The Short-Term and Long-Term Outcomes of Laparoscopy-Assisted Proximal Gastrectomy with Double-Tract Reconstruction versus Laparoscopy-Assisted Total Gastrectomy with Roux-en-Y Reconstruction for Adenocarcinoma of the Esophagogastric Junction: A Multicenter Study Based on Propensity Score Matching Analysis.

Purpose: To compare the antireflux effect, long-term nutritional levels, and quality of life (QoL) between laparoscopy-assisted proximal gastrectomy with double-tract reconstruction (LPG-DTR) and laparoscopy-assisted total gastrectomy with Roux-en-Y reconstruction (LTG-RY) for adenocarcinoma of the esophagogastric junction (AEG). Methods: This multicenter retrospective cohort study collected clinicopathological and follow-up data of AEG patients from January 2016 to January 2021 at five high-volume surgery centers. The study included patients who underwent digestive tract reconstruction with LPG-DTR or LTG-RY after tumor resection. Propensity score matching (PSM) was utilized to minimize confounding factors. The comparison after PSM included postoperative complications, reflux esophagitis, long-term nutritional levels, and QoL. Results: A total of 151 consecutive patients underwent either LPG-DTR or LTG-RY. After PSM, 50 patients from each group were included in the analysis. The frequency of reflux esophagitis and Clavien-Dindo classification did not significantly differ between the two groups (P > 0.05). At 1 year after surgery, the LPG-DTR group showed significantly higher weight and hemoglobin levels than the LTG-RY group (P < 0.05). The overall postoperative Visick grade differed significantly between the groups (P < 0.05), but there was no significant difference in the proportion of patients with Visick≥III (P > 0.05). Conclusion: Both LPG-DTR and LTG-RY are safe and feasible methods for digestive tract reconstruction in patients with AEG. Both methods have similar antireflux effects and postoperative QoL. However, LPG-DTR resulted in superior nutritional levels compared to LTG-RY. Therefore, LPG-DTR is considered a relatively effective method for digestive tract reconstruction in AEG patients.

Clinical efficacy and pathological outcomes of transanal endoscopic intersphincteric resection for low rectal cancer.

BACKGROUND: Transanal endoscopic intersphincteric resection (ISR) surgery currently lacks sufficient clinical research and reporting. AIM: To investigate the clinical effectiveness of transanal endoscopic ISR, in order to promote the clinical application and development of this technique. METHODS: This study utilized a retrospective case series design. Clinical and pathological data of patients with lower rectal cancer who underwent transanal endoscopic ISR at the First Affiliated Hospital of Xiamen University between May 2018 and May 2023 were included. All patients underwent transanal endoscopic ISR as the surgical approach. We conducted this study to determine the perioperative recovery status, postoperative complications, and pathological specimen characteristics of this group of patients. RESULTS: This study included 45 eligible patients, with no perioperative mortalities. The overall incidence of early complications was 22.22%, with a rate of 4.44% for Clavien-Dindo grade ≥ III events. Two patients (4.4%) developed anastomotic leakage after surgery, including one case of grade A and one case of grade B. Postoperative pathological examination confirmed negative circumferential resection margins and distal resection margins in all patients. The mean distance between the tumor lower margin and distal resection margin was found to be 2.30 ± 0.62 cm. The transanal endoscopic ISR procedure consistently yielded high quality pathological specimens. CONCLUSION: Transanal endoscopic ISR is safe, feasible, and provides a clear anatomical view. It is associated with a low incidence of postoperative complications and favorable pathological outcomes, making it worth further research and application.

Development and validation of prediction models for poor sleep quality among older adults in the post-COVID-19 pandemic era.

