Objective:To construct a microfluidic organ-on-a-chip and evaluate its capability in simulating subchondral bone remodeling during the progression of osteoarthritis.Methods:The chip′s main body was designed based on the microfluidic technology and cell co-culture technique. MC3T3-E1 cells were cultured adherently within the cell seeding micro-chamber, with the culture medium perfused at a flow rate of 0.5 ml/min at the bottom of the micro-chamber. Evaluation metrics were as follows: (1) Assessment of the microfluidic organ-on-a-chip: The growth culture medium was perfused and simulation experiments were conducted to test the concentration differences and equilibrium times of the fluid inside and at the bottom of the cell seeding micro-chamber at various time points; live-dead staining was performed to observe the biocompatibility of cells cultured continuously for 3 days and 7 days at a set flow rate, which was divided into 3-day and 7-day groups. (2) Osteogenic potential of the microfluidic organ-on-a-chip: The osteogenic induction medium was perfused, and ALP staining and PCR were performed to compare the number of the black alkaline phosphatase (ALP)-positive cells and the expression levels of osteogenesis-related marker genes including osteoblast-specific transcription factor 2 (RUNX2), type I collagen (COL1A1), bone morphogenetic protein-2 (BMP-2), and osteocalcin (OCN) under static, 3-day and 7-day perfusion conditions, which was divided into static non-induced, static-induced and perfusion-induced groups. (3) Characterization of morphology and size, and biocompatibility of extracellular vesicles (EVs) of three osteoblast subtypes: Three different subtypes of osteoblasts were obtained [endothelial-type osteoblasts (EnOB)-EVs, stromal-type osteoblasts (StOB)-EVs and mineralizing-type osteoblasts (MinOB)-EVs]. Their morphology and size were obtained through transmission electron microscopy and particle size analysis. Growth medium containing EVs of three different cell subtypes was perfused, and cell proliferation/apoptosis assay was performed to compare the biocompatibility of the addition of different EVs concentrations (1, 1.25, 2.5, and 5 μg/ml) for 24 hours, which was categorized into the EnOB-EVs group, StOB-EVs group and MinOB-EVs group. (4) Osteogenic effect of EVs from three subtypes of osteoblasts: Osteogenic induction media containing EVs from three different osteoblast subtypes were perfused for 3 days, and ALP staining and PCR were performed to compare the number of black ALP-positive cells and the expression levels of osteogenesis-related marker genes including RUNX2, COL1A1, BMP-2, and OCN, which was divided into non-EVs group, EnOB-EVs group, StOB-EVs group and MinOB-EVs group.Results:(1) Evaluation of the microfluidic organ-on-a-chip: Simulation results showed that the concentration in the top layer of the upper chamber reached more than 95% of that in the lower chamber and that the concentration in the bottom layer was about 96.5% of that in the lower chamber after 12 hours of continuous perfusion, reaching an equilibrium state of the concentration difference between the upper and lower chambers. The results of live-dead staining showed that the chip was biocompatible at a flow rate of 0.5 ml/min, and the cell survival rate at 3 and 7 days of perfusion was (99.48±0.12)% and (97.07±1.05)% ( P<0.01). (2) ALP staining results showed that at 3 days, the perfusion-induced group showed the highest number of black ALP-positive cells, followed by the static-induced group, and the least in the static non-induced group. At 7 days, the static-induced group had the highest number of black ALP-positive cells, followed by the perfusion-induced group, and the least in the static non-induced group. PCR results indicated that at 3 days, the expression levels of RUNX2, COL1A1, BMP-2, and OCN were 1.00±0.03, 1.00±0.12, 1.00±0.01, and 1.00±0.02 respectively in the static non-induced group; 1.80±0.04, 4.05±0.37, 9.80±1.94, and 4.38±0.89 respectively in the static-induced group, and 2.45±0.23, 5.48±0.42, 91.50±4.56, and 10.82±4.96 respectively in the perfusion-induced group ( P<0.01). At 7 days, the expression levels of RUNX2 was 1.00±0.01 in the static non-induced group, 1.46±0.46 in the static-induced group, and 1.11±0.08 in the perfusion-induced group ( P>0.05); the expression levels of COL1A1, BMP-2, and OCN were 1.00±0.03, 1.00±0.13, and 1.00±0.09 respectively in the static non-induced group, 9.38±0.25, 14.27±4.35, and 84.01±4.02 respectviely in the static-induced group, and 2.39±0.08, 133.64±8.87, and 86.64±8.36 respectively in the perfusion-induced group ( P<0.01). When comparing the static non-induced, static-induced, and perfusion-induced groups at both 3 and 7 days, the perfusion-induced group demonstrated the strongest osteogenic capability. (3) Characterization of morphology and size and biocompatibility of EVs from three osteoblast subtypes: Under the transmission electron microscope, EVs from EnOB-EVs, StOB-EVs, and MinOB-EVs all exhibited a typical saucer-shaped morphology. The particle sizes of EnOB-EVs, StOB-EVs, and MinOB-EVs were (91.3±14.7)nm, (106.0±16.0)nm, and (68.1±10.7)nm, respectively. Cell proliferation/apoptosis assay results indicated that the optimal administration concentration of EnOB-EVs, StOB-EVs, and MinOB-EVs was all 1.25 μg/mL. (4) Validation of osteogenic effect of the microfluidic organ-on-a-chip on three types of EVs: ALP staining results showed that the non-EVs group had the fewest black ALP-positive cells, followed by the EnOB-EVs group, then the StOB-EVs group, and the MinOB-EVs group had the most. PCR results showed that the expression levels of RUNX2, COL1A1, BMP-2, and OCN were 1.00±0.01, 1.00±0.03, 1.00±0.02, and 1.00±0.02 respectively in the non-EVs group, 1.95±0.11, 6.78±2.04, 7.99±0.57, and 6.93±3.83 repectively in the EnOB-EVs group, 0.79±0.12, 5.68±1.53, 12.59±3.15, and 25.59±0.95 respectively in the StOB-EVs group, and 0.68±0.10, 4.36±0.69, 18.75±3.21, and 34.74±3.98 repectively in the MinOB-EVs group ( P<0.01). Compared with the non-EVs group, EnOB-EVs group, StOB-EVs group, and MinOB-EVs group, the MinOB-EVs group showed the most significant osteogenic effect. Conclusions:The microfluidic organ-on-a-chip constructed using microfluidic technology and cell co-culture techniques is capable of maintaining the normal growth of MC3T3-E1 cells, enhancing their proliferation and osteogenic induction differentiation. EVs released by osteoblasts at different stages possess osteogenic effects and can accelerate the bone sclerosis in the remodeling of subchondral bone during the progression of osteoarthritis.

