OBJECTIVE: To explore the effects and mechanisms of the C-X-C motif chemokine ligand 12/C-X-C motif chemokine receptor 4 (CXCL12/CXCR4) signaling axis on apoptosis and autophagy in SH-SY5Y neuronal cells subjected to oxygen-glucose deprivation/reperfusion (OGD/R) model in vitro. METHODS: SH-SY5Y cells were divided into the following groups: OGD/R group and non-OGD/R group, with the OGD/R group subjected to OGD/R modeling and the non-OGD/R group receiving no treatment. Cells were also divided into CXCL12⁺ and CXCL12^- groups; the CXCL12⁺ group received 0.1 mg/L exogenous recombinant CXCL12 (rhCXCL12) at reoxygenation, while the CXCL12^- group did not. Another set of cells was divided into CXCL12+AMD3100 and CXCL12 groups; the CXCL12+AMD3100 group was pretreated with 2.5 mg/L AMD3100, a CXCR4 inhibitor, for 2 hours before OGD/R and received both 2.5 mg/L AMD3100 and 0.1 mg/L rhCXCL12 at reoxygenation, whereas the CXCL12 group received rhCXCL12 only. Additionally, cells were divided into small interfering RNA CXCR4 (siCXCR4) and small interfering RNA negative control (siNC) groups; the siCXCR4 group underwent CXCR4 knockdown before OGD/R modeling and received 0.1 mg/L rhCXCL12 at reoxygenation, while the siNC group, transfected with a negative control, received the same treatment. Protein expression of autophagy-related 16 (ATG16), microtubule-associated protein 1 light chain 3 (LC3), aquaporin-3 (AQP3), and CXCR4 was detected by Western blotting. Apoptosis rate and CXCR4 expression were measured by flow cytometry. RESULTS: Compared with the non-OGD/R group, the OGD/R group showed a significantly increased apoptosis rate and markedly decreased protein expression levels of ATG16, LC3, AQP3, and CXCR4 (all P < 0.05). CXCR4 fluorescent expression was also significantly reduced, suggesting that OGD/R simultaneously affects neuronal apoptosis and autophagy while inhibiting CXCR4 and AQP3 expression in SH-SY5Y cells. Compared with the CXCL12^- group, the CXCL12⁺ group exhibited no significant change in apoptosis rate but demonstrated significantly increased protein expression of ATG16, LC3, and AQP3 (ATG16/GAPDH: 1.21±0.10 vs. 1.00±0.00; LC3/β-actin: 1.22±0.10 vs. 1.00±0.00; AQP3/β-actin: 1.26±0.04 vs. 1.00±0.00; all P < 0.05). CXCR4 expression was also significantly enhanced (fluorescence intensity: 1.19±0.05 vs. 1.00±0.00, P < 0.05), indicating that CXCL12 may promote autophagy in OGD/R-injured SH-SY5Y cells via the CXCR4/AQP3 pathway. Compared with the CXCL12 group, the CXCL12+AMD3100 group showed no significant difference in apoptosis rate but significantly lower protein levels of ATG16 and LC3 (ATG16/GAPDH: 0.75±0.08 vs. 1.00±0.00; LC3/GAPDH: 0.86±0.07 vs. 1.00±0.00; both P < 0.05), suggesting that CXCL12 induces autophagy in OGD/R SH-SY5Y cells through CXCR4. Compared with the siNC group, the siCXCR4 group showed no significant change in apoptosis rate but significantly reduced protein expression of ATG16, LC3, AQP3, and CXCR4 (ATG16/GAPDH: 0.76±0.06 vs. 1.00±0.00; LC3/GAPDH: 0.79±0.11 vs. 1.00±0.00; AQP3/GAPDH: 0.81±0.05 vs. 1.00±0.00; CXCR4/GAPDH: 0.86±0.04 vs. 1.00±0.00; all P < 0.05), indicating that CXCR4 knockdown suppresses OGD/R-induced autophagy in SH-SY5Y cells likely via AQP3. CONCLUSIONS The CXCL12/CXCR4 signaling axis can regulate OGD/R-induced autophagy in SH-SY5Y cells through AQP3 without affecting apoptosis, indicating a role for this pathway in neuronal autophagy during cerebral ischemia/reperfusion injury.
