OBJECTIVE: To review the research progress in biotherapy of rotator cuff injury in recent years, in order to provide help for clinical decision-making of rotator cuff injury treatment. METHODS: The literature related to biotherapy of rotator cuff injury at home and abroad in recent years was widely reviewed, and the mechanism and efficacy of biotherapy for rotator cuff injury were summarized from the aspects of platelet-rich plasma (PRP), growth factors, stem cells, and exosomes. RESULTS: In order to relieve patients' pain, improve upper limb function, and improve quality of life, the treatment of rotator cuff injury experienced an important change from conservative treatment to open surgery to arthroscopic rotator cuff repair. Arthroscopic rotator cuff repair plus a variety of biotherapy methods have become the mainstream of clinical treatment. All kinds of biotherapy methods have ideal mid- and long-term effectiveness in the repair of rotator cuff injury. The biotherapy method to promote the healing of rotator cuff injury is controversial and needs to be further studied. CONCLUSION All kinds of biotherapy methods show a good effect on the repair of rotator cuff injury. It will be an important research direction to further develop new biotherapy technology and verify its effectiveness.
Humans ; Rotator Cuff Injuries/therapy* ; Quality of Life ; Arthroplasty ; Exosomes ; Neurosurgical Procedures

Lipophagy, the selective engulfment of lipid droplets (LDs) by autophagosomes for lysosomal degradation, is critical to lipid and energy homeostasis. Here we show that the lipid transfer protein ORP8 is located on LDs and mediates the encapsulation of LDs by autophagosomal membranes. This function of ORP8 is independent of its lipid transporter activity and is achieved through direct interaction with phagophore-anchored LC3/GABARAPs. Upon lipophagy induction, ORP8 has increased localization on LDs and is phosphorylated by AMPK, thereby enhancing its affinity for LC3/GABARAPs. Deletion of ORP8 or interruption of ORP8-LC3/GABARAP interaction results in accumulation of LDs and increased intracellular triglyceride. Overexpression of ORP8 alleviates LD and triglyceride deposition in the liver of ob/ob mice, and Osbpl8-/- mice exhibit liver lipid clearance defects. Our results suggest that ORP8 is a lipophagy receptor that plays a key role in cellular lipid metabolism.
Animals ; Mice ; Lipid Droplets ; Autophagy ; Autophagosomes ; Homeostasis ; Triglycerides

Objective:To investigate the clinical efficacy of induced membrane technique in the staged treatment of adult chronic hematogenous osteomyelitis (CHOM) of long bone.Methods:The clinical data were retrospectively analyzed of the 22 adult patients with CHOM of long bone who had been admitted to the 920th Hospital, Joint Logistics Support Force of PLA from January 2016 to December 2019. There were 18 males and 4 females, aged from 16 to 56 years (average, 31.81 years). Their disease duration ranged from 0.6 to 42.0 years, averaging 18.4 years. By the Cierny-Mader anatomical classification, 4 cases were type Ⅰ, 6 cases Type Ⅲ, and 12 cases type Ⅳ. In the first stage, the bone defects were filled with antibiotic bone cement after thorough debridement. In the second stage when the infection had been controlled, the bone defects were repaired with bone grafts after removal of the bone cement. Bone healing time and complications were followed up. The treatment effects were evaluated by comparisons of the infection control indexes [including clinical manifestations like local redness, swelling, pus, and pain, and blood white blood cell count, C-Reactive protein (CRP), and erythrocyte sedimentation rate (ESR) as well] before the primary surgery, before the secondary surgery and at the last follow-up.Results:The volumes of the bone defects after stage-one debridement ranged from 54 cm 3 to 176 cm 3 (mean, 90.9 cm 3). All patients were followed up for 20 to 51 months (mean, 30.1 months) after surgery. All bone defects healed after 4 to 11 months (mean, 6.6 months). Postoperatively, infection developed at the bone extraction site of the posterior superior iliac spine in 3 cases and pain was observed at the donor site in one case, but the conditions were relieved after symptomatic treatment. Fracture and plate breakage occurred at the bone defect site in one case who had fallen down 7 months after operation, but responded to reoperation. The last follow-up revealed such symptoms as redness, swelling and pus discharge in none of the patients. The white blood cell count [(5.70 ± 1.57) × 10 9/L and (5.65 ± 1.58) × 10 9/L], CRP [(7.56 ± 2.57) mg/L and (7.25 ± 3.83) mg/L] and ESR [(9.64 ± 2.90) mm/h and (10.55 ± 5.23) mm/h] before the secondary surgery and at the last follow-up were significantly lower than those before the primary surgery [(8.24 ± 2.18) × 10 9/L, (49.54 ± 19.56) mg/L, and (42.68 ± 13.77) mm/h] (all P < 0.05). However, there were no significant differences between the indexes before the secondary surgery and at the last follow-up ( P > 0.05). Conclusion:In the staged treatment of adult CHOM of long bone, the induced membrane technique can effectively control infection, achieve repair of bone defects, and reduce complications.

