BACKGROUND: Previous evidence showed that ambient air pollution and cardiovascular mortality are related. However, there is a lack of evidence towards the modification effect of long-term lifestyle on the association between short-term ambient air pollution and death from cardiovascular events. METHOD: A total of 14,609 death from major adverse cardiovascular events (MACE) were identified among the China Kadoorie Biobank participants from 2013 to 2018. Ambient air pollution exposure including particulate matter 2.5 (PM_2.5), SO₂, NO₂, CO, and O₃ from the same period were obtained from space-time model reconstructions based on remote sensing data. Case-crossover design and conditional logistic regression was applied to estimate the effect of short-term exposure to air pollutants on MACE mortality. RESULTS: We found MACE mortality was significantly associated with PM_2.5 (relative percent increase 2.91% per 10 µg/m³ increase, 95% CI 1.32-4.53), NO₂ (5.37% per 10 µg/m³ increase, 95% CI 1.56-9.33), SO₂ (6.82% per 10 µg/m³ increase, 95% CI 2.99-10.80), and CO (2.24% per 0.1 mg/m³ increase, 95% CI 1.02-3.48). Stratified analyses indicated that drinking was associated with elevated risk of MACE mortality with NO₂ and SO₂ exposure; physical inactivity was associated with higher risk of death from MACE when exposed to PM_2.5; and people who had balanced diet had lower risk of MACE mortality when exposed to CO and NO₂. CONCLUSIONS The study results showed that short-term exposure to ambient PM_2.5, NO₂, SO₂, and CO would aggravate the risk of cardiovascular mortality, yet healthy lifestyle conduct might mitigate such negative impact to some extent.
Humans ; Cardiovascular Diseases/epidemiology* ; China/epidemiology* ; Male ; Female ; Air Pollution/adverse effects* ; Middle Aged ; Air Pollutants/analysis* ; Particulate Matter/analysis* ; Environmental Exposure/adverse effects* ; Life Style ; Aged ; Adult ; Risk Factors ; Cross-Over Studies ; East Asian People

Objective:To evaluate the effectiveness of amplification intervention with hearing aids for restoring binaural auditory function in patients with unilateral moderate to severe sensorineural hearing loss. Methods:This study selected 30 patients with normal hearing in one ear and moderate to severe sensorineural hearing loss in the other ear. They were fitted with hearing aids for the worse ear and underwent more than half a year and one year of adaptation training. The Chinese translation of the Twelve-item version of SSQ（C-SSQ12）, angle identification test, speech recognition score（SRS） at different signal-to-noise ratios（SNR=5 and SNR=10） and audiometric thresholds were used to compare the results before and after hearing aid use to evaluate the effectiveness of the unilateral hearing loss intervention. Results:The results of the audiometric thresholds, C-SSQ12 scores, angle identification test, and SRS at SNR=5 and SNR=10 in the worse ear of the unilateral hearing loss patients after hearing aid use were all statistically significant compared to before hearing aid use（P<0.01）. Conclusion:Amplification intervention with hearing aids has significant effects on restoring binaural auditory function in patients with unilateral moderate to severe sensorineural hearing loss.
Humans ; Hearing Aids ; Hearing Loss, Unilateral/therapy* ; Middle Aged ; Hearing Loss, Sensorineural/rehabilitation* ; Adult ; Female ; Male ; Auditory Threshold ; Young Adult ; Aged

Frostbite is the most common cold injury and is caused by both immediate cold-induced cell death and the gradual development of localized inflammation and tissue ischemia. Delayed healing of frostbite often leads to scar formation, which not only causes psychological distress but also tends to result in the development of secondary malignant tumors. Therefore, a rapid healing method for frostbite wounds is urgently needed. Herein, we used a mouse skin model of frostbite injury to evaluate the recovery process after frostbite. Moreover, single-cell transcriptomics was used to determine the patterns of changes in monocytes, macrophages, epidermal cells, and fibroblasts during frostbite. Most importantly, human-induced pluripotent stem cell (hiPSC)-derived skin organoids combined with gelatin-hydrogel were constructed for the treatment of frostbite. The results showed that skin organoid treatment significantly accelerated wound healing by reducing early inflammation after frostbite and increasing the proportions of epidermal stem cells. Moreover, in the later stage of wound healing, skin organoids reduced the overall proportions of fibroblasts, significantly reduced fibroblast-to-myofibroblast transition by regulating the integrin α5β1-FAK pathway, and remodeled the extracellular matrix (ECM) through degradation and reassembly mechanisms, facilitating the restoration of physiological ECM and reducing the abundance of ECM associated with abnormal scar formation. These results highlight the potential application of organoids for promoting the reversal of frostbite-related injury and the recovery of skin functions. This study provides a new therapeutic alternative for patients suffering from disfigurement and skin dysfunction caused by frostbite.
Animals ; Organoids/metabolism* ; Mice ; Humans ; Wound Healing ; Frostbite/metabolism* ; Skin/pathology* ; Induced Pluripotent Stem Cells/cytology* ; Cicatrix/pathology* ; Fibroblasts/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Extracellular Matrix/metabolism* ; Male