Humans ; Receptors, CXCR4/metabolism* ; Chemokine CXCL12/metabolism* ; Autophagy ; Glucose/metabolism* ; Apoptosis ; Neurons/cytology* ; Oxygen/metabolism* ; Signal Transduction ; Cell Line, Tumor ; Cell Hypoxia ; Benzylamines ; Cyclams

Objective:To investigate the effect of prone position on the prognosis of patients with severe pneumonia in intensive care unit (ICU).Methods:A retrospective cohort study was conducted. The patients with severe pneumonia admitted to the ICU of Qingdao Municipal Hospital from May 2022 to August 2023 were enrolled. The general information, etiology, underlying diseases, vital signs and laboratory indicators at ICU admission, clinical treatment and prognosis during ICU hospitalization were collected. The above clinical data of patients with different prognosis were compared. Multifactorial Logistic regression analysis was used to screen the related factors affecting survival during ICU in patients with severe pneumonia. The change in oxygenation index (PaO 2/FiO 2) of patients with severe pneumonia were observed at 1 hour before the first prone position, 1 hour after the first prone position, and 1 hour after the end of the first prone position. The effect of prone position on oxygenation in patients with severe pneumonia was analyzed. Spearman correlation analysis was used to investigate the correlation between the duration to first prone position and the change in the PaO 2/FiO 2 before and after prone position in patients with severe pneumonia. Results:Finally, a total of 144 patients with severe pneumonia were enrolled, 45 survived and 99 died during ICU hospitalization, with a mortality of 68.8%. Compared with the survival group, the patients in the death group were older [years old: 81.00 (70.75, 86.00) vs. 71.00 (60.50, 81.50), P < 0.01], the proportion of pre-existing lung disease, heart rate (HR), respiratory rate (RR), blood lactic acid (Lac) and the ratio of continuous renal replacement therapy (CRRT) were higher [ratio of pre-existing lung disease: 23.2% (23/99) vs. 8.9% (4/45), HR (bpm): 99.61±22.47 vs. 91.49±18.76, RR (times/min): 22.50 (19.75, 29.25) vs. 20.00 (17.50, 24.50), Lac (mmol/L): 2.00 (1.55, 3.25) vs. 1.60 (1.20, 1.95), CRRT ratio: 25.3% (25/99) vs. 6.7% (3/45), all P < 0.05], and the proportion of prone position was lower [41.4% (41/99) vs. 68.9% (31/45), P < 0.01]. Multifactorial Logistic regression analysis showed that age [odds ratio ( OR) = 0.946, 95% confidence interval (95% CI) was 0.912-0.980, P = 0.002] and Lac ( OR = 0.563, 95% CI was 0.340-0.930, P = 0.025) were negatively correlated with survival during ICU hospitalization in severe pneumonia patients, while prone position was positively correlated with survival ( OR = 2.551, 95% CI was 1.067-6.095, P = 0.035), indicating that prone position was beneficial for improving ICU prognosis in severe pneumonia patients. The results of PaO 2/FiO 2 at different time points in prone position showed that PaO 2/FiO 2 at 1 hour of the first prone position in the patients with severe pneumonia was significantly higher than that at 1 hour before the first prone position [mmHg (1 mmHg ≈ 0.133 kPa): 146.69 (113.92, 257.25) vs. 111.75 (70.15, 212.20), P < 0.01], indicating that the prone position had a relevant effect on the improvement of oxygenation in patients. Spearman correlation analysis showed that the duration of the first prone position in patients with severe pneumonia was significantly and positively correlated with the improvement of oxygenation at 1 hour of the first prone position ( r = 0.565, P < 0.001). Conclusions:The prone position is a therapeutic measure that can independently influence the prognosis of patients with severe pneumonia during ICU hospitalization. The prone position effectively improves oxygenation in patients with severe pneumonia and the first change in oxygenation in patients is related to the duration of the prone position.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

