High-performance phototheranostics with combined photothermal therapy and photoacoustic imaging have been considered promising approaches for efficient cancer diagnosis and treatment. However, developing phototheranostic materials with efficient photothermal conversion efficiency (PCE), especially over the second near-infrared window (NIR-II, 1000-1700 nm), remains challenging. Herein, we report an ultraefficient NIR-II-activated nanomedicine with phototheranostic and vaccination capability for highly efficient in vivo tumor elimination and metastasis inhibition. The NIR-II nanomedicine of a semiconducting biradical oligomer with a motor-flexible design was demonstrated with a record-breaking PCE of 87% upon NIR-II excitation. This nanomedicine inherently features extraordinary photothermal stability, good biocompatibility, and excellent photoacoustic performance, contributing to high-contrast photoacoustic imaging in living mice and high-performance photothermal elimination of tumors. Moreover, a whole-cell vaccine based on a NIR-II nanomedicine with NIR-II-activated performance was further designed to remotely activate the antitumor immunologic memory and effectively inhibit tumor occurrence and metastasis in vivo, with good biosafety. Thus, this work paves a new avenue for designing NIR-II active semiconducting biradical materials as a promising theranostics platform and further promotes the development of NIR-II nanomedicine for personalized cancer treatment.

Acetaminophen (APAP) overdose is a major cause of liver injury. Neural precursor cell expressed developmentally downregulated 4-1 (NEDD4-1) is an E3 ubiquitin ligase that has been implicated in the pathogenesis of numerous liver diseases; however, its role in APAP-induced liver injury (AILI) is unclear. Thus, this study aimed to investigate the role of NEDD4-1 in the pathogenesis of AILI. We found that NEDD4-1 was dramatically downregulated in response to APAP treatment in mouse livers and isolated mouse hepatocytes. Hepatocyte-specific NEDD4-1 knockout exacerbated APAP-induced mitochondrial damage and the resultant hepatocyte necrosis and liver injury, while hepatocyte-specific NEDD4-1 overexpression mitigated these pathological events both in vivo and in vitro. Additionally, hepatocyte NEDD4-1 deficiency led to marked accumulation of voltage-dependent anion channel 1 (VDAC1) and increased VDAC1 oligomerization. Furthermore, VDAC1 knockdown alleviated AILI and weakened the exacerbation of AILI caused by hepatocyte NEDD4-1 deficiency. Mechanistically, NEDD4-1 was found to interact with the PPTY motif of VDAC1 through its WW domain and regulate K48-linked ubiquitination and degradation of VDAC1. Our present study indicates that NEDD4-1 is a suppressor of AILI and functions by regulating the degradation of VDAC1.

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and insulin resistance and there are currently no approved drugs for its treatment. Hyperactivation of mTOR complex 1 (mTORC1) and subsequent impairment of the transcription factor EB (TFEB)-mediated autophagy-lysosomal pathway (ALP) are implicated in the development of NAFLD. Accordingly, agents that augment hepatic TFEB transcriptional activity may have therapeutic potential against NAFLD. The objective of this study was to investigate the effects of nuciferine, a major active component from lotus leaf, on NAFLD and its underlying mechanism of action. Here we show that nuciferine activated ALP and alleviated steatosis, insulin resistance in the livers of NAFLD mice and palmitic acid-challenged hepatocytes in a TFEB-dependent manner. Mechanistic investigation revealed that nuciferine interacts with the Ragulator subunit hepatitis B X-interacting protein and impairs the interaction of the Ragulator complex with Rag GTPases, thereby suppressing lysosomal localization and activity of mTORC1, which activates TFEB-mediated ALP and further ameliorates hepatic steatosis and insulin resistance. Our present results indicate that nuciferine may be a potential agent for treating NAFLD and that regulation of the mTORC1-TFEB-ALP axis could represent a novel pharmacological strategy to combat NAFLD.

