Causes and consequences of tipping points in river delta social-ecological systems.

The sustainability of social-ecological systems within river deltas globally is in question as rapid development and environmental change trigger "negative" or "positive" tipping points depending on actors' perspectives, e.g. regime shift from abundant sediment deposition to sediment shortage, agricultural sustainability to agricultural collapse or shift from rural to urban land use. Using a systematic review of the literature, we show how cascading effects across anthropogenic, ecological, and geophysical processes have triggered numerous tipping points in the governance, hydrological, and land-use management of the world's river deltas. Crossing tipping points had both positive and negative effects that generally enhanced economic development to the detriment of the environment. Assessment of deltas that featured prominently in the review revealed how outcomes of tipping points can inform the long-term trajectory of deltas towards sustainability or collapse. Management of key drivers at the delta scale can trigger positive tipping points to place social-ecological systems on a pathway towards sustainable development.

Differences of bioelectrical impedance in the development and healing phase of pressure ulcers and erythema in mouse model.

Pressure ulcers (PUs) are economically burdensome medical conditions. Early changes in pressure ulcers are associated with erythema. In this study, bioelectrical impedance was used to measure the differences between PUs and blanchable erythema. We divided 21 ICR mice into three groups: control, 1000 mmHg-1h, and 1000 mmHg-6h. Healthy skin, blanchable erythema, and PUs were induced on the dorsal skin. The results indicated an immediate increase in impedance, resistance, and reactance values in the pressure group after release, followed by a subsequent decrease until two days after release. Compared with the control group, impedance and reactance significantly increased by 30.9% (p < 0.05) and 30.1% (p < 0.01), respectively, in the 6 h-loading group immediately after release. One and two days after release, the 1 h-loading and 6 h-loading groups exhibited significantly different degrees of decline. One day after release, impedance and resistance decreased by 30.2% (p < 0.05) and 19.8% (p < 0.05), respectively, in the 1 h-loading group; while impedance, resistance, and reactance decreased by 39.2% (p < 0.01), 26.8% (p < 0.01), and 45.7% (p < 0.05), respectively, in the 6 h-loading group. Two days after release, in the 1 h-loading group, impedance and resistance decreased by 28.3% (p < 0.05) and 21.7% (p < 0.05), respectively; while in the 6 h-loading group, impedance, resistance, and reactance decreased by 49.8% (p < 0.001), 34.2% (p < 0.001), and 59.8% (p < 0.01), respectively. One and two days after release the pressure group reductions were significantly greater than those in the control group. Additionally, we monitored changes during wound healing. Distinguishing early PUs from blanchable erythema by noninvasive bioelectrical impedance technology may have applications value in early assessment of PUs.

Organic carbon accumulation in British saltmarshes.

Saltmarshes are a crucial component of the coastal carbon (C) system and provide a natural climate regulation service through the accumulation and long-term storage of organic carbon (OC) in their soils. These coastal ecosystems are under growing pressure from a changing climate and increasing anthropogenic disturbance. To manage and protect these ecosystems for C and to allow their inclusion in emissions and natural-capital accounting, as well as carbon markets, accurate and reliable estimates of OC accumulation are required. However, globally, such data are rare or of varying quality. Here, we quantify sedimentation rates and OC densities for 21 saltmarshes in Great Britain (GB). We estimate that, on average, saltmarshes accumulate OC at a rate of 110.88 ± 43.12 g C m-2 yr-1. This is considerably less than widely applied global saltmarsh averages. It is therefore highly likely that the contribution of northern European saltmarshes to global saltmarsh OC accumulation has been significantly overestimated. Taking account of the climatic, geomorphological, oceanographic, and ecological characteristics of all GB saltmarshes and the areal extent of different saltmarsh zones, we estimate that the 451.65 km2 of GB saltmarsh accumulates 46,563 ± 4353 t of OC annually. These low OC accumulation rates underline the importance of the 5.20 ± 0.65 million tonnes of OC already stored in these vulnerable coastal ecosystems. Going forward the protection and preservation of the existing stores of OC in GB saltmarshes must be a priority for the UK as this will provide climate benefits through avoided emissions several times more significant than the annual accumulation of OC in these ecosystems.

