconstruct the residual hyperspectral image. Finally, the reconstructed hyperspectral image is the sum of the estimated and residual image. Compared with some state-of-the-art algorithms based on such systems, the proposed method can significantly improve the reconstruction quality of hyperspectral image.

Suppression of JNK/ERK dependent autophagy enhances Jaspine B derivative-induced gastric cancer cell death via attenuation of p62/Keap1/Nrf2 pathways.

Gastric cancer is one of the most common cancers with few effective treatments, a new treatment agent is desperately needed. C-2, a Jaspine B derivative, has shown anti-cancer efficacy in gastric cancer cells. The anti-cancer mechanism, however, remains unknown. As a result, we investigate the anti-cancer effect and the underlying mechanism of C-2 in gastric cancer cells. The results showed that C-2 selectively reduced the proliferation of gastric cancer cells when compared to normal epithelial gastric cells. Western blotting and flow cytometry further demonstrated that Caspase9 is involved in causing cell death. Meanwhile, C-2 triggered autophagy in gastric cancer cells, inhibition of which with LY294002 can enhance the anti-proliferative activity of C-2. Next, we found that C-2 triggered autophagy through activating JNK/ERK, and that inhibitors of these proteins exacerbated C-2 induced cell death. Mechanically, enhanced phosphorylation of JNK/ERK elevated Beclin-1 by disturbing Beclin-1/Bcl-xL or Beclin-1/Bcl-2 complexes, resulting in autophagy and up-regulation of p62. Finally, p62 binds Keap1 competitively to release Nrf2, boosting Nrf2 translocation from the cytoplasm to the nucleus and triggering expression of Nrf2 target genes, so enhancing survival. C-2 inhibited the growth of gastric cancer cells, while JNK/ERK dependent autophagy antagonized C-2 induced cell growth inhibition through p62/Keap1/Nrf2 pathway.

Clinical characteristics, pregnancy outcomes and ovarian function of pregnancy-associated breast cancer patients: a retrospective age-matched study.

BACKGROUND: Pregnancy-associated breast cancer (PABC) is a rare disease with increasing incidence. The prognosis, pregnancy outcomes and subsequent ovarian function of PABC patients are attracting attention. METHODS: Sixty-three PABC patients and 126 age-matched non-PABC patients were obtained in Tongji Hospital from January 2011 to September 2019. The clinical characteristics and ovarian function of PABC patients were compared with those of non-PABC patients. The pregnancy outcomes and neonatal outcomes of patients with breast cancer diagnosed during pregnancy (BCP) were described. Nonparametric tests, the χ2-test Kaplan-Meier, Cox regression and binomial logistic regression were used for analysis. RESULTS: PABC patients were diagnosed with a more advanced tumour stage (II: 47.6% vs. 45.2%, III: 33.3% vs. 19.8%, IV 3.2% vs. 0%, p = 0.003), which caused worse progression-free survival (PFS) (log-rank p = 0.0138) and breast cancer-specific survival (CSS) (log-rank p = 0.0076) than non-PABC patients. Tumour stage (III/IV vs. 0/I/II) (HR 16.017, 95% CI 5.830 ~ 44.006, p < 0.001) and endocrine therapy (HR 0.254, 95% CI 0.099 ~ 0.653, p = 0.004) were predictors of PFS. Tumour stage (III/IV vs. 0/I/II) (HR 30.875, 95% CI 7.232 ~ 131.820, p < 0.001), endocrine therapy (HR 0.200, 95% CI 0.049 ~ 0.818, p = 0.025) and targeted therapy (HR 0.143, 95% CI 0.028 ~ 0.743, p = 0.021) were predictors for breast CSS. Among the 15 BCP patients, 11 patients voluntarily continued their pregnancy, and the newborns had no obvious birth defects, either in 5 patients who received chemotherapy or in 6 patients who did not receive chemotherapy during pregnancy. Among the patients who received chemotherapy and did not receive endocrine therapy, 24 PABC patients and 48 non-PABC patients experienced chemotherapy-induced amenorrhea. There was no significant difference in resumption of menstruation between the two groups at 6 months and 12 months after the end of chemotherapy. No potential factors affecting resumption of menstruation were found. CONCLUSION: Pregnancy at diagnosis or within 1 year after delivery was not a risk factor for a worse prognosis in PABC patients. Compared with non-PABC patients, patients with PABC presented more aggressive tumour characteristics, which could mostly explain the worse prognosis observed in PABC patients. Receiving the appropriate regimen of chemotherapy in the second and third trimesters did not affect the maternal outcomes or neonatal outcomes of BCP patients. The special physiological state during pregnancy and lactation did not interfere with the damage of chemotherapy to ovarian function.

