Based on Ilizarov's law of tension-stress principle, distraction histogenesis technique has been widely applied in orthopaedic surgery for decades. Derived from this technique, cranial bone transport technique was mainly used for treating cranial deformities and calvarial defects. Recent studies reported that there are dense short vascular connections between skull marrow and meninges for immune cells trafficking, highlighting complex and tight association between skull and brain. Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia without effective therapy. Meningeal lymphatics have been recognized as an important mediator in neurological diseases. The augmentation of meningeal lymphatic drainage might be a promising therapeutic target for AD. Our proof-of-concept study has indicated that cranial bone transport can promote ischemic stroke recovery via modulating meningeal lymphatic drainage function, providing a rationale for treating AD using cranial bone maneuver (CBM). This study aims to investigate the effects of CBM on AD and to further explore the potential mechanisms.

Transgenic 5xFAD mice model was used in this study. After osteotomy, a bone flap was used to perform CBM without damaging the dura. Open filed test, novel object recognition test and Barn's maze test were used to evaluate neurological functions of 5xFAD mice after CBM treatment. Congo red and immunofluorescence staining were used to evaluate amyloid depositions and Aβ plaques in different brain regions. Lymphangiogenesis and the level of VEGF-C were examined after CBM treatment. OVA-A647 was intra-cisterna-magna injected to evaluate meningeal lymphatic drainage function after CBM treatment.

CBM significantly improved memory functions and reduced amyloid depositions and Aβ plaques in the hippocampus of 5xFAD mice. A significant increase of meningeal lymphatic vessels in superior sagittal sinus and transverse sinus, and the upregulation of VEGF-C in meninges were observed in 5xFAD mice treated with CBM. Moreover, CBM remarkably enhanced meningeal lymphatic drainage function in 5xFAD mice (n=5-16 mice/group for all studies).

CBM may promote meningeal lymphangiogenesis and lymphatic drainage function through VEGF-C-VEGFR3 pathway, and further reduce amyloid depositions and Aβ plaques and alleviate memory deficits in AD.

The principal of “function priority, early rehabilitation, and return to sports” is now the goal for sports injury rehabilitation. Neuromuscular electrical stimulation for anterior cruciate ligament (ACL) reconstruction is a rising procedure for early rehabilitation. This paper systematically assessed the effects of neuromuscular electrical stimulation on postoperative ACL reconstruction to provide guidance for physiotherapist and patient when designing a suitable rehabilitation protocol.

To evaluate the interventional outcomes of neuromuscular electrical stimulation following ACL reconstruction, we searched PubMed, EMbase, the Cochrane Library, Web of Science and CNKI to collect all randomized controlled trials (RCTs) comparing the effects with neuromuscular electrical stimulation and without intervention on rehabilitation after ACL reconstruction up to January 30, 2022. Two investigators independently performed literature screening, data extraction, bias assessment of risk, and used RevMan 5.3 software to conduct a meta-analysis.

A total of six RCTs were included, and the results showed that the use of neuromuscular electrical stimulation after anterior cruciate ligament reconstruction significantly improved the International Knee Documentation Committee (IKDC) scores (MD 6.33, 95% CI [-0.43, 12.22]; I2 = 66%; p = 0.040), the Lysholm score (MD 7.94, 95% CI [6.49, 9.39]; I2 = 89%; p < 0.001), and the range of motion (ROM) (MD 9.99, 95% CI [7.97, 12.02]; I2 = 81%; p < 0.001) in the knees when compared to the control group without using neuromuscular electrical stimulation.

Existing evidence show that neuromuscular electrical stimulation is beneficial for early rehabilitation after ACL reconstruction. The use of neuromuscular electrical stimulation is encouraged in the design of rehabilitation protocol. However, due to the limited number of RCT studies and the small sample size, further multi-center RCTs with more participants are needed for a higher-level evidence.