Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

The interaction between skeletal aging and systemic aging has emerged as a frontier in the field of aging biology research.Recent studies have indicated that bones serve not only as mechanical support organs but also as endocrine organs that regulate systemic homeostasis through bone-derived factors.This review systematically elaborates the characteristics and mechanisms of skeletal aging, including tissue structural remodeling, cellular phenotypic changes, microenvironmental disruption, and molecular network disorders, etc.In aging organisms, bones interact with other organs to form a "bone-system aging axis", thereby promoting the occurrence and development of geriatric comorbidities.Accordingly, multi-target intervention strategies targeting the "bone-system aging axis" show the potential in decelerating the progression of systemic aging.In-depth research on the characteristic changes in inter-organ communication during the aging process of the body is not only conducive to facilitating the development of more comprehensive systemic anti-aging strategies, but also provides a new perspective for treating geriatric comorbidities and achieving healthy aging.

The interaction between skeletal aging and systemic aging has emerged as a frontier in the field of aging biology research.Recent studies have indicated that bones serve not only as mechanical support organs but also as endocrine organs that regulate systemic homeostasis through bone-derived factors.This review systematically elaborates the characteristics and mechanisms of skeletal aging, including tissue structural remodeling, cellular phenotypic changes, microenvironmental disruption, and molecular network disorders, etc.In aging organisms, bones interact with other organs to form a "bone-system aging axis", thereby promoting the occurrence and development of geriatric comorbidities.Accordingly, multi-target intervention strategies targeting the "bone-system aging axis" show the potential in decelerating the progression of systemic aging.In-depth research on the characteristic changes in inter-organ communication during the aging process of the body is not only conducive to facilitating the development of more comprehensive systemic anti-aging strategies, but also provides a new perspective for treating geriatric comorbidities and achieving healthy aging.

Background::The potential impact of β cell function and insulin sensitivity on adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM) remains uncertain. We aimed to investigate the association between β cell dysfunction, insulin resistance, and the composite adverse pregnancy outcomes.Methods::This observational study included 482 women diagnosed with GDM during pregnancy. Quantitative metrics on β cell function and insulin sensitivity during pregnancy were calculated using traditional equations. The association of β cell dysfunction and insulin resistance with the risk of the composite adverse pregnancy outcomes was investigated using multivariable-adjusted logistic regression models.Results::Multivariable-adjusted odds ratios (ORs) of adverse pregnancy outcomes across quartiles of homeostatic model assessment for insulin resistance (HOMA-IR) were 1.00, 0.95, 1.34, and 2.25, respectively ( P for trend = 0.011). When HOMA-IR was considered as a continuous variable, the multivariable-adjusted OR of adverse pregnancy outcomes was 1.34 (95% confidence interval 1.16-1.56) for each 1-unit increase in HOMA-IR. Multivariable-adjusted ORs of adverse pregnancy outcomes across quartiles of homeostatic model assessment for β cell function (HOMA-β) were 1.00, 0.51, 0.60, and 0.53, respectively ( P for trend = 0.068). When HOMA-β was considered as a continuous variable, the multivariable-adjusted OR of adverse pregnancy outcomes was 0.57 (95% CI 0.24-0.90) for each 1-unit increase in HOMA-β. However, other quantitative metrics were not associated with the composite adverse pregnancy outcomes. Conclusions::We demonstrated a significant association of β cell function and insulin sensitivity with the risk of adverse pregnancy outcomes. We have provided additional evidence on the early identification of adverse pregnancy outcomes besides the glycemic values.

Objective:To evaluate the clinical, radiological and arthroscopic outcomes after surgical repair for chronic lateral meniscus posterior root (LMPR) avulsion combined with anterior cruciate ligament (ACL) reconstruction.Methods:From July 2015 to June 2017, a total of 33 patients who underwent transtibial pull-out suture repair for chronic LMPR avulsion combined with anatomic single-bundle ACL reconstruction with hamstring graft were retrospectively reviewed. There were 30 males and 3 females with an average age of 27.7±7.5 years (range 17-45 years) and a mean BMI of 25.2±3.7 kg/m 2 (range 19.4-36.7 kg/m 2). All patients were available for at least two years of follow-up. A second-look arthroscopy was performed to evaluate the healing status of the repaired meniscus. Subjective knee function was assessed through Lysholm and Tegner scores. Objective knee stability was evaluated using KT-1000 arthrometer side-to-side difference (SSD) and pivot shift test under anesthesia. The tibiofemoral relationship was evaluated by anterior tibial subluxation (ATS) measured on axial MRI. Between patients with preoperative ATS ≥6 mm (18 patients in the ATS positive group) and <6 mm (15 patients in the ATS negative group), the postoperative ATS and the reduction of ATS was also compared. Results:After a mean follow-up of 27.5±4.0 months (range 24-39 months), the LMPR avulsion completely healed in 23 (70%) cases, partially healed in 9 (27%) cases, failed to heal in 1 (3%) case on second-look arthroscopy. The Lysholm score was increased from 60.4±13.6 to 82.7±11.1 at 1 year and to 91.4±9.1 at 2 years operatively ( F=155.996, P<0.001). The Tegner score was increased from 3(2, 5) to 4(3, 5) at 1 year and 6(4, 6) at 2 years postoperatively (χ 2=47.791, P<0.001). The KT-1000 SSD was decreased from 9.1±3.3 mm to 2.0±1.7 mm ( t=11.197, P<0.001). The result of pivot shift test was also improved (10 grade I, 20 grade II, 3 grade III, preoperatively vs 30 grade 0, 3 grade I, postoperatively, U=5.161, P<0.001). The ATS was reduced from 5.7±3.9 mm to 3.5±3.2 mm ( t=3.530, P=0.001). However, there was no statistically significant decrease in the ATS of the ATS negative group ( t=0.400, P=0.695). The ATS of the ATS positive group was reduced from 8.7±1.8 mm to 5.0±3.3 mm ( t=4.765, P<0.001), and the ATS reduction of the ATS positive group was greater than that of the ATS negative group (3.7±3.3 mm vs 0.3±2.8 mm, t=3.115, P=0.004). Conclusion:In patients undergoing ACL reconstruction, the transtibial pull-out suture repair for chronic LMPR avulsion yielded meniscus healing rate of 97% with improved subjective knee function and objective knee stability and better restored the tibiofemoral relationship for patients with excessive ATS.