Objective To investigate the role of caspase-1-medicated canonical pyroptosis pathway in chlorogenic acid(CGA)treatment of acute kidney injury(AKI)in mice.Method Twenty-four C57Bl/6J mice were randomized into sham-operated group,cecal ligation and puncture(CLP)group,CLP+dexamethasone group(CLP+DXM group),and CLP+CGA group(n=6)and subjected to either sham operation(laparotomy only)or CLP.After modeling the mice received intravenous infusion of 10 mg/kg normal saline(in sham and CLP groups),1 μg/kg dexamethasone or 15 mg/kg of chlorogenic acid for 6 h delivered using an intravenous pump.Eight hours after the infusion,renal morphology and histology,renal cell apoptosis,and the renal function parameters such as urea nitrogen(BUN),creatinine(Scr),and kidney injury molecule 1(KIM-1)were compared among the 4 groups;the 7-day survival rates of the mice were recorded,and the expressions of NLRP3 inflammasomes and key proteins of the caspase-1 pathway in the renal tissue were detected.Results CGA treatment significantly improved the 7-day survival rate,reduced renal pathologies of the septic mice(P<0.05),and lowered the levels of BUN,Scr,KIM-1,NLRP3 inflammasome and expressions of key proteins of the caspase-1 pathway.Conclusion CGA alleviates AKI in mice with CLP-induced sepsis by inhibiting NLRP3 inflammasomes and the caspase-1 signaling pathway.

Objective To investigate the role of caspase-1-medicated canonical pyroptosis pathway in chlorogenic acid(CGA)treatment of acute kidney injury(AKI)in mice.Method Twenty-four C57Bl/6J mice were randomized into sham-operated group,cecal ligation and puncture(CLP)group,CLP+dexamethasone group(CLP+DXM group),and CLP+CGA group(n=6)and subjected to either sham operation(laparotomy only)or CLP.After modeling the mice received intravenous infusion of 10 mg/kg normal saline(in sham and CLP groups),1 μg/kg dexamethasone or 15 mg/kg of chlorogenic acid for 6 h delivered using an intravenous pump.Eight hours after the infusion,renal morphology and histology,renal cell apoptosis,and the renal function parameters such as urea nitrogen(BUN),creatinine(Scr),and kidney injury molecule 1(KIM-1)were compared among the 4 groups;the 7-day survival rates of the mice were recorded,and the expressions of NLRP3 inflammasomes and key proteins of the caspase-1 pathway in the renal tissue were detected.Results CGA treatment significantly improved the 7-day survival rate,reduced renal pathologies of the septic mice(P<0.05),and lowered the levels of BUN,Scr,KIM-1,NLRP3 inflammasome and expressions of key proteins of the caspase-1 pathway.Conclusion CGA alleviates AKI in mice with CLP-induced sepsis by inhibiting NLRP3 inflammasomes and the caspase-1 signaling pathway.

