Objective:To prepare hydroxyapatite(HA)coating on polyether ether ketone(PEEK)surface by magnetron sputtering technique and to study its biosafety.Methods:Sulfonated PEEK was used to increase the binding area and HA coating was constructed on it using magnetron sputtering technology.SEM and energy dispersive spectroscopy(EDAX)were used to detect the construction effect.Cell adhesion assay,cytoskeletal fluorescence staining and SEM validation were used to assess cytologrcal safety.In vivo safety tests were conducted in SD rats and golden hamsters.Results:HA coating with gradient morphology was successfully constructed on the PEEK surface using above technique.The coating promoted cell adhesion,extension and proliferation.No systemic toxicity and no sig-nificant influence in HE staining of the main infernal organs samples were observed.The coating alleviated the oral mucosal irritation caused by simple sulfonation to a certain extent.Conclusion:HA coating can be prepared stably with magnetron sputtering technology and can meet the biosafety needs for clinical applications.

Wound healing is a complex process of biological integration in which the adverse conditions such as excessive inflammatory reactions, cell proliferation and migration disorders, and cellular secretion impairment can lead to refractory wounds. Characterized by complex etiology, protracted condition, and high morbidity and recurrence rate, refractory wounds severely impair patients′ physical and mental health. In clinical practice, refractory wounds are primarily treated with surgical debridement and skin transplantation, but there still exist problems such as large surgical wounds, prolonged recovery time, and high recurrence rate. In recent years, owing to the multipotent differentiation, immunomodulatory, and paracrine functions of stem cells, cell-assisted lipotransfer (CAL) technique, which involves intra-body injection of a mixture of autologous adipose-derived stem cells (ADSCs) and granular fat for refractory wound repair, has demonstrated promising application prospects. It is of great significance in its clinical application to clarify the mechanism of effects of CAL technique in refractory wound repair. The authors reviewed the research progress in the mechanism of effects of CAL technique in repairing refractory wounds to provide references for the research and treatment of refractory wounds.

Abstract: Objective To investigate the type and distribution of drug resistance of Mycobacterium tuberculosis (MTB) in Hainan tuberculosis hospital from 2019 to 2021, and to provide reference for the development of drug resistant tuberculosis prevention and control strategy. Methods From 2019 to 2021, a total of 1 687 strains of sputum were isolated and cultured and identified as MTB. Drug sensitivity testing was performed on eight anti-tuberculosis drugs: isoniazid (INH), rifampicin (RFP, R), ethambutol (EMB), streptomycin (SM), kanamycin (KM), capreomycin (CPM), ofloxacin (OFX), and propylthioisoniacamide (PTO). The drug resistance analysis was conducted. Results Among the 1 687 MTB strains, the overall drug resistance rate was 41.32% (697), with a single drug resistance rate of 11.62% (196), a multi-drug resistance rate of 4.10% (69), a extensive drug resistance rate of 23.71% (400), a pan-drug resistance rate of 1.90% (32), and a rifampicin resistance rate of 28.10% (474), and the main drug resistance types were extensive drug resistance and rifampicin resistance. The order of resistance to the eight drugs was OFX (64) > SM (62) > INH (48) > RFP (19) > CPM (2) > KM (1) > EMB (0) and PTO (0). The rate of resistance to INH and RFP of first-line drugs in newly treated patients was lower than that in retreated patients (χ2=0.110, 0.765; P>0.05); the rate of resistance to second-line drugs OFX, CPM and KM in initially treated patients was lower than that in retreated patients (χ2=1.037, 1.212, 1.653; P>0.05). The total drug resistance rate in 2019 was 51.16%, which was higher than that in 2020 (35.08%) and 2021 (38.89%). The difference between groups was significant (χ2=29.25,16.60; P=0.000), but there was no significant difference in overall drug resistance rate between 2020 and 2021 (χ2=1.823, P=0.177). Among the occupational types of tuberculosis patients, farmers were the main ones, accounting for 56.25% (949). The patients with drug-resistant tuberculosis were mainly distributed in Haikou City (165) > Wanning City (72) > Chengmai County(64) > Wenchang City (51) = Dongfang City (51) > Danzhou City (48), and patients in these six areas accounting for 64.71%(451/697). Conclusions The drug resistance rate of tuberculosis in Hainan Province is relatively high, with OFX and SM resistance being the main types of drug resistance. The extensive drug resistance rate is higher than the national average level. Therefore, surveillance and treatment should be strengthened and optimized to reduce the prevalence of drug-resistant tuberculosis.

