Risk factors for severe complications and salvage management in direct-to-implant immediate breast reconstruction: A retrospective study.

Controversies regarding the risk factors affecting direct-to-implant (DTI) immediate breast reconstruction still exist. This study aimed to evaluate the risk factors for severe complications in DTI breast reconstruction and explore potential salvage management strategies. We conducted a retrospective review of 238 patients (240 breasts) who underwent DTI immediate breast reconstruction between 2011 and 2020. Multivariate logistic regression analyses were used to identify the risk factors predicting severe complications. Seventeen (7.08%) reconstructed breasts experienced severe complications, of which only 5 were successfully salvaged through surgical revision, while the others failed and resulted in implant removal. Multivariate analyses demonstrated that mesh use [odds ratio (OR) = 4.054, 95% confidence interval: 1.376-11.945, P = .011] and post-mastectomy radiotherapy (odds ratio = 4.383, 95% confidence interval 1.142-16.819, P = .031) were independent predictors of severe complications. Mesh use and post-mastectomy radiotherapy for breast reconstruction increase the risk of severe complications. Despite positive surgical treatment, the successful salvage rate was poor.

Sialic acid in human milk and infant formulas in China: concentration, distribution and type.

This study compared the concentrations, types and distributions of sialic acid (SA) in human milk at different stages of the postnatal period with those in a range of infant formulas. Breast milk from mothers of healthy, full-term and exclusively breastfed infants was collected on the 2nd (n 246), 7th (n 135), 30th (n 85) and 90th (n 48) day after birth. The SA profiles of human milk, including their distribution, were analysed and compared with twenty-four different infant formulas. Outcome of this observational study was the result of natural exposure. Only SA of type Neu5Ac was detected in human milk. Total SA concentrations were highest in colostrum and reduced significantly over the next 3 months. Approximately 68·7­76·1 % of all SA in human milk were bound to oligosaccharides. Two types of SA, Neu5Ac and Neu5Gc, have been detected in infant formulas. Most SA was present in infant formulas combined with protein. Breastfed infants could receive more SA than formula-fed infants with the same energy intake. Overall, human milk is a preferable source of SA than infant formulas in terms of total SA content, dynamics, distribution and type. These SA profiles in the natural state are worth to be considered by the production of formulas because they may have a great effect on infant nutrition and development.

1,25(OH)2 D3 inhibits Lewis lung cancer cell migration via NHE1-sensitive metabolic reprograming.

High prevalence and metastasis rates are characteristics of lung cancer. Glycolysis provides energy for the development and metastasis of cancer cells. The 1,25-dihydroxy vitamin D3 (1,25(OH)2 D3 ) has been linked to reducing cancer risk and regulates various physiological functions. We hypothesized that 1,25(OH)2 D3 could be associated with the expression and activity of Na+ /H+ exchanger isoform 1 (NHE1) of Lewis lung cancer cells, thus regulating glycolysis as well as migration by actin reorganization. Followed by online public data analysis, Vitamin D3 receptor, the receptor of 1,25(OH)2 D3 has been proved to be abundant in lung cancers. We demonstrated that 1,25(OH)2 D3 treatment suppressed transcript levels, protein levels, and activity of NHE1 in LLC cells. Furthermore, 1,25(OH)2 D3 treatment resets the metabolic balance between glycolysis and OXPHOS, mainly including reducing glycolytic enzymes expression and lactate production. In vivo experiments showed the inhibition effects on tumor growth as well. Therefore, we concluded that 1,25(OH)2 D3 could amend the NHE1 function, which leads to metabolic reprogramming and cytoskeleton reconstruction, finally inhibits the cell migration.

The effects of Ascophyllum nodosum, Camellia sinensis-leaf extract, and their joint interventions on glycolipid and energy metabolism in obese mice.

