[Randomized,double-blind,parallel controlled,multicenter clinical trial of effectiveness and safety of Shexiang Zhuifeng Zhitong Ointment in alleviating pain in knee osteoarthritis(syndrome of cold-dampness obstruction)].

The Shexiang Zhuifeng Zhitong Ointment with the effects of dispelling wind, removing dampness, dissipating cold, and relieving pain is used for treating arthralgia, muscular pain, and sprain pain caused by cold-dampness obstruction. To evaluate the efficacy and safety of Shexiang Zhuifeng Zhitong Ointment in relieving the pain due to knee osteoarthritis(syndrome of cold-dampness obstruction), a randomized, double-blind, parallel controlled, multicenter clinical trial was conducted. The stratified randomization method was used to randomize the 240 subjects into a treatment group and a control group in a ratio of 1∶1. In each group, 60 patients received external application for 12 h and the other 60 patients received external application for 6 h. The treatment group received external application of Shexiang Zhuifeng Zhitong Ointment, while the control group received external application of Shexiang Zhuifeng Ointment. The treatment lasted for 21 days in both groups. Follow-up was conducted on days 7, 14, and 21 of treatment. The results based on the full analysis set were as follows.(1)In visual analog scale(VAS) score, the mean difference in the VAS score between baseline and 12 h post-treatment was 3.02 in the treatment group and 2.31 in the control group, with a significant difference(P<0.05). The mean difference in the VAS score between baseline and 6 h post-treatment was 3.19 in the treatment group and 2.48 in the control group, with a significant difference(P<0.05).(2)Response rate in terms of VAS score, after treatment for 12 h, the response rate was 93.22% in the treatment group and 73.33% in the control group, with a significant difference(P<0.05). After treatment for 6 h, theresponse rate in the treatment group was 88.33%, which was higher than that(63.33%) in the control group(P<0.05).The results showed that Shexiang Zhuifeng Zhitong Ointment applied for 12 and 6 h effectively relieved the knee joint pain of patients with knee osteoarthritis due to cold-dampness obstruction, as demonstrated by the reduced VAS score, Western Ontario and McMaster Universities Arthritis Index(WOMAC), stiffness, and joint function score. Moreover, Shexiang Zhuifeng Zhitong Ointment outperformed the positive control Shexiang Zhuifeng Ointment in terms of reducing the VAS score, demonstrating a definitetherapeutic effect on the pain due to knee osteoarthritis(syndrome of cold-dampness obstruction).In addition, Shexiang Zhuifeng Zhitong Ointment did not cause other adverse reactions except for mild allergic reactions, which were common in the external application of traditional Chinese medicine plasters on the skin, inseveral patients.Neither other adverse reactions nor abnormalities of liver and kidney functions and electrocardiogram were observed. This ointment had high safety and could be popularized in clinical application.

[Correlation analysis of color change and Maillard reaction during processing of Gardeniae Fructus Praeparatus].

The chromaticity space parameters of the samples during the processing of Gardeniae Fructus Praeparatus(Jiaozhizi in Chinese herbal name, JZZ) were measured by the visual analyzer to analyze the color variation rule during the processing of JZZ, and the content changes of total reducing sugar, total amino acid and 5-hydroxymethylfurfural(5-HMF) related to Maillard reaction were measured. Pearson correlation analysis and linear regression analysis of the data were carried out by SPSS 24.0 software. The experimental results showed that the objective coloration of the samples in the processing of JZZ was basically consistent with the traditional subjective color judgment; the contents of total reducing sugar and total amino acids showed a decreasing trend during the processing of JZZ, and the content of 5-HMF showed an increasing trend, which was in line with Maillard reaction law. Pearson correlation analysis results showed that there was a significant correlation between the chromaticity space parameters L~*(lightness value), a~*(red green value), b~*(yellow blue value), E~*ab(total color value) and the contents of total reducing sugar, total amino acid and 5-HMF(P<0.01), among which the values of L~*, a~*, b~*, E~*ab were positively correlated with the contents of total reducing sugar and total amino acid, and negatively correlated with the contents of 5-HMF. The results of linear regression analysis also showed that these two were highly correlated. In this study, by establishing the correspondence relationship between the color change of JZZ processing and Maillard reactants, wecan not only provide a basis for the objective digital expression of subjective color of JZZ, but also provide a reference for explaining the processing mechanism of JZZ from a new perspective.

