BACKGROUND:Mineralized collagen is the fundamental unit of bone structure and function and a major component of the extracellular matrix.Biomimetic methods have been developed to fabricate mineralized collagen with a natural bone nanostructure.Currently,mineralized collagen has been approved by regulatory authorities and applied clinically,playing a positive role in bone defect repair.OBJECTIVE:To present the integration strategies of bioactive factors with mineralized collagen,summarize schemes to enhance the osteogenic potential of mineralized collagen,emphasize the multifunctional coordination applications of mineralized collagen,and finally discuss current research focuses and future trends.METHODS:The authors searched for relevant literature in databases such as PubMed,Web of Science,Medline,WanFang,and CNKI,from 2009 to 2023,using keywords"mineralized collagen,biomimetic,functionalization,bioactive factors,osteogenesis,multi-functional coordination,bone tissue repair"in English and"mineralized collagen,biomimetic,functionalization"in Chinese.Out of 375 initially identified articles,57 were included for review after screening.RESULTS AND CONCLUSION:(1)Mineralized collagen,with its porous structure and large surface area,containing nano-hydroxyapatite,makes it an effective carrier for cells,various growth factors,and drugs.(2)Single or multiple bioactive factors can be efficiently and orderly released through different loading methods or combinations,achieving the multifunctionalization of mineralized collagen.The impact of physicochemical conditions on the bioactivity of factors and their effects on the degradability,hydroxylapatite crystal morphology,nanostructure,and content of mineralized collagen should be considered.Moreover,calcium ions in mineralized collagen can be substituted with various inorganic non-metal ions,enhancing its osteogenic,angiogenic,immunomodulatory,and anti-infective properties.(3)Ultimately,during in situ bone regeneration,functionalized mineralized collagen serves as a scaffold material,providing structural support for bone defects,and as a drug delivery system,continuously delivering various bioactive factors locally,playing roles in anti-infection,immunomodulation,promoting angiogenesis and osteogenesis,and repairing various complex bone defects.

BACKGROUND:Mineralized collagen is the fundamental unit of bone structure and function and a major component of the extracellular matrix.Biomimetic methods have been developed to fabricate mineralized collagen with a natural bone nanostructure.Currently,mineralized collagen has been approved by regulatory authorities and applied clinically,playing a positive role in bone defect repair.OBJECTIVE:To present the integration strategies of bioactive factors with mineralized collagen,summarize schemes to enhance the osteogenic potential of mineralized collagen,emphasize the multifunctional coordination applications of mineralized collagen,and finally discuss current research focuses and future trends.METHODS:The authors searched for relevant literature in databases such as PubMed,Web of Science,Medline,WanFang,and CNKI,from 2009 to 2023,using keywords"mineralized collagen,biomimetic,functionalization,bioactive factors,osteogenesis,multi-functional coordination,bone tissue repair"in English and"mineralized collagen,biomimetic,functionalization"in Chinese.Out of 375 initially identified articles,57 were included for review after screening.RESULTS AND CONCLUSION:(1)Mineralized collagen,with its porous structure and large surface area,containing nano-hydroxyapatite,makes it an effective carrier for cells,various growth factors,and drugs.(2)Single or multiple bioactive factors can be efficiently and orderly released through different loading methods or combinations,achieving the multifunctionalization of mineralized collagen.The impact of physicochemical conditions on the bioactivity of factors and their effects on the degradability,hydroxylapatite crystal morphology,nanostructure,and content of mineralized collagen should be considered.Moreover,calcium ions in mineralized collagen can be substituted with various inorganic non-metal ions,enhancing its osteogenic,angiogenic,immunomodulatory,and anti-infective properties.(3)Ultimately,during in situ bone regeneration,functionalized mineralized collagen serves as a scaffold material,providing structural support for bone defects,and as a drug delivery system,continuously delivering various bioactive factors locally,playing roles in anti-infection,immunomodulation,promoting angiogenesis and osteogenesis,and repairing various complex bone defects.