Objective:To evaluate and compare the early and long-term outcomes of rheumatic patients who underwent left-side heart valve replacement with concomitant tricuspid valve replacement, and analyze the difference of early mortality and long-term survival rate between mild pulmonary artery systolic pressure (PASP) and moderate to severe PASP patients.Methods:From January 2009 to December 2018, 79 cases of patients were reviewed and summarized. The mean age before operation was (45.7±7.8) years old. These patients were divided into mild PASP group(<50 mmHg, 38 cases) (1 mmHg=0.133 kPa) and moderate-severe PASP group (>50 mmHg, 41 cases) . Kaplan- Meier method was used to estimate the overall long-term survival rate and the incidence of complications, and to compare the long-term survival rate of patients with mild and moderate -severe PASP elevation. Results:The mortality rate of early postoperative patients was 8.9% (7/79). The causes of death included: low cardiac output syndrome in 3 cases, multiple organ failure caused by pulmonary infection in 2 cases, acute renal insufficiency in 1 case, sudden cardiac arrest in 1 case. Although the mortality rate of early moderate-severe PASP group (12.2% vs. 5.3%) was higher than that of mild PASP group, there was no significant difference ( P>0.05). The mean follow-up time was (51.8±31.7) months (3-115 months). Kaplan- Meier method was used to estimate the 10-year survival rate, the rate of avoiding thrombosis, the rate of avoiding serious bleeding event and the rate of avoiding reoperation, which were (67.2±10.6)%, (85.7±6.2)%, (83.4± 6.9)% and (93.7 ± 3.7)%, respectively. Although the long-term survival rate of mild PASP (78.0±10.6) % was higher than that of moderate-severe PASP (62.8 ± 13.4) %, there was no significant difference ( P>0.05). Conclusion:The early mortality rate of rheumatic patients who underwent left-side heart valve replacement with concomitant tricuspid valve replacement is still relatively high. The recurrent heart failure is the major causes of long-term death.

Objective:To investigate the biomechanical characteristics and clinical outcomes of arthroscopic superior capsular reconstruction for massive irreparable rotator cuff tears (MIRCT) using the long head of biceps tendon (LHBT) with tenotomizing its distally or not (the "Chinese way" ).Methods:Eight fresh-frozen cadaveric shoulders were used to create a MIRCT model by detaching the footprints of the supraspinatus and infraspinatus tendons on the greater tuberosity. LHBT autograft was transferred and securely fixed onto the footprint of supraspinatus tendon for superior capsular reconstruction. Further, all cadaveric specimens were assigned to the tenotomy group or reservation group (4 cadaveric specimens in each group) according to whether the distal part of LHBT was tentomized or not. Biomechanical tests were conducted to observe the stiffness, ultimate load of fixed LHBT and to measure the length between LHBT tear site and its insertion on the superior labrum. A total of 41 patients with MIRCT who underwent arthroscopic superior capsular reconstruction using LHBT autograft between July 2016 and December 2018 were enrolled in the study. There were 17 males and 24 females, aged from 46 to 76 years (62.6±7.3 years). All patients were assigned to the tenotomy group (23 cases) or reservation group (18 cases) according to whether the distal part of LHBT was tentomized or not. The visual analogue scale (VAS), University of California, Los Angeles (UCLA) score, American Shoulder and Elbow Surgeons (ASES) score, Constant-Murley score and Fudan University Shoulder Score (FUSS) were used to evaluate the clinical outcomes. The range of motion (ROM) of shoulder was recorded before and after operation. Magnetic resonance imaging was used to assess the structural integrity of reconstructed tissue at 12 months after operation (refers to the failure of the transposed LHBT, which may be accompanied by a retear of partial repaired supraspinatus tendon).Results:Biomechanical research showed that the stiffness, ultimate load of fixed LHBT and the length between LHBT tear site and its insertion on the superior labrum in the reservation group (54.0±6.6 N/mm, 141.8±15.9 N, 93.3±12.4 mm, respectively) were significantly higher than those in the tenotomy group (25.7±4.2 N/mm, 80.8±8.0 N, 47.4±2.0 mm, respectively) ( P<0.05). All patients were followed up for 12-18 months (14.5±1.8 months) without significant complications and adverse reactions. No matter the distal part of LHBT was tentomized or not, the ROM and clinical scores (VAS score, UCLA score, Constant-Murley score, ASES score and FUSS) of patients improved significantly at 1 year follow-up than that before operation ( P<0.05). However, there were no significant differences between the reservation group and tenotomy group in terms of postoperative ROM [flexion, abduction, external rotation at side, internal rotation (vertebral level) were 144.3°±15.5° vs. 148.0°±10.3°, 145.1°±14.1° vs. 142.3°±11.2°, 67.3°±14.4° vs. 62.7°±11.7°, 8.3±2.1 vs. 7.8±2.5, respectively], VAS scores (2.3±1.6 vs.1.5±1.2), functional scores (Constant-Murley score, UCLA score, ASES score and FUSS were 88.2±11.4 vs. 85.6±9.6, 29.3±2.8 vs. 31.4±3.5, 86.8±11.8 vs. 82.6±9.2, 92.1±10.1 vs. 88.3±8.2, respectively) and structural failures (35.2% vs. 30.0%, P>0.05). Conclusion:Arthroscopic superior capsular reconstruction using LHBT with reserving its distal part could achieve higher mechanics strength. However, the short-term follow-up showed that tenotomizing the distal part of LHBT exerted no obvious influence on postoperative function and structural integrity.

