Rationale and Design of a Phase II Trial of Combined Serplulimab and Chemotherapy in Patients with Histologically Transformed Small Cell Lung Cancer: a Prospective, Single-arm and Multicentre Study.

AIMS: Transformed small cell lung cancer (T-SCLC) is a highly aggressive clinical disease with a notably poor prognosis. It most often arises from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) following treatment. To date, no standard treatment has been established for T-SCLC. Platinum-etoposide was the most commonly used regimen, but progression-free survival remains unsatisfactory. Therefore, there is an urgent unmet need to develop novel and effective strategies for this population. Our study, a multicentre, open-label, single-arm phase II clinical trial (NCT05957510), aims to evaluate the efficacy and safety of serplulimab plus chemotherapy in untreated T-SCLC patients after histological transformation. MATERIALS AND METHODS: In total, 36 eligible participants experiencing SCLC transformation from EGFR-mutant NSCLC will be enrolled to receive combination therapy of serplulimab, etoposide and carboplatin for four to six cycles, followed by maintenance therapy with serplulimab for up to 2 years. The primary endpoint is progression-free survival; secondary endpoints include objective response rate, overall survival and safety. RESULTS: Enrolment started in July 2023 and is ongoing, with an estimated completion date of December 2025. CONCLUSIONS: This study aims to provide valuable insights into the efficacy and safety of combining serplulimab with chemotherapy for treating patients with T-SCLC originating from EGFR-mutant NSCLC.

Comparison of clinical outcomes between posterolateral approach and modified Hardinge approach in salvage total hip arthroplasty after medial buttress plate failure for femoral neck fractures.

OBJECTIVE: The purpose of this study was to investigate the clinical outcomes of salvage total hip arthroplasty (THA) after medial buttress plate surgery for femoral neck fractures via the modified Hardinge approach (MHA) and posterolateral approach (PLA) through a retrospective analysis. PATIENTS AND METHODS: From October 2016 to October 2020, a total of 41 patients with failed femoral neck fractures treated with cannulated screws and medial buttress plates underwent unilateral salvage THA, and a retrospective study was conducted. According to the surgical approach, patients were divided into PLA group and MHA group. Clinical and radiological data were evaluated. The primary outcome indicators were the Pain Visual Analog Scale (VAS) and Hip Harris Score (HHS). Secondary outcome indicators include hemoglobin (HGB), hematocrit (HCT), creatine kinase (CK), creatine kinase-MB (CK-MB), etc. The occurrence of postoperative complications was also recorded. RESULTS: There were no differences in demographic or clinical characteristics before surgery. There were no differences in postoperative HGB, HCT, CK-MB and radiological parameters. The surgical approach had no effect on the hospitalization period. The PLA group had earlier ambulation time, and the serum level of CK was also low. Analysis of the HHS and VAS showed that on postoperative day 3, the PLA group had superior scores. The incidence of complications did not significantly differ between groups. CONCLUSIONS: The posterolateral approach for salvage THA provides better functional recovery with less muscle damage in the early postoperative period.

Correlation research of serum substance P, CCK-8, and 5-HT values with depression levels in stroke survivors.

OBJECTIVE: This study aimed to investigate the correlation of serum octapeptide cholecystokinin-8 (CCK-8), substance P (SP), and 5-hydroxytryptryptamine (5-HT) values with depression levels in patients with post-stroke depression (PSD). It also aimed to explore the potential approach for the early diagnosis of PSD. PATIENTS AND METHODS: A correlation research between patients' biochemical indicators and depression levels was performed among 70 stroke patients during hospitalization from June 2021 to February 2022. The 70 stroke patients were selected and divided into post-stroke depression and non-depression groups according to the Hamilton Depression Scale (HAMD) score. The concentrations of CCK-8, SP, and 5-HT in both groups were measured, and the relationship between the values of CCK-8, SP, 5-HT and the depression levels was analyzed. RESULTS: Among the 70 stroke survivors, 35 were in the depression group and 35 were in the non-depression group. Significant differences were observed in the concentration of CCK-8, SP, and 5-HT between the patients in the depression and non-depression group (p < 0.05). Accompanied by an increase in the depression level, the SP value gradually increased, but the CCK-8 and 5-HT values gradually decreased. Spearman correlation analysis indicated that the order of the correlation between CCK-8, 5-HT, SP, and the depression levels was CCK-8 > SP > 5-HT. CONCLUSIONS: All the CCK-8, SP and 5-HT values were correlated with the depression levels in stroke survivors. Furthermore, the correlation between CCK-8, SP, and post-stroke depression levels was higher than that of 5-HT, suggesting that the early diagnosis of PSD may be reflected more precisely through the detection of CCK-8, and SP values, thus providing potential priority for biochemical detection in the diagnosis of PSD.

