Background and purpose:Despite Radiation-induced lymphopenia has been associated with poor survival outcomes in certain solid tumors,there is limited evidence for small cell lung cancer(SCLC).The purpose of this study was to investigate whether the absolute lymphocyte count before and after radiotherapy could predict the clinical outcomes for limited-stage SCLC(LS-SCLC)patients.Methods:This was a single-center,retrospective cohort study.A retrospective analysis of patients evaluated at Fudan University Shanghai Cancer Center from January 2007 to December 2017 was conducted.Inclusion criteria:⑴ pathologically confirmed small-cell lung cancer;⑵ limited-stage disease defined by positron emission tomography and computed tomography(PET/CT)and contrast-enhanced brain magnetic resonance imaging(MRI)[American Joint Committee on Cancer(AJCC)8th edition TNM stage M0];⑶ receipt of definitive chemoradiotherapy;⑷ availability of complete blood counts before,during and within 1 month after radiotherapy;⑸ complete survival,relapse,and last-follow-up information retrievable.Exclusion criteria:⑴ distant metastasis at baseline(AJCC 8th edition TNM stage M1,including any distant nodal,visceral,or bone-marrow involvement);⑵ total radiotherapy dose＜50 Gy[calculated as an equivalent biological dose at 2 Gy/fraction,i.e.,a biological effective dose(BED)＜40 Gy];⑶ incomplete laboratory data at any scheduled time point;⑷ inability to ascertain survival or relapse status or insufficient follow-up records.The study protocol was approved by the ethics committee of Fudan University Shanghai Cancer Center(approval number:2303271-15),and the requirement for informed consent was waived.Clinical data extracted comprised age,sex,Eastern Cooperative Oncology Group performance status(ECOG PS)score,smoking history,TNM stage,chemotherapy regimen and number of cycles,radiotherapy dose and fractionation schedule,use of concurrent chemoradiotherapy and administration of prophylactic cranial irradiation(PCI).Laboratory data comprised serial absolute lymphocyte counts obtained within 1 month before,during and after radiotherapy;lymphopenia was graded according to the Common Terminology Criteria for Adverse Events(CTCAE)version 4.0.Progression-free survival(PFS)and overall survival(OS)were estimated using the Kaplan-Meier method and compared with the log-rank test.Results:A total of 170 patients were included.The median age of the patients was 57 years,with 77.6%being male.The median radiation therapy dose was 60 Gy(range:45-66 Gy).For the entire cohort,the median PFS was 22.0 months,the 5-year PFS rate was 31.3%,and the 10-year PFS rate was 19.8%.The median OS was 38.0 months,the 5-year OS rate was 37.5%,and the 10-year OS rate was 24.2%.Before radiation therapy,14 patients(8.2%)had grade 1-2 lymphocytopenia.During radiation therapy,the number of patients with grade 1,2,3 and 4 lymphocytopenia was 7(4.1%),22(12.9%),111(65.3%),and 24(14.1%),respectively.One month after radiation therapy,the number of patients with grade 1,2,3 and 4 lymphocytopenia was 36(21.2%),36(21.2%),11(6.5%)and 1(0.6%),respectively.There were no significant differences in PFS and OS among patients with different grades of lymphocytopenia before,during,or after radiation therapy.Conclusion:Before immunotherapy,radiotherapy-induced lymphopenia did not appear to affect the prognosis of patients with LS-SCLC.

