Although clinical evidence suggests that nonalcoholic fatty liver disease is an established major risk factor for heart failure, it remains unexplored whether sleep disorder-caused hepatic damage contributes to the development of cardiovascular disease (CVD). Here, our findings revealed that sleep fragmentation (SF) displayed notable hepatic detrimental phenotypes, including steatosis and oxidative damage, along with significant abnormalities in cardiac structure and function. All these pathological changes persisted even after sleep recovery for 2 consecutive weeks or more, displaying memory properties. Mechanistically, persistent higher expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in the liver was the key initiator of SF-accelerated damage phenotypes. SF epigenetically controlled the acetylation of histone H3 lysine 27 (H3K27ac) enrichment at the Nox4 promoter and markedly increased Nox4 expression in liver even after sleep recovery. Moreover, fine coordination of the circadian clock and hepatic damage was strictly controlled by BMAL1-dependent Sirtuin 1 (Sirt1) transcription after circadian misalignment. Accordingly, genetic manipulation of liver-specific Nox4 or Sirt1, along with pharmacological intervention targeting NOX4 (GLX351322) or SIRT1 (Resveratrol), could effectively erase the epigenetic modification of Nox4 by reducing the H3K27ac level and ameliorate the progression of liver pathology, thereby counteracting SF-evoked sustained CVD. Collectively, our findings may pave the way for strategies to mitigate myocardial injury from persistent hepatic detrimental memory in diabetic patients.

A major obstacle in type 2 diabetes mellitus (T2DM) is sleep fragmentation (SF), which negatively affects testicular function. However, the underlying mechanisms remain to be elucidated. In this study, we demonstrate that SF induces testicular damage through a mechanism involving lipid metabolism, specifically mediated by melatonin (MEL) receptor 1a (MT1). T2DM mice with SF intervention displayed several deleterious phenotypes such as apoptosis, deregulated lipid metabolism, and impaired testicular function. Unexpectedly, sleep recovery (SR) for 2 consecutive weeks could not completely abrogate SF's detrimental effects on lipid deposition and testicular function. Interestingly, MEL and MT1 agonist 2-iodomelatonin (2IM) effectively improved lipid homeostasis, highlighting MEL/2IM as a promising therapeutic drug for SF-trigged testicular damage. Mechanistically, MEL and 2IM activated FGFR1 and sequentially restrained the crosstalk and physical interaction between TAB1 and TAK1, which ultimately suppressed the phosphorylation of TAK1 to block lipid deposition and cell apoptosis caused by SF. The ameliorating effect of MEL/2IM was overtly nullified in Fgfr1 knockout (Fgfr1-KO ^+/- ) diabetic mice. Meanwhile, testicular-specific overexpression of Tak1 abolished the protective effect of FGF1^mut on diabetic mouse testis. Our findings offer valuable insights into the molecular mechanisms underlying the testicular pathogenesis associated with SF and propose a novel therapeutic approach for addressing male infertility in T2DM.

Traditional Chinese medicine (TCM) serves as a treasure trove of ancient knowledge, holding a crucial position in the medical field. However, the exploration of TCM's extensive information has been hindered by challenges related to data standardization, completeness, and accuracy, primarily due to the decentralized distribution of TCM resources. To address these issues, we developed a platform for TCM knowledge discovery (TCMKD, https://cbcb.cdutcm.edu.cn/TCMKD/). Seven types of data, including syndromes, formulas, Chinese patent drugs (CPDs), Chinese medicinal materials (CMMs), ingredients, targets, and diseases, were manually proofread and consolidated within TCMKD. To strengthen the integration of TCM with modern medicine, TCMKD employs analytical methods such as TCM data mining, enrichment analysis, and network localization and separation. These tools help elucidate the molecular-level commonalities between TCM and contemporary scientific insights. In addition to its analytical capabilities, a quick question and answer (Q&A) system is also embedded within TCMKD to query the database efficiently, thereby improving the interactivity of the platform. The platform also provides a TCM text annotation tool, offering a simple and efficient method for TCM text mining. Overall, TCMKD not only has the potential to become a pivotal repository for TCM, delving into the pharmacological foundations of TCM treatments, but its flexible embedded tools and algorithms can also be applied to the study of other traditional medical systems, extending beyond just TCM.