Objectives: Obesity is often associated with glucolipid and/or energy metabolism disorders. Ascophyllum nodosum extract (seaweed extract, SE) and Camellia sinensis-leaf extract (tea extract, TE) have been reported to promote positive metabolic effects through different mechanisms. We investigated the effects of SE and TE on metabolic homeostasis in diet-induced obese mice and discussed their functional characteristics. Methods: Male C57BL/6J mice fed with high-fat diets for 8 weeks were established as obese models and subsequently divided into different intervention groups, followed by SE, TE, and their joint interventions for 10 weeks. Body weight and food intake were monitored. Fasting glucose and oral glucose tolerance tests were interspersed during the experiment. After the intervention, the effects on obesity control were assessed based on body composition, liver pathology section, blood lipids and glucose, respiratory exchange ratio (RER), energy expenditure (EE1, EE2, and EE3), inflammatory factors, lipid anabolism enzymes, and gut flora of the obese mice. Results: After continuous gavage intervention, the mice in the intervention groups exhibited lower body weight (lower ~4.93 g, vs. HFD 38.02 g), peri-testicular fat masses (lower ~0.61 g, vs. HFD 1.92 g), and perirenal fat masses (lower ~0.21 g, vs. HFD mice 0.70 g). All interventions prevented diet-induced increases in plasma levels of glucose, adiponectin, leptin, and the inflammatory factors IL-1ß and TNF-α. The RER was modified by the interventions, while the rhythm of the RER was not. Blood lipids (total cholesterol, triglycerides, and LDL) decreased and were associated with lower lipid anabolism enzymes. In addition, the SE and TE interventions altered the structure and abundance of specific flora. Different interventions inhibited the growth of different genera positively associated with obesity (Escherichia-Shigella, Helicobacter, etc.) and promoted the growth of Akkermansia and Bacteroides, thus affecting the chronic inflammatory state. Conclusion: SE and TE both have synergistic effects on weight control and glucolipid metabolism regulation by improving insulin sensitivity and reducing lipid synthesis-related enzyme expression, whereas the combination of SE and TE (3:1) has a better effect on regulating energy metabolism and inhibiting chronic inflammation.

Effects of Poria cocos extract and protein powder mixture on glucolipid metabolism and rhythm changes in obese mice.

Herein, we explored the effects of Poria cocos extract, protein powder mixture, and their combined intervention on weight loss in high-fat diet (HFD)-induced obese mice. Male C57BL/6J mice were selected and fed a HFD for 8 weeks; obese mice that were successfully modeled were divided into modeling and five intervention groups, and given the corresponding treatment for 10 weeks. Body weight, fat, and muscle tissue, blood glucose, lipids, inflammatory factors, and other glucose and lipid metabolism-related indicators were measured to evaluate the effect of P. cocos and protein powder intervention on weight loss in obese mice. The body weight of the intervention group was reduced compared with the HFD group. Fat content of mice in F3PM group decreased significantly (p < .05). Levels of blood glucose, lipids, adiponectin, leptin, and inflammatory factors, including interleukin-1 ß and tumor necrosis factor- α showed improvement. Lipoprotein lipase (lower about 2.97 pg/ml, vs. HFD mice 10.65 mmoL/ml) and sterol regulatory element-binding transcription factor (lower about 1413.63 pg/ml, vs. HFD mice 3915.33 pg/ml) levels in liver tissue were decreased. The respiratory exchange rate (RER) of mice in the HFD and subject intervention groups had no circadian rhythm and was maintained at approximately 0.80. The protein powder mixture (PM) group had the lowest RER (p < .05), the P. cocos extract (FL) and F1PM groups had similar RER to the HFD group (p < .05), and the F2PM group had a higher RER than the HFD group (p < .05). And food intake and energy metabolism returned to circadian rhythm, with an increase in the dose of P. cocos extract, the feeding rhythms of F1PM, F2PM, and F3PM were closer to that of the normal diet (ND) group. Feeding intervention with P. cocos and protein powder improved fat distribution, glucolipid metabolism, and energy metabolism, with the combination of F3PM showing more diverse benefits.

Effects of Coix seed extract, Lactobacillus paracasei K56, and their combination on the glycolipid metabolism in obese mice.

Coix seed extract (CSE) and probiotics have been reported to regulate glycolipid metabolism through different modes of action. We tested the effects of CSE, Lactobacillus paracasei K56, and their combination to determine whether they have synergistic effects on glycolipid metabolism of obese mice. We fed male C57BL/6J mice with high-fat diet for 8 weeks to establish an obesity model. The obesity mice were selected and divided into five groups: the model control group and four intervention groups. After 10 weeks of continuous gavage intervention, the mice in the intervention groups exhibited lower body weight (lower about 2.31-4.41 g, vs. HFD 42.25 g, p < 0.01), and epididymal (lower about 0.58-0.92 g, vs. HFD 2.50 g, p < 0.01) and perirenal fat content (lower about 0.24-0.42 g, vs. HFD 0.88 g, p < 0.05); decreased fasting blood glucose, total cholesterol, triglycerides, and VLDL; and increased HLDL, respiratory exchange ratio, energy expenditure, and amount of exercise performed. K56 + CSE-combined intervention groups were more effective in lowering blood glucose, IL-1ß, and TNF-α levels than the CSE and K56 alone interventions. The content of fatty acid synthase and SREBP-1c protein in liver tissue was lower. The combination has synergistic effects on weight control, fat reduction, and blood glucose regulation by improving the chronic inflammatory state and reducing the content of lipid synthesis-related enzymes of obese mice, which can hinder chronic disease progression. PRACTICAL APPLICATION: Coix seed extract can be used in obese people to regulate abnormal glucose and lipid metabolism and delay the development of chronic diseases.