Establishment and verification of a nomogram for predicting severe acute pancreatitis.

OBJECTIVE: The purpose of this study was to establish a nomogram for predicting the severity of acute pancreatitis (AP) and verify its predictive value. PATIENTS AND METHODS: A total of 571 AP patients received by Ordos Central Hospital from January 2015 to December 2018 were included in this study. According to the 2012 Revised Atlanta classification, the included subjects were classified into severe AP (SAP) group and non-severe AP (NSAP) group [including patient with mild AP (MAP) and moderately SAP (MSAP)]. The baseline characteristics, imageological data and pathological data within 24 h after the disease onset between the two groups were analyzed using One-way analysis of variance (one-way ANOVA). R language was used for establishing a predictive nomogram, whose performance was verified by clinical data of 150 AP cases collected from December 2018 to December 2019. RESULTS: One-way ANOVA shows that SAP and NSAP patients show significant differences in sex, calcium ions, creatinine, neutrophils ratio, lymphocytes ratio and eosinophils ratio (p<0.05). A predictive nomogram was accordingly established using the six indicators. Validation on this predictive nomogram showed high internal validation concordance index (C-index) of 0.69 (95% CI, 0.64-0.74), and high external validation C-index of 0.71 (95% CI, 0.67-0.76). CONCLUSIONS: This nomogram can be used as a clinical tool to predict the severity of SAP.

The value of PCT, IL-6, and CRP in the early diagnosis and evaluation of COVID-19.

OBJECTIVE: The aim of the present study was to assess the value of inflammatory factors procalcitonin (PCT), interleukin 6 (IL-6), and C-reactive protein (CRP) in the early diagnosis and evaluation of novel coronavirus pneumonia (COVID-19). MATERIALS AND METHODS: The data of 140 patients with pneumonia in our hospital, including 70 who had COVID-19 and 70 who had community-acquired pneumonia (CAP), were statistically analyzed. The levels of PCT, IL-6, and CRP were measured and statistically analyzed to determine the differences between the two groups. The differences in the COVID-19 group were analyzed after subgrouping into the ordinary type, severe type, and critical type. RESULTS: The PCT and CRP levels in the COVID-19 group were statistically lower than those in the CAP group (p < 0.05), but IL-6 was not statistically different between the two groups (p > 0.05). Statistically significant differences existed in IL-6 and CRP when comparing the COVID-19 subgroups of the critical type, severe type, and ordinary type (p < 0.05). However, there was no clinical meaning in the evaluation of the difference in PCT levels among the three subgroups with COVID-19. CONCLUSIONS: PCT and CRP could be used as indicators in the differentiation between COVID-19 and CAP, but IL-6 was of little significance in the differentiation. The higher the IL-6 and CRP, the more severe the condition of COVID-19 might be.

Different subsets of haematopoietic cells and immune cells in bone marrow between young and older donors.

Young donors are reported to be associated with better transplant outcomes than older donors in allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the mechanism is still unclear. The current study compared the different subsets of haematopoietic stem cells (HSCs) and their progenitors as well as immune cells in bone marrow (BM) between young and older donors. The frequencies of HSCs, multipotent progenitors (MPPs) and myeloid progenitors, including common myeloid progenitors (CMPs) and megakaryocyte-erythroid progenitors (MEPs), were decreased, whereas those of lymphoid progenitors, including multi-potent lymphoid progenitors (MLPs) and common lymphoid progenitors (CLPs), were increased in the BM of young donors compared with in that of older donors. Lower reactive oxygen species (ROS) levels were observed in BM HSCs and six progenitor lines in young donors. Furthermore, young donors demonstrated higher frequencies of naive T cells and immune suppressor cells, such as alternative macrophages (M2) and lower frequencies of memory T cells and immune effectors, including T helper-1 and T cytotoxic-1 cells, in BM than older donors. Multivariate analysis demonstrated that donor age was independently correlated with BM HSC frequency. Although further validation is required, our results suggest that the differences in the frequency and immune differentiation potential of HSCs in BM between young donors and older donors may partly explain the different outcomes of allo-HSCT.

