Comprehensive classifications for the endovascular recanalization of vertebral artery stump syndrome

Background:and purpose:To share our single-center vertebral artery stump syndrome(VASS)treatment experience and assess the role of comprehensive classification based on anatomic development,proximal conditions,and distal conditions(PAD).Materials and methods:Data were retrospectively collected from patients who underwent endovascular thrombectomy(EVT)at the Stroke Center of the First Hospital of Jilin University between January 2016 and December2021.Among patients with acute ischemic stroke in the posterior circulation,those with acute occlusion of the intracranial arteries and occlusion at the origin of the vertebral artery confirmed by digital subtraction angiography were selected.The clinical data were summarized and analyzed.Results:Fifteen patients with VASS were enrolled in the study.The overall success rate of surgical recanalization was 80%.The successful proximal recanalization rate was 70.6%,and the recanalization rates for P1,P2,P3,and P4 were 100%,71.4%,50%,and 66.67%,respectively.The mean operation times for the A1 and A2 types were124 and 120 min,respectively.The successful distal recanalization rate was 91.7%,and the recanalization rates for types D1,D2,D3,and D4 were 100%,83.3%,100%,and 100%,respectively.Five patients experienced perioperative complications(incidence rate:33.3%).Distal embolism occurred in three patients(incidence rate:20%).No dissection or subarachnoid hemorrhage occurred in any patient.Conclusion:EVT is a technically feasible treatment for VASS,and comprehensive PAD classification can,to a certain extent,help initially estimate the difficulty of surgery and provide guidance for interventional procedures.

Efficacy and safety of anlotinib as an adjuvant therapy in hepatocellular carcinoma patients with a high risk of postoperative recurrence

Objective:Hepatocellular carcinoma(HCC)has a high rate of postoperative recurrence and lacks an effective treatment to prevent recurrence.This study aims to investigate the efficacy and safety of anlotinib in postoperative adjuvant therapy for HCC patients with high-risk recurrence factors.Methods:For this multicenter,retrospective study,we recruited 63 HCC patients who received either anlotinib(n=27)or transcatheter arterial chemoembolization(TACE)(n=36)from six research centers in China between March 2019 and October 2020.The primary endpoint was disease-free survival(DFS)and the secondary endpoints were overall survival(OS)and safety.Results:In this study,the median follow-up time was 25.9 and 26.8 months in the anlotinib and TACE groups,respectively.There was no significant difference in the median DFS between the anlotinib[26.8 months,95%confidence interval(95%CI):6.8-NE]and TACE groups(20.6 months,95%CI:8.4-NE).The 12-month OS rates in the anlotinib and TACE groups were 96.3%and 97.2%,respectively.In the anlotinib group,19 of 27patients(70.4%)experienced treatment-emergent adverse events,with the most common events(≥10%)being hypertension(22.2%)and decreased platelet count(22.2%).Conclusions:The results indicate that anlotinib,as a new,orally administered tyrosine kinase inhibitor,has the same efficacy as TACE,and side effects can be well controlled.

Chinese expert consensus on the non-invasive imaging examination pathways of stable coronary artery disease

1 Introduction Early detection and diagnosis of stable coronary artery disease （SCAD） is essential for proactive secondary prevention of myocardial infarction （MI）, control of disease progress, and reduction of mortality. Clinical decision-making in modem medicine is increasingly dependent on cardiovascular imaging techniques. 2012 ACCF/AHA/ACP/AATS/ PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease has been issued by American Heart Association （AHA）. European Society of Cardiology （ESC） has issued 2013 ESC guidelines on the management of stable coronary artery disease.

Intercellular adhesion molecule-1 expression in the hippocampal CA1 region of hyperlipidemic rats with chronic cerebral ischemia

