Glipizide Alleviates Periodontitis Pathogenicity via Inhibition of Angiogenesis, Osteoclastogenesis and M1/M2 Macrophage Ratio in Periodontal Tissue.

New consensus indicates type 2 diabetes mellitus (T2DM) and periodontitis as comorbidity and may share common pathways of disease progression. Sulfonylureas have been reported to improve the periodontal status in periodontitis patients. Glipizide, a sulfonylurea widely used in the treatment of T2DM, has also been reported to inhibit inflammation and angiogenesis. The effect of glipizide on the pathogenicity of periodontitis, however, has not been studied. We developed ligature-induced periodontitis in mice and treated them with different concentrations of glipizide and then analyzed the level of periodontal tissue inflammation, alveolar bone resorption, and osteoclast differentiation. Inflammatory cell infiltration and angiogenesis were analyzed using immunohistochemistry, RT-qPCR, and ELISA. Transwell assay and Western bolt analyzed macrophage migration and polarization. 16S rRNA sequencing analyzed the effect of glipizide on the oral microbial flora. mRNA sequencing of bone marrow-derived macrophages (BMMs) stimulated by P. gingivalis lipopolysaccharide (Pg-LPS) after treatment with glipizide was analyzed. Glipizide decreases alveolar bone resorption, periodontal tissue degradation, and the number of osteoclasts in periodontal tissue affected by periodontitis (PAPT). Glipizide-treated periodontitis mice showed reduced micro-vessel density and leukocyte/macrophage infiltration in PAPT. Glipizide significantly inhibited osteoclast differentiation in vitro experiments. Glipizide treatment did not affect the oral microbiome of periodontitis mice. mRNA sequencing and KEGG analysis showed that glipizide activated PI3K/AKT signaling in LPS-stimulated BMMs. Glipizide inhibited the LPS-induced migration of BMMs but promoted M2/M1 macrophage ratio in LPS-induced BMMs via activation of PI3K/AKT signaling. In conclusion, glipizide inhibits angiogenesis, macrophage inflammatory phenotype, and osteoclastogenesis to alleviate periodontitis pathogenicity suggesting its' possible application in the treatment of periodontitis and diabetes comorbidity.

SAP deficiency aggravates periodontitis possibly via C5a-C5aR signaling-mediated defective macrophage phagocytosis of Porphyromonas gingivalis.

INTRODUCTION: Serum amyloid P component (SAP) regulates the innate immune system and microbial diseases. Periodontitis is an inflammatory oral disease developed by the host immune system's interaction with the dysbiotic oral microbiome, thereby SAP could play a role in periodontitis pathogenicity. OBJECTIVES: To investigate the role of SAP in oral microbiome modulation and peridontitis pathogenicity. METHODS: In this study, wildtype and SAP-knockout (KO) mice were used. Ligature-based periodontitis was developed in mice. Oral microbiome diversity was analyzed by 16 s rRNA sequencing. Macrophages and Porphyromonas gingivalis (P. gingivalis) co-culture system analyzed the effect of SAP in macrophage phagocytosis of P. gingivalis. RESULTS: The level of SAP was upregulated in the periodontitis-affected periodontium of humans and mice but not in the liver and blood circulation. Periodontal macrophages were the key source of upregulated SAP in periodontitis. SAP-KO aggravated periodontal inflammation, periodontitis, and a higher number of M1-type inflammatory macrophage infiltration in the periodontium. The oral microbiome of SAP-KO periodontitis mice was altered with a higher abundance of Porphyromonas at the genus level. SAP-KO macrophages showed compromised phagocytosis of P. gingivalis in the co-culture system. Co-culture of SAP-KO macrophages and P. gingivalis induced the C5a expression and exogenous SAP treatment nullified this effect. Exogenous recombinant SAP treatment did not affect P. gingivalis growth and opsonization. PMX205, an antagonist of C5a, treatment robustly enhanced P. gingivalis phagocytosis by SAP-KO macrophages, indicating the involvement of the C5a-C5aR signaling in the compromised P. gingivalis phagocytosis by SAP-KO macrophages. CONCLUSION: SAP deficiency aggravates periodontitis possibly via C5a-C5aR signaling-mediated defective macrophage phagocytosis of P. gingivalis. A higher abundance of P. gingivalis during SAP deficiency could promote M1 macrophage polarization and periodontitis. This finding suggests the possible protecting role of elevated levels of periodontal SAP against periodontitis progression.

The association between heart failure and risk of fractures: Pool analysis comprising 260,410 participants.

