Objective: To investigate the indoor fine particulate matter (PM 2.5 ) pollution and its influencing factors in children s bedrooms using solid fuel, so as to provide evidence for effective strategy to reduce PM 2.5 pollution. Methods: From December 2019 to November 2020, 198 households (108 in the north, 90 in the south) from two pilots in the north(Jiamusi in Heilongjiang Province) and south of China (Mianyang in Sichuan Province) were selected, and status of solid fuels using were obtained through home visits, dynamic changes in PM 2.5 concentrations in children s bedrooms were monitored by using real time online instruments, and the influencing factors of PM 2.5 pollution were analyzed by using a mixed effects model. Results: During the monitoring period, the daily PM 2.5 concentrations in the northern and southern pilot were 78.33 (40.50, 154.80) and 38.54(26.20, 58.46) μg/m 3, respectively, exceeding standard rates of 44.57% and 33.22%. During the heating period, the daily PM 2.5 concentrations in the northern and southern pilot were 212.50(133.60,244.10) and 104.42(73.97, 134.90) μg/m 3, respectively, with over standard rates of 96.75% and 86.96%. The mixed effects model analysis results showed that children s bedroom PM 2.5 concentrations were associated with solid fuel usage duration, window opening time, room layout (shared entrance door between kitchen and bedroom), indoor smoking, indoor humidity, and solid fuel use in the bedroom ( β =0.19, -0.05, 1.20, 0.43, 0.02, 0.35, all P <0.05). Conclusion Solid fuel combustion significantly comtributes to PM 2.5 pollution in children s bedrooms, with more pronounced impacts observed in northern China compared to southern regions.

Objective To explore the efficacy and safety of ticagrelor de-escalation and nicorandil therapy in elderly patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods A total of 300 elderly patients with ACS were selected from the Sixth and Seventh Medical Center of Chinese PLA General Hospital and Beijing Chaoyang Integrative Medicine Emergency Rescue and First Aid Hospital from November 2016 to June 2019,including 153 males and 147 females,aged>65 years old.All the patients received PCI,and all had double antiplatelet therapy(DAPT)scores≥2 and a new DAPT(PRECISE-DAPT)score of≥25.All patients were divided into two groups by random number table method before operation:ticagrelor group(n=146,ticagrelor 180 mg load dose followed by PCI,and ticagrelor 90 mg bid after surgery)and ticagrelor de-escalation + nicorandil group(n=154,ticagrelor 180 mg load dose followed by PCI,ticagrelor 90 mg bid+nicorandil 5 mg tid after surgery,changed to ticagrelor 60 mg bid+ nicorandil 5 mg tid 6 months later).Follow-up was 12 months.The composite end points of cardiovascular death,myocardial infarction and stroke,the composite end points of mild hemorrhage,minor hemorrhage,other major hemorrhage and major fatal/life-threatening hemorrhage as defined by the PLATO study,and the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding within 12 months in the two groups were observed.Results The comparison of general baseline data between the two groups showed no statistically significant difference(P>0.05).There was also no significant difference in the composite end points of cardiovascular death,myocardial infarction and stroke between the two groups(P>0.05).The cumulative incidence of bleeding events in ticagrelor de-escalation + nicorandil group was significantly lower than that in ticagrelor group(P<0.05),while the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding were also significantly lower than those in tecagrelor group(P<0.05).Conclusion In elderly patients with ACS,the treatment of ticagrelor de-escalation + nicorandil after PCI may not increase the incidence of ischemic events such as cardiovascular death,myocardial infarction or stroke,and it may reduce the incidence of hemorrhagic events.

Objective To investigate the rate of germline variants in patients with pancreatic cancer and clinical characteristics related with germline variants.Methods A total of 271 patients diagnosed with pancreatic cancer were enrolled in this study.Germline variants of 21 tumor susceptibility genes were detected by next-generation sequencing,and the relationship between germline variants and clinical factors such as age of onset,family history and personal history was analyzed.Results The rate of germline P/LP variants was 6.3%in unselected pancreatic cancer patients,but was high as 17.1%in genetic high-risk group patients(those with a family or personal history of cancer,or early-onset).Genes with higher frequency of germline variants in pancreatic cancer patients were PALB2,BRCA2,and ATM.Conclusion The rate of germline variants in overall pancreatic cancer patients is not high,but it increases significantly in genetic high-risk group,proving the importance of clinical factors in the screening of hereditary pancreatic cancer.