Chronic cerebral ischemia is a pathological process in many cerebrovascular diseases and it is induced by long-term hypedipidemia, hypertension and diabetes mellitus. After being fed a high-fat diet for 4 weeks, rats were subjected to permanent occlusion of bilateral common carotid arteries to establish rat models of chronic cerebral ischemia with hypedipiclemia. Intercellular adhesion molecule-1 expression in rat hippocampal CA1 region was determined to better understand the mechanism underlying the effects of hypedipidemia on chronic cerebral ischemia. Water maze test results showed that the cognitive function of rats with hyperlipidemia or chronic cerebral ischemia, particulady in rats with hypedipidemia combined with chronic cerebral ischemia, gradually decreased between 1 and 4 months after occlusion of the bilateral common carotid arteries. This correlated with pathological changes in the hippocampal CA1 region as detected by hematoxylin-eosin staining. Immunohistochemical staining showed that intercellular adhesion molecule-1 expression in the hippocampal CA1 region was noticeably increased in rats with hyperlipidemia or chronic cerebral ischemia, in particular in rats with hyperlipidemia combined with chronic cerebral ischemia. These findings suggest that hyperlipidemia aggravates chronic cerebral ischemia-induced neurological damage and cognitive impairment in the rat hippocampal CA1 region which may be mediated, at least in part, by up-regulated expression of intercellular adhesion molecule-l.

Clinical Analysis on the Effectiveness of Transvaginal Cervical Cerclage in Singleton Pregnancies and Its Predictive Factors

Objective: To evaluate the effectiveness of transvaginal cervical cerclage in singleton pregnancies with cervical incompetence, determine the predictive factors of success and failure, and then compare elective and emergency cerclage. Study Design: This was a retrospective study of 62 patients who underwent cervical cerclage in The First Hospital of Jilin University, China, between May 2015 and January 2018. Successful group was defined as those who delivered live babies and failure group who experienced abortion or stillbirth. Results: Out of 104 patients, 62 met inclusion criteria. In 62 cases, 47 (75.8%) succeeded and 15 (24.2%) failed. In successful group, 21 (44.7%) women delivered pretermly and 26 (55.3%) termly. No severe complications occurred except cervical laceration (2, 3.23%), premature rupture of membranes (13, 20.97%). In 62 cases, 40 (64.5%) have ≤2 previous second-trimester losses and 22 (35.5%) have >2 previous second-trimester losses. No significant differences were found in neonatal outcomes. Analysis revealed that higher postoperative C-reactive protein and presence of premature rupture of membranes were the strongest predictors of cerclage failure. Among 62 cases, 48 (77.4%) were allocated in elective and 14 (22.6%) in emergency cerclage. Pregnancy prolongation was significantly more (P = 0.014) in elective group with no significant differences in premature rupture of membranes, neonatal outcomes (all P > 0.05) except Apgar score at 5 min (P = 0.042). Conclusion: Achieving 75.8% live births proves that transvaginal cervical cerclage is an effective and safe technique in prolonging the gestational age, improving the obstetric outcomes in singleton pregnancies with cervical incompetence under various cerclage indications. Postoperative C-reactive protein and premature rupture of membranes are the predictive factors related to success or failure. Elective cerclage is more effective in prolonging the pregnancy compared to emergency cerclage, no significant differences are seen regarding neonatal outcomes and complications.

Concurrent chemoradiotherapyof different radiation doses and different irradiation fields for locally advanced thoracic esophageal squamous cell carcinoma:A randomized,multicenter,phase Ⅲ clinical trial

Background:Concurrent chemoradiotherapy(CCRT)is the standard treatment for locally advanced esophageal squamous cell carcinoma(ESCC).However,the optimal radiotherapy regimen,particularly in terms of total dose and planned range of irradiation field,remains unclear.This phase III clinical trial aimed to compare the survival benefits between different radiation doses and different target fields.Methods:This trial compared two aspects of radiation treatment,total dose and field,using a two-by-two factorial design.The high-dose(HD)group received 59.4 Gy radiation,and the standard-dose(SD)group received 50.4 Gy.The involved field irradiation(IFI)group and elective nodal irradiation(ENI)group adopted different irradiation ranges.The participants were assigned to one of the four groups(HD+ENI,HD+IFI,SD+ENI and SD+IFI).The primary endpoint was overall survival(OS),and the secondary endpoints included progressionfree survival(PFS).The synergy indexwas used to measure the interaction effect between dose and field.Results:The interaction analysis did not reveal significant synergistic effects between the dose and irradiation field.In comparison to the target field,patients in IFI or ENI showed similar OS(hazard ratio[HR]=0.99,95%CI:0.80-1.23,p=0.930)and PFS(HR=1.02,95%CI:0.82–1.25).TheHDtreatment did not show significantly prolonged OS compared with SD(HR=0.90,95%CI:0.72–1.11,p=0.318),but it suggested improved PFS(25.2 months to 18.0 months).Among the four groups,the HD+IFI group presented the best survival,while the SD+IFI group had the worst prognosis.No significant difference in the occurrence of severe adverse events was found in dose or field comparisons.Conclusions:IFI demonstrated similar treatment efficacy to ENI in CCRT of ESCC.The HD demonstrated improved PFS,but did not significantly improve OS.The dose escalation based on IFI(HD+IFI)showed better therapeutic efficacy than the current recommendation(SD+ENI)and is worth further validation.