OBJECTIVES: Cardiac hypertrophy and fibrosis are major pathological manifestations observed in left ventricular remodeling induced by angiotensin II (AngII). Low-intensity pulsed ultrasound (LIPUS) has been reported to ameliorate cardiac dysfunction and myocardial fibrosis in myocardial infarction (MI) through mechano-transduction and its downstream pathways. In this study, we aimed to investigate whether LIPUS could exert a protective effect by ameliorating AngII-induced cardiac hypertrophy and fibrosis and if so, to further elucidate the underlying molecular mechanisms. METHODS: We used AngII to mimic animal and cell culture models of cardiac hypertrophy and fibrosis. LIPUS irradiation was applied in vivo for 20 min every 2 d from one week before mini-pump implantation to four weeks after mini-pump implantation, and in vitro for 20 min on each of two occasions 6 h apart. Cardiac hypertrophy and fibrosis levels were then evaluated by echocardiographic, histopathological, and molecular biological methods. RESULTS: Our results showed that LIPUS could ameliorate left ventricular remodeling in vivo and cardiac fibrosis in vitro by reducing AngII-induced release of inflammatory cytokines, but the protective effects on cardiac hypertrophy were limited in vitro. Given that LIPUS increased the expression of caveolin-1 in response to mechanical stimulation, we inhibited caveolin-1 activity with pyrazolopyrimidine 2 (pp2) in vivo and in vitro. LIPUS-induced downregulation of inflammation was reversed and the anti-fibrotic effects of LIPUS were absent. CONCLUSIONS These results indicated that LIPUS could ameliorate AngII-induced cardiac fibrosis by alleviating inflammation via a caveolin-1-dependent pathway, providing new insights for the development of novel therapeutic apparatus in clinical practice.

Objective: To investigate the role and mechanism of Hydroxysafflor yellow A (HSYA) in the calcification of vascular smooth muscle cells (VSMC) induced by β-glycerol phosphate (β-GP). Methods: VSMC were cultured with 10% fetal bovine serum+1% double anti-high glucose DMEM medium at 37℃ and 5%CO₂ incubator, and were subcultured according to cell growth density at 1∶4 ratio. The cells were divided into three groups: control group (NC), high-phosphate-induced calcification (HP) group, and HSYA intervention (HSYA) group. The Calcium deposition amount was measured by alizarin red staining and calcium determination kit. The expressions of ALP, RUNX2, RANKL, α-SMA and inflammation indicators TLR4, TNF-α, IL-8 were detected by Western blotting method; Western blotting was also used to detect calcification index alkaline phosphatase (ALP) and Runt-related transcription factor 2 (RUNX2). Nuclear factor kappa B receptor activating factor ligand(RANKL), α-smooth muscle actin (α-SMA), and the expressions of TLR4/NF-κB pathway and inflammatory response-related indicators Toll-like receptor 4 (TLR4), interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-α). The nuclear protein and cytoplasmic proteins were respectively extracted. The expressions of p65 in nucleus and cytoplasm, as well as the expressions of p65 and phosphorylated p65 in total proteins were detected by Western blotting method. Superoxide dismutase (SOD) and malondialdehyde (MDA) kit were used to detect the content of antioxidant enzymes and oxidation end products in cells. Results: Western blotting showed that the expressions of ALP, RUNX2 and RANKL in HSYA group were significantly lower than that in HP group. The expression of α-SMA was increased than that of HP group (all P<0.01). The expression levels of TLR4, TNF-α, IL-8 and p-NF-κB/p65 in HSYA group were decreased compared with that in the HP group, and p65 was decreased in nucleus and increased in cytoplasm (all P<0.05). SOD content in HSYA group was significantly higher than that in HP group, and MDA content was significantly lower than that in HP group (all P<0.01). Conclusions HSYA can reduce calcification and calcium deposition of vascular smooth muscle cells induced by high phosphorus. The mechanism is related to the inhibition of the activation of TLR4/NF-κB pathway and the inhibition of oxidative stress.