BACKGROUND: Corona Virus Disease 2019 (COVID-19) has a significant impact on sleep quality. However, the effects on sleep quality in the post-COVID-19 pandemic era remain unclear, and there is a lack of a screening tool for Chinese older adults. This study aimed to understand the prevalence of poor sleep quality and determine sensitive variables to develop an effective prediction model for screening sleep problems during infectious diseases outbreaks. MATERIALS AND METHODS: The Peking University Health Cohort included 10,156 participants enrolled from April to May 2023. The Pittsburgh Sleep Quality Index (PSQI) scale was used to assess sleep quality. The data were randomly divided into a training-testing cohort (n = 7109, 70%) and an independent validation cohort (n = 3027, 30%). Five prediction models with 10-fold cross validation including the Least Absolute Shrinkage and Selection Operator (LASSO), Stochastic Volatility Model (SVM), Random Forest (RF), Artificial Neural Network (ANN), and XGBoost model based on the area under curve (AUC) were used to develop and validate predictors. RESULTS: The prevalence of poor sleep quality (PSQI >7) was 30.69% (3117/10,156). Among the generated models, the LASSO model outperformed SVM (AUC 0.579), RF (AUC 0.626), ANN (AUC 0.615) and XGBoost (AUC 0.606), with an AUC of 0.7. Finally, a total of 12 variables related to sleep quality were used as parameters in the prediction models. These variables included age, gender, ethnicity, educational level, residence, marital status, history of chronic diseases, SARS-CoV-2 infection, COVID-19 vaccination, social support, depressive symptoms, and cognitive impairment among older adults during the post-COVID-19 pandemic. The nomogram illustrated that depressive symptoms contributed the most to the prediction of poor sleep quality, followed by age and residence. CONCLUSIONS: This nomogram, based on twelve-variable, could potentially serve as a practical and reliable tool for early identification of poor sleep quality among older adults during the post-pandemic period.

The poor sleep quality (PSQI >7) was still prevalent among older adults during the post-COVID-19 pandemic.The LASSO model was the best model to predict poor sleep quality among older adults, compared with SVM, RF, ANN and XGBoost.This prediction model, based on twelve variables, may potentially serve as a practical and reliable tool for the early identification of poor sleep quality among older adults during the post-pandemic period.

A comparative evaluation of chemical composition and nutritional value of bamboo rice and major cereals reveals the potential utility of bamboo rice as functional food.

Bamboo rice refers to the edible seeds collected from bamboo plants, but the nutritional and chemical compositions of bamboo rice are unknown. Here, we evaluated the nutritional value of two types of bamboo seeds by comparing them to rice and wheat. The fiber, protein, and microelement contents were much higher in bamboo seeds than in rice and wheat seeds. The flavonoids content was 5- and 10-folds higher in Moso bamboo seeds than in rice and wheat seeds, respectively. Amino acid profiles exhibited that most of amino acids were abundant in bamboo seeds compared to rice and wheat seeds. While water-soluble B vitamins and fatty acids in bamboo seeds were similar to those in rice and wheat seeds. Accordingly, rice and wheat may thus be substituted by bamboo rice which is a potentially functional food. Its high flavonoid content may be further exploited by the food industry.

Investigation on the relationship between Eysenck personality type and the survival rate of traumatic amputated finger replantation based on preventive psychology.

This paper tried to observe the relationship between the personality of patients with different personalities and the survival rate of replantation of traumatic amputated finger, and analyzed the influencing factors. EPQ psychological quality scores of patients with different gender, average monthly family income and age were significantly different (P < 0.05). In terms of the internal and external tendency score of EPQ, there were statistical requirements for differences in the mean monthly income of patients from different families (P < 0.05). For the concealment degree of EPQ, there were statistical requirements for differences in gender, family income, education level and patient scores (P < 0.05). In terms of mental state, the scores were higher than the standard, whether from the perspective of obsessive-compulsive symptoms, or from the perspective of interpersonal sensitivity, hostility, paranoia and other dimensions, the difference was statistically significant (P < 0.05). Patients with different personality types have different psychological problems after accidental amputation and replantation, which is directly related to the survival rate of postoperative finger amputation. Therefore, in order to effectively improve the survival rate of patients with finger amputation, the psychological condition of patients can be assessed, early detection and intervention of patients' psychological problems, and appropriate intervention measures can be taken according to the personality characteristics of patients.

The potential of bamboo seeds for natural biofortification of dietary zinc and iron.