Background: HF and osteoporosis shared many common etiological risk factors. However, studies exploring whether patients with HF were associated with a higher risk of osteoporotic fracture resulted in inconsistent findings. This meta-analysis aimed to summarize the association between HF and the risk of incident fracture. Methods: Following the Meta-analysis of Observational Studies in Epidemiology group recommendations, we searched multiple electronic databases (PubMed, Cochran Library, and EMBASE) for related studies from inception to April 30, 2021. Studies evaluating the risk of incident fracture in patients with HF compared with those without HF were included for analysis. The random-effects models were used to combine the estimated hazard ratios (HRs) of incident fracture associated with HF. Results: We included 8 observational studies for meta-analysis. The sample size ranged from 5,613 to 87,748 participants, with a total of 260,410 participants included. The median follow-up duration was 5.0 years. Random-effects model analyses showed that compared with control groups, patients with HF were associated with a higher risk of all incident fractures (HR = 1.67, 95% CI = 1.30-2.16, P < 0.001) and hip fracture (HR = 2.20, 95% CI = 1.28-3.77, P < 0.001). The risk of all incident fractures was increased in all subgroup analyses according to age, sample size, sex, and follow-up duration. Conclusions: Patients with HF were associated with a higher risk of incident fracture, as well as hip fracture.

Comparison of low-dose morphine intrathecal analgesia and sufentanil PCIA in elderly patients with hip fracture undergoing single spinal anesthesia - a randomized clinical trial.

BACKGROUND: The complications of postoperative pain, such as hypertension, hypermetabolism, irritability, and postoperative cognitive dysfunction, significantly affect the postoperative rehabilitation of elderly patients. Intrathecal morphine prolongs analgesia after surgery, but has been implicated in nausea and vomiting, pruritus, postoperative respiratory depression, or apneic episodes. The present study explored the effect and safety of low-dose morphine used adjunctively with bupivacaine during single spinal anesthesia or sufentanil patient-controlled intravenous analgesia (PCIA) in elderly patients with hip fracture surgery. Since elderly patients often need anticoagulant therapy in the early postoperative period, single spinal anesthesia was involved in completing the operation in this study. METHODS: Eighty elderly patients aged 70-85 years who underwent elective hip fracture surgery with single spinal anesthesia were divided into two groups, 12.5 mg of 0.5% hyperbaric bupivacaine with 100 µg of morphine (morphine group, group M) and 12.5 mg of 0.5% hyperbaric bupivacaine with 100 µg of sufentanil PCIA (sufentanil group, group S). The analgesia scores using the visual analogue scale (VAS), the Brinell comfort scale (BCS) were evaluated at 6, 12, 24, and 48 h after operation, and adverse reactions were recorded such as nausea and vomiting, pruritus, sedation, respiratory depression, and POD (postoperative delirium) with Delirium Rating Scale-r 98. RESULTS: Within 24 h after operation, the analgesic and BCS scores of group M were better than those of group S (P < 0.05). Group M had higher frequency of skin pruritus than group S within 24 h, and the difference was statistically significant. The incidence of POD in group M (2 cases) was lower than that in group S (6 cases) (5.71% vs 18.18%) (P < 0.05) with the DRS-r 98 scores. No significant difference was observed in nausea and vomiting between the two groups, and the difference of severe respiratory depression was not found in both groups. CONCLUSION: Compared with sufentanil PCIA, low-dose intrathecal morphine has a satisfactory analgesic effect, and little effect on the patient's cognitive function with low medical cost. Under effective respiratory monitoring, it can be used safely and effectively in elderly patients with hip fracture. TRIAL REGISTRATION: Registered with the Chinese Clinical Trial Registry under ChiCTR2100042706 . 26/01/2021.

Does simultaneous soft tissue augmentation around immediate or delayed dental implant placement using sub-epithelial connective tissue graft provide better outcomes compared to other treatment options? A systematic review and meta-analysis.