Objective To investigate the influence mechanism of Cordyceps sinensis (CS) on β-glycerophosphate-induced vascular smooth muscle cell (VSMC) calcification.Methods The effect of CS on VSMC cell viability was detected by CCK-8.The cellular models of rat VSMC calcification were established by treating with β-glycerophosphate (β-GP,10 mmol/L);then CS (10 mg/L),autophagy inhibitor 3-methyladenine (3-MA,5 mmol/L),and AMPK inhibitor compound C (CC,10 μmol/L) were added to the cell cultures.There were a total of 5 experiment groups:VSMC cultured in normal medium (Control),VSMC treated with β-GP,VSMC treated with β-GP and CS,VSMC treated with 3-MA,β-GP and CS,and VSMC treated with CC,β-GP and CS.The calcium nodules and calcium content were examined with alizarin red S staining and the O-cresolphthaleincomplexone method,respectively.The autophagosomes within the VSMC were observed using transmission electron microscope (TEM).Immunofluorescence showed the accumulation of microtubule-associated protein 1 light chain 3 (LC3) puncta.In addition,levels of osteogenic related proteins,autophagy related proteins,and AMPK/mTOR pathway related proteins were evaluated by Western blotting.Results CS increased the number of autophagosomes and the accumulation of LC3 puncta within VSMC.It also upregulated the protein levels of LC3 Ⅱ/LC3 Ⅰ,beclin1,α-SMA,and p-AMPK;whereas,the protein levels of Runx2 and p-mTOR,as well as calcium nodules and calcium content were reduced (all P ＜ 0.01).When the cells were pretreated with 3-MA before treating with β-GP and CS,the autophagosomes,accumulation of LC3 puncta,and protein levels of LC3 Ⅱ/LC3 Ⅰ,beclinl,and α-SMA were decreased (all P ＜ 0.01);however,the protein level of Runx2,and the calcium nodules and calcium content were increased (all P ＜ 0.01).Nevertheless,when the cells were pretreated with CC before giving β-GP and CS,the autophagosomes,the accumulation of LC3 puncta,and the expression levels of p-AMPK,LC3 Ⅱ/LC3 Ⅰ,beclin1,and α-SMA were significantly down-regulated (all P ＜ 0.01);whereas,the expression levels of Runx2 and p-mTOR,as well as calcium nodules and calcium content were increased (all P ＜ 0.01).Conclusions CS can effectively alleviate β-GP-induced VSMC calcification,which may be due to the activation of autophagy by AMPK/mTOR signaling pathway.

