[Techniques for quantifying endotypes of obstructive sleep apnea].

Obstructive sleep apnea (OSA) is the frequent occurrence of apnea and/or hypopnea during sleep, leading to intermittent hypoxia, hypercapnia, and disruption of sleep architecture, further resulting in multisystem damage. The pathophysiological mechanisms include abnormal anatomical structure, low arousal threshold, high loop gain, and poor muscle reactivity, etc. As there are individual differences in the underlying mechanisms of OSA (i.e. endotypes), the effectiveness of treatment and prognosis may also vary according to these characteristics. Understanding the endotype of OSA is critical to understanding which patients are most likely to benefit from non-invasive ventilation therapy. Quantification of endotypes is central to the precision treatment of OSA and may provide the basis for accurate clinical treatment of OSA based on endotypes.

[Prediction models for respiratory event types in OSA patients based on hypoxic parameters].

Objective: To analyze the hypoxic parameters in patients with obstructive sleep apnea (OSA), to explore the difference and association between different types of respiratory events and to construct predictive models for respiratory event types. Methods: Fifty patients [including 41 males and 9 females with age 18-74(45.72±13.39) years ] with OSA diagnosed by polysomnography (PSG) were selected for retrospective analysis, and all respiratory events with pulse oximetry (SpO2) desaturation in the recorded overnight data were divided into hypopnea group (Hyp, 3 316), obstructive apnea group (OA, 5 552), central apnea group (CA, 1 088) and mixed apnea group (MA, 1 369) according to the type of events, and all event records were exported separately from the PSG software as comma-separated variable (.csv) files, which were imported and analyzed using the in-house built Matlab software. A total of 13 hypoxic parameter differences were compared among the four groups, including minimum oxygen saturation of events (e-minSpO2), the depth of desaturation (ΔSpO2), the duration of desaturation and resaturation (DSpO2), the duration of desaturation (d.DSpO2), duration of resaturation (r.DSpO2), duration of SpO2<90% (T90), duration of SpO2<90% during desaturation (d.T90), duration of SpO2<90% during resaturation (r.T90), area under the curve of SpO2<90% (ST90), area under the curve of SpO2<90% during desaturation (d.ST90), area under the curve of SpO2<90% during resaturation (r.ST90), oxygen desaturation rate (ODR) and oxygen resaturation rate (ORR). Hyp model (H), OA model (O), CA model (C) and MA model (M) were constructed respectively; group differences for the different hypoxia parameters were assessed using single factor analysis and Kruskal-Wallis H test. For different categories of respiratory events, binary logistic regression was used to identify the variables included in the regression model. Receiver operating characteristic (ROC) curves were generated to assess and compare the sensitivity, specificity, positive predictive value and negative predictive value of the four models, thereby gauging the predictive precision of each model. Results: ΔSpO2, ODR, ORR, T90, d.T90, r.T90, ST90, d.ST90 and r.ST90 for each type of respiratory events showed MA>OA>CA>Hyp, and e-minSpO2 showed MA

[Relationship between respiratory event-related arousal and increased pulse rate in patients with obstructive sleep apnea].