OBJECTIVE: The clinical benefits of simultaneous implant placement and soft tissue augmentation using different treatment modalities are unclear. The current meta-analysis aimed to compare the effect of simultaneous soft tissue augmentation using subepithelial connective tissue graft (SCTG) around immediate or delayed dental implant placement with other treatment modalities on the peri-implant tissue health and esthetic. METHODS: Up to May 2021, four databases (PubMed, EMBASE, Cochrane Central, and Google Scholar) were searched. Randomized control trials with follow-up >3 months, evaluating simultaneous implant placement (immediate or delayed) and soft tissue augmentation using SCTG compared with other treatment modalities were included. The predictor variables were SCTG versus no augmentation with/without guided bone regeneration (GBR) or other augmentation techniques (Acellular dermal matrix (ADM), Xenogeneic collagen matrix (XCM). The outcome variables were buccal tissue thickness (BTT), mid-buccal gingival level (MGL), marginal bone loss (MBL), and pink esthetic scores (PES). Cumulative mean differences (MD) and 95% confidence interval (CI) were estimated. RESULTS: Twelve studies were included. SCTG along with immediate implant placement (IIP) or delayed implant placement (DIP) showed a statistically significant improvement in BTT (Fixed; MD, 0.74; 95% CI, 0.51; 0.97), MGL (Fixed; MD, 0.5; 95% CI, 0.21; 0.80), PES (Fixed; MD, 0.79; 95% CI, 0.29; 1.29), and less MBL (Fixed; MD, -0.11; 95% CI, -0.14; -0.08) compared to no graft (P<0.05). A statistically insignificant differences in BTT (Random; MD, 0.62; 95% CI, -0.41; 1.65), MGL (Fixed; MD, -0.06; 95% CI, -0.23; 0.11), MBL (Fixed; MD, 0.36; 95% CI, -0.05; 0.77) and PES (Fixed; MD, 0.28; 95% CI, -0.10; 0.67) was observed when SCTG along with DIP was compared with no augmentation plus GBR. Similarly, no statistically significant difference was observed when comparing SCTG along with DIP with acellular dermal matrix (ADM) concerning BTT (MD:0.71, P = 0.18) and KMW (MD: 0.6, P = 0.19). CONCLUSION: There is a very low quality of evidence to provide recommendations on whether simultaneous dental implant placement (IIP or DIP) and soft tissue augmentation using SCTG is superior to no augmentation or is comparable to the other tissue augmentation materials in improving the quality and quantity of peri-implant tissues. Therefore, further, well-designed RCTs with larger sample sizes and long follow-up times are still needed.

Association Between Hemoglobin Glycation Index and Risk of Cardiovascular Disease and All Cause Mortality in Type 2 Diabetic Patients: A Meta-Analysis.

Background: The hemoglobin glycation index (HGI) has been proposed as a marker to quantify inter-individual variation in hemoglobin glycosylation. However, whether HGI is associated with an increased risk of diabetic complications independent of glycated hemoglobin (HbA1c) remains unclear. This meta-analysis aimed to determine the association between HGI and the risk of all cause mortality and composite cardiovascular disease (CVD). Methods: PubMed, and EMBASE databases were searched for related studies up to March 31, 2021. Observational studies reported associations between HGI levels and composite CVD and all cause mortality were included for meta-analysis. A random effect model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CI) for higher HGI. Results: A total of five studies, comprising 22,035 patients with type two diabetes mellitus were included for analysis. The median follow-up duration was 5.0 years. After adjusted for multiple conventional cardiovascular risk factors, an increased level of HGI was associated with a higher risk of composite CVD (per 1 SD increment: HR = 1.14, 95% CI = 1.04-1.26) and all cause mortality (per 1 SD increment: HR = 1.18, 95% CI = 1.05-1.32). However, when further adjusted for HbA1c, the association between HGI and risk of composite CVD (per 1 SD increment of HGI: HR = 1.01, 95% CI = 0.93-1.10) and all cause mortality (per 1 SD increment of HGI: HR = 1.03, 95% CI = 0.96-1.10) became insignificant. Conclusions: High HGI was associated with an increased risk of composite CVD and all cause mortality after adjustment for multiple conventional cardiovascular risk factors. However, the association was mainly mediating by the level of HbA1c.

Comparing differences and correlation between 24-hour ambulatory blood pressure and office blood pressure monitoring in patients with untreated hypertension.

OBJECTIVE: We assessed differences and correlations between 24-hour ambulatory blood pressure (ABP) and office blood pressure (OBP) monitoring. METHODS: We conducted an observational study among 85 untreated patients with essential hypertension and measured 24-hour ABP, OBP, target organ damage (TOD) markers, and metabolism indexes. Variance analysis and the Pearson method were used to compare differences and correlation between the two methods. The Spearman or Pearson method was applied to compare the correlation between TOD markers, blood pressure index, and metabolism index. Linear regression analysis was applied to estimate the quantitative relationship between the blood pressure index and TOD markers. RESULTS: There were significant differences in the mean and variance of systolic blood pressure (SBP) and diastolic blood pressure and a positive correlation between ABP and OBP. Correlations between the left ventricular mass index (LVMI) and average ambulatory SBP, daytime ambulatory SBP, nighttime ambulatory SBP, and fasting blood glucose were significant. Correlations between left intima-media thickness (IMT) and average ambulatory SBP, nighttime ambulatory SBP, right IMT, and nighttime ambulatory SBP were significant. In linear regression analysis of the LVMI (y) and ambulatory SBP (x), the equation was expressed as y = 0.637*x. CONCLUSION: Nighttime ambulatory SBP may be an optimal predictor of TOD.