Risk factors for disease progression in patients with mild to moderate coronavirus disease 2019-a multi-centre observational study.

OBJECTIVES: Since December 2019, the novel coronavirus disease 2019 (COVID-19) that emerged in Wuhan city has spread rapidly around the world. The risk for poor outcome dramatically increases once a patient progresses to the severe or critical stage. The present study aims to investigate the risk factors for disease progression in individuals with mild to moderate COVID-19. METHODS: We conducted a cohort study that included 1007 individuals with mild to moderate COVID-19 from three hospitals in Wuhan. Clinical characteristics and baseline laboratory findings were collected. Patients were followed up for 28 days for observation of disease progression. The end point was the progression to a more severe disease stage. RESULTS: During a follow up of 28 days, 720 patients (71.50%) had recovered or were symptomatically stable, 222 patients (22.05%) had progressed to severe disease, 22 patients (2.18%) had progressed to the critically ill stage and 43 patients (4.27%) had died. Multivariate Cox proportional hazards models identified that increased age (hazard ratio (HR) 2.56, 95% CI 1.97-3.33), male sex (HR 1.79, 95% CI 1.41-2.28), presence of hypertension (HR 1.44, 95% CI 1.11-1.88), diabetes (HR 1.82, 95% CI 1.35-2.44), chronic obstructive pulmonary disease (HR 2.01, 95% CI 1.38-2.93) and coronary artery disease (HR 1.83, 95% CI 1.26-2.66) were risk factors for disease progression. History of smoking was protective against disease progression (HR 0.56, 95% CI 0.34-0.91). Elevated procalcitonin (HR 1.72, 95% CI 1.02-2.90), urea nitrogen (HR 1.72, 95% CI 1.21-2.43), α-hydroxybutyrate dehydrogenase (HR 3.02, 95% CI 1.26-7.21) and D-dimer (HR 2.01, 95% CI 1.12-3.58) at baseline were also associated with risk for disease progression. CONCLUSIONS: This study identified a panel of risk factors for disease progression in individuals with mild to moderate COVID-19.

MiR-135b-5p inhibits the progression of malignant melanoma cells by targeting RBX1.

OBJECTIVE: The aim of this study was to investigate the potential effects of microRNA-135b-5p (miR-135b) on the development of malignant melanoma (MM) and the relevant mechanism. PATIENTS AND METHODS: The expression level of miR-135b in MM tissues and cells was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Online prediction software and luciferase reporter assays were used to predict and verify the possible target of miR-135b, respectively. Furthermore, the effects of the miR-135b on MM A375 cells were determined by Western blotting, MTT, and transwell assays. RESULTS: MiR-135b was significantly down-regulated in MM. RING-box protein 1 (RBX1) was verified as a direct target of miR-135b. Subsequent experiments showed that down-regulation of RBX1 resulted from miR-135b up-regulation could significantly inhibit the proliferation, invasion, and migration abilities of MM cells. CONCLUSIONS: MiR-135b inhibited the progression of MM by targeting RBX1. Our findings revealed that miR-135b/RBX1 might be a potential therapeutic target for the treatment of MM.

Gingko biloba extract EGB761 alleviates heat-stress damage in chicken heart tissue by stimulating Hsp70 expression in vivo in vascular endothelial cells.

1. This study aimed to investigate the protective effects of Gingko biloba extract EGB761 on heat-stressed chicken heart in vivo and its underlying relevance to Hsp70.2. A total of 50 one-day-old female chicks were randomly divided into five groups: control (Con), heat-stress (HS), 0.1% EGB761 plus heat-stress (0.1%EGB+HS), 0.3%EGB761 plus heat-stress (0.3%EGB+HS) and 0.6%EGB761 plus heat-stress (0.6%EGB+HS) groups. After administration of EGB761 for 45 days, the chickens in each group were exposed to a single heat-stress event at 38 ± 1°C for 3 h.3. EGB761 attenuated the abnormal symptoms and pathological scores of myocardium of heat-stressed chickens. Despite a reduction in the transcription and translation of the Hsp70 gene in heat-stressed myocardium, EGB761 induced the expression of Hsp70 in endothelial cells of the microarteries and venules into the blood, and reduced heat-stress damage in vascular endothelial cells.4. Supplementation with EGB761 before heat-stress exposure protected chicken myocardium from damage by increasing serum Hsp70 protein from myocardial cells and cardiac microvascular endothelial cells and protected the microvascular system from adverse injury.