OBJECTIVE: To explore the predictive value of serum sodium variability within 72 hours, lactic acid (Lac), sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation II (APACHE II) in predicting the 28-day prognosis of sepsis patients. METHODS: The clinical data of patients with sepsis admitted to the department of intensive care unit (ICU) of the Affiliated Qingdao Municipal Hospital of Qingdao University from December 2020 to December 2021 were retrospectively analyzed, including age, gender, previous medical history, temperature, heart rate, respiratory rate, systolic pressure, diastolic pressure, white blood cell count (WBC), hemoglobin (Hb), platelet count (PLT), C-reactive protein (CRP), pH value, arterial partial pressure of oxygen (PaO₂), arterial partial pressure of carbon dioxide (PaCO₂), Lac, prothrombin time (PT), activated partial thromboplastin time (APTT), serum creatinine (SCr), total bilirubin (TBil), albumin (Alb), SOFA, APACHE II score, and 28-day prognosis. Multivariate Logistic regression was used to analyze the risk factors of death in sepsis patients. Receiver operator characteristic curve (ROC curve) was used to analyze the predictive value of serum sodium variability within 72 hours, Lac, SOFA, APACHE II alone and in combination on the prognosis of patients with sepsis. RESULTS: A total of 135 patients with sepsis were included, 73 survived and 62 died at 28 days, with 28-day mortality of 45.93%. (1) Compared with the survival group, SOFA, APACHE II, Lac and serum sodium variability within 72 hours in the death group were significantly higher [SOFA: 10.00 (8.00, 12.00) vs. 6.00 (5.00, 8.00), APACHE II: 18.00 (16.00, 21.25) vs. 13.00 (11.00, 15.00), Lac (mmol/L): 3.55 (2.90, 4.60) vs. 2.00 (1.30, 2.80), serum sodium variability within 72 hours: 3.4% (2.6%, 4.2%) vs. 1.4% (1.1%, 2.5%)], the differences were statistically significant (all P < 0.01). (2) Multivariate Logistic regression showed that SOFA, APACHE II, Lac, serum sodium variability within 72 hours were independent risk factors of prognosis in patients with sepsis [SOFA: odds ratio (OR) = 1.479, 95% confidence interval (95%CI) was 1.114-1.963, P = 0.007; APACHE II: OR = 1.163, 95%CI was 1.009-1.340, P = 0.037; Lac: OR = 1.387, 95%CI was 1.014-1.896, P = 0.040; serum sodium variability within 72 hours: OR = 1.634, 95%CI was 1.102-2.423, P = 0.015]. (3) ROC curve analysis showed that SOFA, APACHE II, Lac and serum sodium variability within 72 hours had certain predictive value for the prognosis of sepsis patients [SOFA: the area under the ROC curve (AUC) = 0.858, 95%CI was 0.795-0.920, P = 0.000; APACHE II: AUC = 0.845, 95%CI was 0.776-0.913, P = 0.000; Lac: AUC = 0.840, 95%CI was 0.770-0.909, P = 0.000; serum sodium variability within 72 hours: AUC = 0.842, 95%CI was 0.774-0.910, P = 0.000]. The combined predictive value of the four indicators (AUC = 0.917, 95%CI was 0.870-0.965, P = 0.000) was higher than that of any single indicator, and has higher specificity (79.5%) and sensitivity (93.5%), indicating that the combined index has higher predictive value for the prognosis of sepsis patients than any single index. CONCLUSIONS SOFA, APACHE II, Lac, serum sodium variability within 72 hours are independent risk factors for 28-day death in patients with sepsis. The combination of SOFA score, APACHE II score, Lac and serum sodium variability within 72 hours has higher predictive value for prognosis than single index.
Humans ; Lactic Acid ; Prognosis ; Retrospective Studies ; Sepsis ; Sodium

Baylisascaris schroederi,a roundworm(ascaridoid)parasite specific to the bamboo-feeding giant panda(Ailuropoda melanoleuca),represents a leading cause of mortality in wild giant panda populations.Here,we present a 293-megabase chromosome-level genome assembly of B.schroederi to infer its biology,including host adaptations.Comparative genomics revealed an evolutionary trajectory accompanied by host-shift events in ascaridoid parasite lineages after host separations,suggesting their potential for transmission and rapid adaptation to new hosts.Genomic and anatomical lines of evidence,including expansion and positive selection of genes related to the cuticle and basal metabolisms,indicate that B.schroederi undergoes specific adaptations to survive in the sharp-edged bamboo-enriched gut of giant pandas by structurally increasing its cuticle thickness and efficiently utilizing host nutrients through gut parasitism.Additionally,we characterized the secretome of B.schroederi and predicted potential drug and vaccine targets for new control strategies.Overall,this genome resource provides new insights into the host adaptation of B.schroederi to the giant panda as well as the host-shift events in ascaridoid parasite lineages.Our findings on the unique biology of B.schroederi will also aid in the development of prevention and treatment measures to protect giant panda populations from roundworm parasitism.