Prediabetes and risk of heart failure: the link grows stronger.

In a recently published paper in Cardiovascular Diabetology, Sinha et al. (Association of fasting glucose with lifetime risk of incident heart failure: the Lifetime Risk Pooling Project. Cardiovasc Diabetol. 2021;20(1):66) reported that prediabetes (defined as a fasting plasma glucose concentration of 100-125 mg/dL) was associated with a higher lifetime risk of heart failure in middle-aged White adults and Black women, with the association attenuating in older Black women. This study provides important evidence that the risk of heart failure is increased in people with a fasting plasma glucose concentration as low as 100 mg/dL, supporting the definition of prediabetes according to the American Diabetes Association guideline. The study also strongly supports the notion that prediabetes should be regarded not only as a high-risk state for the development of diabetes but also as a risk factor for cardiovascular morbidity.

Downregulation of Macrophage-Specific Act-1 Intensifies Periodontitis and Alveolar Bone Loss Possibly via TNF/NF-κB Signaling.

Periodontitis is a chronic inflammatory oral disease that affects almost half of the adult population. NF-κB activator 1 (Act1) is mainly expressed in immune cells, including macrophages, and modulates immune cells' function to regulate inflammation in inflammatory diseases. Macrophages play a vital role in the pathophysiology of periodontitis. However, the effect of macrophage-specific Act1 on periodontitis has not been investigated yet. This study aims to unravel the role of macrophage-specific Act1 on the pathophysiology of periodontitis. The expression of Act1 in healthy and periodontitis periodontal tissue was confirmed by immunohistochemistry. Macrophage-specific Act1 expression downregulated (anti-Act1) mice were developed by inserting anti-Act1 antisense oligonucleotides after the CD68 promoter of C57BL/6 mice. Ligature-induced periodontitis (LIP) was induced in anti-Act1 mice and wildtype mice. Micro-CT, histology, and TRAP staining analyzed the periodontal tissue status, alveolar bone loss, and osteoclast numbers. Immunohistochemistry, RT-qPCR, and ELISA analyzed the inflammatory cells infiltration, expression of inflammatory cytokines, and M1/M2 macrophage polarization. mRNA sequencing of in vitro bacterial lipopolysaccharide (LPS)-treated peritoneal macrophages analyzed the differentially expressed genes in anti-Act1 mice during inflammation. Anti-Act1 mice showed aggravated periodontitis and alveolar bone loss compared to wildtype. Periodontitis-affected periodontal tissue (PAPT) of anti-Act1 mice showed a higher degree of macrophage infiltration, and M1 macrophage polarization compared to wildtype. Levels of pro-inflammatory cytokines (IL-1ß, IL-6, and TNFα), and macrophage activity-related factors (CCL2, CCL3, and CCL4) were robustly high in PAPT of anti-Act1 mice compared to wildtype. mRNA sequencing and KEGG analysis showed activated TNF/NF-κB signaling in LPS-treated macrophages from anti-Act1 mice. In vitro studies on LPS-treated peritoneal macrophages from anti-act1 mice showed a higher degree of cell migration and expression of inflammatory cytokines, macrophage activity-related factors, M1 macrophage-related factors, and TNF/NF-κB signaling related P-p65 protein. In conclusion, downregulation of macrophage-specific Act1 aggravated periodontitis, alveolar bone loss, macrophage infiltration, inflammation, and M1 macrophage polarization. Furthermore, LPS-treated macrophages from anti-Act1 mice activated TNF/NF-κB signaling. These results indicate the distinct role of macrophage-specific Act1 on the pathophysiology of periodontitis possibly via TNF/NF-κB signaling.

α-Linolenic Acid and Risk of Heart Failure: A Meta-Analysis.