Moso bamboo has been shown to accumulate high concentrations of iron and zinc in the seeds. However, the bioavailablity of iron and zinc in bamboo seeds is poorly understood. Here, we evaluated the bioaccessibility and bioavailability of iron and zinc in bamboo seeds by using an in vitro digestion protocol. Our evaluations revealed that values of bioaccessibility and bioavailability of iron were 25 and 21 mg kg-1 in bamboo seeds which were 1.6- and 1.7- fold higher than in rice, respectively. Also, values of bioaccessibility and bioavailability of zinc were 20 and 13 mg kg-1 in bamboo seeds which were 1.9- and 2.6- fold higher than in rice, respectively. Boiling process reduced both the bioaccessibility and bioavailability of iron and zinc. In addition, phytic acid concentration in bamboo seeds was only 0.42 times higher than in rice. By contrast, the tannins concentration in bamboo seeds was 2.2 times higher than in rice. Cellular localization results showed that iron and zinc were mainly concentrated in the embryo and the aleurone layer. These results clearly suggest that Moso bamboo seeds are rich in iron and zinc and have potential as a food for iron and zinc biofortification.

Could S-1-based non-platinum doublet chemotherapy be a new option as a second-line treatment for advanced non-small cell lung cancer patients? A multicenter retrospective study.

Background: For patients who have contraindications to or have failed checkpoint inhibitors, chemotherapy remains the standard second-line option to treat non-oncogene-addicted advanced non-small cell lung cancer (NSCLC). This study aimed to investigate the efficacy and safety of S-1-based non-platinum combination in advanced NSCLC patients who had failed platinum doublet chemotherapy. Methods: During January 2015 and May 2020, advanced NSCLC patients who received S-1 plus docetaxel or gemcitabine after the failure of platinum-based chemotherapy were consecutively retrieved from eight cancer centers. The primary endpoint was progression-free survival (PFS). The secondary endpoint was overall response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. By using the method of matching-adjusted indirect comparison, the individual PFS and OS of included patients were adjusted by weight matching and then compared with those of the docetaxel arm in a balanced trial population (East Asia S-1 Trial in Lung Cancer). Results: A total of 87 patients met the inclusion criteria. The ORR was 22.89% (vs. 10% of historical control, p < 0.001) and the DCR was 80.72%. The median PFS and OS were 5.23 months (95% CI: 3.91-6.55 months) and 14.40 months (95% CI: 13.21-15.59 months), respectively. After matching with a balanced population in the docetaxel arm from the East Asia S-1 Trial in Lung Cancer, the weighted median PFS and OS were 7.90 months (vs. 2.89 months) and 19.37 months (vs. 12.52 months), respectively. Time to start of first subsequent therapy (TSFT) from first-line chemotherapy (TSFT > 9 months vs. TSFT ≤ 9 months) was an independent predictive factor of second-line PFS (8.7 months vs. 5.0 months, HR = 0.461, p = 0.049). The median OS in patients who achieved response was 23.5 months (95% CI: 11.8-31.6 months), which was significantly longer than those with stable disease (14.9 months, 95% CI: 12.9-19.4 months, p < 0.001) or progression (4.9 months, 95% CI: 3.2-9.5 months, p < 0.001). The most common adverse events were anemia (60.92%), nausea (55.17%), and leukocytopenia (33.33%). Conclusions: S-1-based non-platinum combination had promising efficacy and safety in advanced NSCLC patients who had failed platinum doublet chemotherapy, suggesting that it could be a favorable second-line treatment option.

The risk factors and early predictive model of hematotoxicity after CD19 chimeric antigen receptor T cell therapy.

Hematotoxicity is the most common long-term adverse event after chimeric antigen receptor T cell (CAR-T) therapy. Here, a total of 71 patients with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) or large B-cell lymphoma (LBCL) were used to develop an early hematotoxicity predictive model and verify the accuracy of this model. The incidences of early hematotoxicity at 3 month following CAR-T infusion in B-ALL and LBCL were 45.5% and 38.5%, respectively. Multivariate analyses revealed that the severity of cytokine release syndrome (CRS) was an independent risk factor affecting early hematotoxicity. The analysis between the peak cytokine levels and early hematotoxicity suggested that tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) were closely associated with early hematotoxicity. Then, an early predictive model of hematotoxicity was constructed based on the peak contents of TNF-α and CRP. This model could diagnose early hematotoxicity with positive predictive values of 87.7% and 85.0% in training and validation cohorts, respectively. Lastly, we constructed the nomogram for clinical practice to predict the risk of early hematotoxicity, which performed well compared with the observed probability. This early predictive model is instrumental in the risk stratification of CAR-T recipients with hematotoxicity and early intervention for high-risk patients.