Stenting versus non-stenting treatment of intermediate stenosis culprit lesion in acute ST-segment elevation myocardial infarction： a multicenter random- ized clinical trial

Background The benefit/risk ratio of stenting in acute ST-segment elevation myocardial infarction （STEMI） patients with single vessel intermediate stenosis culprit lesions merits further study, therefore the subject of the present study. Methods and results It was a pro- spective, multicenter, randomized controlled trial. Between April 2012 and July 2015, 399 acute STEMI patients with single vessel disease and intermediate （40%-70%） stenosis of the culprit lesion before or after aspiration thrombectomy and/or intracoronary tirofiban （15 pg/kg） were enrolled and were randomly assigned （h 1） to stenting group （n = 201） and non-stenting group （n = 198）. In stenting group, patients received pharmacologic therapy plus standard percutaneous coronary intervention （PCI） with stent implantation. In non-stenting group, pa- tients received pharmacologic therapy and PCI （thrombectomy）, but without dilatation or stenting. Primary endpoint was 12-month rate of major adverse cardiac and eerebrovascular events （MACCE）, a composite of cardiac death, non-fatal myocardial infarction （M1）, repeat re- vascularization and stroke. Secondary endpoints were 12-month rates of all cause death, ischemia driven admission and bleeding complica- tion. Median follow-up time was 12.4 ~ 3.1 months. At 12 months, MACCE occurred in 8.0% of the patients in stenting group, as compared with 15.2% in the non-stenting group （adjusted HR： 0.42, 95% Ch 0.19-0.89, P = 0.02）. The stenting group had lower non-fatal MI rate than non-stenting group, （1.5% vs. 5.5%, P = 0.03）. The two groups shared similar cardiac death, repeat revascularization, stroke, all cause death, ischemia driven readmission and bleeding rates at 12 months. Conclusions Stent implantation had better efficacy and safety in reducing MACCE risks among acute STEMI patients with single vessel intermediate stenosis culprit lesions.

Safety and efficacy of a nerve matrix membrane as a collagen nerve wrapping: a randomized, single-blind, multicenter clinical trial

A new nerve matrix membrane derived from decellularized porcine nerves has been shown to retain the major extracellular matrix components, and to be effective in preventing adhesion between the nerve anastomosis sites and the surrounding tissues in a rat sciatic nerve transection model, thereby enhancing regeneration of the nerve. The effectiveness of the membrane may be attributed to its various bioactive components. In this prospective, randomized, single-blind, parallel-controlled multicenter clinical trial, we compared the safety and efficacy of the new nerve matrix membrane with a previously approved bovine tendon-derived type I collagen nerve wrapping. A total of 120 patients with peripheral nerve injury were recruited from Beijing Jishuitan Hospital, The First Bethune Hospital of Jilin University, and Yantai Yuhuangding Hospital, China. The patients were randomly assigned to undergo end-to-end and tension-free neurorrhaphy with nerve matrix membrane(n = 60, 52 male, 8 female, mean age 41.34 years, experimental group) or tendon-derived collagen nerve wrapping(n = 60, 42 male, 18 female, mean age 40.17 years, control group). Patients were followed-up at 14 ± 5, 30 ± 7, 90 ± 10 and 180 ± 20 days after the operation. Safety evaluation included analyses of local and systemic reactions, related laboratory tests, and adverse reactions. Efficacy evaluation included a static 2-point discrimination test, a moving 2-point discrimination test, and a Semmes–Weinstein monofilament examination. Sensory nerve function was evaluated with the British Medical Research Council Scale and Semmes–Weinstein monofilament examination. The ratio(percentage) of patients with excellent to good results in sensory nerve recovery 180 ± 20 days after the treatment was used as the primary effectiveness index. The percentages of patients with excellent to good results in the experimental and control groups were 98.00% and 94.44%, respectively, with no significant difference between the two groups. There were no significant differences in the results of routine blood tests, liver and renal function tests, coagulation function tests, or immunoglobulin tests at 14 and 180 days postoperatively between the two groups. These findings suggest that the novel nerve matrix membrane is similar in efficacy to the commercially-available bovine-derived collagen membrane in the repair of peripheral nerve injury, and it may therefore serve as an alternative in the clinical setting. The clinical trial was approved by the Institutional Ethics Committee of Beijing Jishuitan Hospital, China(approval No. 20160902) on October 8, 2016, the Institutional Ethics Committee of the First Bethune Hospital of Jilin University, China(approval No. 160518-088) on December 14, 2016, and the Institutional Ethics Committee of Yantai Yuhuangding Hospital, China(approval No. 2016-10-01) on December 9, 2016. The clinical trial was registered with the Chinese Clinical Trial Registry(registration number: Chi CTR2000033324) on May 28, 2020.