Multimodal fusion research in traditional Chinese medicine （TCM） inspection has greatly improved the accuracy of identification results with the help of emerging technologies in science and technology. At present， multimodal fusion technology is used in the integration of the parameters collected by the inspection instruments and the analysis of the parameters， which is represented by the development and application of the tongue inspection instrument， the face inspection instrument and the eye inspection instrument. However， the multimodal fusion research of TCM inspection has problems such as insufficient comprehensiveness and accuracy of parameter acquisition， difficulty in parameter integration for fusion analysis， and low clinical practicability of identification results. It is believed that， while keeping up with the cutting-edge science and technology， research on multimodal fusion of TCM inspection should be guided by the holism concept of TCM， and should focus on the enhancement of comprehensiveness and accuracy of multimodal parameter acquisition， standardisation of parameter fusion， and fusion of identification results， so as to gradually promote the objectivity， intelligence and modernisation of the four diagnostic methods of TCM.

BACKGROUND:Unicompartmental knee arthroplasty has been paid more and more attention because of its advantages of fewer traumas,less blood loss,less complications,faster recovery,excellent knee function and high prosthetic survival rate.Most of the relevant reports focused on its clinical effect,but the changes in the levels of relevant inflammatory cytokines in patients after unicompartmental knee arthroplasty were rarely reported. OBJECTIVE:To investigate the effect of unicompartmental knee arthroplasty in patients with medial compartment osteoarthritis of the knee and the changes of interleukin-1,interleukin-6,and tumor necrosis factor-α levels. METHODS:A total of 30 patients with medial compartment osteoarthritis of the knee who received unicompartmental knee arthroplasty from September 2021 to March 2023 and met the inclusion criteria were selected as the study subjects.Medial angle of proximal tibia,femoral and tibial angle,pain visual analog scale score,hospital for special surgery score,knee joint range of motion,synovial fluid interleukin-1,interleukin-6,and tumor necrosis factor-α levels before and after surgery were compared and statistically analyzed. RESULTS AND CONCLUSION:(1)All 30 patients had grade I wound healing.All patients were followed up for more than 6 months after surgery.There were no complications such as prosthesis loosening and dislocation of prosthesis liner in all patients.(2)The medial proximal tibia angle and the femoral and tibial angles measured after operation were significantly improved(P<0.05).(3)The visual analog scale score,hospital for special surgery score and range of motion measured at 1,3,and 6 months after operation were better than those before operation(P<0.05),and showed a gradual improvement(P<0.05).(4)The levels of interleukin-1,interleukin-6,and tumor necrosis factor-α in synovial fluid at 3 and 6 months after operation were decreased gradually compared with those before operation(P<0.05)and showed a gradual downward trend at each time point after operation.(5)It is indicated that unicompartmental knee arthroplasty can effectively treat medial compartment osteoarthritis of the knee,significantly relieve pain,restore knee joint function,improve knee varus deformity and lower limb strength line,and reduce the levels of inflammatory cytokines interleukin-1,interleukin-6,and tumor necrosis factor-α in joints to a certain extent.