The impacts of exposure to risk factors during youth on the increasing global trend of early-onset pancreatic cancer.

OBJECTIVES: An increasing trend of pancreatic cancer in young adults has emerged in some countries. This study aimed to investigate global trends of pancreatic cancer in young adults and explore the impact of exposure to risk factors on pancreatic cancer incidence during youth. METHODS: Global and national data on pancreatic cancer incidence, disability-adjusted life-years, attributive mortality, and summary exposure values of risk factors were retrieved from the Global Burden of Disease 2019. The average annual percent change (AAPC) of incidence and mortality was calculated. Additionally, generalized additive models were applied to explore the non-linear associations between the levels and changes in the Human Development Index and AAPC. RESULTS: Global pancreatic cancer incidence increased during various periods from 1990 to 2019, particularly in adults aged <45 years from 2010 to 2019, at an average annual increase rate of 0.7% (95% confidence interval: 0.4-1.0%). The AAPC of early-onset pancreatic cancer incidence from 2010 to 2019 was negatively correlated with Human Development Index levels in both 2010 and 2019 but positively correlated with Human Development Index acceleration. Significant increases in early-onset pancreatic cancer incidence were observed over this period in 32 of 88 countries, primarily in South America, North America, Oceania, and Africa. Early-onset pancreatic cancer mortality attributed to high body mass index and fasting plasma glucose increased, while that attributed to tobacco use declined. CONCLUSIONS: An increasing trend has emerged in the global incidence and burden of early-onset pancreatic cancer over the last few decades. This rise may partly be attributed to global epidemics of high body mass index and fasting plasma glucose.

Transition from fractal-dendritic to compact islands for the 2D-ferroelectric SnSe on graphene/Ir(111).

Epitaxial growth is a versatile method to prepare two-dimensional van der Waals ferroelectrics like group IV monochalcogenides which have potential for novel electronic devices and sensors. We systematically study SnSe monolayer islands grown by molecular beam epitaxy, especially the effect of annealing temperature on shape and morphology of the edges. Characterization of the samples by scanning tunneling microscopy reveals that the shape of the islands changes from fractal-dendritic after deposition at room temperature to a compact rhombic shape through annealing, but ripening processes are absent up to the desorption temperature. A two-step growth process leads to large, epitaxially aligned rhombic islands bounded by well-defined110-edges (armchair-like), which we claim to be the equilibrium shape of the stoichiometric SnSe monolayer islands. The relaxation of the energetically favorable edges is detected in atomically resolved STM images. The experimental findings are supported by the results of our first-principles calculations, which provide insights into the energetics of the edges, their reconstructions, and yields the equilibrium shapes of the islands which are in good agreement with the experiment.

[To investigate the role of the AAC-8 scoring in predicting restenosis or occlusion of lower extremity arteries after dilatation and angioplasty with DCB].