CT-707 overcomes hypoxia-mediated sorafenib resistance in Hepatocellular carcinoma by inhibiting YAP signaling.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Sorafenib is the first-line treatment for advanced HCC, but the anti-cancer effects remain to be improved as indicated by its low response rates and failure to prolong the progression-free survival (PFS). Thus, it is urgent to explore approaches to improve the clinical outcome. MATERIALS AND METHODS: The effect of Sorafenib in HCC was analyzed by SRB (sulforhodamine B) assay in normoxia and hypoxia, respectively. The different dose combination effect of CT707 and sorafenib was analyzed by SRB assay in hypoxia. Flow cytometry assay was used to detect the cell apoptosis rate with CT707 and sorafenib treatment in hypoxia. Western blotting was used to detect the expression levels of apoptosis -related proteins and the mechanism of CT707 overcome the resistance of sorafenib in hypoxia. RESULTS: Our study showed that the characteristic intratumor hypoxia of advanced HCC is one of the major factors which mediated the drug resistance towards sorafenib in HCC. And CT-707, a novel multi-kinase inhibitor, could sensitize the hypoxic HCC cells towards sorafenib. Further studies showed that CT-707 abolished the nuclear translocation of Yes Associate-Protein (YAP), which has been demonstrated as one of mechanism of hypoxia-mediated sorafenib-resistance in HCC. CONCLUSIONS: Overall, this study not only favors the development of this novel multi-kinase inhibitor CT-707 as a therapeutic agent against HCC, but also provides a potential strategy to overcome the hypoxia-mediated resistance to sorafenib in HCC patients.

MScanFit motor unit number estimation of human anconeus muscle.

INTRODUCTION/AIMS: Motor unit number estimation (MUNE) studies of the anconeus muscle are very limited, although the information they provide is useful for neurophysiological investigations. The objective of this study was to estimate the number of motor units in the anconeus muscle. METHODS: Compound muscle action potential scans of the anconeus muscle were recorded from 11 healthy participants, all of whom were tested on two occasions. MUNE was determined from the MScanFit program. RESULTS: The average MUNE of the anconeus muscle was 55.09 ± 3.27 (mean ± standard error of the mean) for the first test and 54.64 ± 3.70 for the retest, demonstrating excellent measurement reliability, with an intraclass correlation coefficient of 0.90. DISCUSSION: A relatively low motor unit number is found in the anconeus, a muscle not comprehensively studied in literature.

Profiling patient-reported symptom recovery from oesophagectomy for patients with oesophageal squamous cell carcinoma: a real-world longitudinal study.

PURPOSE: Oesophageal squamous cell carcinoma (ESCC) patients have severe symptom burden after oesophagectomy; however, longitudinal studies of symptom recovery after surgery are scarce. This study used longitudinal patient-reported outcome (PRO)-based symptoms to identify severe symptoms and profile symptom recovery from surgery in patients undergoing oesophagectomy. METHODS: Oesophageal cancer patients (N = 327) underwent oesophagectomy were consecutively included between April 2019 and March 2020. Data were extracted from the Sichuan Cancer Hospital's Esophageal Cancer Case Management Registration Database. Symptom assessment time points were pre-surgery and 1, 3, 5, 7, 14, 21, 30, and 90 days post-surgery using the Chinese version of the MD Anderson Symptom Inventory. And each symptom was rated on an 11-point scale, with 0 being 'not present' and 10 being 'as bad as you can imagine'. The symptom recovery trajectories were profiled using mixed effect models and Kaplan-Meier analysis. RESULTS: The most-severe symptoms on day 1 after oesophagectomy were pain, fatigue, dry mouth, disturbed sleep, and distress. The severity of symptoms peaked on day 1 after surgery. The top two symptoms were fatigue (mean: 5.44 [SD 1.88]) and pain (mean: 5.23 [SD 1.29]). Fatigue was more severe 90 days after surgery than at baseline (mean: 1.77 [SD 1.47] vs 0.65 [SD 1.05]; P < .0001). Disturbed sleep and distress persisted from pre-surgery to 90 days post-surgery; average sleep recovery time was up to 20 days, and 50.58% of patients had sleep disturbances 90 days post-surgery. CONCLUSIONS: Early post-operative pain management after oesophagectomy should be considered. Characteristics and intervention strategies of post-operative fatigue, distress, and disturbed sleep in oesophageal cancer patients warrant further studies.