Objective: To investigate the relationship between respiratory event-related arousal and increased pulse rate in patients with obstructive sleep apnea (OSA), and to evaluate whether elevated pulse rate can be used as a surrogate marker of arousal. Methods: A total of 80 patients [40 males and 40 females, age range (18-63 years), mean age (37±13) years] who attended the Sleep Center of the Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital for polysomnography (PSG) from January 2021 to August 2022 were enrolled. Stable PSG recordings of non-rapid eye movement (NREM) sleep to compare the mean pulse rate (PR), the lowest PR 10 seconds before the onset of arousal, and the highest PR within 10 seconds after the end of arousal associated with each respiratory event. At the same time, the correlation between the arousal index and the pulse rate increase index (PRRI), as well as ΔPR1 (highest PR-lowest PR) and ΔPR2 (highest PR-mean PR), respectively, with the duration of respiratory events, the duration of arousal, the magnitude of pulse oximetry (SpO2) decline, and the lowest SpO2 was analyzed. Among the 53 patients, 10 events without arousal and 10 events with arousal (matched for the magnitude of SpO2 decline) were selected for NREM in each of the 53 patients, and ΔPR before and after termination of respiratory events in the two groups was compared. In addition, 50 patients were simultaneously subjected to portable sleep monitoring (PM) and divided into non-severe OSA group (n=22) and severe OSA group (n=28), and ΔPR≥3 times,≥6 times,≥9 times, and≥12 times after respiratory events were used as surrogate markers of arousal, and ΔPR was scored manually and integrated into the respiratory event index (REI) of PM. Then, we compared the agreement between REI calculated from the four PR cut-off points and the apnea-hypopnea index (AHIPSG) calculated by the gold standard PSG. Results: ΔPR1 [(13±7)times/min] and ΔPR2 [(11±6)times/min] were significantly higher in patients with severe OSA than in patients with non-OSA,mild and moderate OSA. The arousal index was positively correlated with the four PRRIs (r 0.968, 0.886, 0.773, 0.687, P<0.001, respectively), and the highest PR [(77±12) times/min] within 10 s after the end of arousal was significantly higher than the lowest PR [(65±10) times/min, t=113.24, P<0.001] and the mean PR [(67±11) times/min, t=103.02, P<0.001]. ΔPR1 and ΔPR2 were moderately correlated with the decrease in SpO2 (r=0.490, 0.469, P<0.001). After matching the magnitude of SpO2 decline, the ΔPR[(9±6)/min] before and after the termination of respiratory events with arousal was significantly higher than that of respiratory events without arousal [(6±5)/min, t=7.72, P<0.001]. The differences between REI+PRRI3 and REI+PRRI6 and AHIPSG in the non-severe OSA group were not statistically significant (P values 0.055 and 0.442, respectively), and REI+PRRI6 and AHIPSG showed good agreement (the mean difference was 0.7 times/h, 95%CI 8.3-7.0 times/h). The four indicators of PM in the severe OSA group were statistically different from AHIPSG (all P<0.05), and the agreement was poor. Conclusions: Respiratory event-related arousal in OSA patients is independently associated with increased PR, and frequent arousal may lead to increased frequency of PR fluctuations, and elevated PR may be used as a surrogate marker of arousal, especially in patients with non-severe OSA, where elevated PR≥6 times significantly improves the diagnostic agreement between PM and PSG.

[Research progress of acetaldehyde dehydrogenase 2 in liver diseases].

Acetaldehyde dehydrogenase 2 (ALDH2) is an important kind of aldehyde dehydrogenase in mitochondria, which has the function of eliminating acetaldehyde and other toxic aldehydes substances. Furthermore, it is abundant in liver and is closely related to the occurrence and development of a variety of liver diseases. ALDH2 genetic polymorphisms plays an important role in the occurrence of a variety of liver diseases in the human population.This paper mainly reviews the research progress of ALDH2 in liver diseases in recent years, with a view to provide theoretical basis for clinical prevention and treatment.

[Value of night pulse oximetry monitoring in obstructive sleep apnea hypopnea syndrome prediction and classification].

Objective: To explore the value of night pulse oximetry monitoring in the prediction and classification of obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: From January 2018 to December 2019, 580 snoring patients admitted to the Sleep Center of Tianjin Medical University General Hospital were analyzed retrospectively. There were 418 males and 162 females, aging 13-85(49±14) years. All subjects underwent polysomnography, and the apnea hypopnea index (AHI)was 0-101.4(43.06±27.47) times/hour. There were 52 cases in the non-OSAHS group (AHI<5 times/h), 69 cases in the mild OSAHS group (5 times/h30 times/h) was 94.74%±0.76%. Conclusion: Based on the signals recorded by the SpO2 monitor, the methods of using MLR model for AHI prediction and using BPNN model for multi-classification may have higher value for the prediction and classification of OSAHS.

Multiple b-value diffusion-weighted imaging in differentiating benign from malignant breast lesions: comparison of conventional mono-, bi- and stretched exponential models.