Objective: To investigate the role of the Abdominal Aortic Calcification-8 (AAC-8) scoring system in predicting restenosis or occlusion of lower extremity arteries after dilatation and angioplasty with drug-coated balloon (DCB). Methods: In this retrospective study, 62 patients who underwent dilatation and angioplasty with DCB for lower limb atherosclerotic obliterans (ASO) were enrolled from September 2018 to June 2022 in Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School. Among them who aged (73.9±11.3) years, 37 were males and 25 were females. Patients were divided into two groups according to the condition of the lower extremity arteries after dilatation and angioplasty with DCB: recurrence group (n=26) and patency group (n=36). Logistic regression was used to analyze the factors associated with restenosis or occlusion of lower extremity arteries after dilatation and angioplasty with DCB. The predictive value of the AAC-8 score for restenosis or occlusion of the lower extremity arteries after dilatation and angioplasty with DCB was analyzed using the receiver operating characteristic curves (ROC curves). Results: The postoperative follow-up was 16.30 (10.97, 24.10) months in the patency group and 9.03 (6.98, 15.31) months in the recurrence group. The results of multifactorial logistic regression analysis showed that an elevated AAC-8 score (OR=1.388, 95%CI: 1.067-1.806, P=0.015) was an associated factor of restenosis or occlusion of the lower extremity arteries after dilatation and angioplasty with DCB. The ROC curve analysis showed that the area under the curve (AUC) of the AAC-8 score for predicting restenosis or occlusion of the lower extremity arteries after dilatation and angioplasty with DCB was 0.687 (95%CI: 0.550-0.824, P=0.013), with a cut-off value of 5.5 points, a sensitivity of 65.4% and a specificity of 69.5%. Conclusions: Elevated AAC-8 score is associated with restenosis or occlusion of the lower extremity arteries after dilatation and angioplasty with DCB. When the cut-off value is 5.5, the AAC-8 score predicts restenosis or occlusion of the lower extremity arteries after DCB dilation and angioplasty with a sensitivity of 65.4% and a specificity of 69.5%.

Individualised prediction of progression of solitary sub-solid pulmonary nodules based on CT semantic and clinical features: a 3-year follow-up study.

AIM: To develop and validate a progressive prediction model for estimating the time to progression (TTP) of sub-solid pulmonary nodules (SSNs). MATERIALS AND METHODS: A total of 126 cases who met inclusion and exclusion criteria were included in the study. The primary endpoint of the study was TTP of SSNs. Baseline characteristics were assessed in terms of clinical and CT semantic features. Kaplan-Meier analysis and Cox regression analysis were performed to determine the relationship between SSNs TTP and factors from the entire data set. The nomogram was constructed based on the result of multivariate analysis and internal validation was performed using the bootstrapping. The nomogram's performance was assessed with the C-index, calibration curves, and decision curve analysis. RESULTS: The median follow-up time of the population was 42.5 (21.5) months. On Kaplan-Meier analysis, patients with higher or positive values of the indices had higher cumulative progression rates (p<0.05). Multivariate Cox regression models identified diameter, consolidation tumour ratio (CTR), morphology, and vasodilation sign (VDS) as independent risk factors of TTP. These predictors were included in the final model to estimate individual probabilities of progression in the 3 years, which performed well in the discrimination (the C-index was 0.901 [95%CI: 0.830-0.981] and 0.875 [95%CI: 0.805-0.942] in the training and internally validation sets). CONCLUSION: The radiological semantic features nomogram is a promising and favourable prognostic biomarker for predicting progression and may aid in clinical risk stratification and decision-making for SSNs.

[Construction and validation of a nomogram model of early related factors for hepatic insufficiency after hemihepatectomy].

