BACKGROUND: Implantation of bone marrow mesenchymal stem cells (BMSCs) is a potential alternative for promoting bone defects healing or osseointegration in osteoporosis. However, the reactive oxygen species (ROS) accumulated and excessive inflammation in the osteoporotic microenvironment could weaken the self-replication and multi-directional differentiation of transplanted BMSCs. METHODS: In this study, to improve the hostile microenvironment in osteoporosis, Poloxamer 407 and hyaluronic acid (HA) was crosslinked to synthetize a thermos-responsive and injectable hydrogel to load MnO2 nanoparticles as a protective carrier (MnO2 @Pol/HA hydrogel) for delivering BMSCs. RESULTS: The resulting MnO2 @Pol/HA hydrogel processed excellent biocompatibility and durable retention time, and can eliminate accumulated ROS effectively, thereby protecting BMSCs from ROS-mediated inhibition of cell viability, including survival, proliferation, and osteogenic differentiation. In osteoporotic bone defects, implanting of this BMSCs incorporated MnO2 @Pol/HA hydrogel significantly eliminated ROS level in bone marrow and bone tissue, induced macrophages polarization from M1 to M2 phenotype, decreased the expression of pro-inflammatory cytokines (e.g., TNFa, IL-1b, and IL-6) and osteogenic related factors (e.g., TGF-b and PDGF). CONCLUSION This hydrogel-based BMSCs protected delivery strategy indicated better bone repair effect than BMSCs delivering or MnO2 @Pol/HA hydrogel implantation singly, which providing a potential alternative strategy for enhancing osteoporotic bone defects healing.

Objective:To evaluate the efficacy of arthroscopic suture combined with perforator tendon double reduction and Endobutton plate technique for the treatment of tibial avulsion fracture of posterior cruciate ligament (PCL).Methods:A retrospective case series study was conducted to analyze the clinical data of 32 patients with tibial avulsion fracture of PCL, who were admitted to First People′s Hospital of Huizhou from January 2018 to October 2022. There were 19 males and 13 females, with age range of 18-65 years [(42.8±15.0)years]. By the Meyers-Mckeever classicfication, 27 patients were type II, and 5 type III. All the patients were treated with arthroscopic suture combined with perforator tendon double reduction and Endobutton plate technique to fix PCL tibial avulsion fracture at the insertion point. The fracture reduction was observed by X-ray films before discharge. Three months postoperatively, the fracture healing was observed by CT imaging, and the stability of knee joint was evaluated by posterior drawer test. The knee active range of motion, visual analogue score (VAS), Lysholm score, and International Knee Documentation Committee (IKDC) score were used to evaluate the pain and knee function before operation, at 3 months after operation, and at the last follow-up. Intraoperative and postoperative complications were observed.Results:All the patients were followed up for 6-36 months [(19.7±8.7)months]. The X-ray films showed satisfactory reduction of the fracture before discharge, and the CT showed that the fracture line was blurred to various degrees at 3 months after operation. Two patients had degree I positive posterior drawer test at 3 months after operation, and the rest were negative. The knee active range of motion was improved from 54.2°(45.0°, 70.0°) preoperatively to 124.8°(120.0°, 130.0°) at 3 months postoperatively and to 130.6°(125.0°, 135.0°) at the last follow-up (all P<0.01). The VAS was decreased from 5.1(3.0, 7.0)points preoperatively to 1.2(1.0, 2.0)points at 3 months postoperatively and to 0.1(0.0, 0.0)points at the last follow-up (all P<0.01). The Lysholm score was improved from 31.2(24.3, 37.0)points preoperatively to 73.6(69.3, 78.8)points at 3 months postoperatively and 92.6(91.0, 95.0)points at the last follow-up (all P<0.01). The IKDC score was increased from (20.9±7.1)points preoperatively to (59.2±8.9)points at 3 months postoperatively and to (77.5±7.0)points at the last follow-up (all P<0.01). Compared with 3 months after operation, the last follow-up showed significantly improved knee active range of motion, significantly decreased VAS, and significantly increased Lysholm score and IKDC score (all P<0.05). No intraoperative nerve vascular injury, postoperative incision infection, or lower limb venous thrombosis was observed. Conclusion:Arthroscopic suture combined with perforator tendon double reduction and Endobutton plate technique can achieve good reduction and high healing rate in patients with tibial avulsion fracture of PCL, with improved joint mobility, relieved pain, good recovery of knee joint function, and few complications.