AIM: To prospectively evaluate multiple b-value diffusion-weighted imaging (DWI) in differentiating malignant from benign breast lesions. MATERIALS AND METHODS: The study cohort included 103 patients who underwent 3 T magnetic resonance imaging (MRI). The conventional sequences included T1-weighted dynamic contrast-enhanced, T1-weighted and T2-weighted fat-suppressed sequences, single b-value (b=0, 1000 s/mm2) DWI, and multiple b-values (12 values, from 0 to 3,000 s/mm2) DWI. Pathological diagnosis of breast lesions was based on the latest World Health Organization (WHO) guide on the pathology and immunohistochemistry of the breast. SPSS Statistics V19.0 was used for the statistics analysis. RESULTS: The following parameters were calculated: apparent diffusion coefficient (ADC), tissue diffusivity (D), perfusion fraction (f), pseudo-diffusion coefficient (D∗), distributed diffusion coefficient (DDC), and alpha (α) by the same radiologist twice (interval time of 3 months). There was good inter/intra-observer agreement for each of the parameters. The D, D∗, f, DDC, and α values were significantly different among malignant tumours, benign lesions, and normal breast tissue (p<0.05). CONCLUSION: D, f, DDC, α, and ADC values have good sensitivity and specificity, respectively. In addition, the combined use of D and f or DDC and α has good diagnostic performance. Thus, the applications of the new multi-b DWI variables or combined variables are promising.

[Clinical characteristics in patients with hypervirulent Klebsiella pneumoniae infection and its capsular serotypes and multilocus sequence typing].

Objective: To describe the clinical characteristics of hypervirulent Klebsiella pneumoniae (hvKP) infection. To analyze the antibiotic susceptibility of hvKP to provide the empiric antibiotic options. To investigate capsule serotype and sequence type (ST) of hvKP and their correlation with clinical profiles. Methods: hvKP was defined as bacteria isolated from patients with community-acquired pyogenic liver abscess (CA-PLA) with co-infection sites outside liver or a bloodstream infection in a host without underlying biliary tract diseases. Patients with CA-PLA hospitalized in the First Hospital of China Medical University were retrospectively analyzed from January 2011 to December 2017. Antibiotic susceptibility was detected by automatic bacterial identification and antibiotic susceptibility analysis system in vitro. Polymerase chain reaction method and gene sequencing were used to detect the main capsule serotype and ST. Results: A total of 140 cases with hvKP infection were enrolled. The co-infections outside liver abscess included 98 bloodstream infections, 53 pneumonia, 11 perianal abscess, 10 urinary system infections, 3 subphrenic abscess, 3 endophthalmitis, 2 spleen abscess, and other miscellaneous infections including 1 peritonitis, 1 skin and soft tissue infection, 1 myelitis, 1 colitis, 1 psoas major abscess and 1 myocardial abscess. Among the 140 cases, 106 presented with single co-infection site, 32 with 2 sites, and 2 with 3 sites. HvKP manifested high antibiotic susceptibility up to 80% for most commonly used antibiotics. Capsule serotyping of 43 revived isolates indicated that K1 serotype accounted for 53.49% (23/43), K2 34.88 (15/43), K54 2.33% (1/43), K57 2.33% (1/43), and other serotypes 6.98%(3/43). There was no significant distribution among K1, K2, K54 and K57 of hvKP capsule serotypes in patients with or without diabetes mellitus (P>0.05). Multilocus sequence typing (MLST) suggested that ST23 and ST65 were predominant accounting for 39.53% (17/43) and 25.58% (11/43) respectively. No serotype or ST predominance was seen in any of the clinical infections. Conclusion: HvKP is related to a wide spectrum of infectious diseases, including multiple extrahepatic sites and bloodstream infections besides CA-PLA with high antibiotic susceptibility. K1 and K2 are the predominant capsule serotypes, and ST 23 and ST65 are the predominant sequence types.

[Autologous peripheral blood stem cell transplantation for POEMS syndrome].