Objectives: To investigate the early related factors for hepatic insufficiency after hemihepatectomy and to construct and validate a nomogram model. Methods: This was a retrospective cohort study.There were 207 patients with liver tumor who underwent hemihepatectomy in the Department of Hepatobiliary Surgery,Cancer Hospital,Chinese Academy of Medical Sciences from October 2016 to December 2022. Using the random number method,patients were randomly divided into a model group(n=166) and a validation group(n=41) according to an 4︰1 ratio. There were 118 males and 48 females in the modeling group,with an age (M(IQR)) of 59.0(13.3) years (range: 22.0 to 81.0 years),42 patients in the group with postoperative liver insufficiency and 124 patients in the group without postoperative liver insufficiency. There were 32 males and 9 females in the validation group, with an age of 54.0(19.0) years (rang: 25.0~81.0 years). The first results of the peripheral blood test of patients within 24 hours after surgery were collected,and the independent related factors for incomplete postoperative liver function were determined by multivariate Logistic regression analysis,and related factors of postoperative incomplete liver function were screened by best subset selection. A nomogram model of the risk of postoperative hepatic insufficiency after hemihepatectomy was constructed using R software,followed by internal and external validation of the model. Results: Multivariate logistic regression analysis showed that elevated D-dimer level and decreased antithrombin Ⅲ (AT-Ⅲ) activity within 24 hours after surgery were independent related factors for the development of postoperative hepatic insufficiency in hemihepatectomized patients. The results of the best subset selection showed that ALT,D-dimer, and AT-Ⅲ activity levels within 24 hours postoperatively were the most relevant factors for postoperative hepatic insufficiency. The R software was applied to build a nomogram prediction model based on the above three indicators in the model set,and the receiver operating characteristic(ROC) curve of the model showed an area under the curve of 0.803 and the calibration curve showed a U-index of -0.012 for the model(P=0.977). The results of the clinical decision analysis and the clinical impact curve indicated that the model had good clinical utility. The internal validation results of the Bootstrap method suggested that the model had reasonable consistency. The area under the ROC curve of the validation group model was 0.806,suggesting that the model had a good generalization prediction ability. Conclusions: The levels of ALT,D-dimer,and AT-Ⅲ activity within 24 hours after hemihepatectomy are valuable indicators for predicting liver insufficiency after hemihepatectomy. The nomogram model is reliable and can be used as an indicator for close postoperative monitoring.

[Clinicopathological features and prognosis of 47 adults with Hirschsprung's disease and Hirschsprung's disease allied disorders].

Objective: To improve understanding and treatment of adult Hirschsprung's disease (HD) and Hirschsprung's disease allied disorders (HAD) by investigating the clinicopatho- logical features, diagnostic and treatment methods, and prognosis. Methods: This was a retrospective observational study. The study cohort comprised patients aged 18-65 years admitted to the Sixth Hospital of Sun Yat-sen University between January 2007 and December 2022 who were diagnosed with adult HD or HAD by postoperative pathological examination. Those with severe cardiovascular disease, diabetes mellitus, or cirrhosis of the liver were excluded, leaving 47 patients in the study cohort. Emergency open surgery was performed on patients with life-threatening manifestations, whereas those whose condition was stable received conservative treatment to stabilize them, following which they underwent a standard surgical procedure. Surgical procedures performed included the Duhamel procedure, Soave procedure, subtotal colonic resection, total colonic resection, and creation of a palliative stoma. Variables studied included clinicopathological characteristics, treatment modalities, postoperative complications, and long-term anal function. Complications were evaluated in accordance with the Clavien-Dindo criteria, and long-term anal function according to the 2005 Krickenbeck International Classification Criteria. Results: Of the 47 patients, 33 were men and 14 women, with a median age of 29 (18-51) years. HD was diagnosed in 41 (87.2%) patients and HAD in six (12.8%). The commonest initial symptom was dyspareunia (70.2%,33/47), followed by abdominal distension (57.4%, 27/47) and abdominal pain (44.7%,21/47). The detection rates of HD/HAD by barium enema + defecography, anorectal manometry, and preoperative rectal biopsy were 86.8% (33/38), 16/19, and 7/7, respectively. Three (6.4%) patients had discrepant preoperative clinical and postoperative pathological diagnoses. None of the three misdiagnosed patients had undergone preoperative rectal biopsy. Of the 47 study patients, three chose non-surgical treatment and 44 surgical treatment. All surgeries were successfully completed. Postoperative complications occurred in 19 patients (43.2%), including one death case who had undergone emergency surgery. The median duration of follow-up after surgery was 65 (12-180) months. Three patients in the surgical treatment group were lost to follow-up. Of the remaining 41 patients, 36, three, and two had excellent, good, and poor long-term anal function, respectively. The differences in outcomes between the surgical and non-surgical treatment groups (no patients, one, and two with excellent, good, and poor long-term anal function, respectively) (Z=-3.883, P=0.001) were statistically significant. Of the 44 patients who underwent surgical treatment, 41 underwent standard surgeries and three emergency surgeries because their conditions were life-threatening. The difference in complication rate between standard surgery and emergency surgery groups (39.0% [16/41] vs. 3/3, χ2=2.115, P=0.146) was not statistically significant. However, the rate of postoperative Grade III-V complications was lower in the standard surgery group (4.9% [2/41] vs. 2/3, Z=-2.668, P=0.008). Long-term anal function was significantly better in the standard surgery than emergency surgery group (94.7% [36/38] vs. 0/3, Z=-4.935, P=0.001). The 41 standard surgeries included 11 Duhamel's procedures, six Soave's procedures, 19 subtotal colonic resections, three total colonic resections, and two palliative colostomies. The incidence of postoperative complications was significantly superior in the Duhanmels procedures and palliative colostomies group(1/11 and 0/2, P=0.041). Of the 41 patients who underwent standard surgery, 23 underwent open surgery and 18 minimally invasive laparoscopic surgery. The incidence of postoperative Grade III-V complications and long-term anal function were significantly superior in the laparoscopic group than in the open group (all P<0.05). Conclusion: It is easy to misdiagnose adult HD and HAD, surgical treatment is safe and feasible, and its long-term efficacy is good.