Objective:To explore the correlations of α-melanocyte stimulating hormone ( α-MSH) levels in serum and synovial fluid with progression of primary knee osteoarthritis (KOA). Methods:A retrospective analysis was conducted of the 96 patients who had been diagnosed as primary KOA at Department of Orthopedics, The First Hospital of Huizhou from October 2018 to October 2019. Radiographic severity of KOA was determined by Kellgren-Lawrence (K-L) grades; α-MSH levels were measured by enzyme-linked immunosorbent assay (ELISA). Levels of pro-inflammatory cytokine interleukin-1 β (IL-1 β) and matrix metalloproteinase-3 (MMP-3) were also detected. Another 64 patients with patellar dislocation, matched in age and gender, were enrolled as controls. The Numeric Pain Scale (NPS) and revised Oxford Knee Score (OKS) were employed to evaluate their symptomatic severity. Receiver operating characteristics (ROC) curve was used to compare α-MSH, IL-1 β and MMP-3 with regard to their diagnostic values in the K-L grading. Results:There were no statistically significant difference in age, gender and body mass index between the 2 groups, showing they were comparable ( P> 0.05). The α-MSH levels in synovial fluid were significantly lower in the KOA patients than in the controls [(16.9±3.8) pg/mL versus (18.8±2.7) pg/mL] ( P<0.001); there were no significant differences between the KOA patients and the controls in the serum α-MSH levels [(24.9±1.8) pg/mL versus (24.8±1.7) pg/mL] ( P>0.05). The α-MSH levels in synovial fluid were negatively correlated with K-L grades ( r=-0.382, P<0.001) and negatively correlated with NPS ( r=-0.382, P<0.001) but positively correlated with OKS ( r=0.339, P<0.001). Moreover, the α-MSH levels in synovial fluid were negatively correlated with the IL-1 β levels in synovial fluid ( r=-0.483, P<0.001) and with the MMP-3 levels in synovial fluid ( r=-0.336, P< 0.001). Conclusions:The level of serum α-MSH may not be correlated with the progression of KOA but the synovial fluid α-MSH is negatively correlated with the progression of KOA. Therefore, the expression level of α-MSH in joint synovial fluid can be used as a potential biomarker for assessment of severity of knee osteoarthritis.

Objective　This study retrospectively analyzed reported cases of subacute combined degeneration of spinal cords(SCD).The purpose of this study was to provide theoretical basis for the prevention,diagnosis,treatment and research of SCD.Methods　We searched the PubMed database for terms related to subacute combined degeneration of spinal cords from March 2,2019 to January 1,1990.255 cases were finally included in the study.Results　The common causes of SCD were Vitamin B12 deficiency (128 cases),inhaled N-2O (70 cases) and copper deficiency (31 cases).The disease usually happened on middle-ager (44.5±19.9) years old.The course of the disease is relatively long (36.5±85.1) weeks.Limbs hypoesthesia was the most common symptom (73.3%),followed by ataxia (61.6%),and limb motor system could also be involved (35.3%).Autonomic nervous system,cranial nerve,consciousness disorder and cognitive disorder are rare.The patients were often complicated with giant cell anemia (72.5%) and hyperhomocysteinemia (80.9%).Spinal cord MR could show abnormal signal shadow in posterior cord (82.9%),most of which occurred in cervical cord.Conclusion　Vitamin B12 deficiency was the most common cause of SCD in adults and N-2O abuse must be paid attention in young people.Most patients of SCD showed peripheral nervous system damage that sensory system damage is common.Abnormal signal shadow in posterior cord of spinal MR was specific for the diagnosis of SCD.Most patients with SCD have a good prognosis after treatment.