To investigate the initial experience of coated metal ureteral stent(CMUS)for treatment of pelvic lipomatosis induced hydronephrosis(PLH).The clinical and follow-up data of 8 patients who were diagnosed as PLH treated with CMUS in Peking University People's Hospital from August 2018 to February 2021 were retrospectively analyzed.Inclusion criteria included:Imaging evidence of excessive adipose tissue around the bladder in the pelvic cavity,bladder elevation in an"inverted pear shape",and bladder wall thickening;Cystoscopy indicated follicular hyperplasia of bladder mucosa and biopsy pathology indicated glandular cystitis;Unilateral or bilateral hydronephrosis and ureteromegaly.Exclusion criteria included:Ureteral atresia;Recurrent obstruction of the bladder outlet.Preoperative baseline data included age,gender,serum creatinine,pelvis width and ureteric stent symptoms questionnaire(USSQ)score.Intraoperative data included the location and length of ureteral stenosis observed by retrograde urography.Postoperative follow-up data included serum creatinine,pelvis width,and USSQ score.In the study,8 patients(11 sides)with PLH were all male,with an average age of(38.7±8.6)years.Uni-lateral hydronephrosis was found in 5 cases and bilateral hydronephrosis in 3 cases.Preoperative mean serum creatinine was(90.0±10.3)μmol/L,and the mean renal pelvis width was(3.0±1.5)cm.The lower ureteral stricture was found in all cases,and the mean stricture length was(1.9±0.9)cm.Before operation,3 patients had ureteral Double-J stents,with USSQ scores of 97.0,68.0 and 100.0,respectively.Five patients underwent retrograde CMUS stenting,and 3 patients retrograde and antegrade.At the last follow-up,the average serum creatinine was(82.0±11.1)μmol/L and the mean renal pel-vis width was(1.9±0.5)cm,which were significantly lower than those before operation(t=3.12,P=0.02;t=3.23,P=0.02).In the 3 patients with Double-J stent before surgery,the USSQ scores were 87.0,62.0 and 89.0,respectively,which were significantly improved after CMUS stenting.The average follow-up time was(10.0±6.3)months.During the follow-up,1 patient developed CMUS re-lated symptoms,and no stent-associated infection and stent encrustation were found.In one case,the stent migrated to the bladder 3 months after operation,and the hydronephrosis disappeared after 3 months follow-up.CMUS stenting for treatment of PLH has certain efficacy and safety,which can explore a new therapeutic method for the long-term treatment of PLH.