Abstract: Objective To investigate the occurrence of multidrug-resistance among tuberculosis patients in Hainan Province from 2014 to 2020 and to analyze the influencing factors, aiming to provide reference for formulating drug-resistant tuberculosis control strategies in this region. Methods This study collected sputum samples from the patients with pulmonary tuberculosis admitted to the Second Affiliated Hospital of Hainan Medical University from 2014 to 2020, and performed isolation and identification of Mycobacterium tuberculosis and drug susceptibility testing. After the strains were identified as positive, drug sensitivity tests were conducted, and multi-drug resistant patients were found. Clinical data was retrospectively collected, and chi-square test and unconditioned logistic regression were used to analyze the influencing factors of multidrug resistance. Results A total of 2 672 patients underwent sputum culture, strain identification, and drug susceptibility testing in TB designated hospitals in Hainan Province from January 1, 2014 to December 31, 2020. Among them, 1 942 patients with available drug susceptibility test results and complete clinical data were enrolled, among which 398 cases with drug-resistant TB were included in the case group, and 1 544 cases without drug resistance were included in the control group. Multivariate logistic regression analysis showed that farmers, rural residence, treatment history of retreatment, irregular medication history, number of pulmonary cavities ≥3, and BMI<18.5 were independent risk factors for MDR-TB. The risk of MDR-TB in farmers was higher than that in non-farmers (OR=1.542, 95%CI: 1.150-2.020); patients living in rural areas had a higher risk of multidrug resistance than those living in urban areas (OR=1.445, 95%CI: 1.095-1.907); the risk of MDR in the retreatment patients was higher than that in the initial treatment patients (OR=5.616, 95%CI: 4.250-7.421); the risk of multi-drug resistance in patients with irregular medication was higher than that in patients with regular medication (OR=2.665, 95%CI: 2.012-3.531); the risk of multidrug resistance in patients with pulmonary cavity number ≥3 was higher than that in patients with pulmonary cavity number <3 (OR=5.040, 95%CI: 3.768-6.740); compared with patients with BMI<18.5, patients with BMI=18.5-24.0 and BMI≥24.0 had a lower risk of multidrug resistance (OR=0.735, 95%CI: 0.555-0.975 and OR=0.447，95%CI:0.225-0.888, respectively). Conclusions Retreatment, farmer occupation, rural residence, irregular medication and low BMI may be the risk factors for multidrug resistance in Hainan Province.

Objective Taking 41 kinds of Chinese herbal medicines commonly used in Meizhou Hakka as the research object,their inhibitory activities against α-glucosidase and α-amylase were screened and the enzyme inhibition types of the species with the strongest activities were explored.Methods The inhibitory activities of 41 commonly used Hakka herbs in Meizhou against α-glucosidase and α-amylase were evaluated by the p-Nitrophenyl a-D-mannopyranoside(pNPG)method and the 3,5-Dinitrosalicylic acid(DNS)method,using the inhibitory rate of half(IC50)as an index.The inhibitory activity of 95%ethanol extracts of 41 Chinese herbal medicines commonly used in Meizhou Hakka on α-glucosidase and α-amylase were analysed.The enzymatic kinetics method and Lineweaver-Burk curve were used to analyze the inhibitory type of the most active species.Results The results showed that 40 Chinese herbal medicines commonly used in Meizhou Hakka had α-glucosidase inhibitory activity,and 23 medicines had α-amylase inhibitory activity,among which Psychotria asiatica Wall.showed the strongest inhibitory activity with the IC50 values aganist α-glucosidase and α-amylase of 0.17±0.001 mg·mL-1 and 0.09±0.001 mg·mL-1,respectively.The inhibition types were reversible competitive inhibition and reversible non-competitive inhibition,respectively.Conclusion The Psychotria asiatica Wall.Chinese herbal medicines commonly used in Meizhou Hakka has significant inhibitory effect on the activity of glucose metabolism enzymes,which has potential value for further research and development on the prevention and treatment of diabetes mellitus.