Background: The α-linolenic acid is a plant origin n-3 fatty acid that may reduce the risk of cardiovascular disease. However, the effect of α-linolenic acid (ALA) on the risk of heart failure (HF) remains unclear. In this meta-analysis, we aimed to determine the role of ALA in the risk of incident HF. Methods: Electronic databases were searched for studies up to August 10, 2021. Studies were included for meta-analysis if the adjusted risk of HF in different dietary intake or circulating levels of ALA was reported. We used the random-effects model to calculate the estimated hazard ratios (HRs) and 95% CI for higher ALA. Results: A total of 6 studies (7 cohorts) comprising 135,270 participants were included for meta-analysis. After a median follow-up duration of 10 years, 5,905 cases of HF were recorded. No significant heterogeneity was observed among all the included studies. Random-effects model analyses showed that there was no significant association between ALA and the risk of incident HF, either assessed as quintiles (highest quintile vs. lowest quintile: HR = 0.95, 95% CI = 0.86-1.06) or per 1 SD increment (HR = 0.99, 95% CI = 0.95-1.01). Furthermore, we did not observe any association between ALA and the risk of HF in subgroup analyses performed according to age, sex, follow-up duration, and measuring method of ALA. Conclusions: We found no association between ALA and the risk of incident HF, suggesting that ALA might not be effective in the prevention of HF.

What is the optimal regimen for intravenous dexamethasone administration in primary total hip arthroplasty?: A protocol of randomized controlled trial.

BACKGROUND: A number of recent studies have investigated the optimal dosage and timing of dexamethasone in total hip arthroplasty (THA) but have inconsistent findings. Therefore, we designed the randomized controlled research to look for the optimal intravenous dexamethasone dose for the treatment of early postoperative pain after the THA. METHODS: The Declaration of Helsinki principles was followed and the Consolidated Standards of Reporting Trials guidelines for randomized controlled trials was adhered in this study. The First Medical Center in People's Liberation Army General Hospital approved the study (2020-089). After written informed consent was obtained, patients aged between 18 and 80 years with Physical Status I to III of American Society of Anesthesiologists, scheduled for primary unilateral THA, were included in this present work. Randomization is the use of a computer-formed list via a secretary, at a ratio of 1:1:1. The major end points were pain scores at 24 hours, 48 hours, and 72 hours after surgery, with visual analog scale (VAS) utilized at rest, and at 45 degrees passive hip flexion. The secondary outcomes involved the total consumption of morphine, opioid-related side effects, hip range of motion, inflammation markers, and the length of hospital stay. RESULTS: We assumed that the patients who received 3 doses of dexamethasone intravenously possessed the best postoperative results compared to those who received 1 or 2 doses of the dexamethasone. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5864).

Surgical treatment of spinal thoracic metastases with nerve injury in patients with moderate-to-severe spinal cord injury.

BACKGROUND: Among spine metastases of malignant tumors, thoracic spine metastases account for about 70%. Spinal metastases cause spinal instability, compression of nerve structures, and function damage, which has a serious impact on patients' quality of life (QOL). At present, surgery is main choice in the treatment of spinal metastases. However, conventional surgery still has certain limitations. This study explored the surgical strategy of nerve rescue in patients with spinal thoracic metastases and moderate-to-severe spinal cord injury. METHODS: In this history case-control study, 42 patients received conventional operation were enrolled as control group, while 38 patients who underwent conventional decompression of laminectomy combined with durotomy were selected as observation group. Perioperative data were recorded for comparisons between the two groups. Visual analogue scale (VAS) of pain, QOL, and 36-item short-form health survey (SF-36) were compared before operation and 3, 6, and 12 months after operation. American Spinal Injury Association (ASIA) grade was evaluated before operation and 1 month after. Complications, recurrence rate, and mortality were also recorded. RESULTS: The VAS scores of the observation group at 3, 6, and 12 months after operation were significantly lower than those before the operation. The QOL and SF-36 scores were increased compared with those taken preoperatively (P<0.05). The VAS score of the observation group was lower than that of the control group, and the QOL and SF-36 scores were higher than those in the control group (P<0.05). The neurological grades of ASIA 3 months after operation in both groups were significantly improved. The improvement in the observation group was greater than that in the control group (P<0.05). The incidences of postoperative complications in the control group and observation group were 19.05% (8/42) and 7.89% (3/38), respectively; the recurrence rates of the two groups were 14.29% (6/42) and 5.26% (2/38), respectively; and the mortality rates of the two groups were 26.19% (11/42) and 18.42%, respectively (7/38) (P>0.05). CONCLUSIONS: Durotomy based on conventional decompression of laminectomy can effectively save nerve function in metastases of the thoracic spine with moderate or severe spinal cord injury, improve QOL, and is thus worthy of being applied in clinic.

SLIT2 Overexpression in Periodontitis Intensifies Inflammation and Alveolar Bone Loss, Possibly via the Activation of MAPK Pathway.