High expression of long noncoding RNA plasmacytoma variant translocation 1 is an independent risk factor for recurrence after radiofrequency ablation in atrial fibrillation patients.

Atrial fibrillation (AF) is a common arrhythmia. Radiofrequency ablation (RFA) is the major AF treatment. Long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) is related to AF diagnosis. This study explored the clinical roles of PVT1 in AF. Totally, 168 AF patients and 100 healthy controls were selected. Plasma lncRNA PVT1 in AF patients before/after RFA was detected and the diagnostic efficacy and postoperative recurrence prediction value in AF were analyzed. Effects of plasma PVT1 expression on AF recurrence and its correlation with transforming growth factor beta 1 (TGF-ß1) in the recurrence and non-recurrence groups were analyzed by Pearson coefficient. The risk factors of AF recurrence were evaluated. Plasma PVT1 was highly expressed in AF patients and diminished after RFA. PVT1 level >1.255 assisted AF diagnosis. The plasma PVT1 level in the recurrence group was higher than that of the non-recurrence group. PVT1 level >1.525 assisted the prediction for postoperative recurrence. AF postoperative recurrence incidence in high PVT1 expression group was clearly higher than that in low PVT1 expression group, and plasma PVT1 expression in patients of the recurrence and non-recurrence groups was positively correlated with TGF-ß1 content. High PVT1 expression was an independent risk factor for postoperative recurrence. Briefly, high PVT1 level assisted AF diagnosis and recurrence evaluation after RFA and was an independent risk factor for AF postoperative recurrence.

Complete mitochondrial genome of the top hat blenny, Omobranchus fasciolatoceps Richardson (Blenniiformes: Blenniinae) in Southern China Coast.

The complete mitochondrial genome sequence of Omobranchus fasciolatoceps was firstly described in this article. The total length of mitogenome was 16,569 bp. It contains 13 protein-coding genes, 22 tRNA genes, and two ribosomal RNA genes. The overall base composition of H-strand was 29.04% A, 27.14% C, 27.89% T, and 15.93% G, with an A＋T bias of 56.93%. The phylogenetic analysis results showed that the O. fasciolatoceps was most closely related to O. elegans.

Clinical Effectiveness of Free Upper Arm Medial Flap in Repairing Skin and Soft Tissue Defects of the Dorsum of the Hand.

Objective: To study the effectiveness of medial upper arm free flap in repairing skin and soft tissue (SST) defects of the dorsum of the hand. Methods: 10 patients with SST defects on the dorsum of the hand who underwent free upper arm medial flap repair in our hospital from March 2017 to August 2018 were included in the study. Hand function, flap survival rate, wound healing, donor wound recovery, and the level of pain in the injured area were recorded before the operation, 1 month, and 6 months postoperatively. Results: The highest score in hand function was seen at the 6-month postoperative interval, followed by that at the 1-month postoperative interval. The lowest score in hand function was the preoperative score (P < 0.05). All flaps were still surviving 6 months postoperatively. Recovery of the function of the donor muscle, the elbow joint, as well as wound healing, all progressed well. 6 months postoperatively, 3 patients developed numbness and stiffness of the hand, but the symptoms were relieved following treatment. Compared to the preoperative scores, the visual analogue scale (VAS) scores at the injured site 1 month and 6 months postoperatively were significantly decreased, with the 6-month postoperative score being lower than the 1-month postoperative score (P < 0.05). Conclusion: The free upper arm medial flap is a good alternative for repairing skin and soft tissue defects of the dorsum of the hand with exposed phalanges, an approach that merits widespread promotion and clinical application.

