Residential greenness and chronic obstructive pulmonary disease in a large cohort in southern China: Potential causal links, risk trajectories, and mediation pathways.

INTRODUCTION: Residential greenness may influence COPD mortality, but the causal links, risk trajectories, and mediation pathways between them remain poorly understood. OBJECTIVES: We aim to comprehensively identify the potential causal links, characterize the dynamic progression of hospitalization or posthospital risk, and quantify mediation effects between greenness and COPD. METHODS: This study was conducted using a community-based cohort enrolling individuals aged ≥ 18 years in southern China from January 1, 2009 to December 31, 2015. Greenness was characterized by normalized difference vegetation index (NDVI) around participants' residential addresses. We applied doubly robust Cox proportional hazards model, multi-state model, and multiple mediation method, to investigate the potential causal links, risk trajectories among baseline, COPD hospitalization, first readmission due to COPD or COPD-related complications, and all-cause death, as well as the multiple mediation pathways (particulate matter [PM], temperature, body mass index [BMI] and physical activity) connecting greenness exposure to COPD mortality. RESULTS: Our final analysis included 581,785 participants (52.52% female; average age: 48.36 [Standard Deviation (SD): 17.56]). Each interquartile range (IQR: 0.06) increase in NDVI was associated with a reduced COPD mortality risk, yielding a hazard ratio (HR) of 0.88 (95 % CI: 0.81, 0.96). Furthermore, we observed per IQR (0.04) increase in NDVI was inversely associated with the risk of multiple transitions (baseline - COPD hospitalization, baseline - death, and readmission - death risks), especially a declined risk of all-cause death after readmission (HR = 0.66 [95 %CI: 0.44, 0.99]). Within the observed association between greenness and COPD mortality, three mediators were identified, namely PM, temperature, and BMI (HR for the total indirect effect: 0.773 [95 % CI: 0.703, 0.851]), with PM showing the highest mediating effect. CONCLUSIONS: Our findings revealed greenness may be a beneficial factor for COPD morbidity, prognosis, and mortality. This protective effect is primarily attributed to the reduction in PM concentration.

Potential causal links and mediation pathway between urban greenness and lung cancer mortality: Result from a large cohort (2009 to 2020).

Urban greenness, as a vital component of the urban environment, plays a critical role in mitigating the adverse effects of rapid urbanization and supporting urban sustainability. However, the causal links between urban greenness and lung cancer mortality and its potential causal pathway remain poorly understood. Based on a prospective community-based cohort with 581,785 adult participants in southern China, we applied a doubly robust Cox proportional hazard model to estimate the causal associations between urban greenness exposure and lung cancer mortality. A general multiple mediation analysis method was utilized to further assess the potential mediating roles of various factors including particulate matter (PM1, PM2.5-1, and PM10-2.5), temperature, physical activity, and body mass index (BMI). We observed that each interquartile range (IQR: 0.06) increment in greenness exposure was inversely associated with lung cancer mortality, with a hazard ratio (HR) of 0.89 (95 % CI: 0.83, 0.96). The relationship between greenness and lung cancer mortality might be partially mediated by particulate matter, temperature, and physical activity, yielding a total indirect effect of 0.826 (95 % CI: 0.769, 0.887) for each IQR increase in greenness exposure. Notably, the protective effect of greenness against lung cancer mortality could be achieved primarily by reducing the particulate matter concentration.

[Acupotomy relieves pain and improves motor function by regulating autophagy and apoptosis of cartilage in rabbits with knee osteoarthritis apoptosis].

