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Prospective evidence regarding the combination of programmed cell death (PD)−1 and angiogenesis inhibitors in treating locally advanced gastric cancer (LAGC) is limited. In this multicenter, randomized, phase 2 trial (NCT04195828), patients with gastric adenocarcinoma (clinical T2-4N + M0) were randomly assigned (1:1) to receive neoadjuvant camrelizumab and apatinib combined with nab-paclitaxel plus S-1 (CA-SAP) or chemotherapy SAP alone (SAP) for 3 cycles. The primary endpoint was the major pathological response (MPR), defined as <10% residual tumor cells in resection specimens. Secondary endpoints included R0 resection rate, radiologic response, safety, overall survival, and progression-free survival. The modified intention-to-treat population was analyzed (CA-SAP [ n  = 51] versus SAP [ n  = 53]). The trial has met pre-specified endpoints. CA-SAP was associated with a significantly higher MPR rate (33.3%) than SAP (17.0%, P  = 0.044). The CA-SAP group had a significantly higher objective response rate (66.0% versus 43.4%, P  = 0.017) and R0 resection rate (94.1% versus 81.1%, P  = 0.042) than the SAP group. Nonsurgical grade 3-4 adverse events were observed in 17 patients (33.3%) in the CA-SAP group and 14 (26.4%) in the SAP group. Survival results were not reported due to immature data. Camrelizumab and apatinib combined with chemotherapy as a neoadjuvant regimen was tolerable and associated with favorable responses for LAGC. Neoadjuvant treatment represents a therapeutic option for locally advanced gastric cancer (LAGC). Here the authors report the results of a randomized phase 2 trial of camrelizumab (anti-PD1) and apatinib (anti-VEGFR2) combined with nab-paclitaxel plus S-1 versus chemotherapy alone as neoadjuvant treatment for LAGC.

Functional group interconversion, a pivotal synthetic technique for precise editing of molecular building blocks, is particularly rare when facilitated by energy transfer catalysis. Herein, we showcase two instances of photochemical rearrangement of isonitriles, facilitated by energy transfer catalysis under visible light. The di-π-ethane rearrangement and di-π-propane rearrangement proceed through a six-membered transition state, offering a fresh synthetic paradigm for constructing three- and five-membered molecular architectures. Notably, these open-shell rearrangements demonstrate a vast substrate scope, compatibility with diverse functional groups, and applicability to complex drug and natural product derivatives, thereby presenting a complementary strategy for advancing energy transfer-enabled functional group interconversion. Furthermore, the photochemical rearrangements of isonitriles have been supported by computational studies. Functional group interconversion, a pivotal synthetic technique for precise editing of molecular building blocks, is rare when facilitated by energy transfer catalysis. Herein, the authors report two instances of photochemical rearrangement of isonitriles, facilitated by energy transfer catalysis under visible light.