Ectopic bronchogenic cyst of liver misdiagnosed as gallbladder diverticulum: A case report

BACKGROUND Ectopic bronchogenic cysts are a type of congenital cystic tumor that are extremely difficult to diagnose and can be ectopically located in various organs,with the possibility of malignant transformation. Here we report a case of an ectopic bronchogenic cyst in the liver initially misdiagnosed as a gallbladder diverticulum.CASE SUMMARY The patient was a middle-aged woman whose chief complaint was intermittent pain in the upper abdomen. Imaging examination revealed a cystic space in the left inner lobe of the liver. She was admitted to our hospital for treatment. Based on abdominal examination and imaging findings, the initial diagnosis was gallbladder diverticulum with cholestasis combined with chronic cholecystitis.However, following intraoperative observations and postoperative pathologic assessment, the diagnosis was revised to ectopic bronchogenic cyst of the liver.CONCLUSION Radiologists, hepatobiliary and pancreatic surgeons, gastrointestinal surgeons,urologists, and even neurosurgeons should be aware and consider a possible diagnosis of ectopic bronchogenic cysts, especially when other types of cyst,cystadenoma, and other diseases are excluded. The disease and its complications should be detected and correctly diagnosed and treated as early as possible in order to avoid adverse outcomes.

Quantitation of bivalirudin,a novel anticoagulant peptide,in human plasma by LC-MS/MS:Method development,validation and application to pharmacokinetics

A rapid and sensitive method based on liquid chromatographtandem mass spectrometry （LC-MS/MS） for the determination of a novel anticoagulant peptide bivalirudin in human plasma has been developed and validated. Plasma samples were precipitated protein with acetonitrile and reextracted with dichloromethane, after which the analyte and triptorelin as an internal standard （IS） were separated on a 300SB-Cl8 column （150 mm x 4.6 mm i.d., 5 gm particle size） using 0.1% formic acid：methanol （45：55, v/v） as mobile phase. The triple-quadrupole mass spectrometer, equipped with electrospray ionization （ESI） interface, was operated in the positive ion mode, and the multiplereaction monitoring （MRM） transitions of bivalirudin and IS were at m/z 1091.0-650.4 and m/z656.5 - 249.3, respectively. The lower limit of quantification （LLOQ） was 1 ng/mL for 100 ng/mL plasma sample and the assay was linear over the concentration range 1 1000 ng/mL. The accuracy was within a range from -0.4% to 0.5% in terms of relative error （RE） and the intra- and inter-day precisions in terms of relative standard deviation （RSD） were 〈2.92 and 〈 3.36, respectively. The method was successfully applied to a pharmacokinetic study involving intravenous administration of bivalirudin （0.5 mg/kg） to Chinese volunteers.