Objective    To examine the high-risk factors and prognosis of patients with superior interlobar lymph nodes (11s nodes) metastasis in non-small cell lung cancer (NSCLC) located in the right middle or lower lobe. Methods    The clinical data of 157 patients with NSCLC in the right middle or lower lobe from January 2015 to July 2020 in our hospital were retrospectively analyzed, including 98 males and 59 females aged 23-86 (60.01±10.58) years. The patients underwent lobectomy and systemic lymph node dissection along with dissection of 11s nodes. They were divided into a 11s (+) group and a 11s (–) group according to whether the 11s nodes were involved. Results    There were 31 patients with invasion in the 11s nodes, and the overall incidence of metastasis was 19.75%, including 13.64% with middle lobe tumors and 20.74%with lower lobe tumors. The 2R+4R nodes involvement was the influencing factor associated with 11s nodes metastasis (P=0.026). The 7th nodes and the inferior mediastinal lymph nodes involvement were high-risk factors affecting the prognosis of patients (P<0.05). The 11s nodes metastasis had nothing to do with the location of the tumor, and it was not an independent factor affecting disease-free survival. Conclusion    The 11s nodes may be a transit for 2R+4R nodes metastasis in the right middle or lower lobe lung cancer, and the 11s nodes should be cleared in the surgical treatment for NSCLC in either the middle or lower lobe of the right lung. The influencing factors for disease-free survival after surgery for lung cancer in the right middle or lower lobe are the metastasis of the subcarinal lymph nodes and the inferior  mediastinal lymph nodes.

BACKGROUND: Pulmonary epithelial-myoepithelial carcinoma is a very rare type of salivary gland lung tumor. No standard treatment plan yet. This article intends to analyze the clinical characteristics of pulmonary epithelial-myoepithelial carcinoma and discuss the diagnosis and treatment of pulmonary epithelial-myoepithelial carcinoma. METHODS: The clinical data of a patient with pulmonary epithelial-myoepithelial carcinoma were analyzed and other relevant clinical literatures were reviewed. RESULTS: Epithelial cells immunohistochemically expressed cytokeratin and myoepithelial cells immunohistochemically expressed SMA and S-100. The next-generation sequencing was mainly HRAS gene mutation and the express of PD-L1 protein was negative. CONCLUSIONS Most of the patients with Pulmonary epithelial-myoepithelial carcinoma have a good prognosis. Diagnosis mainly depends on microscopic examination and immunohistochemistry. The treatment of pulmonary epithelial-myoepithelial carcinoma is mainly surgical resection. The effect of radiotherapy and chemotherapy is not clear.