A Nomogram to Better Predict the In-Hospital Mortality of Trauma Patients with Sepsis in the Intensive Care Unit.

Background: Trauma has a high incidence and mortality worldwide, and sepsis is one of the main causes of mortality in trauma patients. Therefore, it is essential to identify the risk factors of in-hospital mortality for trauma patients with sepsis. Methods: Data were extracted from the Medical Information Mart for Intensive Care III database and divided into a training set and internal validation set, and another Chinese dataset was used as external validation set. Then, risk factors were estimated using univariate and multivariate logistic regression analyses in the training set. Finally, a nomogram was created to predict the probability of in-hospital mortality for trauma patients with sepsis. Results: A total of 503 patients were enrolled in our study (335 in the training set and 168 in the validation set). Multivariate logistic regression analysis revealed that age (1.047 [1.025-1.071]), respiratory rate (1.258 [1.135-1.394]), PTT (1.026 [1.008-1.044]), ventilation (6.703 [1.528-29.408]), and vasopressor use (3.682 [1.502-9.025]) were independent factors associated with in-hospital mortality. The nomogram for trauma-related sepsis predicted in-hospital mortality with AUC values of 0.8939 in the training set, 0.8200 in the internal validation set, and 0.7779 in the external validation set. Conclusions: The new nomogram has a well predicted value for in-hospital mortality for patients with trauma and sepsis in intensive care units.

Oncologic outcomes of fertility-sparing surgery in early stage epithelial ovarian cancer: a population-based propensity score-matched analysis.

OBJECTIVE: To evaluate the safety of fertility-sparing surgery (FSS) in reproductive women (younger than 50 years) with early epithelial ovarian cancer (EOC). METHODS: Reproductive women diagnosed with stage I EOC in the Surveillance, Epidemiology and End Results (SEER) database were identified. Surgeries that did not undergo hysterectomy and/or bilateral salpingo-oophorectomy were categorized as FSS, whereas non-FSS included bilateral salpingo-oophorectomy and hysterectomy. Propensity-score matching (PSM) was conducted to balance the covariates. Risk factor was identified by COX analysis. Kaplan-Meier curves were performed to evaluate the overall survival (OS) and cancer-specific survival (CSS). RESULTS: 3556 patients with stage I EOC were identified and divided into non-FSS group and FSS group. After PSM, 625 pairs of patients with stage I EOC were included. FSS was not inferior to non-FSS in the OS curve [HR 0.9127, 95% CI (0.6971 ~ 0.1.195), P = 0.5174; HR: 0.9378, 95% CI (0.6358 ~ 0.1.383), P = 0.7460] and the CSS curve [HR 0.8284, 95% CI (0.5932 ~ 1.157), P = 0.2949; HR 0.9003, 95% CI (0.5470 ~ 1.482), P = 0.6803] both in overall cohort and in matched cohort. Univariate COX analysis identified older age (45-49), moderate-differentiated to un-differentiation grade, IC stage, bigger tumor size (> 10 cm) and chemotherapy as risk factors of prognostic outcome (P < 0.1). Not only in univariate subgroup analyses but also in bivariate factors subgroup analysis, the evidence was not enough to regard FSS as a harmful factor compared with non-FSS. CONCLUSIONS: Fertility-sparing surgery was comparable to non-FSS in terms of survival in reproductive women with stage I EOC. Patients with high-risk factors could also consider FSS as an effective alternative compared with non-FSS.