Objective To evaluate the value of high-throughput sequencing(HTS)data reanalysis that does not include ERBB2 copy number variation(CNV)analysis,in identifying ERBB2 amplification in patients with colorectal cancer.Methods The HTS data of 252 cases of colorectal cancer diagnosed by pathological biopsy who received peripheral blood cfDNA HTS detection samples were retrospectively analyzed.According to the HTS data of ERBB2 non-amplified samples judged by immunohistochemistry(IHC)and/or fluorescence in situ hybridization(FISH),the number of chromosome 17(Chr17)reads in the total number of reads was calculated the range of the ratio was initially determined as the threshold for prompting ERBB2 amplification.Suspected positive samples were screened according to thresholds and verified by digital PCR,IHC and FISH.Results The proportion of the number of Chr17 reads accounts for the number of total reads in the 89 cases of ERBB2 non-amplified samples determined by IHC and/or FISH ranged from 0.188 to 0.299(0.239±0.192).Using 0.298(1.25 times the mean)as the threshold indicating ERBB2 amplification,the data of 163 samples were analyzed,of which 7 cases were suspected to be positive,and the ratio ranged from 0.302 to 0.853.Among them,5 cases were determined to be positive by IHC and/or FISH,and 6 cases were confirmed to be positive by digital PCR.The ratio of the number of Chr17 reads to the number of total reads was positively correlated with the ratio of ERBB2/EIF2C1,and the correlation was good(r2=0.909).Conclusion The high-throughput sequencing data that does not cover the ERBB2 CNV analysis has a certain hint value for ERBB2 amplification in patients with colorectal cancer.

BACKGROUND:Unilateral biportal endoscopic technique has been widely used in lumbar interbody fusion in recent years,but there is little comparison between its clinical efficacy and that of minimally invasive transforaminal lumbar interbody fusion(MIS-TLIF)in the treatment of lumbar degenerative disease,whether the unilateral biportal endoscopic technique is a safe and effective lumbar fusion remains to be further demonstrated. OBJECTIVE:To compare the clinical efficacy of unilateral biportal endoscopic lumbar interbody fusion(UBE-LIF)and MIS-TLIF in the treatment of lumbar degenerative diseases and explore a more efficient lumbar fusion procedure. METHODS:Patients with single-level lumbar degenerative disease were enrolled in Affiliated Hospital of Guilin Medical College from October 2020 to February 2022,including 35 patients who underwent UBE-LIF and 286 patients who underwent MIS-TLIF.Propensity score matching was used to eliminate confounders.Four covariates including sex,age,disease type and surgical segment were matched 1:1(caliper value 0.01).After matching,29 patients from each group were included in the study.The perioperative operative time,hemoglobin loss and hospital stay were compared between the two groups.Visual analog scale score and Oswestry disability index were used to evaluate the functional recovery of the two groups before,1,6 months and 1 year after operation.The excellent and good rate of the two groups was evaluated by the modified MacNab standard at the last follow-up.The fusion of the two groups was evaluated by Lenke Dynamic X-ray film. RESULTS AND CONCLUSION:(1)The operative time in the MIS-TLIF group was shorter than that in the UBE-LIF group(P＜0.05).The amount of intraoperative hemoglobin loss in the MIS-TLIF group was higher than that in the UBE-LIF group.The hospital stay in the MIS-TLIF group was longer than that in the UBE-LIF group,and the differences were statistically significant(P＜0.05).(2)The visual analog scale scores for lumbago and leg pain,and Oswestry disability index were significantly reduced in both groups 1,6 months,and 1 year after surgery compared to before surgery(P＜0.05).Except for the visual analog scale score for lumbago at 1 month after surgery,there was no significant difference in the visual analog scale score for lumbago and leg pain,and Oswestry disability index between the two groups at the above time points(P＞0.05).(3)At the last follow-up,the modified MacNab standard efficacy evaluation showed that the excellent and good rates were 93%(27/29)in the UBE-LIF group and 90%(26/29)in the MIS-TLIF group;there was no significant difference between the two groups(P＞0.05).(4)Lenke dynamic radiographic evaluation system evaluation for lumbar fusion exhibited that the fusion rate was 90%(grade A,21 cases;grade B,5 cases;grade C,3 cases)in the UBE-LIF group;the fusion rate was 86%(grade A,20 cases;grade B,5 cases;grade C,4 cases)in the MIS-TLIF group;there was no significant difference between the two groups(P＞0.05).(5)It is indicated that UBE-LIF and MIS-TLIF have similar clinical effects in the treatment of single-level lumbar degenerative disease with the advantages of less trauma,less bleeding and shorter hospital stay.In addition,the early postoperative lumbago was relatively mild and the learning curve was relatively smooth.Although the operative time in the UBE-LIF group was longer than that in the MIS-TLIF group,it was still a safe and effective operation.