Long non-coding RNA LINP1 functions as an oncogene in endometrial cancer progression by regulating the PI3K/AKT signaling pathway.

OBJECTIVE: Endometrial cancer (EC) accounts for about 6% of new cancer cases in female and about 3% of cancer-related deaths were caused by EC. The poor prognosis is mainly due to the distant spread and poor differentiation. In the current study, we want to figure out the role of long non-coding RNA (LncRNA) LINP1 in EC progression. PATIENTS AND METHODS: The quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assay was involved to access the expression level of LINP1 in EC cell lines and tissues. The Cell Counting Kit-8 (CCK-8) assay, colony formation assay, transwell and Matrigel assay were recruited to figure out the ability of LINP1 in cell proliferation and metastasis in EC. Subsequently, Western blotting was used to detect the expression level of PI3K/AKT in EC. Besides, we used the tumor formation assay in vivo to examine the ability of LINP1 in tumor formation in vivo. RESULTS: LINP1 was proved to be up-regulated in EC cell lines and tissues by qRT-PCR assay. CCK-8 assay and colony formation assay were conducted and the results indicated that LINP1 over-expression can promote cell proliferation in EC in vitro. The data of transwell and Matrigel assays indicated that up-regulated LINP1 can facilitate cell migration and invasion. The results of Western blotting validated that LINP1 can activate PI3K/AKT signaling. Besides, the tumor formation assay verified that LINP1 can promote tumor formation in vivo. CONCLUSIONS: Our research validated that LINP1 served as an oncogenic role in EC progression. The PI3K/AKT signaling pathway might be the underlying mechanism of EC progression. We hope our study can provide novel treatment targets and biomarkers in EC development and progression.

Long noncoding RNA LSINCT5 is upregulated and promotes the progression of esophageal squamous cell carcinoma.

OBJECTIVE: Long stress-induced noncoding transcripts 5 (LSINCT5) has been reported to be upregulated in several human cancers and related to poor prognosis. However, its involvement in esophageal squamous cell carcinoma (ESCC) remains largely unknown. We aim to evaluate the expression and putative role of LSINCT5 on the progression of ESCC. MATERIALS AND METHODS: LSINCT5 expression was first examined in the ESCC cell lines using RT-qPCR, and the next-generation RNA-Seq technology was employed to analyze and functionally annotate the differential gene expression before and after LSINCT5 knockdown in ESCC was made. Based on the functional annotation results, the effects of LSINCT5 knockdown on cell growth, migration, invasion, and epithelial-to-mesenchymal transition (EMT) were assessed in the ESCC cell lines. Finally, the expression and clinicopathological significance of LSINCT5 in ESCC and corresponding nontumor tissues were further explored using RT-qPCR. RESULTS: The RT-qPCR results showed that LSINCT5 expression was significantly upregulated in the ESCC cell lines. The differential gene expression analysis by next-generation RNA-Seq showed that 138 genes were up-regulated, and 227 genes were downregulated after LSINCT5 was knocked down in the ECA 109 cells. In addition, the functional annotation revealed that the differentially expressed genes were mainly functionally involved in tight junctions, ECM-receptor interactions, and MAPK signaling pathway. Further in vitro studies indicated that the knockdown of LSINCT5 significantly suppressed proliferation, migration, invasion, and EMT in ESCC cells. Finally, a comparative study of paired ESCC and corresponding nontumor tissues showed that LSINCT5 was upregulated in the ESCC tissues, and the increased LSINCT5 expression was related to late clinical stages, large tumor sizes, and lymph node metastasis. CONCLUSIONS: The results indicate that LSINCT5 is upregulated in ESCC and may act as an oncogene promoting the progression of ESCC.