Vaccarin alleviates endothelial inflammatory injury in diabetes by mediating miR-570-3p/HDAC1 pathway.

Vaccarin is a flavonoid glycoside, which has a variety of pharmacological properties and plays a protective role in diabetes and its complications, but its mechanism is unclear. In this study, we aim to investigate whether histone deacetylase 1(HDAC1), a gene that plays a pivotal role in regulating eukaryotic gene expression, is the target of miR-570-3p in diabetic vascular endothelium, and the potential molecular mechanism of vaccarin regulating endothelial inflammatory injury through miR-570-3p/HDAC1 pathway. The HFD and streptozotocin (STZ) induced diabetes mice model, a classical type 2 diabetic model, was established. The aorta of diabetic mice displayed a decrease of miR-570-3p, the elevation of HDAC1, and inflammatory injury, which were alleviated by vaccarin. Next, we employed the role of vaccarin in regulating endothelial cells miR-570-3p and HDAC1 under hyperglycemia conditions in vitro. We discovered that overexpression of HDAC1 counteracted the inhibitory effect of vaccarin on inflammatory injury in human umbilical vein endothelial cells (HUVECs). Manipulation of miRNA levels in HUVECs was achieved by transfecting cells with miR-570-3p mimic and inhibitor. Overexpression of miR-570-3p could decrease the expression of downstream components of HDAC1 including TNF-α, IL-1ß, and malondialdehyde, while increasing GSH-Px activity in HUVECs under hyperglycemic conditions. Nevertheless, such phenomenon was completely reversed by miR-570-3p inhibitor, and administration of miR-570-3p inhibitor could block the inhibition of vaccarin on HDAC1 and inflammatory injury. Luciferase reporter assay confirmed the 3'- UTR of the HDAC1 gene was a direct target of miR-570-3p. In summary, our findings suggest that vaccarin alleviates endothelial inflammatory injury in diabetes by mediating miR-570-3p/HDAC1 pathway. Our study provides a new pathogenic link between deregulation of miRNA expression in the vascular endothelium of diabetes and inflammatory injury and provides new ideas, insights, and choices for the scope of application and medicinal value of vaccarin and some potential biomarkers or targets in diabetic endothelial dysfunction and vascular complications.

Concentration and distribution of sialic acid in human milk and its correlation with dietary intake.

Purpose: This study evaluates the content, distribution, and changing trend of sialic acid in human milk and the correlation between dietary intake of sialic acid and that in human milk. Methods: The study included 33 mothers of full-term and exclusively breastfed infants. At least 2 ml of milk was collected on the 3rd, 8th, 30th, and 90th day after delivery, and 24-h diet recalls of the lactating mothers were obtained each time. The correlation of human milk sialic acid concentration with lactating women's dietary sialic acid intake during lactation was analyzed by statistical analysis software SPSS. Results: The average concentration of sialic acid in colostrum, transition, and 1 and 3 months were 1,670.74 ± 94.53, 1,272.19 ± 128.74, 541.64 ± 55.2, and 297.65 ± 20.78 mg/L, respectively. The total sialic acid concentration in colostrum was about 5.6 times higher than that at 3 months (P < 0.001). The average dietary sialic acid intake of lactating mothers on the 2nd, 7th, 30th, and 90th day after delivery were 106.06 ± 7.51, 127.64 ± 8.61, 120.34 ± 10.21, and 95.40 ± 6.34 mg/day, respectively. The intake of sialic acid was relatively high on the 7th day, and there was no significant difference in dietary intake of sialic acid on different days (P < 0.05). In addition, there was no correlation between the intake of dietary sialic acid and the content of total sialic acid and various forms of sialic acid in milk (P < 0.05). Conclusion: During the lactation period, the distribution of sialic acid in breast milk is relatively stable and its content fluctuates greatly, which may not be affected by the mother's diet, but mainly depends on the self-regulation oft physiological needs.