OBJECTIVE: To observe the effect of acupotomy on the expression of Beclin-1, Bcl-2 and Caspase-3 in the cartilage tissue in rabbits with knee osteoarthritis (KOA), so as to explore its mechanism underling improvement of KOA. METHODS: Twenty-four healthy male New Zealand rabbits were randomly and equally divided into blank control, model and acupotomy groups, with 8 rabbits in each group. By using the modified Videman's methods, the KOA model was established by left hind limb immobilization with a plaster cast for 6 weeks. The severity of KOA (knee pain, swelling and motor function) was assessed using Lequesne score, and the rabbits with a score below 4 were excluded. The acupotomy was applied to "Hedingci" (the attachment of the quadriceps tendon to the patella at the upper edge), "Binneixia" (the medial patellar supporting band attachment of medial inferior patellar margin), "Binwaixia" (the lateral patellar supporting band attachment of the lower lateral patellar margin), "Chengfeijian" (the lateral collateral ligament of the knee passes over the lateral joint space), "Weiyangci" (the medial margin of biceps femoris at the lateral end of popliteus), "Yinlingci" (the medial tibial attachment of anserinus tendon) on the left hind limb once a week for 4 weeks. One week after the last intervention, the left knee joint dysfunction severity(pain, maximum walking distance, and some activities of daily living) was evaluated by using modified Lequesne score. Histopathological changes of the cartilage were observed under light microscope after H.E. staining. The apoptosis of chondrocytes was observed after terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick-end labeling (TUNEL) staining. The autophagolysosomes of chondrocytes were observed using transmission electron microscopy. The expression levels of Beclin-1, Bcl-2 and Caspase-3 (related factors of autophagy and apoptosis) were detected using Real-time PCR and Western blot separately. RESULTS: In comparison with the blank control group, the Lequesne score, apoptosis rate, expression levels of Caspase-3 mRNA and protein were significantly increased (P<0.001), and the number of autophagolysosomes, expression levels of Beclin-1 and Bcl-2 mRNAs and proteins considerably decreased (P<0.001) in the model group. Relevant to the model group, the acupotomy group had an obvious decrease in Lequesne score, rate of apoptosis, and expression levels of Caspase-3 mRNA and protein (P<0.001) and an apparent increase in the number of autophagolysosomes and expression levels of Beclin-1 and Bcl-2 mRNAs and proteins (P<0.001). Findings of H.E. staining showed severe damaged cartilage surface, with a large number of exfoliation defects, few chondrocytes on the surface and disordered arrangement of transitional cells in the model group, which was relatively milder in the acupotomy group. CONCLUSION: Acupotomy can mitigate knee-joint pain and improve functional activity in KOA rabbits, which may be associated with its functions in promoting autophagy and suppressing apoptosis by up-regulating expressions of Beclin-1 and Bcl-2 mRNAs and proteins and down-regulation of Caspase-3 mRNA and protein.

Proteomic Analyses Reveals the Mechanism of Acupotomy Intervention on the Treatment of Knee Osteoarthritis in Rabbits.

Acupotomy intervention (AI) is an available treatment for knee osteoarthritis (KOA) in China, which is a common health problem over the world. However, the underlying mechanism of AI on the KOA treatment is still unknown. To further understand the mechanism of acupotomy in treating KOA, the morphological observation and TMT proteomic analyses were conducted in rabbits. By using X-ray and MRI, we found that the space of the knee joint was bigger in AI than in KOA. Moreover, the chondrocytes were neatly arranged in AI but disordered in KOA. With proteomic analyses in chondrocytes, 68 differently accumulated proteins (DAPs) were identified in AI vs. KOA and DAPs related to energy metabolism and the TCA cycle were suggested to play a central role in response to AI. Furthermore, AIFM1 was proposed to be an important regulator in controlling the energy production in mitochondrial. Besides, FN1, VIM, COL12A1, COL14A1, MYBPH, and DPYSL3 were suggested to play crucial roles in AI for the treatment of KOA. Our study was systematically elucidating the regulation mechanism of acupotomy intervention in the treatment of KOA.

Short-Term Exposure to Ambient Air Pollution and Hospital Admissions for Sequelae of Stroke in Chinese Older Adults.

Extensive evidence suggests that ambient air pollution contributes to a higher risk of hospital admissions for cerebrovascular diseases; however, its association with admissions for sequelae of stroke remains unclear. A time-stratified case-crossover study was conducted among 31,810 older adults who were admitted to hospital for sequelae of stroke in Guangzhou, China during 2016-2019. For each subject, daily residential exposure to fine particulate matter (PM2.5), inhalable particulate matter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) was extracted from a validated grid data set. Conditional logistic regression models were used for exposure-response analyses. In single-pollutant models, each interquartile range (IQR) increase of lag 04-day exposure to CO (IQR: 0.25 mg/m3) and lag 3-day exposure to O3 (69.6 µg/m3) was significantly associated with a 4.53% (95% confidence interval: 1.67%, 7.47%) and 5.63% (1.92%, 9.48%) increase in odds of hospital admissions for sequelae of stroke, respectively. These associations did not significantly vary across age or sex. With further adjustment for each of the other pollutants in 2-pollutant models, the association for CO did not change significantly, while the association for O3 disappeared. We estimated that 7.72% of the hospital admissions were attributable to CO exposures. No significant or consistent association was observed for exposure to PM2.5, PM10, SO2, or NO2. In conclusion, short-term exposure to ambient CO, even at levels below the WHO air quality guideline, was significantly associated with an increased odds of hospital admissions for sequelae of stroke, which may lead to considerable excess hospital admissions.