Objective To investigate the protective effect of microRNA-181b (miR-181b) on aged rats with sepsis-induced hippocampus injury in vivo. Methods Seventy-five male healthy old Sprague-Dawley (SD) rats were randomly divided into five groups (n = 15) using a random number table: sham operation group (Sham group), sepsis group [cecal ligation and puncture (CLP) group], miR-181b Agomir+CLP group (Ag+CLP group), miR-181b Antagomir+CLP group (An+CLP group) and normal saline (NS) control group (NS+CLP group). Rats sepsis model was reproduced by CLP, and in Sham group, the cecum of rats was separated only after abdominal operation without ligation or perforation. The rats in Ag+CLP group were given miR-181b Agomir 10 μL via lateral ventricle at 24 hours before CLP, the rats in An+CLP group were given 10 μL miR-181b Antagomir, and those in NS+CLP group were given 10 μL NS. At 6, 12, 24 hours after CLP, 5 rats of each group were sacrificed randomly, and hippocampus were harvested. The expression of miR-181b in hippocampus was determined by real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR). The expression of nuclear factor-κB p65 (NF-κB p65) was determined by Western Blot. The contents of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA). Results Compared with Sham group, the expression of miR-181b in hippocampus of CLP group was significantly decreased at 6 hours after CLP (2-ΔΔCT: 0.70±0.12 vs. 0.98±0.06, P < 0.05), and the expressions of NF-κB p65, IL-1β and TNF-α were significantly increased [NF-κB p65/Histone H3:0.30±0.03 vs. 0.07±0.01, IL-1β (ng/L): 120.39±8.02 vs. 50.55±11.12, TNF-α (ng/L): 59.48±4.60 vs. 40.31±3.96, all P < 0.05], this trend was continued till 24 hours, and these results indicated that there was obvious inflammation in hippocampus of sepsis rats. There was no statistical difference in the expression of miR-181b, NF-κB p65, IL-1β or TNF-α in hippocampus between NS+CLP group and CLP group, which indicated that injection of NS into the rat lateral ventricle, had not aggravated the damage degree of hippocampus. Compared with CLP group, the expression of miR-181b in hippocampus of Ag+CLP group was significantly increased at 6 hours after CLP (2-ΔΔCT: 1.87±0.25 vs. 0.70±0.12, P < 0.05), and the expressions of NF-κB p65, IL-1β and TNF-α were significantly lowered [NF-κB p65/Histone H3:0.16±0.03 vs. 0.30±0.03, IL-1β (ng/L): 73.76±8.17 vs. 120.39±8.02, TNF-α (ng/L): 49.52±4.77 vs. 59.48±4.60, all P < 0.05]. There was no statistical difference in the expression of miR-181b in hippocampus between An+CLP group and CLP group (2-ΔΔCT: 0.80±0.08 vs. 0.70±0.12 at 6 hours, 0.48±0.03 vs. 0.46±0.05 at 12 hours, 0.61±0.09 vs. 0.63±0.07 at 24 hours, all P > 0.05), but the expressions of NF-κB p65, IL-1β and TNF-α in hippocampus at 6 hours after CLP of An+CLP group were significantly higher than those of CLP group [NF-κB p65/Histone H3: 0.44±0.02 vs. 0.30±0.03, IL-1β (ng/L): 134.21±5.78 vs. 120.39±8.02, TNF-α (ng/L): 67.62±5.86 vs. 59.48±4.60, all P < 0.05], this trend was continued till 24 hours after CLP. The above results showed that overexpression of miR-181b might attenuate the inflammation of hippocampus through down-regulation of NF-κB, IL-1β and TNF-α. Conclusions The expression of hippocampal miR-181b was significantly decreased in septic rats. Up-regulation of miR-181b could inhibit the activation of NF-κB signal pathway and the release of the inflammatory cytokine IL-1β and TNF-α stimulated by sepsis, and alleviate the inflammatory reaction and hippocampus injury in rat with sepsis.

Objective To explore the efficiency and safety of micafungin in preventing fungal infection in neutropenic stage in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods The clinical data of 116 patients with allo-HSCT were collected, among whom 23 patients had a history of pulmonary fungal infection before transplantation. All patients were treated with micafungin for 50 mg daily from the beginning of pretreatment to recovery of neutropenia.Results Six patients were clinically diagnosed as pulmonary fungal infections. No serious adverse reactions were observed during the clinical observation, and concentration of cyclosporin A was not adjusted. By the end of follow-up, 83 patients survived. Conclusion Micafungin is safe and effective in preventing fungal infection in neutropenic stage after allo-HSCT without affecting the concentration of cyclosporine A in blood.

Objective To explore the efficiency and safety of micafungin in preventing fungal infection in neutropenic stage in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods The clinical data of 116 patients with allo-HSCT were collected, among whom 23 patients had a history of pulmonary fungal infection before transplantation. All patients were treated with micafungin for 50 mg daily from the beginning of pretreatment to recovery of neutropenia.Results Six patients were clinically diagnosed as pulmonary fungal infections. No serious adverse reactions were observed during the clinical observation, and concentration of cyclosporin A was not adjusted. By the end of follow-up, 83 patients survived. Conclusion Micafungin is safe and effective in preventing fungal infection in neutropenic stage after allo-HSCT without affecting the concentration of cyclosporine A in blood.