Effects of Coix Seed Extract, Bifidobacterium BPL1, and Their Combination on the Glycolipid Metabolism in Obese Mice.

Coix seed extract (CSE) and probiotics have been reported to regulate glycolipid metabolism via different modes of action. We tested the effects of CSE, Bifidobacterium BPL1, and their combination to determine their effects on glycolipid metabolism in obese mice. Male C57BL/6J mice were fed a high-fat diet for 8 weeks to establish an obesity model. Obese mice were selected and divided into four groups: the model control group and three intervention groups. After 10 weeks of continuous gavage intervention, the mice in the intervention groups exhibited lower body weight (lower about 2.31 g, vs. HFD mice 42.23 g) and epididymal (lower about 0.37 g, vs. HFD mice 2.5 g) and perirenal fat content (lower about 0.47 g, vs. HFD mice 0.884 g); decreased fasting blood glucose, total cholesterol, triglycerides, and VLDL; and increased HLDL, respiratory exchange ratio, energy expenditure, and amount of exercise performed. CSE, BPL1 and their combination can effectively control the weight gain in obese mice, reduce fat content, and regulate blood lipids and abnormal blood sugar. These results may be related to reduce the chronic inflammatory states, improve energy metabolism, exercise, relieve insulin sensitivity, and reduce lipid synthesis via the intervention of CSE, BPL1 and their combination. Compared with the single use of CSE alone, the combination of CSE + BPL1 can better exert the regulation function of intestinal flora, and change in the abundance of bacteria that could improve the level of inflammatory factors, such as increasing Bifidobacterium, reducing Lactococcus. Compared with the use of BPL1 alone, the combination of CSE and BPL1 can better regulate pancreatic islet and improve blood sugar. CSE may act directly on body tissues to exert anti-inflammatory effects. BPL1 and CSE + BPL1 may improve the structure and function of the intestinal flora, and reduce tissue inflammation.

Effects of Gonadotropin-Releasing Hormone Analogs on Ovarian Function Against Chemotherapy-Induced Gonadotoxic Effects in Premenopausal Women With Breast Cancer in China: A Randomized Clinical Trial.

IMPORTANCE: Studies of the use of gonadotropin-releasing hormone analogs (GnRHa) to protect ovarian function have shown mixed results. OBJECTIVE: To determine whether administering GnRHa during chemotherapy in premenopausal women with breast cancer can reduce ovarian impairment. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial, conducted at the Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital and Zhejiang Cancer Hospital in China, was an open-label trial involving premenopausal women aged 18 to 49 years with operable stage I to III breast cancer for which treatment with adjuvant or neoadjuvant cyclophosphamide-containing chemotherapy was planned in 2 parallel groups: treatment with chemotherapy with or without GnRHa. Enrollment occurred from September 2015 to August 2017, and follow-up ended December 2020. The data were analyzed in March 2021. A total of 405 patients were enrolled in the study, among whom 27 patients (6.7%) quit participation voluntarily, 33 (8.1%) did not meet the inclusion criteria and were excluded, and 15 (3.7%) were lost to follow-up. Ultimately 330 patients were included in the primary analysis, including 29 patients with baseline anti-Müllerian hormone levels less than 0.5ng/ mL. INTERVENTIONS: Eligible patients were randomly assigned (1:1) to receive chemotherapy with (n = 165) or without (n = 165) GnRHa. In patients randomized to receive GnRHa, 3.6 mg of goserelin or 3.75 mg of leuprorelin was injected subcutaneously once every 28 days from 1 to 2 weeks before the first cycle of chemotherapy to 4 weeks after the last cycle of chemotherapy. MAIN OUTCOMES AND MEASURES: The primary end point was the rate of premature ovarian insufficiency (POI) at 12 months after chemotherapy. Premature ovarian insufficiency was defined as anti-Müllerian hormone levels of less than 0.5 ng/mL in this study. The secondary end point was overall survival (OS) and tumor-free survival (TFS). RESULTS: A total of 330 eligible patients could be evaluated with complete data, among whom 301 patients (91.2%; GnRHA group: mean [SD] age, 40.6 [6.7] years; control group: mean [SD] age, 40.2 [5.9] years) were eligible for primary end point analysis. At 12 months after the completion of chemotherapy, the POI rate was 10.3% (15 of 146) in the GnRHa group and 44.5% (69 of 155) in the control group (odds ratio, 0.23; 95% CI, 0.14-0.39; P < .001). Anti-Müllerian hormone resumption in the GnRHa group was significantly better than that in the control group (15 of 25 vs 6 of 44; odds ratio, 4.40; 95% CI, 1.96-9.89; P < .001). After a median follow-up of 49 months (range, 25-60 months), the differences in 4-year OS and TFS between the 2 groups were not significant. A post hoc analysis showed that in patients younger than 35 years, the TFS was higher in the GnRHa group than in the control group (93% vs 62%; P = .004; hazard ratio, 0.15; 95% CI, 0.03-0.82; P = .03). CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that administering GnRHa in treatment with chemotherapy for premenopausal patients with breast cancer reduces the risk of POI, which promotes the recovery of ovarian function. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02518191.