Background The clinical use of indocyanine green (ICG) in laparoscopic radical gastrectomy for gastric cancer remains at an exploratory stage. Methods Participants with resectable gastric adenocarcinoma were randomly allocated in a 1:1 ratio. The primary outcome is the number of retrieved lymph nodes (LNs) and has been reported. Herein, we report the 5-year overall survival (OS) rate, 5-year disease-free survival (DFS) rate, and related recurrence patterns. Results Total 258 patients (ICG group, 129; non-ICG group, 129) were included in the final per-protocol analysis. The 5-year OS and DFS rate of the ICG group were superior to those of the non-ICG group (all log-rank P  < 0.05). After a 5-year follow-up, the ICG group had a considerably lower cumulative recurrence rate (26/129, 20.2%) than the non-ICG group (44/129, 34.1%) (Gray’s test P  = 0.011), with a risk difference of − 0.140. Stratified by recurrence types, the ICG group exhibited a notably lower cumulative incidence of locoregional recurrence in comparison to the non-ICG group (ICG vs. non-ICG: 1.6% vs. 7.8%; risk difference = − 0.062; Gray’s test P  = 0.019). Dynamic analysis revealed that, in comparison to the ICG group, the non-ICG group had an earlier peak time and higher peak hazard of overall recurrence (ICG vs. non-ICG: peak time: 13.9 vs. 13.1 months; peak hazard: 0.0065 vs. 0.0138). Furthermore, landmark analysis indicated that the early recurrence (within 2 years) rate in the non-ICG group was 26.8%, which was significantly higher than the 13.1% in the ICG group ( P  = 0.006). Conclusions ICG-guided lymphadenectomy not only significantly improved the 5-year OS and DFS but also noticeably reduced the cumulative incidence of early recurrence. These findings support the routine use of ICG fluorescence-guided lymphadenectomy in laparoscopic radical gastrectomy. Trial registration ClinicalTrials.gov, NCT03050879. Key points Question Can indocyanine green (ICG) fluorescence imaging-guided laparoscopic lymphadenectomy during laparoscopic radical gastrectomy in patients with gastric cancer improve the long-term oncological outcomes than conventional lymphadenectomy? Findings In this randomized clinical trial, 5-year OS, DFS, and cumulative incidence of recurrence were better in the ICG group compared with the non–ICG group. Meaning ICG fluorescence imaging-guided lymphadenectomy not only significantly improved the 5-year OS and DFS but also noticeably reduced the recurrence hazard. The routine application of ICG fluorescence-guided lymphadenectomy is recommended for laparoscopic radical gastrectomy.

Objective To evaluate the effects of three nutritional scoring systems: Prognostic Nutritional Index (PNI), Controlling Nutritional Status (CONUT), and Naples Prognostic Score (NPS) on the short- or long-term prognosis of gastric cancer (GC) patients who underwent radical gastrectomy. Methods The clinicopathological data of 2182 patients who underwent radical gastrectomy at the Fujian Medical University Union Hospital (FMUUH) from 2009 to 2014 were retrospectively analyzed. The effects of the PNI, CONUT, and NPS on the short- or long-term prognosis of GC patients were analyzed. Results Overall, 359 (16.5%) patients had postoperative complications. There was no significant association between the PNI, CONUT, and NPS and postoperative complications ( P  > 0.05); however, high CONUT and NPS were significantly associated with severe postoperative complications ( P  < 0.05). Univariate analysis showed that PNI, CONUT, and NPS were all associated with overall survival (OS) ( P  < 0.001). However, multivariate analysis showed that only PNI was an independent risk factor for OS ( P  = 0.004), and the 5-year OS rate in the low PNI group was significantly lower than that in the normal PNI group (55.5% vs 75.4%, P  < 0.05). The area under the curve (AUC) and the c-index of PNI were significantly higher than those of CONUT and NPS. The prognostic efficiency of combining PNI and TNM stage was also significantly better than that of TNM staging alone ( P  < 0.05). Conclusion The current study demonstrated that CONUT and NPS are important for assessing the risk of severe postoperative complications. However, PNI is an independent risk factor for the long-term prognosis of GC patients who underwent radical gastrectomy and can improve the prognostic efficiency of TNM staging.