Short-term exposure to ambient air pollution and readmissions for heart failure among 3660 post-discharge patients with hypertension in older Chinese adults.

BACKGROUND: Despite ambient air pollution being associated with various adverse cardiovascular outcomes, the acute effects of ambient air pollution on hospital readmissions for heart failure (HF) among post-discharge patients with hypertension remain less understood. METHODS: We conducted a time-stratified case-crossover study among 3660 subjects 60 years or older who were admitted to hospital for HF after discharge for hypertension in Guangzhou, China during 2016-2019. For each subject, individualised residential exposures to ambient particulate matter with an aerodynamic diameter ≤1 µm (PM1), ≤2.5 µm (PM2.5), ≤10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO) and ozone were extracted from our validated grid dataset. RESULTS: An IQR increase of lag 04-day exposure to PM1 (IQR: 11.6 µg/m3), PM2.5 (IQR 21.9 µg/m3), PM10 (IQR 35.0 µg/m3), SO2 (IQR 4.4 µg/m3), NO2 (IQR 23.3 µg/m3) and CO (IQR 0.25 mg/m3) was significantly associated with a 9.77% (95% CI 2.21% to 17.89%), 8.74% (95% CI 1.05% to 17.00%), 13.93% (95% CI 5.36% to 23.20%), 10.81% (95% CI 1.82% to 20.60%), 14.97% (95% CI 8.05% to 22.34%) and 7.37% (95% CI 0.98% to 14.16%) increase in odds of HF readmissions, respectively. With adjustment for other pollutants, the association for NO2 exposure remained stable, while the associations for PM1, PM2.5, PM10, SO2 and CO exposures became insignificant. Overall, an estimated 19.86% of HF readmissions were attributable to NO2 exposure, while reducing NO2 exposure to the WHO and China air quality standards would avoid 12.87% and 0.54% of readmissions, respectively. No susceptible populations were observed by sex, age or season. CONCLUSION: Short-term exposure to ambient NO2 was significantly associated with an increased odds of HF readmissions among post-discharge patients with hypertension in older Chinese adults.

The protective role of social support on prenatal depression among pregnant women of advanced maternal age: a Three-Trimester follow-up study in China.

The aim of this study was to compare the depressive symptoms during pregnancy between pregnant women aged over 35 years and those aged less than 35 years and to evaluate the protective effect of social support in early pregnancy against prenatal depressive symptoms. One hundred and seventy one women aged over 35 years and 342 trimester-matched women aged less than 35 years were included from a level III hospital in Shenzhen, China. The self-report Edinburgh Postnatal Depression Scale (EPDS) and Social Support Rating Scale (SSRS) were used to evaluate prenatal depression and social support in early pregnancy. The proportions of women aged over 35 years who screened positive for prenatal depression were 22.8%, 23.4%, and 24.0% in the first, second and third trimesters, respectively. Advanced maternal age (≥35 years) was a positive predictor of prenatal depressive symptoms (ß = 0.747, P = 0,008). Social support, especially objective support (ß = -0.030, P = 0.002) and subjective support (ß = -0.028, P = 0.006) in early pregnancy, had stronger protective effects against prenatal depressive symptoms for women aged over 35 years than younger women. Our findings support that older pregnant women experience more depressive symptoms than younger pregnant women, and social support could serve as a targeted intervention to decrease prenatal depressive symptoms.Impact statementWhat is already known on this subject? Depressive symptoms, which are strongly associated with adverse psychosocial and birth outcomes, appear to be prevalent and change in nature. Social support is an important protective factor against prenatal depression.What the results of this study add? Pregnant women of advanced maternal age experienced more depressive symptoms than younger women during the prenatal period. Social support, especially objective support and subjective support, had stronger protective effects against prenatal depression for women aged over 35 years than women aged less than 35 years.What the implications of these findings are for clinical practice? Screening of prenatal depression should be strengthened, especially for women aged over 35 years, and improving subjective support could improve their emotional experience.

[Effect of acupotomy intervention on the morphology and ultrastructure of rectus femoris muscle in rabbits with knee osteoarthritis].