Background and purpose:Despite Radiation-induced lymphopenia has been associated with poor survival outcomes in certain solid tumors,there is limited evidence for small cell lung cancer(SCLC).The purpose of this study was to investigate whether the absolute lymphocyte count before and after radiotherapy could predict the clinical outcomes for limited-stage SCLC(LS-SCLC)patients.Methods:This was a single-center,retrospective cohort study.A retrospective analysis of patients evaluated at Fudan University Shanghai Cancer Center from January 2007 to December 2017 was conducted.Inclusion criteria:⑴ pathologically confirmed small-cell lung cancer;⑵ limited-stage disease defined by positron emission tomography and computed tomography(PET/CT)and contrast-enhanced brain magnetic resonance imaging(MRI)[American Joint Committee on Cancer(AJCC)8th edition TNM stage M0];⑶ receipt of definitive chemoradiotherapy;⑷ availability of complete blood counts before,during and within 1 month after radiotherapy;⑸ complete survival,relapse,and last-follow-up information retrievable.Exclusion criteria:⑴ distant metastasis at baseline(AJCC 8th edition TNM stage M1,including any distant nodal,visceral,or bone-marrow involvement);⑵ total radiotherapy dose＜50 Gy[calculated as an equivalent biological dose at 2 Gy/fraction,i.e.,a biological effective dose(BED)＜40 Gy];⑶ incomplete laboratory data at any scheduled time point;⑷ inability to ascertain survival or relapse status or insufficient follow-up records.The study protocol was approved by the ethics committee of Fudan University Shanghai Cancer Center(approval number:2303271-15),and the requirement for informed consent was waived.Clinical data extracted comprised age,sex,Eastern Cooperative Oncology Group performance status(ECOG PS)score,smoking history,TNM stage,chemotherapy regimen and number of cycles,radiotherapy dose and fractionation schedule,use of concurrent chemoradiotherapy and administration of prophylactic cranial irradiation(PCI).Laboratory data comprised serial absolute lymphocyte counts obtained within 1 month before,during and after radiotherapy;lymphopenia was graded according to the Common Terminology Criteria for Adverse Events(CTCAE)version 4.0.Progression-free survival(PFS)and overall survival(OS)were estimated using the Kaplan-Meier method and compared with the log-rank test.Results:A total of 170 patients were included.The median age of the patients was 57 years,with 77.6%being male.The median radiation therapy dose was 60 Gy(range:45-66 Gy).For the entire cohort,the median PFS was 22.0 months,the 5-year PFS rate was 31.3%,and the 10-year PFS rate was 19.8%.The median OS was 38.0 months,the 5-year OS rate was 37.5%,and the 10-year OS rate was 24.2%.Before radiation therapy,14 patients(8.2%)had grade 1-2 lymphocytopenia.During radiation therapy,the number of patients with grade 1,2,3 and 4 lymphocytopenia was 7(4.1%),22(12.9%),111(65.3%),and 24(14.1%),respectively.One month after radiation therapy,the number of patients with grade 1,2,3 and 4 lymphocytopenia was 36(21.2%),36(21.2%),11(6.5%)and 1(0.6%),respectively.There were no significant differences in PFS and OS among patients with different grades of lymphocytopenia before,during,or after radiation therapy.Conclusion:Before immunotherapy,radiotherapy-induced lymphopenia did not appear to affect the prognosis of patients with LS-SCLC.

Objective:To analyze the change characteristics of creatinine level in the early stage of patients with diquat (DQ) poisoning, and to explore the early risk factors and the value of prognosis.Methods:A retrospective analysis was carried out on patients with DQ admitted to the the first affiliated hospital of Zhengzhou University from January 2020 to June 2022. The DQ patients were divided into death group and the survival group according to the 28 days survival status after posioning. The basic data and serum indexes and blood gas analysis of the patients on day 1 (D1), day 3 (D3) and day 5 (D5) were collected. The difference of clinical features between the two groups was analyzed, the variables were screened by multiple logistic regression analysis, and the predictive value of the variables was evaluated by drawing receiver operating characteristic curve (ROC curve).Results:A total of 88 patients were included, including 40 patients in the survival group and 48 patients in the death group. The toxic dose in death group was significantly higher than that in survival group [100(40.00, 120.00) mL vs. 50.00(20.00, 90.00) mL, P=0.003]. The higher the toxic dose, the higher the fatality rate. All 4 patients with oral doses greater than 200 mL died. Compared with the survival group, the levels of alanine aminotransferase (ALT) (D3, D5), creatinine (CR) (D3, D5), blood amylase (AMY) (D5) and oxygen partial pressure (PaO 2) (D5) in the death group were significantly higher than those in the survival group (all P<0.05). Multiple Logistic regression analysis showed that CR (D3) and AMY(D5) were independent risk factors for death after poisoning, and PaO 2(D5) was independent protective factor. ROC curve showed that the areas under ROC curve of CR (D3), AMY (D5) and PaO 2 (D5) were 0.814, 0.741 and 0.702, respectively. Conclusion:The higher the oral dose, the higher the death rate. After admission, CR(D3), AMY (D5) and PaO 2 (D5) were independent factors influencing the prognosis of DQ poisoning. In particular, CR (D3) is more effective in predicting death after poisoning.