OBJECTIVE: To observe the change of the specificity of the microcirculatory blood perfusion at the area of "Feishu" (BL 13) in the rats of chronic obstructive pulmonary disease (COPD). METHODS: According to the random number table, 60 Wistar rats were divided into a 29 d model No. 1 group (C1 group), a 29 d normal control No.1 group (N1 group), a 89 d model No.2 group (C2 group) and a 89 d normal control No. 2 group (N2 group), 15 rats in each one. In the C1 and C2 groups, the smoking and intratracheal drops of endotoxin were used in combination to prepare COPD model. The rats were fed normally in the N1 and N2 groups. "Feishu" (BL 13), "Xinshu" (BL 15), the lateral site of "Feishu" (BL 13) and the lateral site of "Xinshu" (BL 15) were selected as the monitoring points. The pericam perfusion speckle imager (PeriCam PSI System) was adopted to monitor the microcirculatory perfusion unit (PU) at the monitoring points before and in 29 d and 89 d after modeling separately. RESULTS: Before modeling, the differences in PU were not significant at each monitoring point in comparison among the 4 groups and the differences were not significant among "Feishu" (BL 13) and "Xinshu" (BL 15) as well as their lateral sites (all >0.05). After modeling, PU was increased at each monitoring point in the C1 and C2 groups (all <0.05). PU in the C1 group was higher than the N1 group and that in the C2 group was lower than the N2 group, PU at each monitoring point in the C1 group were higher than the C2 group, indicating the significant differences (all <0.05). In the C1 and C2 groups, the specific change occurred, in which PU at "Feishu" (BL 13) was higher than its lateral site. But such specific change did not happen in the N1 and N2 groups. CONCLUSION PU at "Feishu" (BL 13) presents the specific change relevant with the sickness duration in the COPD rats.
Acupuncture Points ; Animals ; Microcirculation ; Pulmonary Disease, Chronic Obstructive ; Rats ; Rats, Wistar

Objective To evaluate surgical treatment of chronic tibial osteomyelitis of Cierny-Mader type Ⅳ with Ilizarov technique and lesion osteotomy. Methods From January 2010 to May 2016, 39 patients with chronic tibial osteomyelitis of Cierny-Mader type Ⅳ were treated at our center. They were 33 males and 6 females, 8 to 54 years of age (average, 33.8 years). After debridement and lesion osteotomy, the tibia was fixated with Ilizarov external fixator. Bone was transported to the bone defect after corticotomy was performed on the proximal and/or distal tibial metaphyses simultaneously. Bifocal corticotomy was per-formed in 11 cases, proximal corticotomy in 21 cases, and distal corticotomy in 7 cases. The transport began 3 to 5 days after operation at a speed of 0.5 to 1.0 mm/d initially. The speed was lowered according to the bone healing and pain. Radiographic examination was done every 2 weeks to observe transporting deviation and osteogenesis in the transporting area. The transporting was adjusted whenever any abnormality was observed. The bone transporting lasted for 50 to 130 days (average, 62.4 days). Results The patients were fol-lowed up for 11 to 49 months (average, 21 months). All the soft tissue wounds healed uneventfully and there was no relapse of osteomyelitis. The bone defects in the 32 cases were reconstructed primarily. Nonunion of fracture ends happened in 5 cases and nonunion of the bone lengthening zone in 2 cases. The 7 cases of nonunion were healed after secondary bone grafting. Malalignment happened in 5 cases, 4 of which responded to timely adjustment of the external fixation and one of which had to receive secondary bone grafting after failure in adjustment of the external fixation. Ankle joint dysfunction occurred in 7 cases, 5 of which re-sponded to functional exercise and 2 of which accepted joint dysfunction because they refused surgery after unsatisfactory functional exercise. Pin tract infection of different severities occurred in 9 cases, one of which was treated by replacement of the K-wires under local anesthesia and the other 8 of which responded to rein-forced dressing change. Conclusions Chronic tibial osteomyelitis of Cierny-Mader typeⅣcan be treated by Ilizarov technique and lesion osteotomy. However, the Ilizarov technique should be improved because of the risks of multiple complications which can be reduced significantly by strengthening postoperative instruction, nursing, and regular follow-up.