A Nomogram to Predict Disease-Free Survival Following Neoadjuvant Chemotherapy for Triple Negative Breast Cancer.

BACKGROUND: Neoadjuvant chemotherapy (NACT) is considered a standard treatment strategy for locally advanced triple negative breast cancer (TNBC). TNBC patients who achieve a pathologic complete response (pCR) are predicted to have a better prognosis while unfavorable chemo-sensitivity is still associated with a higher risk of disease relapse. The objective of this study was to construct a nomogram to predict disease-free survival (DFS) for TNBC patients following NACT. METHODS: A total of 165 TNBC patients who underwent standard NACT and surgery were retrospectively reviewed, and data on their clinicopathological factors before and after NACT were collected. Independent prognostic factors for DFS were identified by Cox regression based on lower Akaike information criteria (AIC) and Bayesian information criterion (BIC). A nomogram to predict the 2-year and 5-year DFS following NACT for TNBC was constructed based on training cohort (n = 132) and validated by a validation cohort (n = 33). RESULTS: Either limited or full pCR (breast-only pCR, node-only pCR, or both-pCR) indicated significantly improved DFS and overall survival (OS) (p < 0.001). Lager residual tumor size (hazard ratio [HR] 1.175, p = 0.011) and the presence of lymphatic vessel invasion (LVI) (HR 3.168, p = 0.001) were identified as independent predictors of disease relapse in the training cohort. Five variables, including age, primary tumor size, histological grade, residual tumor size, and LVI were used to establish the nomogram. The C-index of the nomogram was 0.815, and calibration curves showed an acceptable consistency between the actual and nomogram-predicted 2-year and 5-year DFS. The proposed nomogram demonstrated superior predictive performance compared with Residual Cancer Burden (RCB) classification and the 8th American Joint Committee on Cancer Post Neoadjuvant Therapy Classification (AJCC ypTNM) staging system (area under the curve [AUC] for 2-year DFS: 0.870 vs. 0.758 vs. 0.711, respectively; AUC for 5-year DFS: 0.794 vs. 0.731 vs. 0.702, respectively) in the validation cohort. CONCLUSIONS: The nomogram proposed in our study enabled to quantify the risk of disease relapse and demonstrated superior predictive performance than a survival predict instrument. It was an easy-to-use tool for clinicians to guide individualized surveillance of TNBC patients following standard NACT.

The Guiding Significance of the Number of Positive Sentinel Lymph Nodes in Frozen Section for Intraoperative Axillary Dissection in Early Breast Cancer.

PURPOSE: The results of large randomised trials have changed the treatment strategy of axillary lymph nodes. Axillary lymph node dissection (ALND) can be avoided in some patients with one to two sentinel lymph nodes (SLNs) metastasis based on final paraffin section (FPS) results which called into question the need for intraoperative frozen section (FS). This study aims to assess the guiding value of the number of positive SLN detected via FS for intraoperative ALND. PATIENTS AND METHODS: This study retrospectively analyzed data from 3303 patients with breast cancer who underwent SLN biopsy between 2015 and 2019. Combined with the FPS results, FS sensitivity, specificity, and false negative rate (FNR) were calculated and the difference in the number of positive SLNs between FS and FPS was analyzed. RESULTS: The overall FNR of FS was 23.21%, which was 76.47% in isolated tumor cells, 62.28% in micrometastasis, and 12.09% in macrometastatic disease. The size of SLN metastasis were significantly associated with a higher FNR (p<0.001). The accuracy rate of the number of positive SLNs detected via FS was 92.62%. Human epidermal growth factor receptor 2 (HER2) (p<0.03) and Ki67 (p<0.02) were significant factors affecting the accuracy rate. CONCLUSION: FS is a effective method for SLN biopsy, ALND can be avoided in patients with one or two positive SLNs detected via FS.