OBJECTIVE To evaluate the clinical efficacy and safety of aspirin versus other anticoagulants in the prevention of thromboembolism after orthopedic surgery. METHODS Retrieved from PubMed， Embase， the Cochrane Library， CNKI， Wanfang data and VIP， randomized controlled trials （RCTs） and cohort studies about aspirin （trial group） versus other anticoagulants （control group） were collected during the inception and June 1st， 2023. After literature screening， data extraction and quality evaluation， the meta-analysis was conducted by using RevMan 5.4 software. RESULTS A total of 22 studies were included， involving 9 RCTs and 13 cohort studies. RCT results showed that the incidences of deep vein thrombosis （DVT） [RR＝1.81， 95%CI（1.36， 2.40）， P＜0.000 1] and postoperative pulmonary embolism （PE） [RR＝1.55， 95%CI（1.01， 2.40）， P＝0.05] in trial group were significantly higher than control group. There was no statistically significant difference in the incidences of postoperative massive bleeding， postoperative surgical site infection， all-cause death， or any bleeding after surgery between 2 groups. In the cohort study， the incidence of any bleeding in trial group was significantly lower than control group [RR＝0.71，95%CI （0.64， 0.79）， P＜0.000 1]， while the differences in other indicators were not statistically significant （P＞0.05）. The results of subgroup analysis based on different anticoagulants showed that in RCT， the incidences of DVT and PE after surgery in patients using low-molecular-weight heparin （LMWH） were significantly lower than using aspirin （P＜0.05）； in the cohort study， the incidences of DVT and PE after surgery were significantly lower in patients using direct oral anticoagulants （DOAC） than using aspirin （P＜0.05）. There was no statistically significant difference in the incidence of major bleeding between patients using aspirin and using DOAC and LWMH （P＞0.05） in both RCT and cohort study. CONCLUSIONS Aspirin is equally safe as other anticoagulants for the prevention of thromboembolism after orthopedic surgery， but its efficacy may not be as good as other anticoagulants. After orthopedic surgery， other anticoagulants should be preferred to prevent venous thromboembolism， and aspirin should be carefully considered.

Objective:To investigate the effect and mechanism of isorhynchophylline (IRN) on angiotensin Ⅱ(Ang Ⅱ)-induced cardiac hypertrophy.Methods:H9c2 cells were co-cultured with Ang Ⅱ and different concentrations of IRN (0, 5, 10, 25, 50 μmol/L). The cell surface area and mRNA levels of cardiac hypertrophy markers atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC) were detected to elucidate the effect of IRN on myocardial hypertrophy and the most effective concentration. H9c2 cells were co-cultured with Ang Ⅱ and IRN (25 μmol/L) at different times (0, 6, 12, 24 h) to elucidate the most effective time of inhibition. The phosphorylation levels of the signaling pathway were detected, and the effects of IRN and Akt inhibitor MK2206 on the phosphorylation levels of the signaling pathway were further explored to elucidate the underlying mechanisms.Results:Compared with the control group, the surface area of H9c2 cells, and the mRNA expression of myocardial hypertrophy markers ANP, BNP and β-MHC were significantly increased (all P<0.05). Pretreated with different concentrations of IRN (5, 10, 25, 50 μmol/L) could inhibit the increase in cell surface area induced by AngⅡ (all P<0.05), especially at the concentration of 25 μmol/ L ( P<0.01). IRN could time-dependently inhibit AngⅡ-induced activation of ANP, BNP, β-MHC mRNA (all P<0.05). AngⅡ caused increased phosphorylation levels of Akt, GSK3β, mTOR and FOXO3a. IRN could block AngⅡ-induced phosphorylation of the Akt signaling pathway. Conclusion:IRN attenuates AngⅡ-induced cardiomyocyte hypertrophy by inhibiting the Akt signaling pathway.