OBJECTIVE: To observe the effect of acupotomy on the morphology and ultrastructure of rectus femoris muscle in rabbits with knee osteoarthritis and to reveal the possible therapeutic mechanism involved in the effect of acupotomology on the treatment of knee osteoarthritis(KOA). METHODS: Twenty-four male New Zealand rabbits aged 6 months and weighed (2.0±0.5) kg were randomly divided into blank group, model group and acupotomy group, 8 rabbits in each group. KOA model was established by modified Videman method with left hind limb extended plaster immobility for 6 weeks. In acupotomy group, the transfascial focal points of quadriceps femoris muscle were released by acupotomy under the guidance of Jingjin theory for 4 times and once a week, and the treatment points include Hedingci, Binwaixia, Binneixia. Blank group and model group were fed normally without intervention. One week after the end of the intervention, the pennation angle(PA), muscle thickness(MT), cross-sectional area(CSA) and strain ratio(SR) of rectus femoris were measured by ultrasound. HE staining was used to observe the changes of the tissue morphology, the number of muscle fibers and the average area of muscle fibers. The myofibril of rectus femoris, sarcomere and myofilament were observed by transmission electron microscope. RESULTS: The PA of rectus femoris muscle in the blank group was (9.05±0.21)°. The MT was(1.09±0.09) cm and the CSA was(1.30±0.01) cm2. The PA of rectus femoris muscle in the model group was (3.06±0.15)°. The MT was (0.71±0.02) cm and the CSA was(0.77±0.02) cm2. The PA of rectus femoris muscle in the acupotomy group was (6.94±0.28)°. The MT was (0.80±0.05) cm and the CSA was(0.94±0.03) cm2. The muscle PA, MT and CSA of rectus femoris in the model group were significantly smaller than those in the blank group (P<0.05). Those in acupotomy group were significantly increased compared with those in model group (P<0.05). The SR of rectus femoris muscle was 1.19±0.02 in the blank group, 3.50±0.05 in the model group and 1.99±0.07 in the acupotomy group. The elastic SR of the model group was significantly higher than that of the blank group (P<0.05). These in acupotomy group was significantly lower than that in model group(P<0.05). The results of HE staining showed:in blank group, the fascicles of rectus femoris were arranged neatly, the number of beam of muscle fibers within the fixed visual field was 94.38±3.50 and the average CSA was(0.75±0.22) mm2. In model group, the fascicles of rectus femoris with different sizes were disorganized with a small amount of inflammatory cell infiltration, the number of beam of muscle fibers within the fixed visual field was 196.63±2.62 and the average CSA was(0.26±0.03) mm2. Compared to the blank group, a significant increase in the number of muscle fibers in the fixed field in the model group (P<0.05) and the average CSA decreased significantly(P<0.05). In acupotomy group, the rectus femoris fascicles in the acupotomy group tended to be arranged in a more orderly manner, with the inflammatory cells decreased, the number of beam of muscle fibers within the fixed visual field was 132.88±4.61 and the average CSA was(0.70±0.07) mm2. Compared to the model group, a significant decrease in the number of muscle fibers in the fixed field in the model group(P<0.05) and the average CSA increased significantly(P<0.05). The results of transmission electron microscope showed:compared with the blank group, the overall arrangement of the myofibrils of the rectus femoris in the model group was less structured. There was fracture between the muscle fibers and the sarcomere, the myofilaments were disordered, and the fracture of the Z line was discontinuous. Compared with the model group, the myofibrillar texture of rectus femoris in acupotomy group was clearer, and the Z line was more continuous. CONCLUSION: Based on the jingjin theory, the release of quadriceps femoris by acupotomy can effectively improve the morphology and structure of rectus femoris, and promote the repair and reconstruction of chronic skeletal muscle injury in rabbits with KOA, which may be one of the mechanisms of acupotomy in the treatment of KOA.

Association of short-term exposure to air pollution with recurrent ischemic cerebrovascular events in older adults.

The acute effects of ambient air pollution on recurrence of ischemic cerebrovascular events (ICEs) remains largely unknown. We therefore conducted a time-stratified case-crossover study of 43,896 patients who were 60 years or older and were admitted to hospital for recurrent ICEs including ischemic stroke and transient ischemic attack in Guangzhou, China during 2016-2019. Based on each patient's home address and pollutant data from its neighboring air quality monitoring stations, we used an inverse distance weighting method to assess exposures to particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5), particulate matter with an aerodynamic diameter ≤10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO) and ozone (O3). Conditional logistic regression models were used to quantify exposure-response associations. During the study period, there were 43,896 case days and 149,131 control days. In single-pollutant models, each 10 µg/m3 increase in exposure to PM10, NO2 and CO (mean exposure on date of admission and 1 day prior) was significantly associated with a 0.74% (95% confidence interval [CI]: 0.13-1.36%), 2.15% (1.38-2.93%) and 0.14% (0.07-0.21%) increase in odds of hospital admissions for recurrent ICEs, respectively, and no significant departures from linearity were detected. The association for NO2 exposure remained consistent in 2-pollutant models, while the associations for PM10 and CO disappeared or changed materially with adjustment for other pollutants. Stronger association for NO2 exposure was observed in cool season than that in warm season. We found that short-term exposure to ambient air pollutants, especially NO2, was associated with increased risk of hospital admissions for recurrent ICEs in older adults.