MicroRNA-23a induces apoptosis of hepatocarcinoma cell line MHCC97H via down-regulating KIAP: a mechanism study.

OBJECTIVE: Hepatocarcinoma is a great threat to global health. MicroRNA-23a was suggested to regulate growth and apoptosis in certain cell lines. Our study was focused on growth, proliferation, and apoptosis of hepatocarcinoma cell line MHCC97H under the influence of microRNA-23a, and explored the mechanism of pro-apoptosis microRNA-23a. MATERIALS AND METHODS: MicroRNA-23a and control microRNA (scramble miRNA, for short as miRNA) were synthesized with the routine protocol. Lipofection transfection was performed in hepatocarcinoma cell line MHCC97H. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, caspase-3 activity detection, and flow cytometry were performed to examine growth, proliferation, and apoptosis of hepatocarcinoma cell line MHCC97H, respectively. Kidney inhibitor of apoptosis protein (KIAP) and small interfere RNA (siRNA) was synthesized for inhibition of KIAP. KIAP plasmid was established for activation of KIAP. Western blot was performed to examine the protein expression of KIAP and caspase protein family after transfection of KIAP siRNA or KIAP plasmid. RESULTS: Compared with miRNA transfection, microRNA-23a transfection significantly reduced the growth of MHCC97H cells, and decreased the expression of KIAP (p < 0.05). Enhanced translocation of phosphatidylserine and activation of caspase-3 were observed in microRNA-23a transfection cells. Moreover, inhibition of KIAP enhanced the pro-apoptosis effect of microRNA-23a, while activation of KIAP abrogated pro-apoptosis effect of microRNA-23a. CONCLUSIONS: MicroRNA-23a inhibits growth and proliferation of MHCC97H cells, and induces apoptosis of MHCC97H cells via down-regulating KIAP. KIAP could be a potential therapeutic target for hepatocarcinoma treatment.

Human papillomavirus infection and colorectal cancer in the Chinese population: a meta-analysis.

AIM: Human papillomavirus (HPV) infection has been reported in colorectal cancer in many studies. We conducted a meta-analysis to assess the association between HPV infection and colorectal cancer/adenomas in the Chinese population. METHOD: Relevant studies up to January 2018 were searched in PubMed, EMBASE, China National Knowledge Infrastructure and the Wanfang database. We used a random effects model to determine the prevalence of HPV and odds ratios (ORs) with 95% confidence intervals (CIs). The I2 statistic and P-value from the Cochrane Q-test were used to describe the heterogeneity. RESULTS: Ten case-control studies involving 766 colorectal cancer patients and 470 controls were included in the meta-analysis. Among the colorectal cancer patients, the pooled prevalence was 0.45 (95% CI 0.36-0.53). The pooled estimate for OR was 10.78 (95% CI 4.22, 27.53). Among the 193 patients with colorectal adenoma, the pooled prevalence and OR were 0.31 (95% CI 0.24-0.37) and 2.03 (95% CI 0.79, 5.26), respectively. The prevalence of HPV 16 and HPV 18 among HPV-positive cancers ranged from 57.9% to 100% and 0% to 39.7%, respectively. CONCLUSION: The results indicated that HPV infection, especially HPV 16 and HPV 18, is associated with colorectal cancer in the Chinese population.

MMP-14 aggravates onset of severe preeclampsia by mediating soluble endoglin release.

OBJECTIVE: Gestational hypertension is a pregnancy complication that serious damages the maternal and child health. Early onset severe preeclampsia accounts for about 0.9% of the gestational hypertension disease. Conservative treatment is proposed in recent years to early onset severe preeclampsia through delay delivery. Therefore, it is particularly important to explore the pathogenesis of severe preeclampsia. Soluble endoglin (sEng) has been identified as a central factor to induce endothelium dysfunction of preeclampsia, while its specific mechanism is unclear. MATERIALS AND METHODS: Matrix metallopeptidase 14 (MMP-14) and endoglin expressions and tissue localization in the placenta of preeclampsia and premature were detected by Western blot and immunohistochemistry. Endoglin level, mean arterial blood pressure (MABP), and urinary protein/creatinine ratio were analyzed for correlation to investigate their relationship and the influence of endoglin on eclampsia severity. MMP specific or broad spectrum inhibitor combining MMP-14 siRNA were used in JAR cell line BeWo to explore the regulatory role of MMP-14 on endoglin. RESULTS: MMP-14, endoglin, and sEng expression levels significantly increased in the placenta of severe preeclampsia patients. MMP-14 and endoglin exhibited expression co-localization. Endoglin expression was positively correlated with the severity of eclampsia. MMP-14 directly mediated the release of sEng. CONCLUSIONS: MMP-14 aggravated the onset of severe preeclampsia by mediating sEng release. MMP-14 was proposed as the effective target for the treatment of severe preeclampsia. Blocking the interaction between MMP-14 and endothelial protein may be an important treatment method.