Objective:To explore the efficacy and safety of sivelestat, a neutrophil elastase (NE) inhibitor, in the treatment of acute lung injury (ALI) in the intensive care unit (ICU).Methods:A retrospective analysis was performed on 171 patients with ALI in the ICU of the First Affiliated Hospital of Zhengzhou University from June 2020 to June 2021, including 77 patients in the sivelestat group and 94 patients in the conventional treatment group. Acute physiology and chronic health evaluation (APACHE) Ⅱ score, Murray lung injury score, oxygenation index (PaO 2/FiO 2 ratio), inflammatory cytokines (IL-6, IL-10, TNF-α), ventilator-free days (VFD), the length of ICU stay, and the 28-day mortality were collected to assess the efficacy of sivelestat. At the same time, adverse reactions and laboratory test results within 30 days after the use of sivelestat were recorded to assess the safety. Results:Compared with conventional treatment, oxygenation index, Murray lung injury scores, IL-6, IL-10, and TNF-α were significantly improved after 7 days of sivelestat treatment. Compared with the conventional treatment group, the VFD was significantly longer ( P = 0.0119) and the length of ICU stay was significantly shorter ( P = 0.0269) in the sivelestat group. The mortality was 14.29% in the sivelestat group and 22.34% in the conventional treatment group and, with no statistically significant. In the meantime, sivelestat did not increase adverse reactions within 30 days after treatment. Conclusions:Sivelestat treatment is safe and more effective than conventional treatment for ALI patients in the ICU.

Clinical data of 93 patients with severe craniocerebral injury admitted in the Emergency Intensive Care Unit (EICU) of the First Affiliated Hospital of Zhengzhou University from September 2016 to September 2018 were retrospectively analyzed. Forty six patients received 10% hypertonic salt solution 60 ml (hypertonic salt group) and 47 patients received 20% mannitol 125 ml (mannitol group) for relieving early postoperation cerebral edema. The changes of intracranial pressure, central venous pressure, heart rate, mean arterial pressure (MAP), urine volume and serum sodium level at 2, 4 and 6 h after dehydrating agents were compared between two groups. There were no significant differences in the intracranial pressure, central venous pressure, heart rate and urine volume between two groups at 2, 4 and 6 h after the first dehydration treatment (all P>0.05). The MAP values of the two groups were (88±11) and (80±10), (85±10) and (78±9), (79±12) and (73±13) mmHg (1 mmHg=0.133 kPa) at 2, 4 and 6 h after the first dehydration treatment; and the serum sodium levels were (145±5) and (136±4), (144±6) and (133±5), (140±5) and (135±4) mmol/L, respectively. There were significant differences between two groups (all P<0.05). It is suggested that hypertonic salt can reduce intracranial pressure and increase cerebral perfusion better than mannitol in severe craniocerebral injury.

Objective:To explore the effect of Hsp22 on the activation of cardiac fibroblasts stimulated by TGFβ1 and its possible molecular mechanism.Methods:Cardiac fibroblasts of adult mice were isolated and cultured, and stimulated with TGFβ1 to induce fibroblast activation. Fibroblasts were incubated with Hsp22 of different concentrations (1, 2, 4, 8, 10 μg/mL) for 24 h, and their activation, proliferation and secretion were observed. CCK8 kit was used to detect cell proliferation. RT-PCR was used to detect the transcription of fibrogenic factor. Immunofluorescence was used to detect the expression of α-SMA protein. Immunoblotting was used to detect the possible signal protein.Results:CCK8 results showed that fibroblast increased significantly after TGFβ1 stimulation ( P<0.05). The expression of α-SMA in fibroblasts and the transcription of fibrosis-related genes increased significantly after TGFβ1 stimulation ( P<0.05). Different concentrations (1, 2, 4, 8, and 10 μg/mL) of Hsp22 all inhibited the proliferation of fibroblasts significantly (( P<0.05). Eight μg/mL and 10 μg/mL Hsp22 inhibited the expression of α-SMA ( P<0.05). and reduced the transcription of fibrosis-related genes ( P<0.05). Immunoblotting results indicated that after induced by TGFβ1, the expression of WNT and β-catenin, the phosphorylation level of GSK3β, and the nuclear translocation of β-catenin increased ( P<0.05). Ten μg/mL Hsp22 inhibited the expression of WNT and β-catenin, and reduced the phosphorylation of GSK3β the nuclear translocation of β-catenin and the phosphorylation of smad2 and smad3( P<0.05). Conclusions:Hsp22 could block TGFβ1-induced fibroblast activation, proliferation and secretion via inhibiting the WNT/β-catenin signaling pathway.