Neoadjuvant chemotherapy (NAC) is a standard treatment option for locally advanced gastric cancer (LAGC); however, the indications for adjuvant chemotherapy (AC) in patients with LAGC who received NAC remain controversial. To compare survival rates between patients with LAGC who received AC and those who did not after NAC followed by surgery. This multicenter, international cohort study included 353 patients with LAGC undergoing curative-intent gastrectomy after NAC at 2 tertiary referral teaching hospitals in China between June 1, 2008, and December 31, 2017. To externally validate the findings in the Chinese patients, 109 patients from the US and Italy between June 1, 2006, and June 30, 2013, were reviewed. The follow-up period of the Chinese patients was completed in December 2020, and the follow-up period of the Western patients was completed between February and July 2017. Data analysis was performed from December 1, 2020, to February 28, 2021. Patients who received AC and those who did not were propensity score matched to evaluate the association of AC with survival. Overall survival (OS), disease-free survival, and disease-specific survival. Of 353 patients from China (275 [78.1%] male; mean [SD] age, 58.0 [10.7] years), 262 (74.1%) received AC and 91 (25.9%) did not. After propensity score matching, the 3-year OS was significantly higher in patients who received AC (60.1%; 95% CI, 53.1%-68.1%) than in those who did not (49.3%; 95% CI, 39.8%-61.0%) (P = .02). Lymph node ratio (LNR) was significantly associated with AC benefit (P < .001 for interaction), and a plot of the interaction between LNR and AC demonstrated that AC was associated with improved OS in patients with higher (≥9%) LNRs (3-year OS: 46.6% vs 21.7%; P < .001), but not in patients with LNRs less than 9% (3-year OS: 73.9% vs 71.3%; P = .30). When stratified by AC cycles, only those patients who completed at least 4 AC cycles exhibited a significant survival benefit in the 6-month (hazard ratio, 0.56; 95% CI, 0.33-0.96; P = .03) and 9-month landmark analysis (hazard ratio, 0.50; 95% CI, 0.27-0.94; P = .03). In the external cohort, improved OS with AC administration was also found in patients with LNRs of 9% or greater (3-year OS: 53.0% vs 26.3%; P = .04). In this cohort study, the administration of AC after NAC and resection of LAGC was associated with improved prognosis in patients with LNRs of 9% or greater. These findings suggest that LNR might be valuable in AC selection in future decision-making processes.

Apatinib is a novel treatment option for chemotherapy-refractory advanced gastric cancer (GC), but it has not been evaluated in patients with locally advanced GC. To investigate the effectiveness and safety of apatinib combined with S-1 plus oxaliplatin (SOX) as a neoadjuvant treatment for locally advanced GC. This multicenter, prospective, single-group, open-label, phase 2 nonrandomized controlled trial was conducted in 10 centers in southern China. Patients with M0 and either clinical T2 to T4 or N+ disease were enrolled between July 1, 2017, and June 30, 2019. Statistical analysis was performed from December 1, 2019, to January 31, 2020. Eligible patients received apatinib (500 mg orally once daily on days 1 to 21 and discontinued in the last cycle) plus SOX (S-1: 40-60 mg orally twice daily on days 1 to 14; oxaliplatin: 130 mg/m2 intravenously on day 1) every 3 weeks for 2 to 5 cycles. A D2 gastrectomy was performed 2 to 4 weeks after the last cycle. The primary end point was R0 resection rate. Secondary end points were the response rate, toxic effects, and surgical outcome. A total of 48 patients (mean [SD] age, 63.2 [8.2] years; 37 men [77.1%]) were enrolled in this study. Forty patients underwent surgery (38 had gastrectomy, and 2 had exploratory laparotomy), with an R0 resection rate of 75.0% (95% CI, 60.4%-86.4%). The radiologic response rate was 75.0%, and T downstaging was observed in 16 of 44 patients (36.4%). The pathological response rate was 54.2% (95% CI, 39.2%-68.6%); moreover, this rate was significantly higher in patients who achieved a radiologic response compared with those who did not (12 [80.0%] vs 1 [20.0%]; P = .03) and in those who had an Eastern Cooperative Oncology Group Performance Status score of 0 (20 [76.9%] vs 10 [45.5%]; P = .03) or had tumors located in the upper one-third of the stomach (16 [61.5%] vs 7 [31.8%]; P = .04). Patients who achieved a pathological response (vs those who did not) had significantly less blood loss (median [range]: 60 [10-200] mL vs 80 [20-300] mL; P = .04) and significantly more lymph nodes harvested (median [range]: 40 [24-67] vs 32 [19-51]; P = .04) during surgery. Postoperative complications were observed in 7 of 38 patients (18.4%). Grade 3 toxic effects occurred in 16 of 48 patients (33.3%), and no grade 4 toxic effects or preoperative deaths were observed. This nonrandomized controlled trial found that apatinib combined with SOX was effective and had an acceptable safety profile as a neoadjuvant treatment for locally advanced GC. A large-scale randomized clinical trial may be needed to confirm the findings. ClinicalTrials.gov Identifier: NCT03192735.