SLIT2, a member of neuronal guidance cues, has been reported to regulate inflammation and cancer progression. Periodontitis is an oral inflammatory disease that degenerates periodontal tissue, alveolar bone and tooth. This study aims to explore the expression pattern of SLIT2 in periodontitis and its role in disease progression and bone loss. Gingival tissue of 20 periodontitis patients and 20 healthy-controls was obtained. Ligature-induced periodontitis (LIP) mice-model was developed in Slit2-Tg and wild-type mice. The effect of SLIT2 on inflammation, immune cell infiltration, M1 macrophage polarization, and alveolar bone loss in periodontitis was analyzed extensively. In periodontitis-affected gingival-tissue, SLIT2 expression was 4.4-fold higher compared to healthy-volunteers. LIP enhanced SLIT2 expression in mice periodontitis-affected periodontal tissue (PAPT) and blood circulation of wild-type mice by 4. 6-, and 5.0-fold, respectively. In Slit2-Tg-mice PAPT, SLIT2 expression was 1.8-fold higher compared to wild-type mice. Micro-CT and histomorphometric analysis revealed a 1.3-fold higher cement-enamel-junction to the alveolar-bone-crest (CEJ-ABC) distance and alveolar bone loss in LIP Slit2-Tg-mice compare to LIP wild-type mice. Results from RNA-sequencing, RT-qPCR, and ELISA showed a higher expression of Cxcr2, Il-18, TNFα, IL-6, and IL-1ß in Slit2-Tg-mice PAPT compared to wild-type-mice. Slit2-Tg-mice PAPT showed a higher number of osteoclasts, M1 macrophages, and the upregulation of Robo1 expression. Slit2-Tg-mice PAPT showed upregulation of M1 macrophage marker CD16/32 and osteoclastogenic markers Acp5, Ctsk, and Nfatc1, but osteogenic markers (Alp, Bglap) remained unchanged. Immunohistochemistry unveiled the higher vasculature and infiltration of leucocytes and macrophages in Slit2-Tg-mice PAPT. RNA-sequencing, GO-pathway enrichment analysis, and western blot analysis revealed the activation of the MAPK signaling pathway in Slit2-Tg mice PAPT. In conclusion, SLIT2 overexpression in periodontitis intensifies inflammation, immune cells infiltration, M1 macrophage polarization, osteoclastogenesis, and alveolar bone loss, possibly via activation of MAPK signaling, suggesting the role of SLIT2 on exacerbation of periodontitis and alveolar bone loss.

Fabrication and characterization of strontium-hydroxyapatite/silk fibroin biocomposite nanospheres for bone-tissue engineering applications.

Osteoinductive bone filling biomaterials are in high demand for effective bone defect reconstruction. In this study, we aimed to design both organic and inorganic substances containing strontium-doped hydroxyapatite/silk fibroin (SrHA/SF) biocomposite nanospheres as an osteoinductive bone defect-filling biomaterial. SrHA/SF nanospheres were prepared with different concentration of Sr using ultrasonic coprecipitation method. The nanospheres were characterized using XRD, FTIR, SEM, TEM, ICP-AES and TGA. Solid and dense SrHA/SF nanospheres with 500-700 nm size and rough surfaces were synthesized successfully. Higher crystallinity and HA/SF phase were observed with the increase in Sr-concentration. The doping of different concentration of Sr did not affect the size and surface characteristics of the nanospheres. ICP-AES data showed that Sr/Ca ratio in SrHA/SF is very close to the nominal value. Nanospheres with higher concentration of Sr did not negatively affect the biocompatibility, but enhanced viability of mesenchymal stem cells (MSCs). Moreover, SrHA/SF nanospheres showed higher osteogenic differentiation potential compared to HA/SF nanospheres as indicated by the results from ALP staining, ALP activity, and Runx2, Alp, Col-1 and Opn gene expression assay in MSCs culture. Our findings suggest this novel design of biocompatible and osteoinductive SrHA/SF biocomposite nanospheres as a potential bone defect-filling biomaterial for bone regenerative applications.

Observation of single spinal anesthesia by 25G needle puncture through a lateral crypt for hip surgery in elderly patients.