OBJECTIVE: To explore the predictive value of acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), quick sequential organ failure assessment (qSOFA) and modified early warning score (MEWS) in evaluating the prognosis of patients in intensive care unit (ICU) of secondary hospitals, and to provide guidance for clinical application. METHODS: The clinical data of adult critical patients admitted to the ICU of Wanzhou District First People's Hospital from October 2022 to April 2023 were retrospectively analyzed. According to the clinical outcome of ICU, the patients were divided into improvement group and death group. The general information, blood routine, heart, liver and kidney function indicators, coagulation indicators, blood gas analysis, APACHE II score, SOFA score, qSOFA score, MEWS score at the time of admission to the ICU, the number of cases of invasive mechanical ventilation (IMV) and continuous blood purification (CBP) were compared between the two groups. Univariate analysis was performed, and multivariate Logistic regression analysis was used to analyze the related factors of death. Receiver operator characteristic curve (ROC curve) was used to analyze the predictive value of the four scores in ICU patients. RESULTS: A total of 126 patients were included, of which 45 patients died in the ICU and 81 patients improved and transferred out. Univariate analysis of death-related critically ill patients showed that procalcitonin (PCT), serum creatinine (SCr), blood urea nitrogen (BUN), albumin (ALB), prothrombin time (PT), activated partial prothrombin time (APTT), D-dimer, pH value, HCO₃^-, blood lactic acid (Lac), number of patients treated with IMV and CBP, APACHE II score, SOFA score, qSOFA score and MEWS score were significantly different between the two groups (all P < 0.05). Multivariate Logistic regression analysis showed that the APACHE II score [odds ratio (OR) = 1.115, 95% confidence interval (95%CI) was 1.025-1.213, P = 0.011], SOFA score (OR = 1.204, 95%CI was 1.037-1.398, P = 0.015), MEWS score (OR = 1.464, 95%CI was 1.102-1.946, P = 0.009), and APTT (OR = 1.081, 95%CI was 1.015-1.152, P = 0.016) were independent risk factors affecting the mortality of critically ill patients in the ICU. ROC curve analysis showed that APACHE II, SOFA, qSOFA, and MEWS scores could predict the prognosis of critically ill ICU patients, among which SOFA score had the strongest predictive effect, and the area under the curve (AUC) was 0.808. There was a statistically significant difference in the time required for the four scores (F = 117.333, P < 0.001), among which the MEWS scoring required the shortest time [(1.03±0.39) minutes], and the APACHE II scoring required the longest time [(2.81±1.04) minutes]. CONCLUSIONS APACHE II, SOFA, qSOFA, and MEWS scores can be used to assess the severity of critically ill patients and predict in-hospital mortality. The SOFA score is superior to other scores in predicting severity. The MEWS is preferred because its assessment time is shortest. Early warning score can help secondary hospitals to detect potentially critical patients early and provide help for clinical rapid urgent emergency decision-making.
Adult ; Humans ; Sepsis/diagnosis* ; ROC Curve ; Retrospective Studies ; Critical Illness ; Early Warning Score ; Organ Dysfunction Scores ; Intensive Care Units ; Prognosis ; Hospitals

Objective:To explore the influence of chronic rhinitis on depressive symptoms of college freshmen and the mediating effect of avoidant personality.Methods:A cluster sampling method was used to survey 8 079 college freshmen from April 2018 to October 2018 using the Beck depression inventory and the avoidant personality diagnosis questionnaire based on DSM-Ⅳ.SPSS 25.0 software was used for descriptive statistics and Spearman correlation analysis, and the macro program PROCESS version 3.3 was used for the mediating effect.Results:(1) The detection rates of chronic rhinitis, avoidant personality and depressive symptoms were 22.90% (1 850/8 079), 19.22% (1 553/8 079) and 6.28% (507/8 079). The scores for avoidant personality disorder and depressive symptoms were 1.00 (0, 3.00) and 1.00 (0, 4.00), respectively. (2) The chronic rhinitis, avoidant personality and depressive symptoms were positively correlated ( rchronic rhinitis-avoidant personality=0.094, rchronic rhinitis-depressive symptoms=0.095, ravoidant personality-depressive symptoms=0.416, all P<0.001). (3) Chronic rhinitis could positively predict depressive symptoms ( β=1.113, P<0.001). (4) Avoidant personality played a mediating role between chronic rhinitis and depressive symptoms ( β=1.094, P<0.001), and accounted for 44.92%(0.500/1.113) of the total effect. Conclusion:Chronic rhinitis directly affect the depressive symptoms of college freshmen, and indirectly affect the depressive symptoms of college freshmen through the mediating role of avoidant personality.