Individual exposure to ambient PM2.5 and hospital admissions for COPD in 110 hospitals: a case-crossover study in Guangzhou, China.

Few studies have evaluated the short-term association between hospital admissions and individual exposure to ambient particulate matter (PM2.5). Particularly, no studies focused on hospital admissions for chronic obstructive pulmonary disease (COPD) at the individual level. We assessed the short-term effects of PM2.5 on hospitalization admissions for COPD in Guangzhou, China, during 2014-2015, based on satellite-derived estimates of ambient PM2.5 concentrations at a 1-km resolution near the residential address as individual-level exposure for each patient. Around 40,002 patients with COPD admitted to 110 hospitals were included in this study. A time-stratified case-crossover design with conditional logistic regression models was applied to assess the effects of PM2.5 based on a 1-km grid data of aerosol optical depth provided by the National Aeronautics and Space Administration on hospital admissions for COPD. Further, we performed stratified analyses by individual demographic characteristics and season of hospital admission. Around 10 µg/m3 increase in individual-level PM2.5 was associated with an increase of 1.6% (95% confidence interval [CI]: 0.6%, 2.7%) in hospitalization for COPD at a lag of 0-5 days. The impact of PM2.5 on hospitalization for COPD was greater significantly in males and patients admitted in summer. Our study strengthened the evidence for the adverse effect of PM2.5 based on satellite-based individual-level exposure data.

The mediating effect of engagement in physical activity over a 24-hour period on chronic disease and depression: Using compositional mediation model.

BACKGROUND: Popular mediation method only considers a single activity as a mediator instead of all 24-hour physical activity, such as a four-way decomposition method. We investigated the mediation of 24-hour movement continuum between chronic diseases (cardiovascular disease [CVD] and diabetes) and depression using a novel compositional mediation model. METHODS: 24-hour activity data measured by accelerometer were obtained from NHANES 2005-2006. Adjusted coefficient with 95% confidence interval (95% CI) for PHQ-9 total score and adjusted odds ratio (OR) with 95% CI for depression were computed from compositional mediation models. RESULTS: In total, 2,375 participants aged ≥ 20 were included in our analysis. Both diabetes and CVD were associated with increased sedentary behavior (SB) and sleep and reduced moderate-to-vigorous physical activity (MVPA) and light-intensity physical activity (LPA), leading to an increased likelihood of depression. Although not all component indirect effects were associated with PHQ-9 total score and depression, the total indirect effect was significantly associated with both PHQ-9 total score (coefficient (95% CI) for diabetes: 0.162 (0.081, 0.261); coefficient (95% CI) for CVD: 1.139 (1.061, 1.240)) and depression (OR (95% CI) for diabetes: 0.235 (0.126, 0.362); OR (95% CI) for CVD: 1.200 (1.088, 1.346)) using the compositional mediation model. CONCLUSION: We developed a compositional mediation model for continuous and binary outcomes, which can handle entire compositional mediators as a unit. The mediation of 24-hour movement continuum mediated the association between diabetes, CVD, and depression. Our findings present potential interventions for reducing risk of depression among patients with CVD and diabetes.

[Ultrasound anatomy and needle-knife insertion approach of common tendon lesions in knee osteoarthritis based on meridian sinew theory].