Necrostatin-1 Synergizes the Pan Caspase Inhibitor to Attenuate Lung Injury Induced by Ischemia Reperfusion in Rats.

BACKGROUND: Both apoptosis and necroptosis have been recognized to be involved in ischemia reperfusion-induced lung injury. We aimed to compare the efficacies of therapies targeting necroptosis and apoptosis and to determine if there is a synergistic effect between the two therapies in reducing lung ischemia reperfusion injury. METHODS: Forty Sprague-Dawley rats were randomized into 5 groups: sham (SM) group, ischemia reperfusion (IR) group, necrostatin-1+ischemia reperfusion (NI) group, carbobenzoxy-Val-Ala-Asp-fluoromethylketone+ischemia reperfusion (ZI) group, and necrostatin-1+carbobenzoxy-Val-Ala-Asp-fluoromethylketone+ischemia reperfusion (NZ) group. The left lung hilum was exposed without being clamped in rats from the SM group, whereas the rats were subjected to lung ischemia reperfusion by clamping the left lung hilum for 1 hour, followed by reperfusion for 3 hours in the IR group. 1 mg/kg necrostatin-1 (Nec-1: a specific necroptosis inhibitor) and 3 mg/kg carbobenzoxy-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk: a pan caspase inhibitor) were intraperitoneally administrated prior to ischemia in NI and ZI groups, respectively, and the rats received combined administration of Nec-1 and z-VAD-fmk in the NZ group. Upon reperfusion, expressions of receptor-interacting protein 1 (RIP1), receptor-interacting protein 3 (RIP3), and caspase-8 were measured, and the flow cytometry analysis was used to assess the cell death patterns in the lung tissue. Moreover, inflammatory marker levels in the bronchoalveolar lavage fluid and pulmonary edema were evaluated. RESULTS: Both Nec-1 and z-VAD-fmk, either alone or in combination, significantly reduced morphological damage, inflammatory markers, and edema in lung tissues following reperfusion, and cotreatment of z-VAD-fmk with Nec-1 produced the optimal effect. The rats treated with Nec-1 had lower levels of inflammatory markers in the bronchoalveolar lavage fluid than those receiving z-VAD-fmk alone (P < 0.05). Interestingly, the z-VAD-fmk administration upregulated RIP1 and RIP3 expressions in the lung tissue from the ZI group compared to those in the IR group (P < 0.05). Reperfusion significantly increased the percentages of necrotic and apoptotic cells in lung tissue single-cell suspension, which could be decreased by Nec-1 and z-VAD-fmk, respectively (P < 0.05). CONCLUSIONS: Nec-1 synergizes the pan caspase inhibitor to attenuate lung ischemia reperfusion injury in rats. Our data support the potential use of Nec-1 in lung transplantation-related disorders.

Predictors of Response and Survival Outcomes of Triple Negative Breast Cancer Receiving Neoadjuvant Chemotherapy.

BACKGROUND: In triple negative breast cancer (TNBC) patients receiving neoadjuvant chemotherapy (NACT), pre-treatment predictors for pathological complete response (pCR) have been reported; however, those for progressive disease (PD) remain unidentified. METHODS: We investigated pre-treatment clinicopathological predictors associated with pCR and PD by retrospectively reviewing data for 165 patients treated between 2015 and 2018. Patients with pCR and PD were compared to those without pCR and PD, respectively, using logistic regression and Kaplan-Meier methods. RESULTS: Lack of androgen receptor (AR) was an independent predictor of pCR, while high histological grade, low Ki-67 index, and incomplete NACT courses were independent predictors of PD. Mean disease-free survival and overall survival were significantly poorer in PD patients than in pCR patients (15.7, 21.3 vs. 52.4, 56.3 months). CONCLUSIONS: Insights into the chemo-resistance mechanisms and exploration of novel targeted agents in subgroups as per AR and Ki-67 status are needed to improve survival outcomes in TNBC patients.

A two-locus interaction causes interspecific hybrid weakness in rice.