Objective:To investigate the correlation between preoperative serum γ-glutamyl transferase (GGT) level and the postoperative survival of patients with renal cell carcinoma.Methods:The clinical data of 235 patients with renal cell carcinoma who underwent nephrectomy from December 2005 to December 2011 in the Affiliated Hospital of China University of Mining and Technology were retrospectively analyzed. According to the preoperative serum GGT level at 1.5 times the upper limit of normal value 90 U/L (the upper limit of normal value of samples in this study was 60 U/L), patients were divided into 2 groups: GGT ≤ 90 U/L group (218 cases) and GGT>90 U/L group (17 cases). The correlation between GGT and clinicopathological characteristics as well as postoperative survival of patient with renal cell carcinoma was also analyzed.Results:There were statistically significant differences in gender, age, the level of the aspartate aminotransferase (AST), the level of alanine aminotransferase (ALT), the neutrpphil-to-lymphocyte ratio (NLR), lymph node metastasis, distant metastasis, neoplasm staging between GGT ≤ 90 U/L group and >90 U/L group (all P < 0.05). Kaplan-Meier survival analysis showed that the median overall survival time was 84 months and 54 months, respectively in GGT ≤ 90 U/L group and GGT > 90 U/L group, and the difference was statistically significant of both groups ( χ2 = 4.334, P = 0.037). Univariate Cox proportional risk regression model showed that pathologic type, pathology T staging, preoperative GGT level, lactate dehydrogenase (LDH) level, ALT level were influencing factors of postoperative overall survival in patient with renal cell carcinoma (all P < 0.05). The multivariate Cox regression model analysis showed that the pathological type ( HR = 2.323, 95% CI 1.228-4.396, P = 0.010), GGT level ( HR = 2.406, 95% CI 1.077-5.376, P = 0.032), LDH level ( HR = 2.320, 95% CI 1.080-4.981, P = 0.031) were independent influencing factors of postoperative overall survival in patient with renal cell carcinoma. Conclusions:Preoperative elevated serum GGT level is associated with poor prognosis of patients with renal cell carcinoma, and the monitoring of it may help to evaluate the prognosis of patients and provide guidelines for individual treatment method.