ObjectiveTo retrospectively analyze the clinical efficacy of Xibining Ⅱ prescription in the treatment of knee osteoarthritis with cold-dampness blockage syndrome by oral medication and to explore the influencing factors of endpoint events. MethodA real-world retrospective cohort design was adopted， and medical records of knee osteoarthritis patients with cold-dampness blockage syndrome treated with oral medication from the orthopedics outpatient department of Jiangsu Province Hospital of Chinese Medicine were collected. All patients received conventional Western medicine treatment and were divided into non-exposure group （573 cases） and exposure group （427 cases） according to whether or not they received treatment with Xibining Ⅱ prescription. Descriptive analysis of the baseline data of the 1 000 screened cases was performed using IBM SPSS 27.0. According to the baseline data， 334 pairs were matched using the propensity score matching method， resulting in a total of 668 cases in both groups. The changes in visual analogous scale （VAS）， Western Ontario and McMaster Universities Osteoarthritis Index （WOMAC） total score， Japanese Knee Osteoarthritis Measure （JKOM） score， and traditional Chinese medicine （TCM） syndrome score before treatment and at 2， 6， 12 weeks after treatment， as well as the incidence of adverse reactions， were compared between the two groups. A multivariate logistic regression analysis was conducted to analyze the influencing factors of endpoint events， with clinical cure judged based on the improvement rate of WOMAC total score before and after treatment. ResultAfter 12 weeks of treatment， compared to the results before treatment， the VAS， WOMAC total score， JKOM score， and TCM syndrome score of patients in both groups significantly decreased （P<0.01）. Compared to the non-exposure group， the exposure group showed a more significant reduction in VAS， WOMAC total score， JKOM score， and TCM syndrome score （P<0.01）. After 12 weeks of treatment， the clinical cure rate and significant efficiency were higher in the exposure group than in the non-exposure group （P<0.05）. Compared to the results before treatment within each group， VAS， WOMAC pain， stiffness， function scores， JKOM score， and TCM syndrome score significantly decreased at 2， 6， 12 weeks after treatment in both groups （P<0.01）. Compared to the non-exposure group at the same time points， the exposure group showed a reduction in VAS at 2， 12 weeks， WOMAC pain at 6， 12 weeks， and function scores at 12 weeks （P<0.05， P<0.01）. The JKOM score decreased at 6， 12 weeks， and the TCM syndrome score significantly decreased at 2， 6， 12 weeks in the exposure group （P<0.05， P<0.01）. Multivariate logistic regression analysis at 12 weeks showed that factors affecting clinical cure included the course of disease， history of alcohol consumption， hypertension， coronary heart disease， and the use of Xibining Ⅱ prescription （P<0.05， P<0.01）. Compared to the non-exposure group at the same time points， the incidence of epigastric discomfort in the exposure group was lower at 2， 12 weeks （P<0.01）， the incidence of diarrhea and vomiting was slightly higher than that in the non-exposure group， but the difference was not statistically significant. ConclusionThe clinical application of Xibining Ⅱ prescription combined with conventional Western medicine treatment in the treatment of knee osteoarthritis with cold-dampness blockage syndrome is more effective than conventional Western medicine treatment alone. It can significantly reduce VAS， WOMAC total score， JKOM score， and TCM syndrome score， with more pronounced long-term effects and a low incidence of adverse reactions.

Objective:To develop and validate the Intimate Relationships Happiness Questionnaire(IRHQ).Methods:Firstly,interviews were conducted with 20 participants,investigation were conducted with 100 partici-pants,and vocabulary scoring were conducted with 100 participants formed the originally items.Secondly,801 par-ticipants were recruited to finished the initial scale for items analysis and exploratory factor analysis.Thirdly,480 participants were conducted with the IRHQ,Satisfaction With Life Scale(SLS),Subjective Authentic-Durable Hap-piness Scale(SA-DHS),Chinese Happiness Inventory(CHI)and Marital Happiness Scale(MHS)for confirmatory factor analysis,criterion-related validity and internal consistency analysis.Finally,100 participants were assessed with IRHQ after 2 weeks for test-retest reliability.Results:After items analysis and exploratory factor analysis,29 i-tems were selected as the final scale with a total of four factors that accounted for 63.76％of the variance in all for IRHQ,4 factors including body harmony,mental harmony,fitting-value and sexual relationship satisfac-tion.Confirmatory factor analysis indicated that the four-factor model had a goof structural fit(x2/df=2.89,P＜0.001,TLI=0.93,CFI=0.94,RMSEA=0.04).The scores of IRHQ was positively correlated with the scores of SLS,SA-DHS,CHI and MHS(ICC=0.27-0.72,Ps＜0.001).The internal consistency reliabilities of the total score of the scale and the score of the 4 factors were 0.74,0.73,0.72,0.78 and 0.90.The retest reliabilities were 0.87,0.83,0.88,0.88 and 0.90.Conclusion:The Intimate Relationships Happiness Questionnaire meetsthe psy-chometric standard and could be used to assess the intimate relationship well-being.

China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.