Objective To investigate the efficacy of modified use of Huanglian Jiedu Decoction plus Xijiao Dihuang Decoction in the treatment of patients with psoriasis vulgaris of blood-heat syndrome and to observe its effect on Th1/Th2 balance in the patients.Methods The investigation was carried out in a total of 130 patients with psoriasis vulgaris of blood-heat syndrome,who were admitted to the dermatology department of the First Affiliated Hospital of Henan University of Chinese Medicine between January 2022 and June 2023.The patients were randomly divided into an observation group and a control group by the random number table method,with 65 patients in each group.The control group was treated with conventional western medicine,while the observation group was treated with modification of Huanglian Jiedu Decoction plus Xijiao Dihuang Decoction on the basis of treatment for the control group.Both groups were treated for four consecutive weeks and were followed up for one year.The changes in the scores of Psoriasis Area and Severity Index(PASI)and Dermatology Life Quality Index(DLQI),levels of peripheral blood Th1/Th2 balance indicators,and levels of peripheral Th1/Th2-related factors such as γ-interferon(INF-γ),interleukin 2(IL-2),and interleukin 4(IL-4)in the two groups of patients before and after treatment were observed.Moreover,the clinical efficacy and adverse reactions during treatment were evaluated,and the recurrent cases within one year in the two groups were counted.Results(1)After four weeks of treatment,the total effective rate of the observation group was 90.77%(59/65),and that of the control group was 76.92%(50/65).The intergroup comparison showed that the clinical efficacy of the observation group was significantly superior to that of the control group(P<0.05).(2)After treatment,the scores of PASI and DLQI in the two groups of patients were decreased when compared with those before treatment(P<0.05),and the decrease of PASI and DLQI scores in the observation group was significantly superior to that in the control group(P<0.01).(3)After treatment,the serum levels of Th1/Th2-related factors such as INF-γ and IL-2 in the two groups of patients were decreased when compared with those before treatment(P<0.05),and IL-4 level was increased when compared with that before treatment(P<0.05),and the decrease of serum INF-γ and IL-2 levels and the increase of serum IL-4 level in the observation group were significantly superior to those in the control group(P<0.05 or P<0.01).(4)After treatment,the peripheral blood levels of Th1/Th2 balance indicators of Th1,Th2 and Th1/Th2 in the two groups of patients were decreased when compared with those before treatment(P<0.05),and the decrease of peripheral blood Th1,Th2 and Th1/Th2 levels in the observation group was significantly superior to that in the control group(P<0.01).(5)The recurrence rate of the observation group was 20.69%(12/58)and that of the control group was 38.33%(23/60),and the recurrence time in the observation group was(8.49±1.43)months and that of the control group was(5.36±0.95)months.The intergroup comparison showed that the one-year recurrence rate of the observation group was significantly decreased compared with that of the control group(P<0.05),and the recurrence time was significantly prolonged compared with that of the control group(P<0.05).(6)The medicine-induced adverse reaction rate in the observation group was 10.77%(7/65)and that in the control group was 12.31%(8/65),and the intergroup comparison showed that the difference was not statistically significant(P>0.05).Conclusion Modified use of Huanglian Jiedu Decoction plus Xijiao Dihuang Decoction is effective on enhancing the clinical efficacy of patients with psoriasis vulgaris of blood-heat syndrome,and on improving the balance of Th1/Th2 and the severity of the disease,delaying the recurrence of psoriasis vulgaris,and reducing the recurrence rate,with high safety.

Primary hyperparathyroidism (PHPT) is a disorder of calcium metabolism, which is characterized by elevated blood calcium and PTH urine calcium, which is easy to involve multiple systems. The disease is mainly caused by a benign adenoma of parathyroid tissue, a few of which are parathyroid hyperplasia or parathyroid adenocarcinoma. As awareness of physical examination increased, the proportion of asymptomatic PHPT patients gradually increased. The disease can be cured by surgical resection of the parathyroid gland, most of which is a real good prognosis, but a few of them are complex and difficult to diagnose and treat. At present, there continue to be many controversies about the diagnosis and treatment of PHPT.This article is a review of the progress in the diagnosis and treatment of PHPT.

Objective:To explore the relationship between lymphovascular invasion and non-sentinel lymph node (NSLN) metastasis in early-stage invasive breast cancer with positive sentinel lymph node (SLN) and its significance.Methods:The clinicopathological data of 79 patients with stage cT 1-2N 0M 0 invasive breast cancer who had positive SLN by biopsy and underwent axillary lymph node dissection (ALND) from January 2015 to February 2021 in the Central Hospital of Wuhan were retrospectively analyzed. The correlation between patients' clinicopathological characteristics and NSLN metastasis was analyzed. Results:Among 79 patients, 58 patients (73.4%) underwent total mastectomy, 61 patients (77.2%) were Luminal type, 38 patients (48.1%) had lymphovascular invasion, 64 patients (81.0%) had 1-2 positive SLN, and 42 patients (53.2%) with NSLN metastasis were found after ALND. Univariate analysis showed that the proportions of patients with lymphovascular invasion diagnosed by immunohistochemistry [86.8% (33/38) vs. 51.2% (21/41)], Ki-67 positive index>30% [60.5% (23/38) vs. 36.6% (15/41)], positive human epidermal growth factor receptor 2 [36.8% (14/38) vs. 14.6% (6/41)], and elevated lymph node pathological staging [57.9% (22/38) vs. 31.7% (13/41)] in the lymphovascular invasion group were higher than those in the non-lymphovascular invasion group (all P < 0.05). Multivariate logistic regression analysis showed that lymphovascular invasion was an independent risk factor for NSLN metastasis ( OR = 2.935, 95% CI 1.081-7.970, P = 0.035). Conclusions:Lymphovascular invasion is an independent risk factor for NSLN metastasis in SLN-positive stage cT 1-2N 0M 0 invasive breast cancer. It may help to guide the decision-making of local axillary treatment, so as to avoid over or under treatment.