Based on a new statistical theory, we investigate the thermodynamic anomalies of small quantum systems, such as the negative specific heat (NSH) and negative entropy (NE) within the generalized canonical ensemble. We consider the system–bath heat exchange and “uncompensated heat” in the thermodynamical level which is independent on the details of the system–bath coupling. For ideal finite systems, we calculate two thermodynamic quantities, i.e., the experimental specific heat and the entropy. The results show that the NSH and NE exist in quantum thermodynamics, particularly at low temperatures for small systems. They agree with the results of the reduced partition function theory and reveal that the finite boundary effects of the uncompensated heat and heat exchange of small quantum systems dominate the nonequilibrium irreversible processes.

The first-principles calculations were performed to research effects of elements X (Au, Be, Pd, Y, Ca, Cu, In and Zn) on mechanical and electronic properties of Ag with the density function theory (DFT). A supercell consisting of 107 atoms of Ag and one solute atom X was used. It was found that the bulk modulus of Ag dilute solutions were affected by the bulk modulus of pure alloying elements as well as their volume. The shear modulus G trend to decrease with increase of volume of Ag caused by alloying addition, but Ag-X covalent bond had positive correlation with shear modulus G. All of Ag107X alloys were ductility since theirs B/G ratio, Poisson's ratios ν were larger than 1.75 and 0.33, respectively. Comparing to other calculated Ag107X alloys, Ag107Be and Ag107Cu had the larger Vickers hardness, the value of which were 3.96GPa, 3.86GPa, respectively. There were not only metallic bonds (Ag-Ag) but also covalent bonds (Ag-X) in Ag107X alloys. The strong covalent bonds between Y, Zn, Ca and Ag were mainly caused by orbital hybridization between Y-5p orbital, Zn-3d orbital, Ca-3d orbitals and Ag-4d, 5s and 5p orbitals.

Background：Coronal diffusion-weighted magnetic resonance imaging （DW-MRI） and apparent diffusion coefficient （ADC） values have gradually become applied （following conventional axial DW-MRI） in the renal analysis.To explore whether data obtained using coronal DW-MRI are comparable with those derived using axial DW-MRI,this preliminary study sought to assess the agreement in renal ADC values between coronal DW-MRI and axial DW-MRI.Methods：Thirty-four healthy volunteers were enrolled in the study; written consents were obtained.All subjects underwent respiratory-triggered axial and coronal DW-MRI using a 1.5-MR system with b values of 0 and 800 s/mm2.The signal-to-noise ratios （SNRs） of the two DW-MRI sequences were measured and statistically compared using the paired t-test.The extent of agreement of ADC values of the upper pole,mid-pole,and lower pole of the kidney; the mean ADC values of the left kidney and right kidney; and the mean ADC values of the bilateral kidneys were evaluated via calculation of intraclass correlation coefficients （ICCs） or Bland-Altman method between the two DW-MRI sequences.Results：The SNR of coronal DW-MR images was statistically inferior to that of axial DW-MR images （P ＜ 0.001）.The ICCs of the ADC values of each region of interest,and the mean ADC values of bilateral kidneys,between the two sequences,were greater than 0.5,and the mean ADCs of the bilateral kidneys demonstrated the highest ICC （0.869; 95％ confidence interval：0.739-0.935）.In addition,94.1％ （32/34）,94.1％ （32/34）,and 97.1％ （31/34） of the ADC bias was inside the limits of agreement in terms of the mean ADC values of the left kidneys,right kidneys,and bilateral kidneys when coronal and axial DWI-MRI were compared.Conclusions：ADC values derived using coronal DW-MRI exhibited moderate-to-good agreement to those of axial DW-MRI,rendering the former an additional useful DW-MRI method,and causing the ADC values derived using the two types of DW-MRI to be comparable.