OBJECTIVE: To explore the ultrasonic anatomical characteristics and needle-knife insertion approach of common tendon lesions in knee osteoarthritis (KOA), so as to provide the references for accurate release of KOA by needle- knife along tendon lesions based on meridian sinew theory. METHODS: Sixty patients with one-knee KOA were selected. High-frequency musculoskeletal ultrasound was used to collect sonograms at the anatomical positions of "Hedingci" "Binwaixia" "Binneixia" and "Yinlingshang". The anatomic levels were marked on the sonograms. The anatomic levels and sonographic features of lesions were compared and analyzed, and the relevant data of needle-knife simulation approach was measured. RESULTS: The "Hedingci" lesions were mainly located at the attachment of quadriceps tendon to patella and suprapatellar bursa. The "Binwaixia" and "Binneixia" lesions were mainly located at the attachment of retinaculum patellae laterale and retinaculum patellae mediale to patella and infrapatellar fat pad. The "Yinlingshang" lesions were mainly located at the attachment of goose foot tendon to medial tibial condyle and bursa of goose foot. With "Hedingci" as an example, when the needle-knife entry point was 1 cm above the patella, the attachment of quadriceps tendon to patella was released, and the average depth of needle-knife was (3.60±0.10) cm, and the needle body was perpendicular to the skin. The average depth of needle-knife for releasing suprapatellar bursa was (2.35±0.17) cm, and the needle body was 45° towards head. CONCLUSION: The musculoskeletal ultrasound could clearly show the local detailed anatomical level, ultrasonic characteristics and anatomical level of common tendon lesions of KOA, and could improve the accuracy of needle-knife along tendon lesions with non-direct vision, which has important reference value for needle-knife medical standardization and standardized operation.

Classifying depression using blood biomarkers: A large population study.

BACKGROUND: Depression is a common mood disorder characterized by persistent low mood or lack of interest in activities. People with other chronic medical conditions such as obesity and diabetes are at greater risk of depression. Diagnosing depression can be a challenge for primary care providers and others who lack specialized training for these disorders and have insufficient time for in-depth clinical evaluation. We aimed to create a more objective low-cost diagnostic tool based on patients' characteristics and blood biomarkers. METHODS: Blood biomarker results were obtained from the National Health and Nutrition Examination Survey (NHANES, 2007-2016). A prediction model utilizing random forest (RF) in NHANES (2007-2014) to identify depression was derived and validated internally using out-of-bag technique. Afterwards, the model was validated externally using a validation dataset (NHANES, 2015-2016). We performed four subgroup comparisons (full dataset, overweight and obesity dataset (BMI≥25), diabetes dataset, and metabolic syndrome dataset) then selected features using backward feature selection from RF. RESULTS: Family income, Gamma-glutamyl transferase (GGT), glucose, Triglyceride, red cell distribution width (RDW), creatinine, Basophils count or percent, Eosinophils count or percent, and Bilirubin were the most important features from four models. In the training set, AUC from full, overweight and obesity, diabetes, and metabolic syndrome datasets were 0.83, 0.80, 0.82, and 0.82, respectively. In the validation set, AUC were 0.69, 0.63, 0.66, and 0.64, respectively. CONCLUSION: Results of routine blood laboratory tests had good predictive value for distinguishing depression cases from control groups not only in the general population, but also individuals with metabolism-related chronic diseases.

[Effects of "knot-loosing" of acupotomy on motor function and morphological changes of knee joint in knee osteoarthritis rabbits].

OBJECTIVE: To observe the effect of "knot-loosing method" of acupotomy on morphological changes in knee osteoarthritis (KOA) rabbits, so as to provide experimental basis for clinical acupotomy treatment of KOA. METHODS: Male New Zealand rabbits were randomly divided into blank control, model and acupotomy groups, with 8 rabbits in each group. By using the modified Videman method, the left hindlimb was immobilized for 6 weeks with a plaster cast to replicate the KOA model. The knot-loosing manipulation of acupotomy was applied to "Hedingci" (located at the attachment of the positive upper margin of the quadriceps tendon and the patella),"Binneixia"（at "Neixiyan" ［EX-LE4］, the medial side of ligamentum patella）, "Binwaixia" （at "Waixiyan" ［ST35］, the lateral side of patellar ligament）, "Chengfeijian" (at the lateral collateral ligament of the knee in the la-teral joint space), "Weiyangci"(at the medial margin of the biceps femoris and the lateral side of the transverse striation), and "Yinlingci"(at the end-point of the medial tibia of the goose foot tendon), respectively, once a week for 4 times. One week after the last intervention, the left knee joint dysfunction severity (pain, maximum walking distance, and some activities of daily living) was evaluated by using modified Lequesne Index score. X-ray and magnetic resonance imaging(MRI)examinations were conducted to assess the articular space size, effusion and cartilage smoothness of the left knee for which the MRI Osteoarthritis Knee Score (MOAKS) was given according to their severity. The histopathologic changes of the cartilage of the left knee were observed by Hematoxylin-eosin (H.E.) staining and light microscope, which Mankin score was given. In addition, the surface of the cartilage was also examined by macroscopic observation. RESULTS: ①Following modeling, the Lequesne Index score, MOAKS, macroscopic observation score and Mankin score were significantly increased in the model group (P<0.05). X-ray and MRI imaging showed a narrower joint space, more effusion, rough cartilage surface; and H.E. staining displayed rough cartilage surface, and disordered arrangement and occasional clusters of the chondrocytes in the left knee joint. ②In comparison with the blank control group, the Lequesne Index, MOAKS, macroscopic observation and Mankin scores were significantly down-regulated in the acupo-tomy group (P<0.05). The abovementioned injury changes shown by X-ray, MRI, macroscopic and microscopic observations were relatively milder in the acupotomy group. CONCLUSION: Acupotomy loosing based on the "Jingjin theory" of traditional Chinese medicine can effectively improve the motor ability of knee joint and repair pathological changes of the cartilage in KOA rabbits.