Six patients with POEMS syndrome who received autologous peripheral blood stem cell transplantation (auto-PBSCT) were retrospectively analyzed. Conditioning regimen was high dose melphalan. Peripheral blood stem cells were collected after mobilization with cyclophosphamide (CTX) and growth factors. One patient presenting hydrothorax and ascites was treated with 3 cycles of lenalidomide and dexamethasone before mobilization. Auto-PBSCT was fairly tolerable. Hematopoietic reconstitution was successful in all patients without transplantation-related mortality. A decrease or normalization of serum vascular epithelial growth factor (VEGF) was observed in all patients at 3 months after transplantation. The neurological remission was seen in 5/6 patients.

[Effects of intermittent hypoxia exposure on renal tubular epithelial cell injury and autophagy in rats].

Objective: To investigate the effects of intermittent hypoxia (IH) exposure on renal tubular epithelial cell injury and autophagy in rats. Methods: A total of 12 Sprague Dawley (SD) rats were randomly divided into two groups: normal control (NC) group and IH group, with 6 rats in each group. An IH animal model was established to observe the effects of IH on renal tubular epithelial cell damage and autophagy in rats. Microalbumin (mAlb) was detected by immunoturbidimetry. Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1(KIM-1)in urine were assessed by enzyme-linked immunosorbent assay (ELISA) test. The pathological damage of renal tubules was observed by hematoxylin-eosin (HE) staining. The expression of autophagy marker protein light chain 3 (LC3) and Beclin-1 were detected by immunohistochemistry and immunoblotting. Results: At the end of the test, the levels of mAlb [(34.7±6.7) mg/L vs (11.1±3.3) mg/L, P=0.011], NGAL [(17.3±3.9) ng/ml vs(4.0±1.7)ng/ml, P=0.011] and KIM-1 [ (10.8±2.7) ng/ml vs (2.6±1.0) ng/ml, P=0.016] in urine of IH group were higher than those of control group, and the differences were statistically significant (all P<0.05). Pathological injury was showed by HE staining in IH group. The increase of autophagy in IH group was more obvious than that in NC group. Besides, the expression level of autophagy markers (protein LC3 and Beclin-1) was significantly higher in IH group than that in NC group (P<0.05). Conclusions: IH can not only cause renal tubular injury, but also induce increased autophagy in renal tubular epithelial cells. Autophagy activation might participate in renal tubular epithelial cell injury induced by IH.

[Efficiency of DA-EPOCH and MA chemotherapy in the mobilization of autologous peripheral blood stem cells in non-Hodgkin's lymphoma].

Objective: To study the effect and safety of the DA-EPOCH chemotherapy combined with G-CSF and the MA chemotherapy combined with G-CSF on mobilizing and collecting the peripheral blood stem cells and the later hematopoietic recovery. Methods: A total of 40 patients accepted mobilization and collection of peripheral blood stem cells(PBSC) after being treated by DA-EPOCH+ G-CSF and MA+ G-CSF therapy respectively, and performed auto-transfusion. The effect of mobilization, the adverse effects and the hematopoietic recovery after autologous transplantation were analyzed retrospectively. Results: Two cases in DA-EPOCH group and 1 case in MA group did not achieve the collection goal and required a G-CSF mobilization therapy again. During the DA-EPOCH mobilization therapy, the lowest median WBC was[0.7(0.5, 0.9)]×10(9)/L and the median lowest platelet (PLT) count was[75.0 (53.0, 107.0)]×10(9)/L.Low-grade fever occurred in 7 cases (37.5-38.3 ℃) and platelet transfusion was required in 2 cases. The collection of MNC number was (5.8±1.8)×10(8)/kg, and the median CD34(+) cell number was[3.7(2.8, 6.7)]×10(6)/kg; for the MA therapy groups, the numbers were[0.4 (0.2, 0.9)]×10(9)/L and[12.0 (6.0, 16.0)]×10(9)/L, respectively. High fever occurred in 8 cases (above 39 ℃). PLT transfusion was required in 15 cases and red blood cell(RBC) transfusion in 4 cases. The collected number of MNC was (6.0±2.9)×10(8)/kg, and CD34(+) median cell number was[8.5(2.6, 11.2)]×10(6)/kg. There are significant differences between the lowest PLT counts and CD34(+) cell numbers in the two groups of patients(P<0.05). A peripheral blood leukocyte increase in 10(9, 11) days and platelet implantation in 12(11, 16) days were observed after ASCT by DA-EPOCH therapy. In MA group, the number were 10(9, 11) and 12(11, 15) days. The hematopoietic recovery in both groups were successful, without any statistically difference(P>0.05). No death occurred during the process of transplantation. Conclusions: DA-EPOCH and MA chemotherapy could effectively mobilize the peripheral blood stem cells in suitable NHL patients.DA-EPOCH chemotherapy was higher in safety and lower in price, and required less transfusion compared with MA therapy.