[Participation rate and detection of colorectal neoplasms based on multi-round fecal immunochemical testing for colorectal cancer screening in the Chinese population].

Objective: To evaluate the participation rate and detection of colorectal neoplasms based on annual fecal immunochemical testing (FIT) for three consecutive years in a population-based colorectal cancer screening program in China. Methods: Based on a population-based colorectal cancer screening program conducted from May 2018 to May 2021 in 6 centers in China, 7 793 eligible participants aged 50-74 were included and offered free FIT and colonoscopy (for those who were FIT-positive on initial screening). At baseline, all participants were invited to receive FIT. In subsequent screening rounds, only FIT-positive participants who did not undergo colonoscopy or FIT-negative participants were invited to have repeated FIT screening. FIT-positive participants were recommended to undertake colonoscopy and pathological examination (if abnormalities were found during colonoscopy). An overall of three rounds of annual FIT screening were conducted. The primary outcomes of the study were the participation rate of FIT screening, the compliance rate of colonoscopy for FIT-positive participants, and the detection rate of colorectal neoplasms. Results: Among the 7 793 participants included in this study, 3 310 (42.5%) were male, with age of (60.50±6.49) years. The overall participation rates for the first, second and third round of FIT screening were 94.0%(7 327/7 793), 86.8% (6 048/6 968) and 91.3% (6 113/6 693), respectively. Overall, 7 742 out of 7 793 participants (99.3%) attended at least one round of screening, and 5 163 out of 7 793 participants (66.3%) attended all three rounds of screening. The positivity rate was significantly higher in the first (14.6%, 1 071/7 327) round compared with the second (5.6%, 3 41/6 048) and third (5.5%, 3 39/6 113) screening rounds (P<0.001). The overall compliance rates of colonoscopy examination among FIT-positive subjects were over 70% in three rounds, which were 76.3% (817/1 071), 75.7% (258/341) and 71.7% (243/339), respectively. In a multivariate logistic regression model considering factors including sex, education background, smoking, alcohol drinking, previous colonoscopy examination, colonic polyp history and family history of colorectal cancer among first-degree relatives, gender and smoking status were related factors affecting the participation rate of FIT screening, with higher rate in males and non-smokers. In addition, logistic regression analysis also found that age was negatively correlated with the compliance rate of colonoscopy in FIT positive patients. The detection rate of advanced tumors (colorectal cancer + advanced adenoma) declined from the first round to subsequent rounds [1st round: 1.15% (90/7 793); 2nd round: 0.57% (40/6 968); and 3rd round: 0.58% (39/6 693)], however, the positive predictive value for advanced neoplasms increased round by round, and was 11.02% in the first screening round, 15.50% in the second screening round, and 16.05 % in the third screening round. In each screening round, the detection rate for advanced neoplasms was higher in men than that in women, and increased with age. Conclusions: Annual repeated FIT screening has high acceptance and satisfying detection rates in the Chinese population. To optimize and improve the effectiveness of colorectal cancer screening, multi-round repeated FIT screening should be implemented while ensuring high participation rates.