Mfn2 Regulates High Glucose-Induced MAMs Dysfunction and Apoptosis in Podocytes via PERK Pathway.

The endoplasmic reticulum (ER) stress and mitochondrial dysfunction in high glucose (HG)-induced podocyte injury have been demonstrated to the progression of diabetic kidney disease (DKD). However, the pathological mechanisms remain equivocal. Mitofusin2 (Mfn2) was initially identified as a dynamin-like protein involved in fusing the outer mitochondrial membrane (OMM). More recently, Mfn2 has been reported to be located at the ER membranes that contact OMM. Mitochondria-associated ER membranes (MAMs) is the intercellular membrane subdomain, which connects the mitochondria and ER through a proteinaceous tether. Here, we observed the suppression of Mfn2 expression in the glomeruli and glomerular podocytes of patients with DKD. Streptozotocin (STZ)-induced diabetic rats exhibited abnormal mitochondrial morphology and MAMs reduction in podocytes, accompanied by decreased expression of Mfn2 and activation of all three unfolded protein response (UPR) pathways (IRE1, ATF6, and PERK). The HG-induced mitochondrial dysfunction, MAMs reduction, and increased apoptosis in vitro were accompanied by the downregulation of Mfn2 and activation of the PERK pathway. Mfn2 physically interacts with PERK, and HG promotes a decrease in Mfn2-PERK interaction. In addition, Mfn2-silenced podocytes showed mitochondrial dysfunction, MAMs reduction, activation of PERK pathway, and increased apoptosis. Conversely, all these effects of HG stimulation were alleviated significantly by Mfn2 overexpression. Furthermore, the inhibition of PERK phosphorylation protected mitochondrial functions but did not affect the expression of Mfn2 in HG-treated podocytes. Therefore, this study confirmed that Mfn2 regulates the morphology and functions of MAMs and mitochondria, and exerts anti-apoptotic effects on podocytes by inhibiting the PERK pathway. Hence, the Mfn2-PERK signaling pathway may be a new therapeutic target for preventing podocyte injury in DKD.

Temperature Variability and Hospital Admissions for Chronic Obstructive Pulmonary Disease: Analysis of Attributable Disease Burden and Vulnerable Subpopulation.

Purpose: Chronic obstructive pulmonary disease (COPD) is a major cause of chronic diseases causing considerable social and economic burden globally. Despite substantial evidence on temperature-COPD association, few studies have investigated the acute effect of temperature variability (TV), a potential trigger of exacerbation of COPD disease, and it remains unknown what fraction of the disease burden of COPD is attributable to TV. Patients and Methods: Based on 71,070 COPD hospitalizations during 2013-2015 in Guangzhou, China, we conducted a time-series analysis using quasi-Poisson regression to assess the association between TV and hospital admission for COPD after adjusting for daily mean temperature. Short-term TV was captured by the standard deviation of hourly or daily temperatures across various exposure days. We also provided the fraction (total number) of COPD attributable to TV. Stratified analyses by admission route, sex, age, occupation, marital status and season were performed to identify vulnerable subpopulations. Results: We found a linear relationship between TV and COPD hospitalization, with a 1°C increase in hourly TV and daily TV associated with 4.3% (95%CI: 2.2-6.4) and 4.0% (2.3-5.8) increases in COPD, respectively. The greater relative risks of TV identified males, people aged 0-64 years, blue collar, and divorced/widowed people as vulnerable population. There were 12.0% (8500 cases) of COPD hospitalization attributable to hourly TV during the study period. Daily TV produced similar estimates of relative effects (relative risk) but grater estimates of absolute effects (attributable fraction) than hourly TV. Conclusion: We concluded that TV was an independent risk factor of COPD morbidity, especially among the susceptible subgroups. These findings would be helpful to guide the development of targeted public intervention.

