Current situation and prospect of 3D printing technology in pharmaceutical preparations / 中国药科大学学报

@#With the rapid advancement of science and technology, the application of 3D printing technology for personalized drug manufacturing is becoming increasingly sophisticated.Compared to traditional manufacturing technology, 3D printing can easily customize preparations with specific sizes, shapes and release behaviors for personalized drug use.This review summarizes the principles of several 3D printing technologies commonly used in drug manufacturing, lists the unique advantages and application examples of 3D printing technology for pharmaceutical preparation, analyses the current research status and development trends of the global industry of drug 3D printing, and summarizes the current problems and challenges facing drug 3D printing, aiming to provide some guidance for researchers of 3D printed drugs.

Activation of TGR5 Attenuates Renal Fibrosis after Renal Ischemia Reperfusion Injury / 中山大学学报(医学科学版)

ObjectiveTo investigate the role of bile acid receptor TGR5 activation in renal fibrosis induced by unilateral ischemia reperfusion injury and contralateral nephrectomy （uIRIx） model. MethodsIn vivo： C57BL/6J mice were randomly divided into Sham group， uIRIx group and uIRIx+ lithcholic acid （LCA） group with 6 mice in each group. Kidney fibrosis was induced by uIRIx model， kidney function was evaluated by blood and urine biochemical indexes， and the degree of kidney injury was evaluated by HE staining. Masson staining and immunohistochemistry were used to evaluate the degree of renal fibrosis， and Western Blotting was used to detect the expression of related index proteins of renal cortical fibrosis. Sham group and uIRIx group were set in TGR5+/+ mice and TGR5-/- mice respectively， with 6 mice in each group. The degree of renal fibrosis in each group was detected by Western Blotting. In vitro： TGF-β1 was administered to induce pro-fibrosis response in human renal tubular epithelial cell line （HK2 cells）， LCA was used for drug intervention， cytoskeleton was labeled with phalloidin-FITC staining and the expression of fibrosis related indicator protein in HK2 cells was detected by Western Blotting. ResultsIn vivo： Compared with the Sham group， plasma creatinine level （P=0.007） and urinary albumin/creatinine ratio （P=0.041） in uIRIx group were significantly increased， renal cortical protein TGR5 expression （P=0.002） was decreased， Fibronectin expression （P=0.020） and COL1A1 expression （P<0.001） were increased. At the same time， the kidney structure was damaged and collagen deposition was aggravated. LCA intervention effectively improved the kidney function and alleviated the degree of kidney injury and fibrosis. TGR5 gene knockout increased uIRIx-induced Fibronectin expression （P<0.001） and COL1A1 expression （P=0.001） compared with TGR5+/+ mice. In vitro： TGF-β1 induced morphological changes of HK2 cells， cytoskeletal depolymerization and recombination， and promoted the up-regulation of fibrosis index protein. LCA effectively inhibited the morphological changes and skeletal depolymerization induced by TGF-β1， and down-regulated the expression of fibrosis related indicator proteins. ConclusionsLCA alleviated renal fibrosis induced by uIRIx model， and knockout of TGR5 gene aggravated uIRIx induced renal fibrosis； In HK2 cells， LCA alleviated fibrogenic reaction induced by TGF-β1. This indicates that activation of TGR5 alleviates renal fibrosis induced by uIRIx.

Preparation of 3D printed metoprolol tartrate chewable tablets and optimization of printing process / 药学学报

With the growing demand of personalized medicine for children, it is especially important to develop medicines for children. In this study, using metoprolol tartrate as model drug, we developed 3D printed chewable tablets suitable for children with automated dosage distribution using semi-solid extruded (SSE) 3D printing technology. Based on the quality by design concept, this study prepared a semi-solid material with good printability using gelatin as the substrate, constructed 3D models and printed tablets with the aid of computer-aided design. The printing parameters were optimized and determined as follows: print temperature of 35-37 ℃, print speed of 25 mm·s-1, fill rate of 15%, and number of outer profile layers of 2. Subsequently, the printing process and the quality uniformity of the tablets were verified, and a linear relationship between the dose and the number of model layers was obtained. Finally, 3D printed chewable tablets were superior in terms of appearance, dose accuracy and compliance compared with traditional split-dose commercially available tablets. In this study, 3D printed metoprolol tartrate chewable tablets with good performance were successfully prepared to address the personalized medication needs of pediatric patients.