BACKGROUND: Lumbar spine hyperosteogeny and ligament calcification are common in the elderly and anesthesia puncture through the conventional approach is difficult in this age group, and repeated puncture can increase the risk of spinal hematoma and nerve injury. This study aimed to observe the feasibility and safety of single spinal anesthesia administered with 25G needle through the lateral crypt for lower-extremity fracture surgery in elderly patients. METHODS: The subjects were 60 elderly patients in our hospital (aged 65-80 years; ASA grades I and II) scheduled for lower-extremity fracture surgery (procedure was predicted to last within 2 h) under single spinal anesthesia by different approaches through L3-4. They were randomly divided into 2 groups: in the first group, 25G needle was used in a vertical approach (group C, n=30); in the second, 25G needle was passed through the inner edge of the small joints of L3-4 to the lateral crypt (group L, n=30). After successful completion of the puncture procedure, 2.5 mL of 0.5% hyperbaric ropivacaine was used for spinal anesthesia. We then recorded the puncture times, sensory block level, and adverse reactions (e.g., headache, lumbago, and lower limb pain). RESULTS: No significant differences in onset time, sensory block level and adverse reaction were noted between the 2 groups. The puncture success rate in group L was not significantly higher and the number of attempts per puncture was not significantly less than that in group C (93.3% vs 70%) (P = .063). Nerve-root irritation was more frequent in group L than in group C but with no significant difference (P > .05). CONCLUSION: Single spinal anesthesia through the lateral crypt approach is safe and effective for lower-extremity fracture surgery in elderly patients. Thus, this approach is a feasible alternative when the conventional approach fails.

A comparative study of the effects of concentrated growth factors in two different forms on osteogenesis in vitro.

Extending the release cycle of growth factors to match the cycle of bone remodeling is difficult. When using concentrated growth factors (CGFs), the release of growth factors is excessively rapid. In the present study, CGF samples were prepared by centrifugation. CGF samples were then lyophilized and grinded into a powder, which was termed freeze­dried CGF. The freeze­dried CGF samples were mixed with chitosan­alginate composite hydrogels, and the mixture was lyophilized. The result was a chitosan­alginate composite CGF membrane, which was called sustained­release CGF. This study investigated whether freeze­dried CGF in a chitosan­alginate composite gel can release CGF steadily to achieve effective osteogenesis. The proliferation and osteogenic expression of MC3T3­E1 cells induced by the supernatants from incubation with freeze­dried CGF and sustained­release CGF were evaluated. The concentrations of the growth factors, transforming growth factor ß1 (TGF­ß1), insulin­like growth factor­1 (IGF­1), platelet­derived growth factor­AB (PDGF­AB) and vascular endothelial growth factor (VEGF), in these two experimental groups at different times were determined by ELISA kits. The freeze­dried CGF showed better osteogenic performance than the sustained­release CGF in the early stages. At later stages, the sustained­release CGF had significant advantages over freeze­dried CGF in terms of promoting osteogenic mineralization. By characterizing the biologic properties of the CGF in the two different forms in vitro, we obtained a better understanding of their clinical effects.

[Correlation between resting heart rate and blood glucose level in elderly patients with coronary heart disease and diabetes mellitus].

OBJECTIVE: To explore the correlation between resting heart rate (RHR) and blood glucose level in elderly patients with coronary heart disease (CHD) complicated by diabetes mellitus. METHODS: Between April and July, 2011, a total of 1336 outpatients over 60 years of age recruited from 165 hospitals were asked to complete a questionnaire and received blood glucose and RHR examination. According to baseline RHR, the patients were divided into 3 groups with HRH <70 min-1 (group I, 372 cases), between 70 and 79 min(-1) (group II, 533 cases), and ≥80 min(-1) (group III, 431cases) for analysis of the relationships of RHR with blood glucose control rate. RESULTS: HbA1c levels in the total, male and female patients differed significantly among the 3 groups (F=15.436, 15.436, and 24.270, respectively, P<0.05), and increased in the order from group I to group III. Blood glucose control rate in the total, male and female patients also differed significantly among the 3 groups (χ(2)=13.471, 6.752, and 6.522, respectively, P<0.05), and was significantly lower in group III than in group I (P<0.05). RHR was found to positively correlate with FPG, 2 hPG and HbA1c by Pearson correlation analysis (r=0.058, 0.085, and 0.058, respectively; P<0.05) and multiple linear regression analysis (ß=0.075, 0.075, and 0.018, respectively; P<0.05). Multivariable logistic regression equation showed that compared with patients with RHR <70 min-1, the total, male and female patients with RHR ≥80 min(-1) had OR values of blood glucose control failure of 1.99 (95% CI: 1.23-2.37, P<0.05), 1.81 (95% CI: 1.17-2.77, P<0.05), and 2.18 (95% CI: 1.12-3.74, P<0.05), respectively. CONCLUSION: RHR in elderly CHD patients with MD is positively correlated with their blood glucose level, and an increased RHR is associated with an increased risk of poor blood glucose control. Rigorous RHR control in such high-risk patients may prove beneficial for both blood glucose control and secondary prevention of CHD.

[Current status of blood pressure control rate and antihypertensive drug use in the elderly coronary heart disease patients with diabetes mellitus and hypertension].