Prognostic differences of refractory/relapsed nodal and extranodal diffuse large B-cell lymphoma in the chimeric antigen receptor T cell therapy era.

BACKGROUND: Extranodal involvement is recognized as a poor prognostic factor for diffuse large B-cell lymphoma (DLBCL). However, the prognostic differences of patients with refractory/relapsed (R/R) nodal and extranodal DLBCL in the chimeric antigen receptor T cell (CART) therapy era are still unclear. MATERIALS AND METHODS: In this study, 18 R/R nodal DLBCL (R/R N-DLBCL) and 19 R/R extranodal DLBCL (R/R EN-DLBCL) were enrolled to compare clinical outcomes. RESULTS: The median follow-up time was 13 (range, 1-47) months and one-year progression-free survival (PFS; 83.3% vs. 42.1%, P = 0.008) and one-year overall survival (OS; 94.4% vs. 63.2%, P = 0.020) were significantly different between nodal and extranodal patients. In the multivariable Cox regression analysis, R/R EN-DLBCL was associated with worse PFS (hazard ratio [HR] = 4.263, P = 0.018) and OS (HR = 9.589, P = 0.034) compared to R/R N-DLBCL. Additionally, autologous hematopoietic stem cell transplantation (ASCT) combined with CART therapy (ASCT + CART) was correlated with better PFS (HR = 0.164, P = 0.003) compared to CART treatment alone. CONCLUSIONS: The clinical outcomes of R/R EN-DLBCL were worse than R/R N-DLBCL in patients receiving CART therapy and ASCT + CART therapy is a promising alternative treatment for patients with R/R EN-DLBCL.

What Is Long-Term Survival and Which First-Line Immunotherapy Brings Long-Term Survival for Advanced Wild-Type Non-Small Cell Lung Cancer: A Network Meta-Analysis Based on Integrated Analysis.

Background: Immune checkpoint inhibitors (ICIs) have significantly improved survival for advanced wild-type non-small cell lung cancer, but there is no direct comparison to confirm which first-line treatment may lead to the longest overall survival. What qualifies as long-term survival (LS) is even unclear. Methods: By searching PubMed, Embase, and the Cochrane Central Register of Controlled Trials from January 2005 to December 2020, we included randomized controlled trials (RCTs) of first-line ICI-containing treatments to perform an integrated analysis (IA) to determine the criterion of LS and then screened regimens with LS for network meta-analysis (NMA). The main outcomes for NMA were median overall survival (mOS), 1-year survival rate (1ySR), and 2-year survival rate (2ySR); those for IA were the pooled mOS (POS), 1ySR (P1SR), and 2ySR (P2SR). Results: By IA of 16 first-line ICIs from 20 RCTs, the POS was 16.20 (95% CI 14.79-17.60) months, with P1SR of 63% (95% CI 59-66%) and P2SR of 37% (33-41%). Thus, we defined LS as mOS ≥ POS (16.20 m) for regimens and screened for RCTs with outcomes meeting this criterion. Eleven ICI-based regimens can bring LS for the overall population, among which ICI with bevacizumab and chemotherapy achieved the longest POS of 19.50 m (16.90-22.10 m) and the highest P1SR (74%, 61%-87%) and P2SR (49%, 38%-61%). Pembrolizumab with chemotherapy ranked first in mOS and 1ySR, while atezolizumab plus bevacizumab and chemotherapy ranked first in 2ySR. Conclusions: Through the IA of first-line treatment regimens, a POS of 16.20 m can be determined as the LS standard. Further considering 1ySR and 2ySR, atezolizumab combined with bevacizumab and chemotherapy or pembrolizumab plus chemotherapy are likely to bring the longest LS in the overall population, while single ICI may be adequate for patients with a high PD-L1 expression. ICIs with bevacizumab and chemotherapy may be the best combination for LS for its further advantage over time.

Deep Learning-Based Electrocardiograph in Evaluating Radiofrequency Ablation for Rapid Arrhythmia.