Phosphodiesterase 5 Inhibitors Attenuate Unilateral Ureteral Obstruction-Induced Renal Fibrosis / 中山大学学报(医学科学版)

ObjectiveTo investigate whether phosphodiesterase （PDE） 5 inhibitors sildenafil （SIL） or LW1646 prevented renal interstitial fibrosis induced by unilateral ureteral obstruction （UUO）. MethodsMale C57BL/6 mice were randomly divided into four groups （n =6）， namely the Sham group， 7UUO group， 7UUO+SIL group and 7UUO+LW1646 group. Sildenafil （SIL） or LW1646， or vehicle was administered 1 hour before surgery， and the mice were continuously treated once daily （i. g.， 50 mg/kg） for 7 days. The obstructed kidneys were harvested on day 7. Hematoxylin-eosin （HE） and Masson’s staining was used to examine renal histology. Immunoblotting and RT-qPCR were used to detect the expression levels of protein and mRNA for fibrosis， apoptosis， endoplasmic reticulum （ER） stress， autophagy， and pro-fibrotic factors. Human proximal tubule epithelial cells （HK-2） were treated with TGF-β1 for 48 hours or tunicamycin for 24 hours， respectively， to evaluate whether cyclic guanosine monophosphate （cGMP） or PDE5 inhibitors prevents ER stress and pro-fibrotic responses. ResultsAt the 7th days after UUO， the body weight of the mice showed a significant decrease （P< 0.000 1） compared with that in the sham group. The obstructed kidneys showed a significant tubular dilation and interstitial inflammation. The levels of protein and mRNA expression in apoptosis， ER stress， autophagy-related protein and pro-fibrotic factors were also markedly increased in UUO mice （P <0.05）. In contrast， SIL or LW1646 treatment was associated with attenuated tubular dilation， infiltration of inflammatory cells and collagen content in the obstructed kidney of the mice. The protein and mRNA expression levels of renal TGF-β1 were markedly decreased， and the protein expression levels of apoptosis， endoplasmic reticulum stress， and autophagy markers were also significantly downregulated by PDE5 inhibitors. In HK-2 cells， TGF-β1 induced increased expression levels of fibronectin and BiP， which was at least partially reversed by cGMP， a product of PDE inhibition. Additionally， PDE5 inhibitors were found to modulate aberrant levels of autophagy and apoptosis. ConclusionIn conclusion， PDE5 inhibitors， in particular， LW1646， can alleviate the progression of fibrosis by improving ER stress， apoptosis and autophagy as well as downregulating protein and mRNA expression of TGF-β1.

Comparison of clinical effects of two anterior cervical decompression with fusion on treating two segment cervical spondylotic myelopathy / 中国骨伤

OBJECTIVE@#To explore the clinical effects of anterior cervical discectomy with fusion (ACDF) and anterior cervical corpectomy with fusion (ACCF) in treating adjacent two-segment cervical spondylotic myelopathy (CSM).@*METHODS@#The clinical data of 37 patients with adjacent two segment CSM treated from January 2016 to December 2017 were retrospectively analyzed, including 15 males and 22 females, aged from 43 to 69 years old with an average of 54.6 years. The patients were divided into ACDF group (group A, =17) and ACCF group (group B, =20) according to the different surgery. The operation time and intraoperative blood loss were recorded;the Cobb angle and cervical curvature in the cervical fusion segments before surgery and 1, 12 months after surgery were observed;Japanese Orthopaedic Association (JOA) score was used to evaluate the surgical efficacy, and the postoperative complications were analyzed.@*RESULTS@#All patients were followed up for 12 to 24 months with an average of 18.5 months. Operation time and intraoperative blood loss in group A were (106.3±22.6) min, (52.2±26.4) ml, respectively, while were (115.6±16.8) min, ( 61.7±20.7) ml in group B. There was no statistically significant in operation time between two groups(>0.05);intraoperative blood loss in group B was larger than group A(0.05). At the final follow up, in group A, dysphagia occurred in 2 cases, cage displacement in 1 case, and no titanium plate screw loose was found;and in group B, dysphagia occurred in 4 cases, titanium mesh collapse in 2 cases, titanium plate screw loose in 1 case.@*CONCLUSION@#Two types of anterior cervical decompression and fusion for the treatment of two segment cervical spondylotic myelopathy can effectively decompress and improve the Cobb angle and cervical curvature of the affected vertebra. The ACDF surgical procedure can directly removethe compressive thing at intervertebral level, which will lead to little vertebral body damage and favorably recovered cervical curvature. The ACCF surgical procedure has a large operation space, which can easily remove the posterior vertebral osteophyte and the calcified posterior longitudinal ligament. Long-term follow-up shows that ACDF and ACCF have good surgical procedures, mature technology, and close efficacy.