Unmanipulated haploidentical transplantation conditioning with busulfan, cyclophosphamide and anti-thymoglobulin for adult severe aplastic anaemia.

We conducted a retrospective analysis to evaluate outcomes of haploidentical transplantation in adult severe aplastic anaemia (SAA) patients. Fifty-one adults received haploidentical transplantation between May 2011 and December 2016. Patients were administered busulfan (Bu), cyclophosphamide (Cy) and anti-thymoglobulin (ATG) as conditioning regimens, followed by bone marrow and peripheral blood transplantation. The patients' median age was 25 years. Forty-nine patients survived for more than 28 days and all achieved donor myeloid engraftment. The median time for myeloid engraftment and platelet recovery was 13 days (range, 10-21) and 17.5 (range, 7-101) days. The cumulative incidence (CI) of grade II-IV and III-IV acute GvHD) was 20.00±0.33% and 6.00±0.12%, respectively. The incidence of chronic GvHD was 14.00±0.36% and 25.90±0.71%, and that of moderate-severe chronic GvHD was 2.51±0.06% and 6.92±0.25% at 1 and 3 years, respectively. The 3-year estimated overall survival and failure-free survival were both 83.5±5.4% with a median follow-up of 21.1 months. Multivariate analysis showed hematopoietic cell transplantation-specific comorbidity index (HCT-CI) score of ⩾3 was significantly associated with worse outcome. Haploidentical transplantation conditioning including Bu/Cy/ATG was a safe and effective strategy for adult SAA patients, and HCT-CI might be an outcome predictor in these patients.

Donor and recipient age, gender and ABO incompatibility regardless of donor source: validated criteria for donor selection for haematopoietic transplants.

Prior data indicate similar outcomes after transplants from human leukocyte antigen (HLA)-haplotype-matched relatives, HLA-identical siblings and HLA-matched unrelated donors. We used our prospective data set to answer a clinically important question: who is the best donor for a person with acute leukaemia transplanted in first complete remission. Patients were randomly divided into training (n=611) and validation (n=588) sets. A total of 1199 consecutive subjects received a transplant from an HLA-haplotype-matched relative using granulocyte colony-stimulating factor and anti-thymocyte globulin (n=685) or an HLA-identical sibling (n=514); 3-year leukaemia-free survivals (LFSs) were 75 and 74% (P=0.95), respectively. The multivariate model identified three major risk factors for transplant-related mortality (TRM): older donor/recipient age, female-to-male transplants and donor-recipient ABO major-mismatch transplants. A risk score was developed based on these three features. TRMs were 8%, 15% and 31% for subjects with scores of 0-1, 2 and 3, respectively, (P<0.001). Three-year LFSs were 78%, 74% and 58%, respectively, (P=0.003). The risk score was validated in an independent cohort. In conclusion, our data confirm donor source is not significantly correlated with transplant outcomes. Selection of the best donor needs to consider donor-recipient age, matching for gender and ABO incompatibility among persons with acute leukaemia receiving related transplants under our transplant modality.

Clinical significance of dynamic measurements of seric TNF-α, HMGBl, and NSE levels and aEEG monitoring in neonatal asphyxia.