Objective:To explore the clinical outcome of early endoscopic realignment with flexible cystoscope for pelvic fracture urethral injury.Methods:We retrospectively collected and analyzed the clinical data of patients with pelvic fracture urethral injuries in ER of Beijing Jishuitan Hospital from March 2018 to June 2022.Seventy-six male patients with PFUI were reviewed and 60 patients were included due to the integrity of data collected. The patients were divided into early endoscopic realignment (EER) group and suprapubic cystostomy (SC) group according to the acute management. There were 33 patients and 27 patients in EER group and SC group, respectively. The age of the patients were (42.2±13.8)years and (44.1±15.0) years in EER group and SC group, respectively. The causes of the injuries were car accident, falling and crush, the percentage of the patients were 60.6%(20 cases), 33.3%(11 cases), 6.1%(2 cases) and 55.6%(15 cases), 44.4%(12 cases), 0 in EER group and SC group, respectively. The difference between two groups was statistically insignificant. The procedure of EER began with a cystostomy guided by B ultrasound, then an antegrade cystoscopy was performed through the cystostomy while negociating the bladder neck to the proximal side of injured urethra. A ureteral stent was inserted into the broken urethra and retrieved by a forceps through retrograde urethroscopy with another flexible cystoscope. We inserted a guidewire into the ureteral stent before removing it and placed a 16F urethral catheter along the guidewire. We analyzed the difference between two groups including the incidence, the length and the management of urethral stricture and the complexity of urethroplasty if needed. The simple urethroplasty was defined as performing anastomosis after dissection of the bulbar urethral and removing the scar tissue, while the procedure was defined as complex urethroplasty if ancillary procedures, such as separating the corporal bodies and partial pubectomy, was needed.Results:The EER group and SC group had 33 patients and 27 patients, respectively. The mean operation time of EER was (24.5±7.0)minutes and there was no intra-operative complications. Postoperatively, 4 cases of bleeding and 2 cases of UTI were found, which were successfully treated by conservative managements. Twenty-eight out of 33 patients(84.8%) in EER group developed urethral stricture and the mean length of it was (3.10±1.20)cm. However, all patients in SC group developed urethral stricture (100.0%) with the mean stricture length of (3.83±1.18)cm. The difference between two groups in term of the length of stricture was statistically significant ( P=0.026). 24 patients(85.7%) in EER group were treated by urethroplsty, 2 patients(7.1%) with endoscopic urethrotomy and 2 patients (7.1%) with dilation. All were treated with urethroplasty but 2 patients with endoscopic in SC group. In EER group, 8 strictures (33.3%)finished with simple urethroplasty and 16 strictures (66.7%) with complex urethroplasty.While in SC group, 6 strictures(24.0%) completed with simple urethroplasty and 19 strictures (76.0%)with complex urethroplasty. The complexity of urethroplasty performed in EER group was not statistically significant when compared with it in SC group( P=0.538). Conclusions:The procedure of EER with flexible cystoscope is reliable and safe. Most patients with formed urethral stricture after PFUI would be treated with urethroplasty. EER can reduce the urethral stricture formation and may decrease the need of the ancillary procedures during the urethroplasties if needed.

The adipose-derived stem cell exosomes are subcellular structures of adipose stem cells. They are nano-sized membrane vesicles that can transport various cell components and act on target cells by paracrine, and they play an important role in the exchanges of substance and information between cells. Scar healing is the commonest way of healing after skin tissue injury. Pathological scar can not only cause movement dysfunction, but also lead to deformity, which affects the appearance of patients and brings life and mental pressure to the patients. In recent years, many researches have shown that the adipose-derived stem cell exosomes contain a variety of bioactive molecules, which play an important role in reducing scar formation and scar-free wound healing, by affecting the proliferation and migration of fibroblasts and the composition of extracellular matrix. This article reviewed the recent literature on the roles and mechanisms of adipose-derived stem cell exosomes in scar formation, and prospected the future application and development of adipose-derived stem cell exosomes in scar treatment.

Objective: To investigate the effect of casein kinase 2 interacting protein-1 (CKIP-1) on craniofacial soft tissues and hard tissues, to provide the basis for the study and treatment of craniomaxillofacial related diseases. Methods: 6-month- old male CKIP-1 knockout (KO) mice were selected as the experimental group, and wild-type (WT) mice were selected as the control group. The craniomaxillofacial hard tissues (parietal bone, nasal bone, incisors and molars) were analyzed through micro- CT, and the morphological changes of maxillofacial soft tissues (nasal cartilage, lip mucosa and tongue) were analyzed through HE staining and toluidine blue staining. Results: CKIP-1 negatively regulated bone mass of cancellous bone of cranial and maxillofacial bones and dentin mineralization. Compared with the WT mice, the thickness of the parietal baffle layer increased by 93% in KO mice, while cortical bone showed no significant difference between the two groups. The nasal cancellous bone thickness increased by 160% in KO-mice, while cortical bone showed no significant difference between the two groups; the enamel thickness was normal, but the pulp cavity became smaller and the dentin thickness increased by 48%. Compared with the WT mice, the HE staining and toluidine blue staining analyses of the soft tissues revealed that the thickness of the alar cartilage plate of KO mice increased by 57%, and local ossification was found within the cartilage plate. The thickness of the keratinized layer of the labial mucosa increased by 170% in KO mice and the muscle fiber diameter of the lingual muscle increased by 45%. Conclusion CKIP-1 genes have different effects on the growth and development of various soft and hard tissues in the maxillofacial region of mice.