Aim： To investigate the therapeutic potential of adeno-associated virus （AAV）-mediated expression of vascular endothelial growth factor （VEGF） and bone morphogenetic protein （BMP）. Methods： Four experimental groups were administered the following AAV vector constructs： rAAV-hVEGF165-internal ribosome entry site （IRES）-hBMP-7 （AAV-VEGF/BMP）, rAAV-hVEGF165-GFP （AAV-VEGF）, rAAV-hBMP-7-GFP （AAV-BMP）, and rAAV-IRES-GFP （AAV-GFP）. VEGF165 and BMP-7 gene expression was detected using RT-PCR. The VEGF165 and BMP-7 protein expression was determined by Western blotting and ELISA. The rabbit ischemic hind limb model was adopted and rAAV was administered intramuscularly into the ischemic limb. Results： Rabbit bone marrow-derived mesenchymal stem cells （BMSCs） were cultured and infected with the four viral vectors. The expression of GFP increased from the 7th day of infection and could be detected on the 28th day post-infection. In the AAV-VEGF/BMP group, the levels of VEGF165 and BMP-7 increased with prolonged infection time. The VEGF185 and BMP-7 secreted from BMSCs in the AAV-VEGF/BMP group enhanced HUVEC tube formation and resulted in a stronger osteogenic ability, respectively. In rabbit ischemic hind limb model, GFP expression increased from the 4th week and could be detected at 8 weeks post-injection. The rAAV vector had superior gene expressing activity. Eight weeks after gene transfer, the mean blood flow was significantly higher in the AAV-VEGF/BMP group. Orthotopic ossification was radiographically evident, and capillary growth and calcium deposits were obvious in this group. Conclusion： AAV-mediated VEGF and BMP gene transfer stimulates angiogenesis and bone regeneration and may be a new therapeutic technique for the treatment of avascular necrosis of the femoral head （ANFH）.Aim： To investigate the therapeutic potential of adeno-associated virus （AAV）-mediated expression of vascular endothelial growth fac- tor （VEGF） and bone morphogenetic protein （BMP）. Methods： Four experimental groups were administered the following AAV vector constructs： rAAV-hVEGF16s-internal ribosome entry site （IRES）-hBMP-7 （AAV-VEGF/BMP）, rAAV-hVEGF165-GFP （AAV-VEGF）, rAAV-hBMP-7-GFP （AAV-BMP）, and rAAV-IRES-GFP （AAV-GFP）. VEGF165 and BMP-7 gene expression was detected using RT-PCR. The VEGF165 and BMP-7 protein expression was determined by Western blotting and ELISA. The rabbit ischemic hind limb model was adopted and rAAV was administered intramuscularly into the ischemic limb. Results： Rabbit bone marrow-derived mesenchymal stem cells （BMSCs） were cultured and infected with the four viral vectors. The expression of GFP increased from the 7th day of infection and could be detected on the 28th day post-infection. In the AAV-VEGF/BMP group, the levels of VEGF165 and BMP-7 increased with prolonged infection time. The VEGF165 and BMP-7 secreted from BMSCs in the AAV-VEGF/BMP group enhanced HUVEC tube formation and resulted in a stronger osteogenic ability, respectively. In rabbit ischemic hind limb model, GFP expression increased from the 4th week and could be detected at 8 weeks post-injection. The rAAV vector had superior gene expressing activity. Eight weeks after gene transfer, the mean blood flow was significantly higher in the AAV-VEGF/BMP group. Orthotopic ossification was radiographically evident, and capillary growth and calcium deposits were obvious in this group. Conclusion： AAV-mediated VEGF and BMP gene transfer stimulates angiogenesis and bone regeneration and may be a new therapeutic technique for the treatment of avascular necrosis of the femoral head （ANFH）.