Linear Breit-Wheeler process driven by compact lasers.

We report a proposal to observe the two-photon Breit-Wheeler process in plasma driven by compact lasers. A high-charge electron bunch can be generated from laser plasma wakefield acceleration when a tightly focused laser pulse propagates in a subcritical density plasma. The electron bunch scatters with the laser pulse coming from the opposite direction and resulting in the emission of high brilliance x-ray pulses. In a three-dimensional particle-in-cell simulation with a laser pulse of ∼10 J, one could produce an x-ray pulse with a photon number higher than 3×10^{11} and brilliance above 1.6×10^{23} photons/s/mm^{2}/mrad^{2}/0.1%BW at 1 MeV. The x-ray pulses collide in the plasma and create more than 1.1×10^{5} electron-positron pairs per shot. It is also found that the positrons can be accelerated transversely by a transverse electric field generated in the plasma, which enables the safe detection in the direction away from the laser pulses. This proposal enables the observation of the linear Breit-Wheeler process in a compact device with a single shot.

Gate-controlled suppression of light-driven proton transport through graphene electrodes.

Recent experiments demonstrated that proton transport through graphene electrodes can be accelerated by over an order of magnitude with low intensity illumination. Here we show that this photo-effect can be suppressed for a tuneable fraction of the infra-red spectrum by applying a voltage bias. Using photocurrent measurements and Raman spectroscopy, we show that such fraction can be selected by tuning the Fermi energy of electrons in graphene with a bias, a phenomenon controlled by Pauli blocking of photo-excited electrons. These findings demonstrate a dependence between graphene's electronic and proton transport properties and provide fundamental insights into molecularly thin electrode-electrolyte interfaces and their interaction with light.

[Value of fecal immunochemical test in colorectal cancer screening].

Screening and early diagnosis and treatment have been proven effective in reducing the incidence and mortality of colorectal cancer. Colonoscopy combined with pathological examination is the gold standard for colorectal cancer screening. However, due to the invasiveness, high cost and the need for professional endoscopists of colonoscopy, it is not feasible to directly use this method for mass population screening. Fecal immunochemical test (FIT) is one of the screening techniques recommended by authoritative international guidelines for colorectal cancer screening, and has been widely used in population-based colorectal cancer screening programs in countries around the world. This paper elaborates on the value of FIT in colorectal cancer screening from different aspects, such as the technical principles, the screening efficiency, the screening strategies, and the population effects and benefits. Additionally, it describes the current situation of colorectal cancer screening in China and summarizes the challenges faced in colorectal cancer screening in order to optimize the FIT-based colorectal cancer screening strategies in the population and provide theoretical reference for effective colorectal cancer screening.

[Effects and mechanisms of bariatric surgery on sexual function in males with obesity].

Obesity has been identified as one of the risk factors for male sexual dysfunction, and it also has a certain impact on fertility. For people with obesity, sexual function is an important aspect of quality of life, but it is often overlooked. Society's stigma against obesity exacerbates the psychological stress of patients with obesity and negatively affects sexual function. Current studies have found that bariatric surgery can reduce body weight and improve sexual function in patients with obesity, and obesity-related gonadal dysfunction is also improved or even subsided after surgery. However, attention needs to be paid to postoperative body mass management and mental health status of patients to prevent postoperative body mass recovery and reversal of sex hormones and sexual function. In addition, there is still controversy about the change in sperm quality after bariatric surgery, and there is a lack of research data on sexual function and sperm parameters and mechanisms after bariatric surgery. Therefore, this article reviews the latest research progress of bariatric surgery and sexual dysfunction, as well as related mechanisms and sperm parameters, to provide a reference for bariatric surgery in patients with obesity with sexual dysfunction.