Effect observation of percutaneous pedicle screw fixation combined with percutaneous vertebroplasty for the treatment of osteoporotic thoracolumbar fractures / 中国骨伤

<p><b>OBJECTIVE</b>To evaluate the clinical effects of percutaneous pedicle screw fixation(PPSF) combined with percutaneous vertebroplasty(PVP) for the treatment of osteoporotic thoracolumbar fractures.</p><p><b>METHODS</b>The clinical data of 94 patients with osteoporotic thoracolumbar fractures treated from January 2014 to December 2015 were retrospectively analyzed. There were 31 males and 63 females, aged from 65 to 70 years old with an average of 67.2 years. Fracture level was T₁₁ on 15 cases, T₁₂ on 32 cases, L₁ on 29 cases and L₂ on 18 cases. The patients were divided into two groups according to different therapeutic methods. Percutaneous pedicle screw fixation combined with percutaneous vertebroplasty were applied in 43 patients(group A) and percutaneous vertebroplasty was applied to 51 patients(group B). Operation time, intraoperative blood loss, bone cement volume, postoperative in-bed time were recorded; preoperatively, 3 d, 1 year after the operation, the ratios of anterior border heights, sagittal Cobb angles, visual analogue scale(VAS) scores were compared between two groups. The condition of postoperative complication in two groups was analyzed.</p><p><b>RESULTS</b>All the patients were followed up for 12 to 24 months with an average of 18.5 months. Operation time of group A [(96.2±28.7) min] was longer than that of group B [(31.8±10.6) min]. Intraoperative blood loss of group A[(62.2±25.5) ml] was more than that of group B [(25.4±10.9) ml]. Bone cement volume of group A [(5.5±0.5) ml] was larger than that of group B [(4.9±1.1) ml]. Postoperative in-bed time of group A[(5.1±1.8) d] was longer than that of group B[(1.8±0.7) d]. There were significant differences in operation time, intraoperative blood loss, bone cement volume, postoperative in-bed time between two groups(<0.05). Three days, 12 months after the operation, the ratios of anterior border heights and Cobb angles in two groups were significantly improved. At final follow-up, the ratio of anterior border height and Cobb angle of group A[(85.6±3.5)%, (11.9±5.3)°] were better than of group B[(84.2±4.5)%, (15.3±3.4)°](<0.05). Three cases in group B had re-collapse of cemented vertebral bodies. Postoperative at 3 d, 1 year, VAS score of all patients had significantly decreased(<0.05), and there was no significant difference between two groups(>0.05).</p><p><b>CONCLUSIONS</b>Compared to simple PVP, PPSF combined with PVP in treating osteoporotic thoracolumbar fracture can obtain stronger vertebral strength and stiffness, furthermore to improve vertebral reduced effect, keeping vertebral heights, and preventing vertebral re-collapse.</p>

Acceleration of wound healing by a porous collagen/silk fibroin scaffold carrying zinc oxide nanoparticles / 中国组织工程研究

BACKGROUND:Anti-infective ability determine the success or failure of skin grafting. It is one of the commonly used methods to enhance the anti-infective ability of implants by compounding antibacterial materials with scaffolds. OBJECTIVE:To investigate the effect of porous collagen/silk fibroin scaffolds carrying zinc oxide nanoparticles against infection and inflammation, and to evaluate its effect on wound healing. METHODS:Thirty-two Sprague-Dawley rats with a full-thickness wound on the back skin were randomly divided into two groups. In experimental groiup, porous collagen/silk fibroin scaffolds containing zinc oxide nanoparticles were implanted, while only collagen/silk fibroin scaffolds were implanted in control group. Wound healing was compared between the two groups by measuring residual wound area at 1, 2, 4, 8 weeks post implantation. Hematoxylin-eosin and interleukin 6 immumohistochemical staining were performed at 1, 2, 4 weeks post implantation to observe wound morphology and inflammatory reactions. Meanwhile, expression of interleukin 6 and interleukin 1β was detected by real-time PCR. RESULTS AND CONCLUSION:(1) At 2, 4, 8 weeks post implantation, significantly increased healing rate was observed in the experiment group compared with the control group (P<0.05). (2) Findings from the hematoxylin-eosin staining showed that obvious inflammatory cell infiltration was observed in the control group, but less inflammation with vigorous growth of granulation tissues on the wound surface occurred in the experimental group at 1 week after implantation. Then, the wound repair was basically completed in the experimental group presenting with complete and compact epidermal tissue structure, while scar formation with no skin cover was found in the control group at 4 weeks after implantation. (3) Findings from the interleukin 6 immumohistochemical staining showed that there was interleukin 6 positive expression in both two groups to different extents; at 4 weeks after implantation, the expression of interleukin 6 was remarkably reduced in the control group, but it was still a strong positive expression, while week positive expression of interleukin 6 was observed in the experimental group. (4) Compared with the control group, the mRNA expression of interleukin 6 and interleukin 1β was both lower in the experimental group at 1, 2, 4 weeks after implantation, but there was a significant difference between the two groups at 1 and 2 weeks after implantation (P<0.05). Overall, the porous collagen/silk fibroin scaffold carrying zinc oxide nanoparticles can effectively reduce inflammations following skin injury, and accelerate skin wound healing.