This study is aimed at analyzing the important role of deep learning-based electrocardiograph (ECG) in the efficacy evaluation of radiofrequency ablation in the treatment of tachyarrhythmia. In this study, 158 patients with rapid arrhythmia treated by radiofrequency ablation were divided into effective treatment group (142 cases) and ineffective treatment group (16 cases). ECG examination was performed on all patients, and the indicators of ECG examination were quantified by the deep learning-based convolutional neural network model. The indicators of ECG examination of the effective treatment group and the ineffective treatment group were compared. The results showed that compared with the ineffective treatment group, the end-systolic volume (ESV), end-diastolic volume (EDV), end-systolic volume index (ESVI), and end-diastolic volume index (EDVI) of the effective treatment group were significantly decreased, and the left ventricular ejection fraction (LVEF) was significantly increased (P < 0.05). After radiofrequency ablation, the ventricular rate of patients in the effective treatment group was significantly lower than that of the ineffective treatment group at 12 h and 24 h after treatment (P < 0.05). In addition, compared with patients in the ineffective treatment group, the QT dispersion of the ECG in the effective treatment group was significantly higher (P < 0.05). The accuracy, specificity, and sensitivity of ECG in evaluating the therapeutic effect of patients with tachyarrhythmia were 86.81%, 84.29%, and 77.27%, respectively. The area under the curve was determined as 0.798 according to the receiver operating characteristic (ROC) curve of the subjects. In summary, indicators of ECG examination based on deep learning can provide auxiliary reference information for the efficacy evaluation of radiofrequency ablation in the treatment of tachyarrhythmia.

Chimeric antigen receptor T-cell therapy combined with autologous stem cell transplantation improved progression-free survival of relapsed or refractory diffuse large B-cell lymphoma patients: A single-center, retrospective, cohort study.

Autologous hematopoietic stem cell transplantation (ASCT) and chimeric antigen receptor T-cell therapy (CART) are salvage therapies that are utilised for treatment of relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, whether the combination therapy of ASCT and CART (ASCT-CART) can improve the survival of R/R DLBCL remains unknown. Overall, 67 R/R DLBCL patients were included, among which 21 patients underwent ASCT-CART therapy and 46 patients underwent ASCT therapy. The median number of mononuclear cells numbers that were infused in the ASCT-CART and ASCT groups was 4.71 × 108 /kg and 5.36 × 108 /kg, respectively (p = 0.469). The median number of CD34+ cell numbers that were infused in the ASCT-CART and ASCT groups was 2.41 × 106 /kg and 3.05 × 106 /kg, respectively (p = 0.663). The median number of CART cells that were infused was 2.63 × 106 /kg with a median transduction rate of 59.83%. The objective response rates to ASCT-CART and ASCT therapy were 90% and 89%, respectively (p = 1.000). However, the ASCT-CART group showed higher complete remission (CR) rates than the ASCT group (71% vs. 33%; p = 0.003). The ASCT-CART group demonstrated superior 3 year progression-free survival (PFS) (80% vs. 44%; p = 0.036) and lower 3 year relapse/progression rate (15% vs. 56%; p = 0.015) compared to the ASCT group. However, the 3 year overall survival results indicated that there were no differences between the two groups (80% vs. 69%; p = 0.545). For R/R DLBCL patients, ASCT-CART therapy is associated with higher CR rate, better PFS, and lower relapse/progression rate. These data support that ASCT-CART therapy can be used as a salvage therapy for R/R DLBCL patients.

Integrative transcriptomic and metabolomic data provide insights into gene networks associated with lignification in postharvest Lei bamboo shoots under low temperature.

Lei bamboo (Phyllostachys violascens) shoots are delicious food in Asia. Here, the molecular basis of lignification in postharvest Lei bamboo shoots under low temperature (LT) is revealed by transcriptomic and metabolomics analyses for the first time. We identified substantial accumulations of jasmonates (JAs) and major lignin biosynthesis precursors (coumarin, trans-4-coumaric acid, trans-ferulic acid and L-phenylalanine). Transcriptome analysis indicated that some regulatory genes were significantly differentially expressed, and the expression patterns of them were highly consistent with the changes in the key lignin precursors or JA profiles. Co-expression analysis showed that the LT responsive genes PvCRPK-4/-5, PvICE2-1/2, PvDREB2B might form a network module with the lignin (PvC3H-2/3, PvC4H-2/4, PvCAD-1/2/3/4, etc.) or JA biosynthesis genes (PvOPR2, PvJAZ-4 and PvPEX5, etc.), indicating a LT-lignification or LT-JA-lignification regulatory pathway in Lei bamboo shoots. Above all, our findings provide new an insight into the LT-associated lignification in postharvest bamboo shoots.