AIM:This study investigates the effect of fibroblast growth factor 21(FGF21)long-acting ana-logue PF-05231023 on promoting the"browning"of white adipose tissue(WAT)by inhibiting mitophagy in WAT and the molecular mechanisms involved.METHODS:Using a high-fat diet(HFD)to replicate an obesity model in mice,18 C57BL/6J mice were divided into three groups:normal control(NC)group,HFD group,and PF-05231023 intervention(PF+HFD)group,each consisting of 6 mice.After 12 weeks of feeding,the mice were anaesthetized,their eyeballs were removed to collect blood samples,and serum was separated to measure levels of total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C)、alanine aminotransferase(ALT),and aspartate aminotransferase(AST)in mouse serum.The inguinal WAT(iWAT),epididymal WAT(eWAT)and liver were collected.Part of the tis-sues were used for Western blot experiments to measure the protein levels of"browning"related markers uncoupling pro-tein-1(Ucp-1)and peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α),as well as mitophagy-related markers PTEN-induced kinase 1(Pink1),parkin,beclin-1 and microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ).Another part of the tissues was fixed in paraformaldehyde for subsequent HE and immunohistochemical staining.3T3-L1 cells were induced to mature adipocytes using the classic"cocktail"method.The CCK-8 assay was used to assess the impact of different concentrations of PF-05231023 intervention on cell viability.After 48 h of PF-05231023 intervention,the 3T3-L1 cell clumps were collected for Western blot experiments to measure the expression levels of"browning"related markers Ucp-1 and PGC-1α,as well as mitochondrial autophagy-related markers Pink1,parkin,beclin-1,and LC3-Ⅱ proteins.Oil red O staining was performed to detect cell accumulation,and immunofluorescence staining was used to mea-sure Ucp-1 protein content.Subsequently,3T3-L1 cells were divided into the normal group,PF-05231023 intervention group,Pink1 agonist MTK458 intervention group,and MTK458+PF-05231023 intervention group.Cell clumps were col-lected for Western blot experiments to measure the markers as mentioned above.RESULTS:The key findings of our study indicate that the PF-05231023 intervention did not affect energy intake in mice but significantly reduced the weight,liver weight,and fat weight of mice induced by a high-fat diet(P<0.05).The intervention also decreased lipid accumula-tion(TC,TG、LDL-C)and liver damage(ALT,AST)and alleviated hepatocyte vacuolization and adipocyte size(P<0.05).Compared with the HFD group,the PF-05231023 intervention increased the levels of Ucp-1 and PGC-1α protein expression in iWAT and eWAT(P<0.01).Immunohistochemical staining showed higher Ucp-1 protein content in the PF-05231023 intervention group than in the HFD group.The PF-05231023 intervention dose-dependently increased Ucp-1 and PGC-1α protein expression levels in mature 3T3-L1 cells(P<0.01),reduced cellular lipid accumulation,and immu-nofluorescence staining showed increased Ucp-1 protein content in mature 3T3-L1 cells after PF-05231023 intervention.The PF-05231023 intervention inhibited mitochondrial autophagy-related indicators Pink1,parkin,beclin-1,and LC3-Ⅱ protein expression levels in iWAT,eWAT,and induced mature 3T3-L1 cells(P<0.05).The MTK intervention increased Pink1,parkin,beclin-1,and LC3-Ⅱ protein expression levels,increased Ucp-1 protein expression level,compared with the MTK intervention group,after MTK and PF-05231023 co-intervention,partially decreased Pink1,parkin,beclin-1,and LC3-Ⅱ protein expression levels,and partially restored Ucp-1 protein expression level(P<0.01).CONCLUSION:(1)Intervention with PF-05231023 can improve obesity and related metabolic disorders induced by a high-fat diet in mice;(2)PF-05231023 intervention can inhibit white adipose tissue(WAT)and induce mature 3T3-L1 cell mitochondria autophagy,promoting"browning"by inhibiting mitochondrial autophagy;(3)Its mechanism may be related to the inhibi-tion of the Pink1-parkin signalling pathway.

The vast majority of patients with hepatocellular carcinoma (HCC) in China originate from hepatitis B cirrhosis, while 90% of cirrhotic patients may develop portal hypertension, and the HCC patients with portal hypertension account for 15%-30%. Portal hypertension is a group of clinical syndromes characterized by elevated portal venous pressure and formation of portal-systemic collateral circulation, and it is one of the most important complications of liver cirrhosis. HCC and portal hypertension affect each other, and portal hypertension seriously affects the prognosis of HCC patients. The development of systemic treatment regimens for HCC provides more treatment options for patients with advanced HCC, including molecular-targeted drug therapy, immunotherapy, and chemotherapy. Different systemic therapeutic drugs for HCC have different impacts on portal hypertension, and this article reviews the effect of commonly used systemic therapeutic drugs for HCC on portal hypertension.