[Correlation between C-reactive protein to albumin ratio and restenosis after femoral popliteal stenting in patients with lower extremity arteriosclerotic obliterans].

Objective: To investigate the study of the correlation between C-reactive protein to albumin ratio (CAR) and restenosis after stenting in patients with lower extremity atherosclerotic occlusive disease(LEASO). Methods: The clinical data of 95 patients with LEASO admitted to the Department of Vascular Surgery of Nanjing Drum Tower Hospital from June 2020 to December 2022 were retrospectively analyzed. There were 67 males and 28 females,aged (73.1±9.4) years (range:51 to 92 years). The patients were classified into the restenosis group (n=61) and the patency group (n=34) according to the CT angiography results. Independent sample t test,Mann-Whitney U test and χ2 test were used to compare the data between two groups. Risk factors for restenosis after femoropopliteal artery stenting in patients with LEASO were analyzed using multivariate Cox regression. The relationship between preoperative CAR level and restenosis after stent placement was analyzed. Subject operating characteristic(ROC) curves of CAR were plotted to assess the predictive value of CAR for restenosis after stenting,and the results were expressed as area under the curve (AUC). Results: The aortoiliac calcification grade,number of stents,length of stents,C-reactive protein and CAR levels in restenosis group were higher than those in the patency group,and the serum albumin level was lower than that in the patency group(all P<0.05). And the results of multifactorial Cox regression analysis showed that higher pre-procedure CAR level and lower ABI value was an independent risk factor for in-stent restenosis. The AUC of the ROC curve for restenosis was 0.737(95%CI:0.617 to 0.856),the AUC of the ROC curve for 12-month restenosis was 0.709(95%CI:0.602 to 0.815), and the AUC of the ROC curve for 24-month restenosis was 0.702(95%CI:0.594 to 0.811). Conclusion: Higher pre-procedural CAR levels in patients with LEASO is risk factor for in-stent restenosis,and CAR has a predictive value for restenosis after lower extremity arterial stent dilatation and angioplasty.

Neoadjuvant nivolumab plus chemotherapy versus chemotherapy for resectable NSCLC: subpopulation analysis of Chinese patients in CheckMate 816.

BACKGROUND: Neoadjuvant nivolumab plus chemotherapy significantly improved event-free survival (EFS) and pathologic complete response (pCR) versus chemotherapy alone in patients with resectable non-small-cell lung cancer (NSCLC) in the global phase III CheckMate 816 study. Here, we report post hoc exploratory efficacy, safety, and surgical outcomes in the Chinese subpopulation of this study. METHODS: Adults with stage IB-IIIA resectable NSCLC were randomized to receive nivolumab 360 mg plus chemotherapy or chemotherapy alone every 3 weeks for three cycles followed by surgery. Primary endpoints included EFS and pCR (both per blinded independent review). EFS and pCR results were from 14 October 2022, and 16 September 2020, database locks, respectively. RESULTS: The Chinese subpopulation comprised 97 patients (nivolumab plus chemotherapy, 44; chemotherapy, 53). At 38.2 months of minimum follow-up, median EFS was not reached [95% confidence interval (CI) 23.4 months-not reached] in the nivolumab plus chemotherapy arm and 13.9 months (95% CI 8.3-34.3 months) in the chemotherapy arm (hazard ratio 0.47, 95% CI 0.25-0.88). pCR rates were 25.0% (95% CI 13.2% to 40.3%) and 1.9% (95% CI 0.0% to 10.1%), respectively (odds ratio 11.05; 95% CI 1.41-86.49). Of 97 Chinese patients, 36 (82%) in the nivolumab plus chemotherapy arm and 41 (77%) in the chemotherapy arm underwent definitive surgery. Grade 3-4 treatment-related adverse events occurred in 18/43 patients (42%) treated with nivolumab plus chemotherapy and 22/53 patients (42%) treated with chemotherapy. CONCLUSIONS: Consistent with findings in the global study population of CheckMate 816, neoadjuvant nivolumab plus chemotherapy improved EFS and pCR versus chemotherapy in the Chinese subpopulation without impacting treatment tolerability or the feasibility of surgery. These findings support the use of nivolumab plus chemotherapy as a standard neoadjuvant treatment option for Chinese patients with resectable NSCLC.