Objective:To investigate the correlation of mRNA and protein levels of Ghrelin in shoulder tissue and synovial fluid with severity of rotator cuff tear(RCT) and frozen shoulder(FS).Methods:Recruited for this study were 66 RCT and 66 FS patients who had been definitely diagnosed at Department of Orthopedics, The First Hospital of Huizhou from January 2018 to September 2019. Another 60 patients with rotator instability were recruited as a control group. After the severity of RCT was evaluated by ultrasonographic images, the RCT group was further divided into 3 subgroups according to the severity of RCT: a massive full thickness tear (MFTT) subgroup, a non massive full thickness tear (MFTT) subgroup, and a partial thickness tear (PTT) subgroup. The FS group was conventionally divided into 31 cases of acute phase and 35 cases of adhesive phase. Samples of subacromial bursa and shoulder joint bursa tissues and shoulder joint synovial fluid were collected. The expression of Ghrelin mRNA was detected by RT-PCR and the expression of Ghrelin protein in joint synovial fluid was detected by ELISA. The symptoms and functions of shoulder joint were evaluated by visual analogue scale (VAS) and Constant-Murley functional score.Results:There were no significant differences in gender or age between the RCT, FS and control groups, showing compatibility ( P>0.05).The expression of Ghrelin mRNA in subacromial synovial capsule and shoulder joint capsule and the expression of Ghrelin protein in shoulder synovial fluid in the RCT and FS groups were significantly lower than those in the control group ( P<0.05).The expression of Ghrelin mRNA in subacromial synovial capsule and shoulder joint capsule and the expression of Ghrelin protein in shoulder synovial fluid in the PTT subgroup were the highest, followed sequentially by NMFTT and MFTT subgroups, with significant differences between subgroups ( P<0.05). For FS patients, the expression levels of Ghrelin mRNA and protein in the acute phase were significantly lower than in the adhesive phase ( P<0.05). The relative expression of Ghrelin mRNA in joint capsule and the expression of Ghrelin protein in shoulder synovial fluid were negatively correlated with VAS scores and IL-6 levels (all P<0.05), and positively correlated with the Constant-Murley scores (all P<0.05). Conclusions:The expression of Ghrelin in shoulder tissue and synovial fluid is negatively correlated with the progress of rotator cuff tear and frozen shoulder.Local supplementation of Ghrelin may be a potential therapy for rotator cuff tear and frozen shoulder.

Objective To apply intervention of integrated pharmaceutical care (IPC) for asthma-COPD overlap syn-drome patients,so as to reduce the side effects of drugs,enhance medication compliance,promote reasonable drug application,cut down the medical expenses in ACOS patients. Methods A total of 60 ACOS patients were randomly divided into IPC group (group A) (n=34) and contrast group(group B) (n=26).The patients in group A were given IPC measurements such as noso-comial guidance,classroom teaching,regular follow-up,life coaching and psychological advice.While the patients in group B were not given any intervention measures. Results In group A,patients' awareness rate of action and side-effects of drugs were ob-viously increased;Knowledges of inhalation preparation were greatly improved;the ratio of ADRs was significantly reduced;The FEV1 and the value added of FEV1 was dramatically improved.Furthermore,the differences showed statistical significance as com-pared with group B(P<0.05).Total medical costs and anti-bacterial drug costs per year were significantly lower in group A than group B. Conclusion IPC is beneficial to enhance drug compliance,promote reasonable drug application and bring down the medical expenses in ACOS patients.