Comparison of Efficacy and Safety of Third-Line Treatments for Advanced Gastric Cancer: A Systematic Review With Bayesian Network Meta-Analysis.

BACKGROUND: Although various third-line treatments of advanced gastric cancer (AGC) significantly improved the overall survival, the optimal regimen has not been determined by now. This study aims to evaluate the efficacy and safety of multiple third-line treatments of AGC via integrated analysis and network meta-analysis (NMA) to provide valuable evidence for the optimal third-line systemic therapy for AGC. METHODS: By searching the databases of PubMed, Embase and the Cochrane Central Register of Controlled Trials from Jan 01, 2005 to Dec 31, 2020, we included phase II/III randomized clinical trials (RCTs) of the third-line treatments for AGC to perform NMA. The main outcomes for NMA were median overall survival (mOS), median progression-free survival (mPFS), disease control rate (DCR) and adverse events (AEs). We also included phase IB/II non-RCTs and II/III RCTs of the third-line immune checkpoint inhibitors (ICIs) for integrated analysis for pooled mOS (POS), pooled mPFS (PPFS) and other outcomes. RESULTS: Eight phase II/III RCTs and 2 ICIs-related phase IB/II non-RCTs were included for analysis, involving 9 treatment regimens and 3012 AGC patients. In terms of mOS, apatinib (hazard ratio [HR] 0.61, 95% credible interval [CrI] 0.48-0.78) and nivolumab (HR 0.62, 95% CrI 0.51-0.76) were the most effective treatments compared with placebo. Apatinib also significantly improved mPFS versus placebo (HR 0.38, 95% CrI 0.29-0.49). Nivolumab ranked first among all regimens for 1-year OS rate and achieved the best OS in patients with HER-2 positive tumor, patients with gastroesophageal junction (GEJ) cancer and patients without gastrectomy history. TAS-102 (OR 7.46, 95% CrI 4.61-12.51) was the most toxic treatment in terms of AEs of grade 3 and higher (≥3 AEs). Pembrolizumab was more likely to cause immune related adverse event. Finally, the POS, pooled 1-year OS rate, pooled ORR and PPFS of AGC patients treated with third-line ICIs were 5.1 months, 25%, 10% and 1.71 months respectively. CONCLUSIONS: Apatinib and nivolumab are the most effective treatments for the third-line treatment of AGC in contrast to the third-line chemotherapy. For AGC patients with HER-2 positive tumor, patients with GEJ cancer and patients without gastrectomy history, ICIs could be the optimal third-line treatment choice.

Real-World Analysis of the Efficacy and Safety of a Novel Irreversible HER2 Tyrosine Kinase Inhibitor Pyrotinib in Patients with HER2-Positive Metastatic Breast Cancer.