Analysis of the Influence of Different MCV Level on the Platelet False Increase Counts / 现代检验医学杂志

Objective To evaluate the influence of the mean corpuscular volume (MCV) in different ranges on PLT counts,provide the theoretical basis for making PLT counts review rules in laboratory.Methods From March 2016 to August 2016 in Xijing Hospital department of outpatient who perform complete blood cell count were randomly divided into 3 groups,MCV≤65 fl in A group,65 fl＜MCV≤70 fl in B group and 70 fl＜MCV≤75 fl in C group.The reference method (Coulter principle) compared with the fluorescence method,accuracy analysis of different monitoring methods of counting PLT.Results PLT I and PLT F count values in A group was (322.8± 109.1) × 109/L and (282.60± 100.5) × 109/L respectively,and there was significant differences between the two groups (t=6.799,P＜0.05).In B group,the count values was (305.7 ± 111.7)× 109/L and (304.8 ± 112.3)× 109/L respectively,and there was no differences between two groups.In C group,the count values was (292.2±84.4) × 109/L and (291.6±84.4) × 109/L respectively,and there was no differcnces between two groups neither.Conclusion When small red blood cells or blood cell debris present in blood circulation,MCV≤65 fl,the reference testing (Coulter principle)of platelets causes a false increase in platelet count.

Research on Traditional Chinese Medicine Healthy Life-style Guiding Principles Based on Delphi Indagate / 世界科学技术-中医药现代化

Through the expert questionnaire (Delphi Indagate) to form Traditional Chinese Medicine (TCM) Healthy Lifestyle Guiding Principles.We conducted two rounds of surveys of TCM experts in the field of preventive health care on the basis of previous literature research.This study was aimed to form the framework in order to entry to the TCM Healthy Life-style Guiding Principles.The results showed that the positive coefficient of experts in two rounds of investigation were 84.31％ and 100％,respectively.The authoritative decree were both more than 0.7.The expert opinion score mean median was 9.21 and 9.085.Median mean values were 7.965 and 7.925.The median scores of full marks were higher than 65.12％ and 66.67％.The minimum coefficients of variation were 0.11 and 0.10.It was concluded that in the investigation and study,the enthusiasm of the experts,professional standards and credibility were high.Expert opinion is more concentrated.Expert opinion is well coordinated and gradually converges through two rounds of surveys.Through the Delphi indagate,the basic framework and items of TCM guiding principles of healthy lifestyle were established,which laid the foundation for further standardizing the guiding principles of TCM in healthy lifestyle.

Interferon-induced transmembrane protein 3 knock-down inhibits proliferation and invasion of hepatocellular carcinoma HepG2 cells in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the abnormal expression of interferon-induced transmembrane protein 3 (IFITM3) in hepatocellular carcinoma (HCC) and the effect of IFITM3 knock-down on the biological behaviors of hepatocellular carcinoma HepG2 cells.</p><p><b>METHODS</b>Western blot analysis and immunohistochemical staining were used to determine the expression of IFITM3 protein in 60 HCC samples and paired adjacent tissues. A small interfering RNA fragments of IFITM3 (IFITM3 siRNA) was transiently transfected into HepG2 cells and expressions of IFITM3 at mRNA and protein levels were examined by qRT-PCR and Western blotting. The changes in the proliferation of the transfected cells were determined using cell counting kit 8 (CCK8) assay, and the cell invasion and migration were tested using Transwell assay and wound-healing assay.</p><p><b>RESULTS</b>Compared with the adjacent tissues, HCC tissues expressed significantly higher levels of IFITM3. In HepG2 cells, transfection with IFITM3 siRNA resulted in significant down-regulation of IFITM3 expression at both the protein and mRNA levels and obviously suppressed cell proliferation, invasion, and migration ability as compared with the cells transfected with scrambled siRNA and control cells (P<0.05).</p><p><b>CONCLUSIONS</b>IFITM3, which is overexpressed in HCC, plays a vital role in the proliferation and invasion of HCC cells and may serve as a potential target for gene therapy of HCC.</p>