[Distribution of electroencephalograph power density in patients with severe obstructive sleep apnea during different sleep stages].

Objective: To investigate the variation of electroencephalograph(EEG) power density during different sleep stages in OSA for understanding of the mechanisms underlying the brain dysfunction in OSA as well as its earlier diagnosis and treatment. Methods: Sixteen-channel EEGs from OSA patients and normal controls in stage wake, sleep stage 1, sleep stage 2, sleep stage 3 and rapid eye movement stage were analyzed by time-frequency analysis method. The EEG power density in different frequency bands (including δ, θ, α, σ, ß and γ) was respectively compared between the 2 groups. The correlation between the variation in the EEG power and primary indices of polysomnography was further analyzed. Results: The EEG power density in δ band in stage wake [OSA: (0.82±0.13) µV(2)/Hz, Control: (0.66±0.02) µV(2)/Hz, t=4.309, P<0.05], stage 1 [OSA: (1.28±0.07) µV(2)/Hz, Control: (0.92±0.04) µV(2)/Hz, t=-3.369, P<0.05] and stage 3 [OSA: (2.74±0.22) µV(2)/Hz, Control: (2.04±0.07) µV(2)/Hz, t=-2.669, P<0.05] was significantly higher in OSA, compared with that in the control. Statistical analysis showed that the EEG power density was significantly higher in frontal and central regions in stage wake [frontal: OSA: (0.90±0.02) µV(2)/Hz, Control: (0.66±0.02) µV(2)/Hz, t=8.539, P<0.01; central: OSA: (1.15±0.06) µV(2)/Hz, Control: (0.72±0.02) µV(2)/Hz, t=6.669, P<0.01] and stage 1 [frontal: OSA: (1.23±0.03) µV(2)/Hz, Control: (0.99±0.03) µV(2)/Hz, t=5.983, P<0.01; central: OSA: (1.52±0.05) µV(2)/Hz, Control: (1.14±0.04) µV(2)/Hz, t=5.714, P<0.01], as well as central region in stage 3 [OSA: (3.24±0.17) µV(2)/Hz, Control: (2.71±0.08) µV(2)/Hz, t=2.707, P<0.05]. The correlation analysis showed that the power density in central region in stage 1 and stage 3 was positively correlated with arousal index (r=0.877 in stage 1, 0.656 in stage 3), implying that sleep fragmentation was closely related to the variation of EEG power density during nocturnal sleep in OSA. Conclusions: The feature stages for OSA are stage wake, stage 1 and stage 3. The EEG power density in OSA (δ band) was significantly higher than that in the control. The EEG power density in OSA and the control shows differences in frontal and central regions in stage wake and stage 1, as well as in central region in stage 3. The results indicate that low-frequency EEG power density giving priority to frontal area and central area has improved in severe OSA, which may be related to the neurologic deficits in corresponding brain areas.

[Interleukin-17 expression and clinical significance in the lung tissue of patients with stable chronic obstructive pulmonary disease].