[Establishment of extraction method for Gardeniae Fructus extract and its application in evaluating different Gardeniae Fructus decoction pieces].

In this experiment,the gradation analysis method was used to evaluate the quality of different pieces of Gardeniae Fructus through the extraction rate difference and the difference analysis of the main components in the extract. In this experiment cold-dip and hot-dip methods were used to compare the yield of Gardeniae Fructus extract and the content of chemical constituents with water,25%,50%,75% and 95% ethanol fractions. By weighted calculation,the optimal extraction method of Gardeniae Fructus was determined,and this was verified by practical application. RESULTS:: showed that for the water-soluble extract,cold dip method was better than the hot dip method; and for alcohol-soluble extract,75% ethanol under cold dip method was best. The verification results showed that water-soluble extracts under cold dip methods could be used to significantly distinguish the raw Gardeniae Fructus( GF) and processed( stir-baked) GF( GFP) collected from the market. Meanwhile,this method could be also used to distinguish the same batch of GF,GFP and carbonized GF( GFC) with significant differences,respectively( P<0. 05). Ethanol-soluble extract can be used to clearly distinguish GFP and GFC pieces in the same batch( P<0. 05). The results of content determination showed that the variation coefficient of components in GF processed products was higher than that in extracts,and the content of hydroxygeniposide was the most significant component between GF and its processed products. It is suggested that the method of water-soluble extract of GF and the determination of the content of gardoside should be combined together to evaluate the quality of GF and its heat processed products.

[Study on quality standard of rice as excipients during rice stir-frying method].

Commercially available japonica rice and indica rice with different trade names were collected,and then based on the method of rice stir-frying,their many indexes were evaluated,for example the physical and chemical properties such as appearance color,grain type,broken kernel ratio,length-width ratio,1 000-grain weight,specific heat capacity,moisture content,amylose content,and protein content. The discriminant function analysis was used to determine the effective factors affecting the quality of rice as excipients. The results showed that two types of rice could be distinguished by rice color parameter a*,grain parameter circularity,1 000-grain weight and amylose content. These four effective factors can be used as the quality evaluation indexes for fried rice as excipients.Protein is one of the main components of rice,and its content affects the quality of rice. There is a significant difference in the protein content between japonica rice and indica rice. Therefore,protein content should be used as one of the evaluation indexes for rice quality. After comprehensive consideration,it is suggested that the red-green value a*shall not be less than 0. 50; the circularity not less than 53. 0,the 1 000-grain weight not less than 16. 0 g,the amylose content not less than 12. 0% and the protein content not less than4. 0% in the japonica rice; the red-green value a*shall not be lower than-1. 0,the circularity not less than 41. 0,the 1 000-grain weight not less than 13. 0 g,the amylose content not less than 9. 0% and the protein content not less than 3. 5% in the indica rice. In this study,the quality evaluation standards for rice as excipients( japonica rice,indica rice) were supplemented and improved,laying foundation for the development of quality standards for rice as excipients with the rice stir-frying method.

Efficacy of Transosseous Tunnel Placement for Triple Endobutton Plate in Acromioclavicular Joint Reconstruction: A Three-Dimensional Printing Guide Design Technology.

OBJECTIVE: Explore an accurate transosseous tunnel drilling method based on three-dimensional (3D) printing technology for acromioclavicular joint reconstruction (ACD), design a guide design, and evaluate its accuracy. METHODS: Using Mimics software to reconstruct 100 cases of acromioclavicular joint computed tomography (CT) data. In design 2, the non-collinear tunnel is superimposed on the 3D model, and a virtual drilling is performed between the clavicle and the coracoid using a triple inner gusset. Then, in the Geomagic Studio software model, an elliptical plane is calculated and extracted as a guide design for precise drilling. Then put the design and the 3D shoulder model together for 3D printing. Ten lengths were measured, and the effects of the virtual model, the actual model, and the guide rail design were compared. RESULTS: We successfully compared 10 parameters of 3D virtual model and actual model. There was no significant difference between actual and virtual bone tunnels in 10 measurements (P > 0.05). CONCLUSIONS: The accuracy of ACD combined with 3D printing guidance design technology in the transosseous tunnel of adult shoulder is reliable.