Objective To observe the influences of hyperoxia on the migration of human lens epithelial cells (HLECs) and the inhibitory effects of glutathione 2 (Grx2) on excessive migration of HLECs induced by hyperoxia.Methods The HLECs were divided into the hyperoxic model group and normoxic control group.HLECs were cultured in 80％ oxygen mixture for 2 days to establish the oxidative damage model of HLECs induced by hyperoxia in vitro (hyperoxia model group),and cultured in normoxia mixture as the normoxic control group.Cell migration was observed by scratch test,cytoskeleton morphology was observed by phalloidin staining,and Grx2 mRNA level was detected by real-time quantitative PCR.HLECs in the hyperoxic model group and the normoxic control group were subdivided into empty plasmid transfection group and Grx2 plasmid transfection group,respectively.The migration behavior and cytoskeleton changes of hyperoxic model cells in different transfection groups were observed.MitoSOX staining was used to detect reactive oxygen species (ROS) content of mitochondria under flow cytometry,and JC-1 staining was used to observe the changes of mitochondrial membrane potential under laser-scanning confocal microscopy.Results In the process of cell culture,the cells grew well.Twenty-four hours and 48 hours after scratching,the scratch distance of the hyperoxic model group was smaller than that of the normoxic control group,with significant differences between them (both at P＜0.05).The cell circumference of the hyperoxic model group was increased compared with that of the normoxic group,with a significant difference between them (t =-2.254,P＜0.05).After 2 days culture,the relative expression level of Grx2 mRNA in the hyperoxic model group was 0.54±0.11,which was significantly lower than that in the normoxic control group (t =7.128,P＜0.01).The transfection efficiency of Grx2 was higher than 90％.At 24 hours and 48 hours after scratching,the scratch distance in the Grx2 transfected hyperoxic model group was wider than that in the empty plasmid transfected hyperoxic model group,with significant differences between them (both at P ＜ 0.05).The relative expression level of Grx2 mRNA in Grx2 transfected cells was up-regulated compared with that in empty plasmid transfected cells,with a significant difference between them (P＜0.01).Compared with the normoxic control group,the cell circumference of the hyperoxic model group was decreased,with a significant difference between them (P＜0.05).The relative mean fluorescence intensity of mitochondrial ROS in the Grx2 transfected hyperoxic model group was lower than that in the empty plasmid transfected hyperoxic model group,with a significant difference between them (P＜0.05).Under the hyperoxic condition,the red/green fluorescence intensity of Grx2 transfected group was higher than that of the empty plasmid transfected group,with a significant difference between them (P＜0.01).Conclusions Grx2 may inhibit the excessive migration of HLECs under hyperoxia by regulating oxidative stress in mitochondria.

Objective: To observe the relationship between impaired myocardial untwisting and left ventricular diastolic dysfunction in patients with autoimmune diseases (AD). Methods: In this retrospective study, 95 AD patients (27 males, (38.6±14.2) years old) were enrolled as AD group and 71 gender and age matched healthy subjects (24 males, (37.6±12.2) years old) were enrolled as control group, all underwent transthoracic echocardiography and two-dimensional speckle-tracking echocardiography (STE) in our hospital between January 2014 and June 2018. Left ventricular untwisting and diastolic function parameters were measured. Multiple logistic regression analysis was used to identify related factors of left ventricular diastolic dysfunction in AD patients. Receiver operating characteristic (ROC) curve was used to identify the diagnosis value of untwisting parameters for left ventricular diastolic dysfunction in AD patients. Results: Compared with control group, left ventricular ejection fraction was lower (58(47, 66)% vs. 67 (62, 71) %, P<0.001), E/e′ was higher (10.78 (7.28, 13.65) vs. 6.30 (5.55, 7.25) , P<0.001), isovolumic relaxation time was longer (73.5 (56.5, 88.0) ms vs. 62.0 (58.0, 68.5) ms, P<0.001),and untwist slope during isovolumic relaxation period (USIR) was lower (31.92 (14.09, 54.92) °/s vs. 59.90 (40.09, 87.18) °/s, P<0.001) in AD group than in control group. Multiple logistic regression analysis showed heart rate (OR=0.885, 95%CI 0.840-0.931, P<0.001), E/e′ (OR=0.655, 95%CI 0.537-0.798, P<0.001) and USIR (OR=0.986, 95%CI 0.974-0.998, P=0.020) were independently related with left ventricular diastolic dysfunction in AD patients. ROC curve showed that area under the curve (AUC) was 0.919 (P<0.001), sensitivity was 87.6%, and specificity was 88.7%, when combining the heart rate, E/e′, and USIR as assessment parameters for the diagnosis of left ventricular diastolic dysfunction in AD patients at a cutoff of 0.51. Conclusions Impairment of myocardial untwisting indicates the presence of early stage left ventricular diastolic dysfunction in AD patients. USIR may be a sensitive parameter to evaluate early stage left ventricular diastolic dysfunction in AD patients.