BACKGROUND: As a novel irreversible pan-ErbB inhibitor recently approved in China, pyrotinib has exhibited promising anticancer efficacy and acceptable safety profile in HER2-positive metastatic breast cancer (mBC). The aim of this retrospective study was to estimate the efficacy and safety of pyrotinib treatment in Chinese mBC patients. METHODS: We retrospectively reviewed the real-world clinicopathological and treatment data of HER2-positive mBC patients receiving pyrotinib-based treatment from August 2018 to July 2019 in Qilu Hospital of Shandong University and other medical centers of Shandong Province in China. RESULTS: A total of 64 patients treated with pyrotinib were included for analysis, and the median follow-up duration was 260 days (interquartile range, 199.0 to 339.0 days). Fifty-nine (92.2%) patients had been previously treated with trastuzumab and/or T-DM1, while 11 (17.2%) patients had been exposed to lapatinib. The objective response rate (ORR) of all patients was 73.4%, and the disease control rate (DCR) was 98.4%, with a clinical benefit rate (CBR) of 87.5%. Patients with exposure to lapatinib responded well to pyrotinib-based treatment, although the ORR was significantly lower compared with that of patients without exposure to lapatinib (44.1% vs 77.5%, p=0.037). Previous lapatinib exposure was negatively associated with the objective response of pyrotinib treatment (odds ratio [OR]=0.248, 95% confidence interval [CI] 0.063-0.970, p=0.045). The median progression-free survival (mPFS) for patients with previous lapatinib exposure and patients with visceral metastasis was 299 days (95% CI 240.1-357.9 days) and 359 days (95% CI 258.3-459.7 days), respectively. But the mPFS of the whole cohort has not been reached until the cut-off date. Cox multivariate analysis revealed that only visceral metastasis was an independent predictor of significantly shorter PFS (p=0.041) but not previous exposure to lapatinib (p=0.092). Diarrhea (28.1%), hand-foot syndrome (17.2%), and neutropenia (9.4%) were the most common grade 3 adverse events associated with pyrotinib treatment. CONCLUSION: Pyrotinib is highly beneficial to HER2-positive metastatic breast cancer patients, even in patients with previous lapatinib exposure. Pyrotinib is a feasible replacement of lapatinib in combination with chemotherapeutic drugs or as a monotherapy. Adverse effects are tolerable and easily manageable.

Green Conversion of Saponins to Diosgenin in an Alcoholysis System Catalyzed by Solid Acid Derived from Phosphorus Tailings.

This work proposed to prepare solid acid from phosphorus tailings and successfully convert Dioscorea zingiberensis C.H. Wright (DZW) into diosgenin from the perspective of solid waste resource reuse and clean production. The results showed that SiO2-SO3H solid acid could catalyze the production of diosgenin from total saponins under solvothermal reaction conditions. In addition, the parameters of a single factor, such as the amount of SiO2-SO3H, solvent volume, reaction temperature, and reaction time, were optimized to confirm the optimal range of reaction conditions, and the optimal process conditions were determined by the response surface method. The yield of diosgenin was 2.45 ± 0.17% under the optimum conditions, and the yield of diosgenin was increased by 12.90% compared with the traditional acid hydrolysis process. Except the relatively higher catalytic activity, the alcoholysis approach for the production of diosgenin has no waste liquid to discharge. The products were analyzed by high-performance liquid chromatography-mass spectrometry, and the pathway to convert total saponins into diosgenin under SiO2-SO3H has been proposed. Moreover, the adopted catalyst can be prepared with very low cost from phosphorus tailings. Considering the obvious superiorities, the alcoholysis approach in this work could be a promising strategy for green production of diosgenin as well as a possible utilization pathway of phosphorus tailings.

Hexavalent chromium in drinking water: Chemistry, challenges and future outlook on Sn(II)- and photocatalyst-based treatment.

Chromium (Cr) typically exists in either trivalent and hexavalent oxidation states in drinking water, i.e., Cr(III) and Cr(VI), with Cr(VI) of particular concern in recent years due to its high toxicity and new regulatory standards. This Account presented a critical analysis of the sources and occurrence of Cr(VI) in drinking water in the United States, analyzed the equilibrium chemistry of Cr(VI) species, summarized important redox reaction relevant to the fate of Cr(VI) in drinking water, and critically reviewed emerging Cr(VI) treatment technologies. There is a wide occurrence of Cr(VI) in US source drinking water, with a strong dependence on groundwater sources, mainly due to naturally weathering of chromium-containing aquifers. Challenges regarding traditional Cr(VI) treatment include chemical cost, generation of secondary waste and inadvertent re-generation of Cr(VI) after treatment. To overcome these challenges, reductive Cr(VI) treatment technologies based on the application of stannous tin or electron-releasing titanium dioxide photocatalyst hold extreme promise in the future. To moving forward in the right direction, three key questions need further exploration for the technology implementation, including effective management of residual waste, minimizing the risks of Cr(VI) re-occurrence downstream of drinking water treatment plant, and promote the socioeconomic drivers for Cr(VI) control in the future.