OBJECTIVE: To observe the interleukin-17 (IL-17) expression in lung tussiue of patients with stable chronic obstructive pulmonary disease (COPD) and investigate the clinical significance. METHODS: A total of 50 patients receiving lung resections in General Hospital, Tianjin Medical University for lung cancer from October 2010 to October 2011 were included and divided into non-smoking COPD group (NS group), smoking non-COPD group (S group), smoking COPD group (COPD group) according to smoking status and 2013 COPD diagnosis standard. The expression of IL-17 was detected by immumohistochemical staining. The volume of IL-17 in the airway and lung parenchyma was calculated by immumohistochemical staining scores which was product of dyeing cells positive rate and intensity. Pearson correlation analysis was used to analyze the relationships between expression of IL-17 in the airway and lung parenchyma and forced expiratory volume in 1 second/predicted value (FEV1%pred), carbon monoxide diffusion amount accounting for the percentage of the expected value (DLCO%pred), COPD assessment test (CAT) score, body mass index (BMI). RESULTS: The expressions of IL-17 in airway and lung parenchyma in S group (5.6±3.1, 6.4±2.5) were higher than those in NS group (1.6±1.4, 1.4±1.2) (both P<0.05), while expressions in COPD group (7.3±2.5, 7.8±2.1) were further higher than S group (both P<0.05). In the S group and COPD group, the expressions of IL-17 in the airway and lung parenchyma were positively correlated with smoking (r=0.453, P=0.007 and r=0.573, P<0.001); In the COPD group, the expressions of IL-17 in the airway and lung parenchyma were negatively correlated with FEV1%pred (r=-0.729, P=0.001 and r=-0.489, P=0.039), negatively related with DLCO%pred (r=-0.493, P=0.038 and r=-0.520, P=0.027), positively correlated with COPD CAT score (r=0.730, P=0.001 and r=0.644, P=0.004) and negatively related with BMI (r=-0.653, P=0.003 and r=-0.485, P=0.041). CONCLUSION: Smoking increases inflammation of lung tissue, increases IL-17 expression in airway and lung parenchyma; the expression of IL-17 is closely related to the severity of disease, the quality of life and prognosis in COPD patients.

[Current status of warfarin therapy in Chinese patients with nonvalvular atrial fibrillation: a single center analysis].

Objective: To investigate the current status of warfarin therapy and the related factors in patients with nonvalvular atrial fibrillation(NVAF) based on data from a single center. Methods: We analyzed clinical data including baseline clinical characteristics, complications, concomitant medications and anti-thrombotic treatment in patients who were admitted to our hospital with NVAF from January 2014 to June 2014. The data were analyzed by t test, Chi-square test, fisher exact test and binary logistic regression analysis for the above indexes with warfarin utilization. Results: A total of 600 patients enrolled in this study, 560(93.3%) patients had a CHA2DS2-VASc score≥1, 162(28.9%) patients received warfarin (alone or in combination with antiplatelet agents), 244(43.6%) patients were treated with aspirin, 137(24.5%) patients did not receive anti-thrombotic treatment. Of the 600 patients, 172(28.7%) patients were treated in line with the current guideline recommendation, 266(44.3%) patients were treated improperly, 23(3.8%) patients were over-treated, 139(23.2%) patients received no anti-thrombotic treatment. Factors associated with anti-thrombotic treatment were persistent atrial fibrillation (OR=3.92, 95%CI 1.43-10.78, P=0.008), radiofrequency ablation (OR=26.82, 95%CI 7.03-102.38, P<0.001), the use of statins (OR=3.35, 95%CI 1.30-8.63, P=0.012), anti-arrhythmic therapy (OR=3.42, 95%CI 1.29-9.07, P=0.014), and aspirin (OR=0.02, 95%CI 0-0.07, P<0.001). Conclusions: In this study, 428 (71.3%) NVAF patients were either un-treated, over-treated or inadequately treated. Intensive efforts are necessary to improve anti-thrombotic therapy status in NVAF population in China.

A Study of Patients with "Interface Respiratory Failure" Due to Chronic Obstructive Pulmonary Diseases.