Objective:To compare the effects of left bundle branch pacing(LBBP)and right ventricular pacing(RVP)on pacing threshold value,pacing perception,pacing impedance,QRS wave complex duration,interventricular mechanical delay(IVMD)time,left ventricular end diastolic diameter(LVEDD)and left ventricular ejection fraction(LVEF).Methods:The Chinese databases included China Biology Medicine Disc(CBMdisc),China National Knowledge Infrastructure(CNKI),Wanfang Database,China Science and Technology Journal Database,and foreign databases included PubMed,Cochrane library and Embase were adopted to retrieve research literatures about LBBP.The retrieval duration was from January 2018 to November 2021.The literatures were screened according to the inclusion and exclusion criteria of literatures,and the qualities of the literatures that met the inclusion criteria were respectively evaluated.The extracted relevant data of LBBP and RVP,which included pacing threshold value,pacing perception,pacing impedance,QRS wave complex duration,IVMD time,LVEDD and LVEF,were adopted to conduct Meta-analysis by using Revman5.4.Results:A total of 14 relevant literatures were included according to the inclusion and exclusion criteria of research literatures,which included 9 Chinese literatures and 5 English literatures.The duration of publication times of these literature was from 2018 to 2021.In these literatures,640 patients involved to LBBP and 551 patients involved to RVP.There were no significant differences between LBBP and RVP in the effects on pacing threshold value,pacing perception and pacing impedance[95%CI(-0.05-0.02),(-0.28-0.42),(-22.34-16.19),P>0.05],respectively.There were significant differences between LBBP and RVP in the effects on QRS wave complex duration,IVMD and LVEF[95%CI(-45.92--42.09),(-16.49--10.86),(3.01-5.13),P<0.05],respectively.There were two different results in the effects of LBBP and RVP on LVEDD.The five literatures among of them conducted effect size merging for the extracted LVEDD values.There was significant difference between two kinds of pacing methods in the effect on LVEDD[95%CI(-2.21--0.54),P<0.05].There was significant difference between two kinds of pacing methods in the effect on LVEDD after the literature(ShigengZhang2020)was excluded.Conclusion:The Meta-analysis about the application of LBBP in patients with bradyarrhythmia has demonstrated the effectiveness of LBBP.Compared with RVP,LBBP is more close to physiological pacing,and LBBP pacing parameters(threshold value,perception and impedance)are stable.

Radiation-induced brain injury (RBI) is one of the complications after radiotherapy for head and neck malignant tumors, which seriously affects the quality of life of patients. The pathophysiological mechanism of RBI is not completely clear. Current studies suggest that it is involved in a variety of cells in the central nervous system (CNS), whereas astrocyte, as the largest number of glial cells in the CNS, plays an important role in maintaining the CNS homeostasis and responding to CNS injury. In this article, the role of astrocytes in RBI was reviewed.