OBJECTIVE： To investigate the effects of Danhong injection （DHI） on gene expression profile of acute myocardial infarction （AMI） model rats. METHODS： Male SD rats were randomly divided into sham operation group， model group and DHI group （0.76 mL/kg）， with 10 rats in each group. AMI model was established by ligation of left anterior descending coronary artery in model group and DHI group. After modeling， sham operation group and model group were given constant volume of normal saline intramuscularly， and DHI group was given relevant medicine intramuscularly， once a day， for consecutive 14 days. After last administration， myocardial tissue in the marginal zone of infarction was separated. The change of gene expression profile was detected by gene chip technique. Using fold-change of relative expression as index， differentially expressed microRNA （miRNA） were screened. On the basis of retrieving their corresponding genes， gene ontology （GO） and KEGG pathway enrichment analysis were carried out by using DAVID bioinformatics resource database and KEGG pathway database， respectively. TargetScan database was used to predict the target gene messenger RNA （mRNA） corresponding to differentially expressed miRNA. Cytoscape 3.6.1 software was used to construct and analyze the miRNA-mRNA network. Agilent GeneSpring GX v11.5 software was used to screen target genes and miRNA related to inflammation in the above networks. RESULTS： Compared with sham operation group， there were 22 differentially expressed miRNAs in model group， 5 up-regulated and 17 down-regulated. Compared with model group， there were 26 differentially expressed miRNAs in DHI group， and all of them were up-regulated. The differentially expressed miRNAs related to DHI therapy for AMI included rno-let-7a-5p， rno-let-7d-5p， rno-let-7f-5p， rno-miR-26b-5p， rno-miR-29b-3p， cel-miR-39-3p， cel-miR-39-5p， rno-miR-142-5p， rno-miR-191a-5p， rno-miR-409a-3p. Results of GO analysis and KEGG pathway enrichment analysis showed that differentially expressed miRNAs were mainly concentrated in membrane-bound organelles， cytoplasm， endometrial system and other cell components. The molecular functions such as protein binding and ion binding were exerted through biological processes such as anatomical structure development， multicellular tissue development and development process，which were mainly enriched in calcium signaling pathway， PPAR signaling pathway， VEGF signaling pathway， cell apoptosis， glycosylphosphatidylinositol anchored biosynthesis， valine， leucine and isoleucine degradation， etc. miRNA-mRNA network analysis showed that there were 25 target gene mRNAs corresponding to differentially expressed miRNA and 24 miRNAs related to it. There were 6 inflammation-related target genes （IL6， IL1b， TNF， TLR4， CRP， CXCL12） in this network， involving 19 differentially expressed miRNAs. CONCLUSIONS： The therapeutic effect of DHI on AMI may be related to regulating the expression of related miRNA， affecting signal transduction of calcium ion， PPAR and VEGF pathways， and regulating the secretion of inflammatory markers such as interleukin， chemokine and C-reactive protein.

Objective To investigate the effect of arthroscopy-assisted latissimus dorsi transfer (LDT) on posterosuperior massive rotator cuff tear (psMRCT) and analyze factors related to the outcome.Methods A retrospective case cohort study was conducted to analyze 31 patients with psMRCT admitted from January 2013 to December 2015.There were 13 males and 18 females,aged 52-67 years [(58.4 ± 4.5) years].The mean duration of symptoms was (1.9 ± 0.9) years.All patients received arthroscopy assisted LDT combined with rotator cuff repair.Postoperative rehabilitation training was carried out according to the standard procedures.Before operation and at the last follow-up,X-ray films were taken to measure the acromiohumeral talus,and magnetic resonance imaging was obtained to check the integrity of repaired tissue.Visual analog scale (VAS),active range of motions,Constant-Murley score and Fudan University Shoulder Score (FUSS) were measured to assess the shoulder joint function,and complications were documented.Furthermore,subgroup analysis was made according to "concomitant subscapularis tendon tear or not","concomitant pseudoparalysis or not","Goutallier Ⅲ/Ⅳ level fatty infiltration","complete or partial rotator cuff repair",and " Hamada Ⅰ/Ⅱ level acromiohumeral distance".Pearson correlation analysis was performed to detect the relationship of subgroup factors with postoperative Constant-Murley score and FUSS score.Results All patients were followed up for (38.8 ± 13.0) months.No complications including fever,infection,adhesion or neural malfunction were reported.Mean acromiohumeral distance increased from preoperative (5.4 ± 0.9) mm to (7.0 ± 1.0) mm at the last follow-up (P ＜ 0.05).MRI image showed intact fixation of rotator cuff and transferred latissimus dorsi tendon.At the last follow-up,VAS score decreased from preoperative (4.8 ± 1.4)points to (0.6 ± 0.7)points;the active range of motions was restored significantly;the Constant-Murley score improved from (32.9 ± 9.5) points to (67.4 t 6.7) points;the FUSS score increased from (53.3 ± 9.1) points to (85.1 ± 4.8) points (all P ＜ 0.01).Pearson Correlation analysis indicated that,among subgroup factors,only partial rotator cuff repair was significantly inversely associated with ConstantMurley score (P ＜ 0.05) and FUSS score (P ＜0.01),and the Constant-Murley score and FUSS score of patients with complete repair were significantly higher than those of patients with partial repair (P ＜ 0.05 and P ＜ 0.01,respectively).Conclusions For psMRCT,the effect of arthroscopy-assisted LDT is confirmed,which can relieve pain,restore range of motion and improve shoulder function.Preoperative pseudoparalysis,subacapularis tendon tear,Goutallier Ⅳ level fatty infiltration and Hmada Ⅱ level acromiohumeral distance do not significantly influence postoperative outcome.The torn rotator cuff tear should be repaired as possible.