BACKGROUND: Many studies have demonstrated the benefit of complete multivessel revascularization versus culprit-only intervention in patients of ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease. However, only a few single-center retrospective studies were performed on small Chinese cohorts. Our study aims to demonstrate the advantage of multivessel percutaneous intervention (PCI) strategy on 30-day in-hospital outcomes to patients with STEMI and multivessel disease in larger Chinese population. METHODS: From the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) project, 5935 patients with STEMI and multivessel disease undergoing PCI and hospitalized for fewer than 30 days were analyzed. After 5: 1 propensity score matching, 3577 patients with culprit-only PCI and 877 with in-hospital multivessel PCI were included. The primary outcome was major adverse cardiovascular and cerebrovascular event (MACCE), defined as a composite of myocardial infarction, all-cause death, stent thrombosis, heart failure, and stroke. RESULTS: Multivariable logistic regression analysis revealed that in-hospital multivessel PCI was associated with lower risk of 30-day MACCE (adjusted OR = 0.75, 95% CI: 0.57-0.98, P = 0.032) than culprit-only PCI and conferred no increased risk of all-cause death, myocardial infarction, stent thrombosis, stroke, or bleeding. Subgroup analysis showed that MACCE reduction was observed more often from patients with trans-femoral access (OR = 0.34, 95% CI: 0.15-0.74) than with trans-radial access (OR = 0.87, 95% CI: 0.66-1.16, P for interaction = 0.017). CONCLUSIONS The in-hospital multivessel PCI strategy was associated with a lower risk of 30-day MACCE than culprit-only PCI in patients with STEMI and multivessel coronary artery disease.

Objective To evaluate the quality of postoperative recovery of patients undergoing cardiac great vessels surgery by 15-item Recovery Quality Score Scale(QoR-15),to retrospectively analyze the influence of perioperative multi-factors on postoperative recovery quality,and to establish the predictive model.Methods Clinical data of patients who underwent cardiac great vascularsur-gery from March 2020 to September 2022 were collected through electronic medical record system and the postoperative QoR-15 score were evaluated.The data including gender,age,postoperative follow-up time,American Society of Anesthesiologists(ASA)classification,preoperative lactate level,co-morbidities,emergency or not,extracorporeal circulation or not,etc.were collected.The modified frailty index(mFI)was also calculated.Surgical patterns,operation time,extracorporeal circulation time,aortic block time,type of heart recurrence,perioperative fluid therapy,extracorporeal circulation temperature,and other postoperative data as well as postoperative data including ICU retention time after surgery,total length of stay and QoR-15 score were recorded.The univariate and multivariate Logistic regression analysis were then applied to construct a prediction model,and its accuracy was validated.Results A total of 213 patients were included,in which 15 patients were excluded,and 198 postoperative QoR-15 score sheets were received.Gender,ASA classification,preoperative lac-tate level,postoperative follow-up time,and mFI were significant influencing factors on the quality of rehabilitation of patients undergoing cardiac or great vascular surgery.The prediction model of ln(p/1-p)=-5.571+0.862 × gender+3.844 × ASA classification+3.143 × preoperative lactate level+2.001 × postoperative follow-up time+3.712 × mFI,which had good predictive and classifi-cation effects.Conclusion Gender,ASA classification,preoperative lactate level,postoperative follow-up time and mFI are influencing factors on the recovery quality of patients after cardiac great vascular surgery.