Objective:To explore the clinical significance of thrombelastography (TEG) and conventional coagulation tests (CCTs) in the diagnosis of trauma-induced coagulopathy(TIC) and the risk factors for TIC.Methods:Traumatic patients hospitalized in PICU at Shengjing Hospital of China Medical University from December 1, 2017 to January 31, 2019 were divided into three groups according to injury severity score(ISS): non-severe group(≤16 points), severe group (17-25 points) and extremely severe group(>25 points). All patients received 2.5 mL of venous blood at admission/after 6 h, 12 h, 24 h, and 48 h injury to detect TEG and CCTs.The prevalence, time of onset, recovery time of coagulation function and risk factors for TIC were summarized.Results:A total of 64 cases were collected, including 18 non-critical cases, 28 critical cases and 18 extremely critical cases.TEG and CCTs were used to diagnose TIC in nine cases(14.1%)and four cases(6.3%), respectively.TIC could be diagnosed by TEG at 6 hours after trauma, and 12 hours for CCTs.TEG was used to diagnose four cases of hypercoagulability.Univariate analysis showed that female, blood transfusion, transfusion, shock, multiple organ dysfunction syndrome, mechanical ventilation, hypothermia, low age, low glasgow coma scale (GCS) and high ISS were all risk factors for TIC.Logistics regression analysis found that children with high-risk factors such as girl, hypothermia, shock and mechanical ventilation were 4.333, 17.889, 10.208, and 4.479 times more likely to develop TIC than those without high-risk factors.For every 1 score increase in the ISS score, the risk of TIC increased by 1.147.As the age increased by 1 year, GCS increased by 1 point, and the risk of TIC decreased by 0.765 and 0.817, respectively, which were protective factors for TIC.Conclusion:TEG and CCTs are consistent in the diagnosis of TIC, but TEG is more sensitive at an earlier stage and can detect hypercoagulability.Female, shock, hypothermia, low age, high ISS, and low GCS are risk factors for TIC.

Objective To evaluate the change of clinicopathological features and prognosis of papillary thyroid cancer over a 15-year period.Methods The clinicopathological features and outcomes of papillary thyroid cancer patients were analyzed in three groups according to the time of diagnosis:group Ⅰ (1997-2001),group Ⅱ (2002-2006),and group Ⅲ (2007-2011).Results As time advanced,the average age of papillary thyroid cancer patients increased,tumor stage,like size,extrathyroid invasion and lymph node metastasis decreased dramatically (P ＜ 0.01).The percentage of multifocality and bilaterality increased.The long-term follow up data (median follow up time was 6.6 years),indicated that the 15-year over all survival was 97.8％ and the 15-year disease-free survival was 90.2％.Tumor ≥3 cm,bilaterality,extrathyroid invasion,lymph node metastasis and AJCC stage were correlated with tumor recurrence.By multivariate COX-regression analysis only lymph node metastasis and bilaterality were independent risk factors.Conclusion The clinicopathological features of papillary thyroid cancer changed over 15 years,with the percentage of early-staged patients increased.Lymph node metastasis and bilaterality are two risk factors for tumor recurrence.