Reproductive barriers perform a vital role during speciation. Hybrid weakness, the poorer development of hybrids compared with their parents, hinders gene exchange between different species at the postzygotic stage. Here we show that two incompatible dominant loci (Hwi1 and Hwi2) involving three genes are likely to determine the high temperature-dependent expression of hybrid weakness in interspecific hybrids of rice. Hwi1 comprises two leucine-rich repeat receptor-like kinase (LRR-RLK) genes, 25L1 and 25L2, which are specific to wild rice (Oryza rufipogon) and induce hybrid weakness. Hwi2, a rare allele that is predominantly distributed in indica rice (Oryza sativa), encodes a secreted putative subtilisin-like protease. Functional analysis indicated that pyramiding of Hwi1 and Hwi2 activates the autoimmune response in the basal nodes of hybrids, interrupting root formation and then impairing shoot growth. These findings bring new insights into our understanding of reproductive isolation and may benefit rice breeding.

The analgesic efficacy of subcostal transversus abdominis plane block compared with thoracic epidural analgesia and intravenous opioid analgesia after radical gastrectomy.

BACKGROUND: The transversus abdominis plane (TAP) block has been shown to provide effective postoperative analgesia in lower abdominal surgery. Subcostal TAP block has also been proposed as a new technique to provide analgesia for the supraumbilical abdomen. We compared the analgesic and opioid-sparing effects of a single-injection subcostal TAP block with continuous thoracic epidural analgesia and IV opioid analgesia. METHODS: Ninety patients undergoing elective radical gastrectomy were randomized to receive either combined general-subcostal TAP anesthesia (group TAP), combined general-epidural anesthesia (group EA), or general anesthesia (group GA), and were analyzed on an intention-to-treat basis. In group TAP, a bilateral subcostal TAP block was performed after induction of general anesthesia using 20 mL of 0.375% ropivacaine. In group EA, a thoracic epidural was placed between T8 and T9 and bolused with 8 mL of 0.25% ropivacaine before induction of general anesthesia. The epidural was maintained with 5 mL/h of 0.25% ropivacaine during the surgery. Group GA received standard general anesthesia. In the postanesthesia care unit (PACU), all groups received IV morphine titration for visual analog scale (VAS) pain scores >3. All patients were started on IV patient-controlled analgesia with morphine after morphine titration in the PACU, while group EA also had their epidural maintained with 5 mL/h of 0.125% bupivacaine with 8 µg/mL morphine. Patients were assessed in the PACU and at 1, 3, 6, 24, 48, and 72 hours postoperatively. Primary outcomes measured were morphine consumption at 24 hours and all VAS pain scores. RESULTS: Data from 82 of 90 (91.1%) patients were included in the study. Group TAP demonstrated decreased cumulative morphine consumption at 24 hours (98.75% confidence intervals, -29 to -9 mg) and noninferiority on VAS pain scores at all measurement times, as compared with group GA with standard opioid analgesia. However, group EA was superior to group TAP regarding cumulative morphine consumption at 24 hours (98.75% confidence intervals, -23 to -4 mg) and noninferior to group TAP on VAS pain scores at all comparison points. Group TAP had reduced morphine consumption from PACU admission to 6 hours as compared with group GA, but increased morphine consumption for 6 to 24 hours as compared with group EA. CONCLUSION: Single-injection subcostal TAP block was more effective than IV opioid analgesia, while continuous thoracic epidural analgesia was more effective than the single-injection subcostal TAP block.

Genetic and physiological analysis of a novel type of interspecific hybrid weakness in rice.

Hybrid weakness is an important reproductive barrier that hinders genetic exchange between different species at the post-zygotic stage. However, our understanding of the molecular mechanisms underlying hybrid weakness is limited. In this study, we report discovery of a novel interspecific hybrid weakness in a rice chromosome segment substitution line (CSSL) library derived from a cross between the indica variety Teqing (Oryza sativa) and common wild rice (O. rufipogon). The dominant Hybrid weakness i1 (Hwi1) gene from wild rice is genetically incompatible with Teqing and induced a set of weakness symptoms, including growth suppression, yield decrease, impaired nutrient absorption, and the retardation of crown root initiation. Phytohormone treatment showed that salicylic acid (SA) could restore the height of plants expressing hybrid weakness, while other phytohormones appear to have little effect. Fine mapping indicated that Hwi1 is located in a tandem leucine-rich repeat receptor-like kinase (LRR-RLK) gene cluster. Within the 13.2-kb candidate region on the short arm of chromosome 11, there are two annotated LRR-RLK genes, LOC_Os11g07230 and LOC_Os11g07240. The Teqing allele of LOC_Os11g07230 and the wild rice allele of LOC_Os11g07240 encode predicted functional proteins. Based on the genetic inheritance of hybrid weakness, LOC_Os11g07240 is implicated as the candidate gene for Hwi1. Functional analysis of Hwi1 will expand our knowledge of the regulation of hybrid weakness in rice.