OBJECTIVE: To explain a definition of "interface respiratory failure" as arterial blood gas assay with arterial oxygen partial pressure in the range of 60-75 mmHg. SUBJECTS AND METHODS: We compared arterial blood gases (ABGs), resting respiratory drive and its derivatives, mechanics of respiratory muscles, resistance and compliance of the respiratory tract and some important cytokines (interleukin-4 and interferon-γ) of stable chronic obstructive pulmonary disease (COPD) subgroups (total 50 cases) and control group (25 cases). RESULTS: The patients attaining the "interface respiratory failure" stage developed great changes in respiratory mechanics parameters and inflammatory mediator, which might cause the exacerbation of COPD and the inclination to generate "real respiratory failure" and COPD progression. CONCLUSIONS: The definition of interface respiratory failure is scientific, direct and its width is appropriate. We should intervene appropriately and positively to avoid progression from "interface respiratory failure" to the "real respiratory failure" stage, and this avoidance means a higher survival rate and a lower medical expense. Interventions should focus on oxygen therapy, bronchodilators, improving respiratory compliance, cytokines and anti-infective agents, respectively.

Inflammation Triggers Chondrocyte Ferroptosis in TMJOA via HIF-1α/TFRC.

Inflammation and loss of articular cartilage are considered the major cause of temporomandibular joint osteoarthritis (TMJOA), a painful condition of the temporomandibular joint (TMJ). To determine the cause of TMJ osteoarthritis in these patients, synovial fluid of TMJOA patients was compared prior to and after hyaluronic lavage, revealing substantially elevated levels of interleukin (IL) 1ß, reactive oxidative stress (ROS), and an overload of Fe3+ and Fe2+ prior to lavage, indicative of ferroptosis as a mode of chondrocyte cell death. To ask whether prolonged inflammatory conditions resulted in ferroptosis-like transformation in vitro, we subjected TMJ chondrocytes to IL-1ß treatment, resulting in a shift in messenger RNA sequencing gene ontologies related to iron homeostasis and oxidative stress-related cell death. Exposure to rat unilateral anterior crossbite conditions resulted in reduced COL2A1 expression, fewer chondrocytes, glutathione peroxidase 4 (GPX4) downregulation, and 4-hydroxynonenal (4-HNE) upregulation, an effect that was reversed after intra-articular injections of the ferroptosis inhibitor ferrostatin 1 (Fer-1). Our study demonstrated that ferroptosis conditions affected mitochondrial structure and function, while the inhibitor Fer-1 restored mitochondrial structure and the inhibition of hypoxia-inducible factor 1α (HIF-1α) or the transferrin receptor 1 (TFRC) rescued IL-1ß-induced loss of mitochondrial membrane potential. Inhibition of HIF-1α downregulated IL-1ß-induced TFRC expression, while inhibition of TFRC did not downregulate IL-1ß-induced HIF-1α expression in chondrocytes. Moreover, inhibition of HIF-1α or TFRC downregulated the IL-1ß-induced MMP13 expression in chondrocytes, while inhibition of HIF-1α or TFRC rescued IL-1ß-inhibited COL2A1 expression in chondrocytes. Furthermore, upregulation of TFRC promoted Fe2+ entry into chondrocytes, inducing the Fenton reaction and lipid peroxidation, which in turn caused ferroptosis, a disruption in chondrocyte functions, and an exacerbation of condylar cartilage degeneration. Together, these findings illustrate the far-reaching effects of chondrocyte ferroptosis in TMJOA as a mechanism causing chondrocyte death through iron overload, oxidative stress, and articular cartilage degeneration and a potential major cause of TMJOA.

Environmental variability and the transmission of haemorrhagic fever with renal syndrome in Changsha, People's Republic of China.

The transmission of haemorrhagic fever with renal syndrome (HFRS) is influenced by climatic, reservoir and environmental variables. The epidemiology of the disease was studied over a 6-year period in Changsha. Variables relating to climate, environment, rodent host distribution and disease occurrence were collected monthly and analysed using a time-series adjusted Poisson regression model. It was found that the density of the rodent host and multivariate El Niño Southern Oscillation index had the greatest effect on the transmission of HFRS with lags of 2­6 months. However, a number of climatic and environmental factors played important roles in affecting the density and transmission potential of the rodent host population. It was concluded that the measurement of a number of these variables could be used in disease surveillance to give useful advance warning of potential disease epidemics.