OBJECTIVE: To assess health related quality of life (HRQOL) in patients with kidney stones and to predict risk factors for reduced HRQOL in the patients by the Chinese version of Wisconsin stone quality of life questionnaire (C-WISQOL). METHODS: The patients with renal stones admitted to Peking University People ' s Hospital from July 2020 to June 2021 were prospectively enrolled. The inclusion criteria included the patients with renal stones aged 18-80 years and sufficient Chinese language foundation, and the exclusion criteria included the patients with internal ureteral stents, malignant tumors, sepsis, etc. Demographic data and clinical data related to kidney stones were collected, and the C-WISQOL and the short form 36 health survey (SF-36) questionnaire completed by the patients was recorded. C-WISQOL included four domains (D): emotional impact (D1), social impact (D2), stone-related impact (D3) and vitality impact (D4). Cronbach ' s α coefficient was used to verify the internal consistency of C-WISQOL, Spearman ' s rho coefficient was used to verify the criterion validity between C-WISQOL and SF-36 questionnaire, confirmatory factor analysis was used to verify the structural validity, convergent validity and discrimination validity of C-WISQOL, and univariate and multivariate analyses were used to explore the risk factors leading to the decline of HRQOL in the patients with kidney stones. RESULTS: The study included 307 patients with kidney stones, of whom 212 (69.1%) were male, with a mean age of (51.9±13.5) years, and a mean body mass index (BMI) of (25.4±3.6) kg/m². 160 (52.1%) patients were complicated with metabolic syndrome (MS), 202 (65.8%) had history of calculi, 217 (70.7%) had calculi related symptoms, 53 (17.3%) had bilateral renal calculi, 82 (26.7%) had ureteral calculi, 199 (64.8%) had hydronephrosis, 78 (25.4%) had renal insufficiency, and urinary tract infection (UTI) was found in 168 patients (54.7%) with an average diameter of (15.6±5.9) mm. The mean total score of C-WISQOL questionnaire for all the patients was (94.9±13.7) points, D1 was (27.2±4.2) points, D2 was (23.8±3.7) points, D3 was (27.0±3.6) points, and D4 was (10.1±1.9) points. The Cronbach ' s α coefficient of the total score of C-WISQOL questionnaire was 0.968 and the four dimensions ranged from 0.860 to 0.898. The Spearman' s rho co- efficient between C-WISQOL and SF-36 total score was 0.564, and the Spearman' s rho coefficient between dimensions was 0.684-0.901, indicating that C-WISQOL had good internal consistency and criterion validity. Confirmatory factor analysis showed that C-WISQOL had good structural validity, convergent validity and discrimination validity. Univariate analysis showed that the patients with MS (OR=1.607, P < 0.001), calculi related symptoms (OR=1.268, P < 0.001), bilateral kidney stones (OR=1.900, P < 0.001), combined with ureteral calculi (OR=1.018, P < 0.001), accompanied by hydronephrosis (OR=1.685, P < 0.001), and UTI (OR=1.275, P < 0.001) were risk factors for decreased HRQOL in the patients with kidney stones, and multivariate analysis showed that the patients with MS (OR=1.475, P < 0.001), calculi related symptoms (OR=1.546, P=0.043) and UTI (OR=1.646, P=0.005) were independent risk factors for HRQOL decline in the patients with renal calculi. The t-test results showed that C-WISQOL scores were significantly higher in the patients without MS, stone-related symptoms and UTI than those in the patients with associated risk factors (P < 0.001). CONCLUSION C-WISQOL the questionnaire can be used to evaluate the HRQOL of patients with kidney stones with good reliability. The combination of MS, stone-related symptoms and UTI were independent risk factors for HRQOL reduction in the patients with renal stones.
Humans ; Quality of Life ; Kidney Calculi/psychology* ; Surveys and Questionnaires ; Middle Aged ; Male ; Adult ; Female ; Risk Factors ; Aged ; Prospective Studies ; China/epidemiology* ; Adolescent ; Aged, 80 and over ; Language ; Young Adult

Objective To investigate the protective effects of isopimaric acid ( ISO), the BKCa channel activator, on cognitive function and synaptic plasticity in APP/PS1 mice. Methods Alzet osmotic pump was loaded with ISO or DMSO only and assembled with ALZET Brain Infusion Kit III. The cannula was implanted into the lateral ventricle of 4-month-old male APP/PS1 mice or matched wild type ( WT) mice. Two weeks later, open field test and Morris water maze were conducted. Paired-pulse facilitation ( PPF) and TBS-induced long-term potentiation ( LTP ) were recorded in CA1 region of hippocampus. Results The open field test showed that there was no significant difference among the four groups in spontaneous activities and vertical plane movement distance within 30 minutes. Floor plane movement distance was significantly greater in APP/PS1+DMSO group than that in WT+DMSO group(P<0.05) . Compared with the WT+DMSO group, APP/PS1+DMSO group had significantly longer escape latency from the third to fifth day and lower percentage of time spent in the target quadrant ((43.27±3.24)% vs (34.19±2.56)%) and the number of crossing through the platform ((4.25±0.66)times vs (1.93±0.33)times)(P<0.05). Compared with the APP/PS1+DMSO group, the APP/PS1+ISO group had significantly shorter escape latency from the fourth to fifth day and higher percentage of time spent in the target quadrant ((46.16±3.51)%) and the number of crossing through the platform ((3.41±0.34) times) (P<0.05). PPF in APP/PS1+DMSO group significantly reduced compared with that in WT+DMSO group at 30-50ms interstimulus interval(P<0.05). PPF in APP/PS1+ISO group((224.50±13.79)%) was significantly augment compared with APP/PS1+DMSO ((174.99 ±6.68)%) group at 40 ms interstimulus interval (P<0.05). The LTP at 60 min post-TBS was significantly smaller in the APP/PS1+DMSO group ((135.19±1.32)%) than that in the WT+DMSO group ((172.17± 4.15)%)(P<0.001). The LTP of the APP/PS1+ISO group((160.48±1.19)%) became significantly in-creased compared with that in the APP/PS1+DMSO group(P<0.001).Conclusion BKCa channel activator ISO improve the learning and memory function of APP/PS1 mice by promoting PPF and increasing LTP to recover synaptic plasticity in the hippocampus.