Objective:To explore the risk factors of primary anterior cruciate ligament (ACL) reconstruction failure.Methods:From November 2015 to May 2017, a total of 178 consecutive patients with clinically diagnosed non-contact ACL injury were treated and followed-up more than 2 years. Twenty-five patients (post-operative failure group) who underwent completely ruptured ACL graft confirmed by MRI, positive pivot-shift test, more than 5 mm side-to-side difference (SSD) measured by KT-1000 arthrometer, more than 5 mm static anterior tibial translation (ATT) measured on MRI were determined to be ACL reconstruction failure. They were matched in a 1∶2 fashion to 50 non-failure patients (post-operative non-failure group), who showed intact ACL graft 2 years after ACL reconstruction. The sex, age, body mass index (BMI), affected side, meniscal injury side, time from injury to surgery, KT-1000 SSD, pivot shift test under anesthesia, follow-up duration, posterior tibial slope (PTS) and ATT measured on the pre-operative weight-bearing whole leg radiographs between the two groups were compared using univariate analysis. Moreover, the predictors of ACL reconstruction failure were assessed by multivariable conditional Logistic regression analysis.Results:Post-operative failure group had a significantly higher PTS and ATT values than those in the post-operative non-failure group (17.21°±2.20° vs 14.36°±2.72°, t=4.395, P<0.001; 8.29±3.42 mm vs 4.09±3.06 mm, t=5.504, P<0.001). The sex, age, BMI, affected side, meniscal injury side, time from injury to surgery, KT-1000 SSD, pivot shift test under anesthesia, follow-up duration between the two groups showed no significant difference ( P>0.05). Multivariable Logistic regressions indicated that PTS≥17° ( OR=15.62, P=0.002) and ATT≥6 mm ( OR=9.91, P=0.006) were independent risk factors for primary ACL reconstruction failure. However, sex, age, BMI, meniscal lesions, degree of pivot shift test, KT-1000 SSD were not the independent risk factors. Conclusion:PTS≥17° and ATT≥6 mm could increase the risk of primary ACL reconstruction failure.

Objective To investigate the prediction of axillary lymph node metastasis in patients with early breast cancer by sentinel lymph node biopsy (SLNB) combined with preoperative ultrasound.Methods From Jun 2014 to Oct 2018,340 patients with early breast cancer were enrolled in the 5th Department of General Surgery of Second Hospital of Lanzhou University.113 cases were grouped into ultrasound examing,75 patients in the SLNB,and 152 patients in the SLNB combined with preoperative ultrasound.Using the results of axillary lymph node dissection as gold standard,the 3 groups were compared.Results The sensitivity of SLNB,ultrasound and SLNB combined with ultrasound for suspicious axillary lymph node biopsy were 90.1％,85.7％,and 96.4％,respectively.The specificity was 84.0％,76.3％,and 100％,and the accuracy was 91.6％,83.0％,and 97.4％,respectively.The false negative rates were 8.6％,14.3％,and 3.6％,respectively.Conclusion Preoperative ultrasound diagnosis of axillary lymph node status combined with sentinel lymph node biopsy can significantly improve the diagnosis rate of axillary lymph node metastasis in early breast cancer.

Objective To evaluate the effect of fast-track TKA upon the recovery time and degree of satisfaction of the patients.Methods 208 patients with primary osteoarthritis between 2013 and March 2015 were randomly divided into 2 groups.In fast-track TKA group was established in peri-operative analgesia,blood management,postoperative anticoagulation,surgical skill and mitigation of perioperative stress.In TKA group,conventional surgical management mode was followed.Identical discharge standards were established for patients in 2 groups to evaluate the recovery time.The patients' degree of satisfaction at postoperative 2 weeks was assessed by numerical rating scale (NRS).The degree of satisfaction about acquisition of preoperative information,degree of satisfaction about postoperative analgesia and postoperative function were statistically compared between 2 groups.Postoperative complication,blood transfusion rate,infectious events within postoperative 3 months,thrombosis-related events,re-operation and death were recorded.Results In fast-track TKA group,the mean discharge time was (2.3±1.2) d,significantly shorter compared with (4.7±5.1) d in TKA group.The mean NRS score in fast-track TKA group was 9.8±0.5 and 9.1±1.4 in TKA group.In fast-track TKA group,the mean scores of the degree of satisfaction about acquisition of preoperative information,degree of satisfaction about postoperative analgesia and postoperative function were 27.7±7.3,9.8± 1.7 and 9.6± 1.3,significantly higher than 15.5±10.1,9.2±2.2 and 8.7±1.8 in the TKA group.In fast-track TKA group,postoperative blood transfusion rate was 3.9％,considerably lower than 11.4％ in TKA group.Conclusion Fast-track TKA can shorten the length of hospital stay,not increase the mortality rate and postoperative complication,accelerate the recovery of daily activity and effectively enhance the degree of satisfaction of the patients.