Objective To investigate the development and application of blood purification in PICU. Methods The demographic data,diagnosis,length of stay,prognosis,patterns and frequency of blood purifi-cation and complications of PICU patients treated with blood purification in our hospital from 2010 to 2017 were retrospectively analyzed. Results The patients with blood purification accounted for 3. 1％ of hospital-ized children in the same period. From 2010 to 2017,the patients and times with blood purification increased by 370. 6％ and 398. 3％ respectively. The times of continuous veno-venous hemodiafiltration(CVVHDF), plasma exchange and hemoperfusion increased by 135. 2％,6300％ and 1600％ respectively. The frequency of CVVHDF,plasma exchange and hemoperfusion accounted for 42. 8％(492/1151),33. 5％(386/1151), and 23. 7％ (273/1151) respectively. Drug and toxic poision accounted for the highest proportion of 28. 6％(81/284),neurological diseases accounted for 20. 8％(59/284),sepsis with multiple organ dysfunction syn-drome accounted for 18. 0％( 51/284 ) , digestive system diseases, autoimmune diseases, renal diseases and metabolic diseases accounted for 14. 4％( 41/284 ) ,4. 9％( 14/284 ) ,4. 9％ ( 14/284 ) and 4. 2％( 12/284 ) respectively. The cure rate was 63. 8％. Complication included thrombus. Conclusion Blood purification has become the preferred modality for the management of critically ill children. Pediatric blood purification tech-niques have developed rapidly in our PICU and domestic pediatric. Further specification is required,so that it may represent the adequate choice for critical ill children.

Objective:To modify Ganodermalucidum polysaccharides(GLP) with sulfate and observe the protective effect of Ganodermalucidum polysaccharide sulfate (GLPS) on the cerebral ischemia reperfusion injury in the rats,and to investigate its mechanism.Methods:GLP was modified by sulfation to obtain GLPS.A total of 100 SD rats were randomly divided into sham operation group, model group, GLP group (40 mg·kg-1·d-1), GLPS group (40 mg·kg-1·d-1) and nimodipine group (1 mg·kg-1·d-1).The cerebral ischemia reperfusion models were established by middle cerebral artery occlusion method in the rats.The neurologic deficit score and the content of water in brain tissue of the rats with cerebral ischemia reperfusion injury were detected and the activities of superoxide dismutase(SOD) and the levels of malondialdehyde (MDA) were detected.The levels of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB),tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6) in the brain tissue homogenate were detected by ELISA.Western blotting method was used to detect the protein expression levels of HSP70 and p-Akt in the brain tissue of the rats.Results:Compared with model group, the neurological function scores of the rats in GLP group and GLPS group were decreased(P<0.01),the water contents in brain tissue were decreased(P<0.05), the SOD activities were increased and the MDA levels were decreased(P<0.05), and the levels of NF-κB, TNF-α, IL-1 and IL-6 were decreased(P<0.05);the effect in GLPS group was significantly better than that in GLP group(P<0.05).The results of Western blotting method showed that the p-Akt protein expression levels in the brain tissue of the rats in GLP and GLPS groups were increased compared with model group (P<0.05);compared with model group, the HSP-70 protein expression level in the brain tissue of the rats in GLPS group was increased(P<0.01),but the effect in GLP group was not obvious.Conclusion:Sulfation can significantly improve the protective effect of GLP on the cerebral ischemia reperfusion injury in the rats and its mechanism may be related to regulating the HSP70/PI3K/Akt signaling pathway and inhibiting the inflammatory reaction damage to the nerve cells of reperfusion.

Objective:To prepare the velvet antler polypeptide-collagen/chitosan composite materials,and to investigate its promotive effect on cicatrization of mandibular defect and possible mechanism.Methods:The collagen and chitosan solution were mixed.The composite material was prepared by glutaraldehyde crosslinking method.The microstructure of the composite material was observed by transmission electron microscope (SEM).The unilateral mandibular defect models of 36 rabbits were established.The rabbits were divided into experiment and control groups,and each group was divided into 4-,8-and 12-week subgroups,and there were 6 rabbits in each sub group.The rabbits in experiment group were implanted with velvet antler polypeptide-collagen /chitosan composite materials and the rabbits in control group were treated.4,8 and 12 weeks after operation,the histology of bone defect and peripheral nerve reconstruction of the rabbit models were detected by CT;the expression of vascular endothelial growth factor (VEGF) in bone tissue of the rabbits was detected by immunohistochemistry;the ultrastructure of bone defect was observed by SEM.Results:The structure of composite materials had layered folds and the inner diameter of the stent became larger and mainly dominated by sheet structure,which was the ideal structure of biological materials.4 weeks after operation,the new bone was formatted in experiment group,most of the new bone like-tissue materials were degraded,and the VEGF expression showed an increasing trend;8 weeks after operation,the trabecular bone in the bone defect of the rabbits in experiment group was increased obviously and the expression of VEGF was decreased.12 weeks after operation,the new bone formation and the density in experiment group was consistent with the normal tissue,and the expression level of VEGF returned to normal.At each the point after operation,the degree of bone defect healing and bone formation rate in experiment group were obviously prior to control group.Conclusion:Velvet antler polypeptide-collagen /chitosan composite material has the promotive effect on the fracture healing of mandibular defect of the rabbits and its possible mechanism may be related to promoting the expression of VEGF.