Objective: To investigate the history, risk factors for prognosis of malignant biliary stricture (MBS) patients receiving conservative therapy after endoscopic retrograde cholangiopancreatography(ERCP) and to set up a predictive model for overall survival (OS). Methods: MBS patients who underwent ERCP and conservative therapy in Xijing Hospital and PLA No.451 Hospital from January 2009 to December 2013 were enrolled to the present study. Predictive factors associated with OS were identified in the training cohort by stepwise multivariate Cox regression analysis. A predictive model was then developed and externally validated in the validation cohort. Results: Between January 2009 and December 2013, 152 and 149 patients were eligible to the training and validation cohort respectively. In the training cohort, tumors were mainly originated from bile duct (33.6%), pancreas (23.5%) or ampulla (20.4%). 76.3% (116/152) patients died during the observation period. The median OS for the training population was 5.0 months (3.9-6.2 months). CA19-9≥1 000 U/mL, non-ampulla tumor, metastasis, pre-ERCP total bilirubin≥7 mg/dL and hilar stricture were identified as independent predictive factors of poor OS (all P<0.05). Based on these factors, the COMTH predictive model was developed. The median OS of patients with COMTH>8 in the training and validation cohorts were both 3.0 months, which were significantly shorter than those with COMTH≤8 (10.0 and 6.9 months in the training and validation cohorts respectively, both P<0.001). Conclusion The prognosis of MBS patients undergoing ERCP is poor. The survival chance of patients with COMTH>8 is even more dismal.

Objective:To bring to doctors' attention to the first time attack of epilepsy in the patients with Parkinson' s disease, enhance the rational drug use and reduce the occurrence of adverse reactions in clinics. Methods: A Parkinson patient with the first time attack of epilepsy was synthetically analyzed on the mechanism of disease, therapy regimen and pharmaceutical care. Results:It was difficult to distinguish the symptom of epilepsy during the treatment of Parkinson' s disease from that of L-dopa induced dyskinesia, therefore, the suitable treatment was difficult to perform. Moreover, antiepileptic drug valproic acid could aggravate Parkinson syn-drome imperceptibly, which was easy to be ignored in clinics. Conclusion:L-dopa induced dyskinesia should try to avoid during the treatment of Parkinson, and should distinguish from the first time attack of epilepsy in order to choose proper antiepileptic drugs.

Objective To examine the prevalence of chikungunya virus in brain tissue samples from rat?like animals in Xiamen, Shenzhen and Guangzhou, and to explore whether the rat?like animals are potential sources of human chikungunya fever infections and the host of the virus. Methods Rat?like animals were trapped in residential areas, city parks, hospitals, markets and schools in Xiamen, Shenzhen and Guangzhou (Yuexiu and Baiyun districts) between January 2013 and June 2016. Brain tissue samples of the trapped animals were collected under sterile. Chikungunya virus was detected by using reverse transcription polymerase chain reaction (RT?PCR). Results Totally 1092 rat?like animals were trapped, which belonged to 7 species, 3 genera, 2 families, 2 orders. Rattus norvegicus was the dominant species in the indoor environment, Rattus losea was dominant in wild environment, and 1092 brain tissue samples were collected. No detectable chikungunya virus was found in the brain tissue samples by RT?PCR. Conclusion There is a low possibility that rat?like animals act infectious sources of human chikungunya fever infections and the host of the virus.

Aim To observe the effect of mineralocor-ticoid receptor blockade eplerenone on cell proliferation in obstructed kidney of rats. Methods Renal intersti-tial fibrotic animals were made with unilateral ureteral obstruction (UUO) and treated with eplerenone100 mg · kg - 1 · d - 1 . The kidneys were harvested on the 10th day and proliferating cell nuclear antigen ( PC-NA ), serum and glucocorticoid induced kinase-1 (SGK-1 ) and transforming growth factor-β1 ( TGF-β1 ) were detected with immunohistochemistry and Western blot. Results Renal histopathology showed large quantities extracellular matrix (ECM) accumula-tion in kidney with UUO, large numbers of inflammato-ry cells infiltrated in renal interstitium, renal tubular expansion and exfoliation of epithelial cells . The cell proliferation and ECM accumulation were inhibited in eplerenone treated rats significantly. Immunohisto-chemistry and Western blot showed that expressions of PCNA,SGK-1 and TGF-β1 were significantly up-regu-lated with UUO and down-regulated by eplerenone. Conclusion Eplerenone plays the role in inhibiting the cell proliferation and reducing ECM accumulation by down-regulating expression of SGK-1 pathway in rats with unilateral ureteral obstruction.