[Pathological study on the relationship between nucleic acid oxidative stress and heart failure with preserved ejection fraction in patients aged over 85 years].

Objective: To investigate the level of nucleic acid oxidation in myocardial tissue of patients aged over 85 with heart failure with preserved ejection fraction (HFpEF) and the correlation with myocardial amyloid deposition. Methods: This was a retrospective case-control study. Data of patients≥85 years old who underwent systematic pathological autopsy in Beijing Hospital from 2003 to 2017 were retrospectively collected. Twenty-six patients were included in the HFpEF group and 13 age-and sex-matched patients who had not been diagnosed with heart failure and died of non-cardiovascular diseases served as the control group. The left ventricular myocardium slices of both groups were semi-quantitatively analyzed using immunohistochemical staining of 8-oxidized guanine riboside (8-oxo-G) and 8-oxidized guanine deoxyriboside (8-oxo-dG) to evaluate the oxidation of RNA and DNA in cardiomyocytes. Using the median of the mean absorbance value of 8-oxo-G immunohistochemical staining as the cut-off value, patients were divided into high-absorbance group and low-absorbance group. Congo red staining was used to compare myocardial amyloid deposition between the two groups. Results: The mean age of patients in HFpEF group was (91.8±3.7) years, 24 (92.3%) were males. The mean age of patients in control group was (91.7±3.7) years old, 11 (84.6%) were males. The median mean optical absorbance value of 8-oxo-G immunohistochemical staining of myocardium was significantly higher in HFpEF patients than in control group (0.313 8 (0.302 2, 0.340 6) vs. 0.289 2 (0.276 7, 0.299 4), Z=-3.245, P=0.001). The median mean absorbance value of 8-oxo-dG immunohistochemical staining of myocardial tissue was similar between the two groups (0.300 0 (0.290 0, 0.322 5) vs. 0.300 0 (0.290 0, 0.320 0), Z=-0.454, P=0.661). Proportion of patients with moderate and severe cardiac amyloid deposition was significantly higher in the high-absorbance group than in the low-absorbance group ((85.0%, 17/20) vs. (31.6%, 6/19), P=0.001). Conclusion: The RNA oxidation degree of myocardium in HFpEF patients is higher than that in elderly people without heart failure. Degree of myocardial amyloid deposits is higher in patients with high levels of RNA oxidation.

Measurement of Ultra-High-Energy Diffuse Gamma-Ray Emission of the Galactic Plane from 10 TeV to 1 PeV with LHAASO-KM2A.

The diffuse Galactic γ-ray emission, mainly produced via interactions between cosmic rays and the interstellar medium and/or radiation field, is a very important probe of the distribution, propagation, and interaction of cosmic rays in the Milky Way. In this Letter, we report the measurements of diffuse γ rays from the Galactic plane between 10 TeV and 1 PeV energies, with the square kilometer array of the Large High Altitude Air Shower Observatory (LHAASO). Diffuse emissions from the inner (15°10 TeV). The energy spectrum in the inner Galaxy regions can be described by a power-law function with an index of -2.99±0.04, which is different from the curved spectrum as expected from hadronic interactions between locally measured cosmic rays and the line-of-sight integrated gas content. Furthermore, the measured flux is higher by a factor of ∼3 than the prediction. A similar spectrum with an index of -2.99±0.07 is found in the outer Galaxy region, and the absolute flux for 10≲E≲60 TeV is again higher than the prediction for hadronic cosmic ray interactions. The latitude distributions of the diffuse emission are consistent with the gas distribution, while the longitude distributions show clear deviation from the gas distribution. The LHAASO measurements imply that either additional emission sources exist or cosmic ray intensities have spatial variations.