Objective To compare the clinical efficacy of high-flow nasal cannula oxygen therapy (HFNC) with non-invasive positive pressure ventilation (NPPV) in patients with traumatic cervical spinal cord injury complicated with acute respiratory failure (ARF).Methods A prospective randomized controlled trial was performed in EICU of the First Affiliated Hospital of Zhengzhou University from May 2016 to January 2018.One hundred sixty-eight consecutive patients with traumatic cervical spinal cord injury complicated with ARF,who did not respond to conventional oxygen therapy,were assigned to the HFNC or NPPV treatment group sequenced by the random number table.The baseline clinical characteristics of randomized participants and respiratory frequency (RR),PaCO2,mean arterial pressure (MAP) at 1,12,24,48 h after treatment were evaluated.Comfortable scale,tracheal intubation rate within 28 d,duration of mechanical ventilation,length of stay in ICU and mortality rate were compared as well.Results There was no significant differences in baseline clinical characteristics,such as sex,age.between the two groups (P＞0.05).RR and PaCO2 were lower in the HFNC group at all time point.In addition,the HFNC group had significantly lower PaCO2 than the NPPV group at 24 and 48 h after treatment (P＜0.01);Oxygenation index (PaO2/FiO2) was improved in both groups,and the HFNC group had superior oxygenation index than the NPPV group at 12,24,48 h after treatment (P＜0.01).Furthermore,the HFNC group had better comfort scale (6.93±0.71 vs 4.29±0.93,P＜0.01),shorter length of stay in ICU and duration of mechanical ventilation compared to the NPPV group (P＜0.01).There was no significant differences in tracheal intubation rate and mortality rate between the two groups (P＞0.05).Conclusions In addition to the superior efficacy in improving respiratory function and shortening length of stay in ICU,HFNC was well tolerated by patients with traumatic cervical spinal cord injury complicated with ARF,and could be recommended in clinical practice.

Objective To compare the neck skin dose between fixed-field dynamic intensity-modulated radiation therapy (dlMRT),volumetric modulated arc therapy (VMAT),and helical tomotherapy (HT) in the treatment of early-stage nasopharyngeal carcinoma.Methods A total of 16 early-stage nasopharyngeal carcinoma patients undergoing radiotherapy were enrolled as subjects.The neck skin was delineated by contraction of the outer edge of neck by 3 mm.Dose planning was made by the traditional method (TP group)and a new method (NP group),in which the neck skin was considered as the organ at risk.Dmean and V5-V70 for the neck skin were recorded.The paired t-test was used to analyze the differences between two plans in each radiotherapy method.An analysis of variance was used to compare the same plan between the three radiotherapy methods.Results The HT group had significantly higher Dmean and V5-V70 for the neck skin than the dIMRT group and the VMAT group (P=0.00,0.00,0.00,0.00,0.00,0.00,0.00,0.02).Using dIMRT,the D and V10-V60 for the neck skin were reduced by 7％,8％,22％,25％,38％,59％,and 85％ in the NP group than in the TP group (P=0.00,0.00,0.00,0.00,0.00,0.00,0.00).Using VMAT,the D and V20-V40 for the neck skin were reduced by 4％,19％,29％,and 34％ in the NP group than in the TP group (P=0.02,0.01,0.02,0.01).Using HT,the V30-V60 for the neck skin were reduced by 20％,29％,50％,and 67％ in the NP group than in the TP group (P=0.00,0.00,0.00,0.00,0.03).Conclusions In the treatment of early-stage nasopharyngeal carcinoma,HT causes a higher radiation dose to the neck skin than dIMRT and VMAT,while dIMRT and VMAT have similar neck skin doses.The neck skin dose can be significantly reduced with the neck skin as the organ at risk.