OBJECTIVE: To investigate the current status of blood pressure control rate and the use of antihypertensive drugs in elderly patients with coronary heart disease, diabetes mellitus and hypertension. METHODS: The elderly coronary heart disease patients with diabetes mellitus and hypertension (≥ 60 years old) were recruited from 165 hospitals in 21 provinces or cities across China from April to July 2011 in this multicenter, non-intervention and cross-sectional survey. The current status of blood pressure control rate in different antihypertensive target value, methods for application in antihypertensive drugs and standardized treatment recommended by guideline were investigated in the survey. RESULTS: 1 379 cases were eventually selected from the total 7 962 elderly patients (accounted for 17.3%). (1) The blood pressure control rate was 17.1% for antihypertensive target value (<130/80 mmHg); the control rate for 140/80 mmHg was 27.5%; the control rate for 140/90 mmHg was 39.6%; the success rate for 150/90 mmHg were 51.7%; control rate of elderly patient (≥ 70 years old) gradually increased with increasing of age; success rate of elderly patient (≥ 85 years old) was the highest, whereas control rate of elderly patient aged 71-71 years old was lowest; success rate for male patients was close to female patients, and success rate for men were slightly higher than those in women; (2) 1 347 cases had clear medication history (32 cases were missed) in the survey, 1 317 effective cases received antihypertensive therapy (effective rate was 97.8%, 1 317/1 347); the more commonly used drugs were angiotensin receptor blockers (ARB) /angiotensin converting enzyme inhibitors (ACEI) (usage rate was 76.8%), followed by dihydropyridine calcium channel blockers (CCB) (65.5%), ß-blockers (usage rate was 44.6%), thiazide diuretics (26.3%) respectively; (3) combinations of two drugs was the most common way in antihypertensive medication (accounted for 41.2%), three drugs or more was 28.9%, and single drug was 23.9%; CCB was the commonly used single drug (accounted for 8.8%); combinations of CCB and ARB were the most common way in combination of two drugs(11.7%), CCB combined with ARB and ß-blockers was frequently used in combination of three drugs or more (9.2%); (4) 987 cases received standardized treatment recommended by guideline (accounted for 76.6%); the percentage of standardized usage in combinations of two drugs was 71.9%, the percentage of standard usage in combinations of three drugs or more was 66.1%. CONCLUSION: The percentage of antihypertensive therapy is high, however, the overall blood pressure control rate is low. ACEI /ARB are the major drugs in antihypertensive medication, diuretic drugs are now rarely used; combined medication is the common method of antihypertensive therapy; the consciousness following the guidelines has improved, but still need to be strengthened.

[Analysis of prognostic factors in 68 patients with cancer of unknown primary site].

OBJECTIVE: The aim of this study was to analyze the clinical characteristics and prognostic factors in patients with cancer of unknown primary site (CUP). METHODS: The clinical and follow-up data of 68 CUP patients (46 adenocarcinoma patients, 22 squamous cell carcinoma patients), were retrospectively analyzed. Univariate and multivariate analysis were conducted to determine the correlation of survival with clinical features, tumor markers, blood test, liver function and so on. RESULTS: The median survival time of the 68 CUP patients was 123 days. The results from univariate Cox regression analysis showed that the prognostic factors were related to a performance status, presence or absence of liver metastases, the number of metastatic sites, carcinoembryonic antigen (CEA), lactate dehydrogenase (LDH), hypoalbuminemia, hypohemoglobinemia and lymphocyte count. Multivariate Cox regression analysis of the clinical factors identified that a performance status (PS) ≥ 2, liver metastasis, elevated serum carcinoembryonic antigen (CEA) and lactate dehydrogenase (LDH) levels, hypoalbuminemia (< 35 g/L) and lymphopenia (≤ 0.7 × 10(9)/L) were significant independent unfavorable predictive factors. Based on the number of the unfavorable predictive factors, we divided all the patients into three subgroups: subgroup involving 0-1 unfavorable factor, subgroup involving 2 - 3 unfavorable factors and subgroup involving 4 - 6 unfavorable factors. The median survival time was 390 days, 138 days and 77 days, respectively, in the 3 subgroups. Compared with the other two groups, the survival of the subgroup involving 0 - 1 unfavorable factor was significantly longer (P < 0.05), the survival between the subgroup involving 2 - 3 unfavorable factors and subgroup involving 4 - 6 unfavorable factors was not significantly different (P > 0.05). CONCLUSIONS: A performance status ≥ 2, liver metastasis, elevated serum carcinoembryonic antigen and lactate dehydrogenase levels, hypoalbuminemia and lymphopenia are independent unfavorable prognostic factors in patients with cancer of unknown primary site. The patients who had more than 2 unfavorable prognostic factors have a worse prognosis.