Association of β-cell function and insulin resistance with pediatric type 2 diabetes among Chinese children

BACKGROUND In addition to insulin resistance,impaired insulin secretion has recently been identified as a crucial factor in the pathogenesis of type 2 diabetes mellitus(T2DM).Scarce clinical data exist for pediatric T2DM.AIM To investigate the association ofβ-cell function and insulin resistance with pediatric T2DM in the first Chinese multicenter study.METHODS This multicenter cross-sectional study included 161 newly diagnosed T2DM children and adolescents between January 2017 and October 2019.Children with normal glycemic levels(n=1935)were included as healthy control subjects.The homeostasis models(HOMAs)were used to assess theβ-cell function(HOMA2-%B)and insulin resistance(HOMA2-IR)levels.The HOMA index was standardized by sex and age.We performed logistic regression analysis to obtain odds ratios(ORs)for T2DM risk using the standardized HOMA index,adjusted for confounding factors including sex,Tanner stage,T2DM family history,body mass index z-score,and lipid profile.RESULTS The male-female ratio of newly diagnosed T2DM patients was 1.37:1(OR=2.20,P=0.011),and the mean ages of onset for boys and girls were 12.5±1.9 years and 12.3±1.7 years,respectively.The prevalence of related comorbidities including obesity,elevated blood pressure,and dyslipidemia was 58.2%,53.2%,and 80.0%,respectively.The T2DM group had lower HOMA2-%B levels(P<0.001)and higher HOMA2-IR levels(P<0.001)than the control group.Both the decrease in HOMA2-%B z-score(OR=8.40,95%CI:6.40-11.02,P<0.001)and the increase in HOMA2-IR z-score(OR=1.79,95%CI:1.60-2.02,P<0.001)were associated with a higher risk of T2DM,and the decrease in HOMA2-%B z-score always had higher ORs than the increase in HOMA2-IR z-score after adjusting for confounding factors.CONCLUSION Besides insulin resistance,β-cell function impairment is also strongly associated with Chinese pediatric T2DM.Gender difference in susceptibility and high comorbidities warrant specific T2DM screening and prevention strategies in Chinese children.

IVF Development and Analysis of Neonatal Conditions

This paper first discusses the developmental origin of IVF (In vitro fertilization) and analyzes the four generations of IVF technology in detail. Then, combined with its own work experience, it discusses the neonatal situation of IVF, in order to improve reference for other medical staff.

Nanoscale Phase Separation-Induced Suppression of Geminate Recombination in Low Bandgap Polymer-Fullerene Solar Cells

The short-circuit current of polymer solar cells based on a PCPDTBT：PC71BM blend is substantially increased by using a processing additive. It is found that the significant geminate recombination in the PCPDTBT：PC71 BM blend film is dramatically suppressed by using a processing additive which can produce a nanoscale PCPDTBT and PC71BM phase separation. The processing additive-induced aggregation of PCPDTBT polymer chains and PC71BM molecules can give rise to a driving force for the separation of charge-transfer states at the donor/acceptor interfaces into the free charge carriers and thus geminate recombination is suppressed.

Current understanding concerning intestinal stem cells

In mammals, the intestinal epithelium is a tissue that contains two distinct pools of stem cells: active intestinal stem cells and reserve intestinal stem cells. The former are located in the crypt basement membrane and are responsible for maintaining epithelial homeostasis under intact conditions, whereas the latter exhibit the capacity to facilitate epithelial regeneration after injury. These two pools of cells can convert into each other, maintaining their quantitative balance. In terms of the active intestinal stem cells, their development into functional epithelium is precisely controlled by the following signaling pathways: Wnt/β-catenin, Ras/Raf/Mek/Erk/MAPK, Notch and BMP/Smad. However, mutations in some of the key regulator genes associated with these signaling pathways, such as APC, Kras and Smad4, are also highly associated with gut malformations. At this point, clarifying the biological characteristics of intestinal stem cells will increase the feasibility of preventing or treating some intestinal diseases, such as colorectal cancer. Moreover, as preclinical data demonstrate the therapeutic effects of colon stem cells on murine models of experimental colitis, the prospects of stem cell-based regenerative treatments for ulcerous lesions in the gastrointestinal tract will be improved all the same.