Objective To evaluate the quality of postoperative recovery of patients undergoing cardiac great vessels surgery by 15-item Recovery Quality Score Scale(QoR-15),to retrospectively analyze the influence of perioperative multi-factors on postoperative recovery quality,and to establish the predictive model.Methods Clinical data of patients who underwent cardiac great vascularsur-gery from March 2020 to September 2022 were collected through electronic medical record system and the postoperative QoR-15 score were evaluated.The data including gender,age,postoperative follow-up time,American Society of Anesthesiologists(ASA)classification,preoperative lactate level,co-morbidities,emergency or not,extracorporeal circulation or not,etc.were collected.The modified frailty index(mFI)was also calculated.Surgical patterns,operation time,extracorporeal circulation time,aortic block time,type of heart recurrence,perioperative fluid therapy,extracorporeal circulation temperature,and other postoperative data as well as postoperative data including ICU retention time after surgery,total length of stay and QoR-15 score were recorded.The univariate and multivariate Logistic regression analysis were then applied to construct a prediction model,and its accuracy was validated.Results A total of 213 patients were included,in which 15 patients were excluded,and 198 postoperative QoR-15 score sheets were received.Gender,ASA classification,preoperative lac-tate level,postoperative follow-up time,and mFI were significant influencing factors on the quality of rehabilitation of patients undergoing cardiac or great vascular surgery.The prediction model of ln(p/1-p)=-5.571+0.862 × gender+3.844 × ASA classification+3.143 × preoperative lactate level+2.001 × postoperative follow-up time+3.712 × mFI,which had good predictive and classifi-cation effects.Conclusion Gender,ASA classification,preoperative lactate level,postoperative follow-up time and mFI are influencing factors on the recovery quality of patients after cardiac great vascular surgery.

Multidrug resistance (MDR) is the main cause of clinical treatment failure and poor prognosis in cancer. Targeting P-glycoprotein (P-gp) has been regarded as an effective strategy to overcome MDR. In this work, we reported our preclinical studies of the triazolo[1,5-a]pyrimidine-based compound WS-716 as a highly potent, specific, and orally active P-gp inhibitor. Through direct binding to P-gp, WS-716 inhibited efflux function of P-gp and specifically reversed P-gp-mediated MDR to paclitaxel (PTX) in multiple resistant cell lines, without changing its expression or subcellular localization. WS-716 and PTX synergistically inhibited formation of colony and 3D spheroid, induced apoptosis and cell cycle arrest at G2/M phase in resistant SW620/Ad300 cells. In addition, WS-716 displayed minimal effect on the drug-metabolizing enzyme cytochrome P4503A4 (CYP3A4). Importantly, WS-716 increased sensitivity of both pre-clinically and clinically derived MDR tumors to PTX in vivo with the T/C value of 29.7% in patient-derived xenograft (PDX) models. Relative to PTX treatment alone, combination of WS-716 and PTX caused no obvious adverse reactions. Taken together, our preclinical studies revealed therapeutic promise of WS-716 against MDR cancer, the promising data warrant its further development for cancer therapy.

Objective:To analyze the safety and efficacy of left atrial appendage closure(LAAC)with Watchman in patients ≥85 years with atrial fibrillation(AF).Methods:515 elderly patients with atrial fibrillation, including 73 patients aged 85 years or older(85~91), who had undergone Watchman LAAC at Zhoupu Hospital affiliated to Shanghai Health Medical College from August 2016 to December 2020, were retrospectively analyzed.Of those ≥85 years, 44(60.3%)with transesophageal echocardiography records were assigned to the elderly group.Fifty-three patients aged 60 to 65 were selected as the control group.Differences in baseline data, intraoperative conditions, antithrombotic treatment plans and 1-year follow-up prognosis were compared between the two groups.Results:Compared with the control group, there was no difference in AF types, history of ischemic stroke/transient ischaemic attack(all P>0.05), but there were higher incidences of coronary heart disease and renal insufficiency, more severe heart failure, higher CHA 2DS 2-VASC(6.0±1.5 vs.3.6±1.5), HAS-BLED(3.2±1.2 vs.2.3±1.3)scores( t values were 7.682 and 3.871, respectively, P<0.05), and a lower one-stop surgery rate(6 cases or 13.6% vs. 27 cases or 50.9%, χ2=10.517, P<0.05)in the advanced age group.There was no difference in the diameter of the Watchman device, rate of device replacement, compression percentage and residual flow between the two groups during the perioperative period.The incidences of device-related thrombosis were 4.5%(2/44)and 3.8%(2/53)for the advanced age group and the control group, respectively, but the difference was not statistically significant( P>0.05). During the 12-month follow-up, there were no cases of ischemic stroke or intracerebral hemorrhage.Three died of heart failure and 1 died of cancer. Conclusions:LAAC with Watchman is safe and effective for patients over 85 years with AF, but the decision on the procedure should be based on careful assessment of patients' cardiac and renal function and general health.