The novel quantitative trait locus GL3.1 controls rice grain size and yield by regulating Cyclin-T1;3.

Increased crop yields are required to support rapid population growth worldwide. Grain weight is a key component of rice yield, but the underlying molecular mechanisms that control it remain elusive. Here, we report the cloning and characterization of a new quantitative trait locus (QTL) for the control of rice grain length, weight and yield. This locus, GL3.1, encodes a protein phosphatase kelch (PPKL) family - Ser/Thr phosphatase. GL3.1 is a member of the large grain WY3 variety, which is associated with weaker dephosphorylation activity than the small grain FAZ1 variety. GL3.1-WY3 influences protein phosphorylation in the spikelet to accelerate cell division, thereby resulting in longer grains and higher yields. Further studies have shown that GL3.1 directly dephosphorylates its substrate, Cyclin-T1;3, which has only been rarely studied in plants. The downregulation of Cyclin-T1;3 in rice resulted in a shorter grain, which indicates a novel function for Cyclin-T in cell cycle regulation. Our findings suggest a new mechanism for the regulation of grain size and yield that is driven through a novel phosphatase-mediated process that affects the phosphorylation of Cyclin-T1;3 during cell cycle progression, and thus provide new insight into the mechanisms underlying crop seed development. We bred a new variety containing the natural GL3.1 allele that demonstrated increased grain yield, which indicates that GL3.1 is a powerful tool for breeding high-yield crops.

Dissecting the genetic basis of extremely large grain shape in rice cultivar 'JZ1560'.

Rice grain shape, grain length (GL), width (GW), thickness (GT) and length-to-width ratio (LWR), are usually controlled by multiple quantitative trait locus (QTL). To elucidate the genetic basis of extremely large grain shape, QTL analysis was performed using an F(2) population derived from a cross between a japonica cultivar 'JZ1560' (extremely large grain) and a contrasting indica cultivar 'FAZ1' (small grain). A total number of 24 QTLs were detected on seven different chromosomes. QTLs for GL, GW, GT and LWR explained 11.6%, 95.62%, 91.5% and 89.9% of total phenotypic variation, respectively. Many QTLs pleiotropically controlled different grain traits, contributing complex traits correlation. GW2 and qSW5/GW5, which have been cloned previously to control GW, showed similar chromosomal locations with qGW2-1/qGT2-1/qLWR2-2 and qGW5-2/qLWR5-1 and should be the right candidate genes. Plants pyramiding GW2 and qSW5/GW5 showed a significant increase in GW compared with those carrying one of the two major QTLs. Furthermore, no significant QTL interaction was observed between GW2 and qSW5/GW5. These results suggested that GW2 and qSW5/GW5 might work in independent pathways to regulate grain traits. 'JZ1560' alleles underlying all QTLs contributed an increase in GW and GT and the accumulation of additive effects generates the extremely large grain shape in 'JZ1560'.

Rice carotenoid ß-ring hydroxylase CYP97A4 is involved in lutein biosynthesis.

Lutein is the most abundant plant carotenoid and plays essential roles in photosystem assembly and stabilization, as well as protection against photostress. To date, only a few lutein biosynthesis genes have been identified in crop plants. In this study, the rice Cyt P450 gene CYP97A4 encoding a carotenoid ß-ring hydroxylase was shown to be involved in lutein biosynthesis. The results revealed that CYP97A4 was preferentially expressed in leaf compared with spikelet, sheath, stalk and root, and encoded a protein localized at the subcellular level to the chloroplasts. Compared with the wild type, the three allelic mutants of CYP97A4 displayed lutein reductions of 12-24% with substantially increased α-carotene, while Chl a/b levels were unaltered. The increased α-carotene in the mutants led to greater sensitivity under high light stress. Similarly, reactive oxygen species (ROS) imaging of leaves treated with intense light showed that the mutants generally accumulated greater levels of ROS compared with wild-type plants, which probably caused detrimental effects to the plant photosystem. In conclusion, this study demonstrated the important role of CYP97A4 in α-carotene hydroxylation in rice, and knock-out of the gene reduced lutein and increased α-carotene, contributing to sensitivity to intense light.