Objective To evaluate the effect of slow-release microcapsules of HCF( hepatocyte growth factor) on angiogenesis in infracted myocardium.Method Myocardial infarction was induced in 30 New Zealand rabbits by ligating the middle of left descending coronary artery. Group Ⅰ ( n = 10) was served as a control group, group Ⅱ ( n =10) as a blank microcapsule group, group Ⅲ ( n = 10) as experimental group with each microcapsule contains 1 μgHGF as HCF group. In group Ⅱ andⅢ, 5 blank microcapsules or FGF slow-release microcapsules were implanted into myocardium under epicedium between the left descending coronary artery and left circumflex branch. The heart function of each rabbit was evaluated with echocar-diography and cheterization, angiogenesis was evaluated by immunohistochemical technique 6 weeks later.Result As compared with group Ⅰ and Ⅱ , rabbits treated with HGF had higher microvessel counts ( P < 0. 01), and LVFS and EF were significantly increased [ (101. 28±19. 50,105. 28 ±18. 28,161. 28 ±15. 85, P <0.01 ]. Conclusion Subepicardial implantation of HGF slow release microcapsule in the infracted rabbit model can enhance effective angiogenesis and improve left ventricular function.

Objective To study the clinical application of Multi-slice spiral CT angiography (MSCTA) in renal arterial stenosis. Methods 36 patients clinically suspected of renovascular hypertension were examined by 16 slice or 64 slice spiral CT angiography. After scanning , three dimensional reconstruction of the blood vessels were operated. 28 cases were detected diseases of renal vessels and perivascular, and then compared with DSA. Results In the 36 cases, MSCTA showed 19 renal areterial stenosis, 3 adrenal gland neoplasms, 2 adrenal hyperplasia, 1 polycystic kidney disease. In 19 cases with MSCTA , there were 2 double renal areterial stenosis and 2 renal areterial anatomical variants. DSA showed 21 renal areterial stenosis with various degree, the accordant rate of MSCTA and DSA exceeded 90%. Conclusion MSCTA play an important role in clinical application in diagnosis of renal arterial stenosis.

Objective To research the validity of PET/CT in clinic for detecting lung cancer. Method There were 20 subjects who may have lung cancer according to the result form other detecting way, including 15 males and 5 females with an average age from 54 to 86. Results Malignant lesions were found in 15 cases and benign lesions in 5 cases. Discussion The examination of chest with PET/CT is suit for early diagnosis of lung cancer. The number of patient of false postive and false negative is decreased by controlling some factor.

OBJECTIVETo explore the promoting effects of cograft of auto-microskin and allo-dermal matrix on burn wound healing.

METHODSForty-six patches of full skin loss wounds were made in the backs of 6 small white swines. Auto-microskin and meshed acellular allo-dermal matrix were simultaneously prepared. The 46 wounds were averagely divided into test (T) and control (C) groups. The wounds in T group were covered with auto-microskin and allo-dermal matrix (1:4) and split-thick allo-porcine skin. While the wounds in C group were grafted with autoskin and allo-dermal matrix.

RESULTSThe skin survival rate exhibited no difference between C and T groups (P > 0.05). There was similar histological exhibition in the two groups after skin grafting. The structure of collagen fibres appeared integrated, clear with regular arrangement and steady diameter at 8 - 20 post-operative weeks. Simultaneously, it was revealed by histological examination that normal vascular structure could be identified in the grafted skin and that inflammatory reaction ameliorated gradually and that epithelium combined well with dermis. It was also found that the epidermal papillar across the basement membrane fixed well to allo-dermis. The skin appeared smooth, elastic and functioned well at 5 months after skin grafting.

CONCLUSIONThe grafted skin survived well after the cograft of auto-microskin and allo-dermal matrix, which might be ideal covering material for the major deep burn wound healing.

Animals ; Burns ; therapy ; Disease Models, Animal ; Female ; Graft Rejection ; Male ; Skin Transplantation ; Skin, Artificial ; Swine