Objective To discuss the effect of arthroscopic latissimus dorsi transfer with rotator cuff repair for posterosuperior irreparable massive rotator cuff tear (iMRCT).Methods From September 2014 to December 2015,data of 13 iMRCT including 4 male and 9 female who underwent arthroscopic latissimus dorsi transfer with rotator cuff repair were retrospectively analyzed.The age was ranged from 54 to 65,with a mean age of 58.5±4.3.The mean duration of symptom was 2.1±0.6 years.During operation,complete or partial rotator cuff repair was performed,followed by complete repair of injured subscapularis tendon and tenotomy or tenodesis of the long head of biceps tendon.An arc incision was then made in the axillary fossa to harvest latissimus dorsi tendon from its humeral insertion.The tendon was then introduced into subacromial space and fixed at the footprint of greater tuberosity arthroscopically.X-ray and MRI were conducted prior to and one day after the surgery and at the last follow-up.Pain visual analog scale (VAS) and active range of motion in all planes as well as Constant-Murley score and Fudan University shoulder score (FUSS) were documented before the surgery and at the last follow-up.Results All 13 patients accomplished the follow-up,with a duration from 17 to 22 months and a mean period of 19.6±0.9 months.No complications occurred.No re-tear was identified.The mean acromiohumeral distance increased from 5.4± 1.1 mm to 7.0±0.6 mm.The mean VAS decreased from 4.8± 1.3 to 0.5± 0.7.The mean 0° abduction external rotation,90° abduction external rotation,flexion,as well as abduction increased from 17.3°± 10.5°,12.4°±7.8°,89.2°±41.2°,87.3°±40.7° to 41.2°±12.5°,56.5°±16.6°,120.5°±25.1°,and 113.5°±25.4° respectively.Constant-Mur ley score and FUSS increased from 33.5±9.9 and 50.9±7.6 to 62.8±8.1,and 81.7±7.0,respectively.The improvement in all measurements was significant.Condclion For posterosuperior iMRCT,arthroscopic latissimus dorsi transfer with rotator cuff repair can decrease shoulder pain and improve shoulder function.

BACKGROUND:Tissue-engineered transplantation technique has become an ideal therapeutic regimen for degenerative disc diseases through reconstituting the biological functions of the degenerated intervertebral discs.
OBJECTIVE:To construct a novel tissue-engineered annular fibrosus scaffold.
METHODS:Konjac glucomannan, nano-hydroxyapatite and colagen were used to fabricate a new tissue-engineered annular fibrosus scaffold by wet spinning, chemical crosslinking, and freeze drying methods. Afterwards, X-ray diffraction and Fourier transform infrared spectrometer were used to analyze the scaffold qualitative components, physico-chemical property, biomechanical performance and cytocompatibility.
RESULTS AND CONCLUSION:The bionic scaffold had a three-dimensional porous structure, with the average pore size of (425.8±47.3) μm, the average porosity of (73.4±5.6)%, and the water absorption of (718.6±24.3)%. In addition, the compressive strength of the scaffold was similar with that of the natural annular fibrosus. More importantly, the scaffold had good biocompatibility without cytotoxicity. These results show that the tissue-engineered annular fibrosus scaffold constructed by konjac glucomannan, nano-hydroxyapatite and colagen has proper three-dimensional porous structure, biocompatibility, porosity, water absorption and biomechanical strength.