Objective:To observe and preliminary investigate the influencing factors of exudative retinal detachment in patients with severe preeclampsia (S-PE) and its influence on pregnancy outcome.Methods:A total of 89 patients of S-PE patients diagnosed in Department of Obstetrics in The Third Central Hospital of Tianjin from July 2018 to June 2020 were included in this study. According to whether the patients were complicated with exudative retinal detachment, they were divided into retinal detachment group (43 cases) and non retinal detachment group (46 cases). All patients underwent direct ophthalmoscopy, and those with suspected or definite retinal detachment underwent optical coherence tomography or B-mode ultrasonography. The age, course of disease, body mass index, systolic blood pressure, diastolic blood pressure, laboratory serum albumin level, 24 h urinary protein, platelet count, mean platelet volume, platelet distribution width and serum uric acid content were collected. The average age ( t=-1.01), body mass index ( t=-1.799), course of disease ( t=-1.657) and constituent ratio of primipara and multipara in the two groups were compared ( χ2=1.411), the difference was not statistically significant ( P>0.05). The end of pregnancy time, systemic complications, fetal outcomes and neonatal Apgar scores were analyzed, retrospectively. Independent sample t test was used to compare the quantitative data between the two groups; Chi square test was used to compare qualitative data. Binary logistic regression analysis to screen the influencing factors of exudative retinal detachment in S-PE. Results:Systolic blood pressure and diastolic blood pressure were higher in the retinal detachment group than in the non retinal detachment group, and the difference was statistically significant ( t=2.087, 2.810; P=0.040, 0.006). Serum albumin ( t=-10.404), 24-hour urinary protein quantification ( t=6.401), blood uric acid ( t=3.910), platelet count ( t=-6.124) and platelet distribution width ( t=2.992) were compared between the two groups, and the differences were statistically significant ( P<0.05). There were 30 (69.77%, 30/43) cases in retinal detachment group and 14 (30.43%, 14/46) cases in non retinal detachment group with severe systemic complications; The average time of ending pregnancy was 34.66±3.29 and 38.25±1.62 weeks; The average Apgar scores at birth were 7.28±3.40 and 9.46±1.59. The incidence of severe systemic complications in two groups ( χ2=13.755), the end of pregnancy time ( t=-6.448), Apgar score at birth ( t=-3.824), the differences were statistically significant ( P=0.000、0.000、0.000). Fetal distress and death were 8 (18.60%, 8/43), 7 (16.28%, 7/43) and 7 (15.22%, 7/46), 1 (2.17%, 1/46) in retinal detachment group and non retinal detachment group respectively. There was no significant difference in the incidence of fetal distress between the two groups ( χ2=0.182, P=0.670). The difference of fetal mortality was statistically significant ( P= 0.027). Logistic regression analysis showed that serum albumin and uric acid were associated with exudative retinal detachment in patients with S-PE ( P<0.05). Conclusions:Serum albumin and uric acid are the influencing factors of exudative retinal detachment in patients with S-PE. Patients with exudative retinal detachment are prone to adverse pregnancy outcomes.

Objective To investigate the correlation between smoking, white blood cell counts, and serum bilirubin levels in male radiation workers, and to explore the role of systemic inflammatory response in the changes of serum bilirubin level induced by smoking. Methods Occupational health examination data of 1 320 male radiation workers in a medical institution was collected. Linear regression analysis method was used to analyze the correlations between smoking and white blood cell counts, between smoking and serum bilirubin levels, and between white blood cell counts and serum bilirubin levels. Results There was a significant positive correlation between smoking and white blood cell counts (P< 0.05). Both smoking and white blood cell counts were significantly negatively correlated with serum bilirubin levels (P < 0.05). However, after adjusting the white blood cell counts, the correlation between smoking and serum bilirubin levels was not statistically significant (P > 0.05). By dividing white blood cell counts into two groups, an inverse correlation was found between smoking and serum bilirubin levels in the high white blood cell count group (P < 0.05). Conclusion Serum bilirubin may be an effective indicator of early health damage caused by smoking in male radiation workers. Smoking may induce inflammatory reaction, thus deplete serum bilirubin and cause its levels to drop.

Background/Aims: Incorporation of complementary and provocative test swallows to the high-resolution manometry (HRM) protocol offers potential to address limitations posed by HRM protocols that involve only a single swallow type. The aim of this study is to describe normal findings of a comprehensive HRM testing protocol performed on healthy asymptomatic volunteers. Methods: Thirty healthy asymptomatic volunteers completed HRM with 5-mL liquid swallows in the supine position. They also completed 5-mL liquid swallows in the upright position, viscous swallows, solid test swallows, multiple rapid swallows, and a rapid drink challenge.HRM studies were analyzed via Chicago classification version 3.0. Results: The median (5th-95th percentiles) for integrated relaxation pressure (IRP) on supine swallows was 11 (4-16) mmHg; IRP was lower than supine on upright liquid 9 (0-17) mmHg, viscous 6 (0-15) mmHg, solid 9 (1-19) mmHg, multiple rapid swallows 3 (0-12) mmHg, and rapid drink challenge 5 (–3-12) mmHg; P < 0.005. While an “elevated” IRP value was observed on 1 to 2 test maneuvers in 8/30 (27%) subjects, all 30 subjects had an IRP value < 12 mmHg on at least one of the test maneuvers. Conclusions Normal values and findings from a comprehensive HRM testing protocol are reported based on evaluation of 30 healthy asymptomatic volunteers. Isolated “abnormalities” of IRP and contractile parameters were observed in the majority (80%) of these asymptomatic subjects, while all subjects also had normal features observed. Thus, the definition of “normal” should be recalibrated to focus on the entirety of the study and not individual metrics.