Case-control study on minimally invasive percutaneous plate osteosynthesis for the treatment of distal tibial comminuted fractures at different operation times / 中国骨伤

<p><b>OBJECTIVE</b>To compare clinical outcomes of minimally invasive percutaneous plate osteosynthesis (MIPPO) in treating distal tibial comminuted fractures at early and delayed stage.</p><p><b>METHODS</b>From January 2006 to January 2012,66 patients with distal tibial comminuted fractures were treated by MIPPO. All patients were divided into primary group and delayed group according to operation time. There were 31 patients in primary group, including 18 males and 13 females aged 21 to 57 years old with an average of (39.0 +/- 17.8), treated by MIPPO at primary stage,according to Tscherne soft tissue injury, 18 cases were grade I ,12 cases were grade II and 1 case were grade III. Thirty-five patients were treated by MIPPO at delayed stage, including 16 males and 19 females aged 24 to 55 years old with an average of (39.5 +/- 15.2), according to Tscherne soft tissue injury, 6 cases were grade I, 26 cases were grade II and 3 cases were grade III. Operation time, blood loss, hospital stay, fracture healing time and complications of two groups were recorded and observed, Lowa scoring of ankle joint were used to evaluated therapeutic effects at final following and AP and lateral X-rays were used to evaluated fracture reduction and alignment.</p><p><b>RESULTS</b>All patients were followed up, the time of following-up of primary group was (13.5 +/- 3.5) months, (15.2 +/- 3.8) months in delayed group, there was no significant meaning between two groups (t = 1.882, P = 0.064). There was no significant differences between two groups in operation time and blood loss (P > 0.05), but hospital stay in primary group was shorter than that of delayed group(P<0.05). There was no significant meaning between primary group (5.5 +/- 2.8) and delayed group (6.2 +/- 3.1) in fracture healing time (t = 0.958, P = 0.342); there was no significant meaning between primary group (87.6 +/- 6.8) and delayed group (89.6 +/- 5.2) in Lowa scores at final following-up (t = 1.351, P = 0.182). Two cases occurred postoperative superficial inflammatory reaction around fibular incision in primary group, 1 case occurred postoperative superficial inflammatory reaction around fibular incision and 1 case occurred delayed deep incision infection in delayed group at four months after operation. There was no significant differences in incidence of postoperative soft tissue complications between primary group (6.5%) and delayed group (5.7%) (t = 0.016, P = 0.900).</p><p><b>CONCLUSION</b>For distal tibial comminuted fractures with grade I and II of Tscherne soft tissue injury, MIPPO at primary stage can not increase incidence of soft tissue complications, also can obtain the same clinical outcomes just like delayed MIPPO.</p>

Case control study of different fixing methods for intertrochanteric fractures / 中国骨伤

<p><b>OBJECTIVE</b>To compare the clinical effects of different fixing methods for intertrochanteric fractures and make theoretical analysis.</p><p><b>METHODS</b>From June 2003 to June 2007, 321 patients with intertrochanteric fractures, male 132 and female 189, ranging in age from 20 to 93 years with an average of 56.8 years, were treated with different fixation including Richard nail (142 cases), proximal femora nail (PFN, 94 cases) and external fixator (85 cases). The clinical data of all the patients were retrospectively analyzed, including the incidence of complications, joint function of hip (according Kudema modified Merli D'Aubigne criteria).</p><p><b>RESULTS</b>All patients were followed up from 10 months to 4 years with an average of 14 months. About the incidence of complications, there was significant difference between the external fixator group and the others two groups (P < 0.05); there was no significant difference between the Richard nail group and the PFN group (P > 0.05). There was significant difference in joint function of hip among three methods. PEN group was best than others two groups.</p><p><b>CONCLUSION</b>There is the best clinical effects and lowest incidence of complications with PFN method, which is the better choice in treating intertrochanteric fractures.</p>