Sestrin­2 regulates podocyte mitochondrial dysfunction and apoptosis under high­glucose conditions via AMPK.

Diabetic kidney disease (DKD) is a severe form of microangiopathy among diabetic patients, of which podocyte injury is one of the more predominant features. There is increasing evidence to suggest that mitochondrial dysfunction is associated with podocyte injury, thus contributing to the progression of DKD. Initially identified as a p53 target protein, the endogenous antioxidant protein, sestrin­2 (sesn2), has recently attracted attention due to its potential function in various inflammatory diseases. However, the association between sesn2 and podocytes in DKD remains unclear. In the present study, to elucidate the role of sesn2 in podocyte mitochondrial dysfunction, the effects of sesn2 on the regulation of AMP­activated protein kinase (AMPK) were examined in vitro and in vivo. Abnormal mitochondria were found in rats with streptozotocin­induced diabetes, and hyperglycemia downregulated the expression of sesn2. The upregulation of sesn2 increased the level of AMPK phosphorylation, and thus ameliorated mitochondrial dysfunction under high glucose conditions (HG). On the whole, these results suggest that sesn2 is associated with mitochondrial dysfunction in podocytes under HG conditions. In addition, the decreased expression of sesn2 may be a therapeutic target for DKD.

The effects of excess degree-hours on mortality in Guangzhou, China.

BACKGROUND: Prior studies that examined the association between temperature and mortality relied on mean temperature, maximum temperature, minimum temperature, humidex, and daily temperature variability, not accounting for variations in hourly temperature throughout the day. We proposed an indicator, excess degree-hours, to examine the association between temperature and mortality. METHODS: A distributed lag non-linear model (DLNM) was used to determine the hot (27.8 °C) and cold (24.3 °C) threshold. Hourly temperature in Guangzhou, China were summarized with extreme heat expressed as sum of degree-hours >27.8 °C and extreme cold as sum of degree-hours <24.3 °C within one day from January 1, 2012 to December 31, 2015. We then estimated the associations of daily mortality with hot and cold degree-hours in both hot and cold season. We also calculated the mortality burden of excess degree-hours. RESULTS: An interquartile range (IQR) increase of hot degree-hours was associated with 2.11% (95% confidence interval [95% CI]: 1.25%, 2.98%), 3.74% (95% CI: 0.71%, 6.86%), and 2.63% (95% CI: 0.70%, 4.59%) increments in non-injury related death, respiratory mortality, and cardiovascular mortality, respectively. While the corresponding excess risk for an IQR increase of cold degree-hours was 2.42% (95% CI: 1.97%, 2.88%), 3.16% (95% CI: 2.57%, 3.76%), and 2.93% (95% CI: 1.98%, 3.88%). The estimated mortality burdens for hot and cold degree-hours were 1366,2465, respectively. CONCLUSION: The excess degree-hours reduced to a single indication in duration and intensity is an approach and shows a different perspective and significant extreme weather effects on human health.

Teacher respiratory health symptoms in relation to school and home environment.

PURPOSE: Few studies have evaluated teachers' respiratory health, especially its relationship with school/home environment, and school policies. This study assessed asthma and smoking prevalence among teachers in Romania, teacher's perception and knowledge of the school environment, policies and asthma management, and how school and home environment affected asthma, allergy, and respiratory infection symptoms. METHODS: This cross-sectional study obtained information from 104 Romanian teachers utilizing teacher questionnaire data for Romania only, as part of the Schools Indoor Pollution and Health: Observatory Network in Europe (SINPHONIE) study, a multicenter European research project conducted between 2010 and 2012. The SINPHONIE questionnaire collected comprehensive information on school and home environment, respiratory symptoms, smoking, and school policies. We used unconditional logistic regression analysis to examine environment-outcome relationships while controlling for socio-demographics and co-exposures. RESULTS: Our results showed the prevalence of asthma-like symptoms and smoking among teachers in Romania was higher than in other SINPHONIE schools and among US teachers. Factors statistically associated with asthma, allergy, and respiratory infection (all p < 0.05) include perception of health related to poor air quality in school, inappropriate cleaning of ventilation systems, dwelling proximity to busy traffic, and multiple school/home exposures. We also found lack of asthma management and environmental policies in the investigated Romanian schools. CONCLUSION: We concluded that multiple school and home environmental factors were related to respiratory and allergic symptoms. High asthma burden and smoking are important public health problems in Romania. Future studies including larger sample size and exposure measurements are needed to confirm our findings.