A drug-eluting Balloon for the trEatment of coronarY bifurcatiON lesions in the side branch:a prospective multicenter ranDomized (BEYOND)clinical trial in China

Background:Treatment of coronary bifurcation lesions remains challenging;a simple strategy has been preferred as of late,but the disadvantage is ostium stenosis or even occlusion of the side branch(SB).Only a few single-center studies investigating the combination of a drug-eluting stent in the main branch followed by a drug-eluting balloon in the SB have been reported.This prospective,multicenter,randomized study aimed to investigate the safety and efficacy of a paclitaxel-eluting balloon(PEB)compared with regular balloon angioplasty(BA)in the treatment of non-left main coronary artery bifurcation lesions.Methods:Between December 2014 and November 2015,a total of 222 consecutive patients with bifurcation lesions were enrolled in this study at ten Chinese centers.Patients were randomly allocated at a 1:1 ratio to a PEB group(n=113)and a BA group(n=109).The primary efficacy endpoint was angiographic target lesion stenosis at 9 months.Secondary efficacy and safety endpoints included target lesion revascularization,target vessel revascularization,target lesion failure,major adverse cardiac and cerebral events(MACCEs),all-cause death,cardiac death,non-fatal myocardial infarction,and thrombosis in target lesions.The main analyses performed in this clinical trial included case shedding analysis,base-value equilibrium analysis,effectiveness analysis,and safety analysis.SAS version 9.4 was used for the statistical analyses.Results:At the 9-month angiographic follow-up,the difference in the primary efficacy endpoint of target lesion stenosis between the PEB(28.7%±18.7%)and BA groups(40.0%±19.0%)was-11.3%(95%confidence interval:-16.3%to-6.3%,Psuperiority<0.0001)in the intention-to-treat analysis,and similar results were recorded in the per-protocol analysis,demonstrating the superiority of PEB to BA.Late lumen loss was significantly lower in the PEB group than in the BA group(-0.06±0.32 vs.0.18±0.34 mm,P<0.0001).For intention-to-treat,there were no significant differences between PEB and BA in the 9-month percentages of MACCEs(0.9%vs.3.7%,P=0.16)or non-fatal myocardial infarctions(0 vs.0.9%,P=0.49).There were no clinical events of target lesion revascularization,target vessel revascularization,target lesion failure,all-cause death,cardiac death or target lesion thrombosis in either group.Conclusions:In de novo non-left main coronary artery bifurcations treated with provisional T stenting,SB dilation with the PEB group demonstrated better angiographic results than treatment with regular BA at the 9-month follow-up in terms of reduced target lesion stenosis.Trial registration:ClinicalTrials.gov,NCT02325817;https://clinicaltrials.gov.

Decoding epigenetic codes: new frontiers in exploring recovery from spinal cord injury

Spinal cord injury that results in severe neurological disability is often incurable.The poor clinical outcome of spinal cord injury is mainly caused by the failure to reconstruct the injured neural circuits.Several intrinsic and extrinsic determinants contribute to this inability to reconnect.Epigenetic regulation acts as the driving force for multiple pathological and physiological processes in the central nervous system by modulating the expression of certain critical genes.Recent studies have demonstrated that post-SCI alteration of epigenetic landmarks is strongly associated with axon regeneration,glial activation and neurogenesis.These findings not only establish a theoretical foundation for further exploration of spinal cord injury,but also provide new avenues for the clinical treatment of spinal cord injury.This review focuses on the epigenetic regulation in axon regeneration and secondary spinal cord injury.Together,these discoveries are a selection of epigenetic-based prognosis biomarkers and attractive therapeutic targets in the treatment of spinal cord injury.

Expert consensus on clinical standardized application of high-flow nasal cannula oxygen therapy in adults

High-flow nasal cannula oxygen therapy(HFNC)is a novel respiratory support technology and has been extensively applied in clinics in recent years.This therapeutic equipment mainly includes an air-oxygen blender,an active humidifier,a high-flow nasal cannula,and a connecting inspiratory circuit.It provides patients a humidified high-flow gas(8-80 L/min)with relatively stable oxygen concentration(21-100%),temperature(31-37℃)and performs oxygen therapy via a nasal cannula,which is very comfortable.