OBJECTIVE: This study investigates the clinical value of monitoring blood levels of tumor necrosis factor-α (TNF-α), high mobility group protein Bl (HMGBl), and neuron-specific enolase (NSE), and examining an amplitude-integrated electroencephalogram (aEEG) for the diagnosis and short-term prognosis of brain damage caused by neonatal asphyxia. PATIENTS AND METHODS: Sixty full-term neonates born in Yidu Central Hospital from January to December 2015 were enrolled in the study. The neonates were classified into one of 3 groups: 23 neonates in the mild asphyxia group, 7 in a severe asphyxia group and 30 in a control group admitted to the NICU but without asphyxia. The neonates presenting asphyxia received standard neonatal resuscitation before they were transferred to the NICU. The dynamic changes of the umbilical artery/peripheral blood TNF-α, HMGBl, and NSE levels and aEEG results were monitored and compared among the groups. RESULTS: The umbilical artery and serum TNF-α, HMGBl, and NSE levels at day 1 were significantly higher in the two asphyxia groups than in the control group; and the values were higher in the severe asphyxia group (p <0.05). Furthermore, the correlation coefficients between TNF-α and HMGB1, TNF-α and NSE, and HMGB1 and NSE at all the monitoring time points were positive: 0.5516, 26.943 and 15.87, respectively (p <0.001). Additionally, the neonates with abnormal aEEG results at 6 hours postpartum had higher serum TNF-α, HMGBl and NSE levels than those with normal aEEG results (p <0.05). The patients with persistently abnormal or progressively deteriorating aEEG results usually had a poor evolution. CONCLUSIONS: The dynamic monitoring of TNF-α, HMGBl, and NSE levels combined with aEEG can provide useful evidence for the early diagnosis, the determination of severity and the short-term prognosis of brain damage caused by neonatal asphyxia.

Immune reconstitution in patients with acquired severe aplastic anemia after haploidentical stem cell transplantation.

Immune recovery (IR) after haploidentical stem cell transplantation (haplo-SCT) in severe aplastic anemia (SAA) patients remains relatively unknown. In this study, we examined immune cell subset counts and immunoglobulins in 81 SAA patients from day 30 to day 365 after haplo-SCT. Simultaneously, we determined which factors influence IR and analyzed the effects of immune cell subsets on transplant outcomes. We found that: (i) The reconstitution of different immune cell subsets occurred at different rates after haplo-SCT. Monocytes were the first to recover, followed by CD8+ T and CD19+ B cells, and finally CD4+ T cells. (ii) In the multivariate analysis, lower recipient age, female gender, high mononuclear cell counts in the graft and absence of CMV reactivation were associated with improved IR after transplant. (iii) A CD4/CD8 ratio less than 0.567 on day 30 post transplantation was associated with higher overall survival after haplo-SCT in SAA patients. In conclusion, SAA patients showed a faster recovery of monocytes and CD8+ T cells after haplo-SCT, whereas the recovery of the CD4+ T-cell subset was delayed. Our results may provide insight into methods for better predicting and modulating IR of SAA patients and subsequently improving outcomes after transplantation.

A positive crosstalk between CXCR4 and CXCR2 promotes gastric cancer metastasis.

The molecular mechanism underlying gastric cancer (GC) invasion and metastasis is still poorly understood. In this study, we tried to investigate the roles of CXCR4 and CXCR2 signalings in gastric cancer metastasis. A highly invasive gastric cancer cell model was established. Chemokines receptors were profiled to search for the accountable ones. Then the underlying molecular mechanism was investigated using both in vitro and in vivo techniques, and the clinical relevance of CXCR4 and CXCR2 expression was studied in gastric cancer samples. CXCR4 and CXCR2 were highly expressed in a high invasive gastric cancer cell model and in gastric cancer tissues. Overexpression of CXCR4 and CXCR2 was associated with more advanced tumor stage and poorer survival for GC patients. CXCR4 and CXCR2 expression strongly correlated with each other in the way that CXCR2 expression changed accordingly with the activity of CXCR4 signaling and CXCR4 expression also changed in agreement with CXCR2 activity. Further studies demonstrated CXCR4 and CXCR2 can both activated NF-κB and STAT3 signaling, while NF-κBp65 can then transcriptionally activate CXCR4 and STAT3 can activate CXCR2 expression. This crosstalk between CXCR4 and CXCR2 contributed to EMT, migration and invasion of gastric cancer. Finally, Co-inhibition of CXCR4 and CXCR2 is more effective in reducing gastric cancer metastasis. Our results demonstrated that CXCR4 and CXCR2 cross-activate each other to promote the metastasis of gastric cancer.