Objective To investigate the possible mechanism of sclerostin/Lrp4 in calcification of VSMC induced by high phosphorus and the protective effect of Ginkgo biloba extract.Methods Aortic vascular smooth muscle cells (VSMCs) of SD rats were extracted and identified.VSMCs were divided into normal control group,high phosphorus induced calcification group (10 mmol/L β-glycerophosphate+50 μg/ml ascorbic acid),and high phosphorus induced calcification+Ginkgo biloba extract intervention group (10 mmol/L β-glycerophosphate+50 μg/ml ascorbic acid+0.5 mg/ml GBE),cultured in different mediums for 14 days.Vonkossa staining and alizarin red staining were used to detect the calcification of VSMCs.The mRNA level of BGP was detected by real time PCR,and the protein expressions of sclerostin and Lrp4 were detected by Western blot.Results Compared with normal control group,vonkossa staining and alizarin red staining showed significant calcium deposition in calcification group.Compared with calcification group,calcium salt deposition was significantly reduced in GBE treatment group.Real time PCR results showed β-catenin and BGP mRNA expressions in VSMC calcification group were higher than those in normal control group (P＜ 0.05).mRNA expressions of β-catenin and BGP in GBE treatment group were lower than those in calcification group (all P ＜ 0.05).Compared with normal control group,the protein expression of sclerostin was increased,but the protein expression of Lrp4 was decreased in calcified group (all P ＜ 0.05).Compared with calcification group,the protein expression of sclerostin decreased and the protein expression of Lrp4 increased in GBE treatment group (all P ＜ 0.05).Conclusions High phosphorus can induce VSMC calcification by activating Wn/β-catenin signaling pathway.Sclerostin/Lrp4 is involved in hyperphosphine-induced VSMC calcification.GBE can reduce the high phosphorus induced VSMC calcification by regulating the Wnt/β-catenin signaling pathway.

Objective To retrospectively analyze the injury characteristics of victims and treatment strategies in the explosion accident on the 17th May 2018 in Xixia county (Xixia "May 17th" explosion accident). Methods Based on the practice featured in pre-hospital emergency of Henan province and Nanyang city Emergency Center in the explosion accident, a retrospective analysis for the Level Three medical rescue was conducted, where a total of thirteen survived victims in Xixia "May 17" explosion accident were studied retrospectively. The data included the gender, age, burned extent and depth of the patients, burns complicated by trauma, complication of burn, respiratory function maintenance, resuscitation during shock stage, skin grafting with excision and scab. Furthermore, the data of organ function and the effect of the 90-day comprehensive treatment for the burned victims wereanalyzed. Results completion the Level Three treatment on time, which was depended on the leading role played by the regional trauma centers was the main rescuing mode of the work in Xixia county, where the primary and secondary treatments were the key parts. The three-level treatment model includes: the local hospital acts as a level-one emergency medical institution, county hospitals function as secondary emergency medical institutions, and other higher medical institutions are the tertiary first aid medical institutions. The pre-hospital and in-hospital emergency procedures were initiated immediately after the large-scale explosive burn being identified, the key to the successfully rescue was to set up a comprehensive treatment team for burns and trauma. Rescue team should involve burn department and other related departments, including the departments of emergency, general surgery, orthopedic, thoracic surgery, neurosurgery, plastic surgery, intensive care unit, blood transfusion unit, anesthesiology, and interventional radiology, etc. All the thirteen burned patients were male, with inhalation injury, blast injury, hemopneumothorax, brain injury, bone fractures, and etc. Eight of them (61.54%) had multiple organ dysfunction syndrome (MODS). MODS mainly involved respiratory, circulatory, liver, gastrointestinal tract, kidney and coagulation function. With the multi-discipline treatment, the wound of 6 severely-burned patients started healing and can be discharged after keeping the patency of airway, applying resuscitation fluid and comprehensive treatments such as debridement and dressing change. Among 7 patients with extensive deep burns, one case with skull-based fracture, open craniocerebral, extensive intracranial hemorrhage and hemopneumothorax, died 9 hours later. Another case died within 24 hours after injury due to obvious exudation on the site of early incision and relaxation of wound. The escharotomy, micro-dermis and allograft skin transplantation were carried out for five cases with extensive deep burns from the 4th day after the recovery of shock. One week later, the second stage of microsphere skin transplantation was performed. But all died of sepsis or fungal infection. Conclusions MODS and infection often occur during the course especially for patients with extensive and deep burns due to the great explosion in Xixia county, most of whom were accompanied with MODS and infection. Therefore, assembling multi-discipline team for treating the group of explosively-burned patients can increase the survival rate and reduce the possibility of disability.