Multiplexed imaging of tumor immune microenvironmental markers in locally advanced or metastatic non-small-cell lung cancer characterizes the features of response to PD-1 blockade plus chemotherapy

Background:Although programmed cell death 1(PD-1)blockade plus chemotherapy can significantly prolong the progression-free survival(PFS)and overall survival(OS)in first-line settings in patients with driver-negative advanced non-small-cell lung cancer(NSCLC),the predictive biomarkers remain undetermined.Here,we investigated the predictive value of tumor immune microenvironmental marker expression to characterize the response features to PD-1 blockade plus chemotherapy.Methods:Tumor tissue samples at baseline were prospectively collected from 144 locally advanced or metastatic NSCLC patients without driver gene alterations who received camrelizumab plus chemotherapy or chemotherapy alone.Tumor immune microenvironmental markers,including PD-1 ligand(PDL1),CD8,CD68,CD4 and forkhead box P3,were assessed using multiplex immunofluorescence(mIF)assays.Kaplan-Meier curveswere used to determine treatment outcome differences according to their expression status.Mutational profiles were compared between tumors with distinct expression levels of these markers and their combinations.Results:Responders had significantly higher CD8/PD-L1(P=0.015)or CD68/PD-L1 co-expression levels(P=0.021)than non-responders in the camrelizumab plus chemotherapy group,while no difference was observed in the chemotherapy group.Patients with high CD8/PD-L1 or CD68/PD-L1 co-expression level was associated with significantly longer PFS(P=0.002,P=0.024;respectively)and OS(P=0.006,P=0.026;respectively)than those with low co-expression in camrelizumab plus chemotherapy group.When comparing survival in the camrelizumab plus chemotherapy with chemotherapy by CD8/PD-L1 co-expression stratification,significantly better PFS(P=0.003)and OS(P=0.032)were observed in high co-expression subgroups.The predictive value of CD8/PD-L1 and CD68/PD-L1 co-expression remained statistically significant for PFS and OS when adjusting clinicopathological features.Although the prevalence of TP53 or KRAS mutations was similar between patients with and without CD8/PD-L1 or CD68/PD-L1 co-expression,the positive groups had a significantly higher proportion of TP53/KRAS co-mutations than the negative groups(both 13.0%vs.0.0%,P=0.023).Notably,enriched PI3K(P=0.012)and cell cycle pathway(P=0.021)were found in the CD8/PD-L1 co-expression group.Conclusion:Tumor immune microenvironmental marker expression,especially CD8/PD-L1 or CD68/PD-L1 co-expression,was associated with the efficacy of PD-1 blockade plus chemotherapy as first-line treatment in patients with advanced NSCLC.

Oncometabolic surgery:Emergence and legitimacy for investigation

Studies on morbid obesity have shown remarkable improvement of diabetes in patients who have undergone bariatric operations.It was subsequently shown that these operations induce diabetes remission independent of the resultant weight loss;as a result,surgeons began to investigate whether operations for gastric cancer(GC)could have the same beneficial effect on diabetes as bariatric operations.It was then shown in multiple reports that followed that certain operations for GC were able to improve or even cure type 2 diabetes mellitus(T2 DM)in GC patients.This finding gave rise to the concept of"oncometabolic surgery",in which a patient diagnosed with both GC and T2 DM undergo a single operation with the purpose of treating both diseases.With the increasing incidence of T2 DM,oncometabolic surgery has the potential to improve the quality of life and even extend survival of many GC patients.However,because the GC patient population and the bariatric patient population are wildly different and because different GC operations have different properties,the effect of oncometabolic surgery must be carefully assessed and engineered in order to maximize benefit and avoid harm.This manuscript aims to summarize the findings made so far in the field of oncometabolic surgery and to provide an outlook regarding the possibility of oncometabolic surgery being incorporated into standard clinical practice.

Improved Charge-Collection Efficiency in PCDTBT:PC_(71)BM-Based Solar Cells via CS_(2)Solvent Vapor Annealing

Photo-generated charge collection is strongly correlated with the alignment and connectivity of the individual domains of donor and acceptor in bulk heterojunction polymer solar cells.It is found that CS_(2)vapor annealing on PCDTBT:PC71BM(1:4)blend effectively improves the hole-transport pathways of PCDTBT domains,which reduces accumulation of photo-generated charges and improves charge collection efficiency.The PCDTBT:PC71BM-based solar cells with the active layer subjected to CS_(2)vapor annealing demonstrate a high fill factor of 0.71–0.73 and a power conversion efficiency of 6.68%,about a 10%increase in comparison with the control cell.