Relationship between Classification of Fabellae and the Severity of Knee Osteoarthritis: A Relevant Study in the Chinese Population.

OBJECTIVE: To classify the fabellae and discuss the relationship between the classification of fabellae and the severity of knee osteoarthritis (KOA) in Chinese. METHODS: From February 2019 to February 2020, 136 patients were measured and classified using three-dimensional computed tomography (CT) reconstruction. According to the CT imaging characteristics, the fabellae were divided into five types: type I, a fabella on the lateral femoral condyle; type II, a fabella on the medial femoral condyle; type III, a fabella on the lateral femoral condyle and a fabella on the medial femoral condyle; type IV, two fabellae on the medial femoral condyle; and type V, two fabellae on the lateral femoral condyle. The severity of KOA was assessed on the Recht grade by magnetic resonance imaging (MRI). The data were analyzed with SPSS 24.0. RESULTS: The classification of fabellae were correlated with KOA grades (χ2  = 35.026, P < 0.05). In terms of KOA grades, grade I and grade II were occupied most by fabellar type II (32, 72.8%); type II and other types showed significant statistical difference (P < 0.05). Grade I and grade II were also mainly fabellar type IV (four, 100%). Fabellar type V's biggest component was grade III and grade IV (six, 75%). Type IV and type V showed significant statistical difference (P < 0.05). CONCLUSION: The classification of fabellae were correlated with KOA grades. The type II may mean the lower KOA grades while type V may mean the higher KOA grades.

Computed Tomography-Based Determination of the Optimal Locations of Bone Tunnels for Coracoclavicular Ligament Reconstruction.

OBJECTIVE: An agreement has not been reached on optimal locations of bone tunnels for coracoclavicular ligament (CCL) reconstruction for acromioclavicular joint dislocation (ACD). This study aims to identify the convergence point (cP) between the coracoid process and clavicle in the Chinese population to assist surgeons in reconstructing the CCL for ACD. METHODS: From 2014 to 2020, 483 CT scans of the shoulders of 270 male and 213 female patients (247 right and 236 left shoulders) were collected and studied retrospectively. By overlapping the images of the transverse plane of the coracoid process and the clavicle, points a and b, and the midpoint ab (cP) were determined. Then, a series of parameters through point cP in the transverse and sagittal planes were measured. In the transverse plane this included the distance from point cP to the tip of the coracoid process (cP-cor),the distance between the medial and lateral margins of the coracoid process through point cP (Med-lat cor), the distance from point cP to the acromioclavicular joint (cP-ac), and the distance between the anteroposterior margin of the clavicle through point cP (Ap-clav). In the sagittal plane, this included the craniocaudal segment of the coracoid process (Cc-cor), and the craniocaudal segment of the clavicle (Cc-clav). The sex and side differences of these measurements were also analyzed by two radiologists. RESULTS: Based on the following measurements, point cP was determined. For male patients, the cP-cor was 28.02 ± 3.43 mm, Med-lat cor was 22.78 ± 2.80 mm, Cc-cor was 15.11 ± 2.13 mm, cP-ac was 29.24 ± 3.84 mm, Ap-clav was 18.27 ± 2.46 mm, and Cc-clav was 10.09 ± 1.56 mm. For female patients, the cP-cor was 25.20 ± 3.26 mm, Med-lat cor was 20.21 ± 2.97 mm, Cc-cor was 13.03 ± 1.77 mm, cP-ac was 26.66 ± 3.45 mm, Ap-clav was 16.10 ± 2.30 mm, and Cc-clav was 8.91 ± 1.40 mm. All the measurements of female patients were lower than those of male patients (p < 0.01). Between sides, only cP-ac of the left shoulders was significantly lower than those of the right shoulders (p < 0.05), with no significant differences in other parameters between sides (p > 0.05). CONCLUSION: The results of this study identified the locations of bone tunnel-cP in the coracoid process and clavicle for the CCL reconstruction in ACD. Moreover, the findings indicated that surgeons should be more cautious in operating on female patients and that the cP-ac of left shoulders should be set lower than that of right shoulders.

The Relationship between Calcaneal Spur Type and Plantar Fasciitis in Chinese Population.

Plantar heel pain is a common disease with a high incidence in different races. It significantly reduced the quality of life of patients. However, the cause of PHP is still controversial and there were varieties of physiological factors associated with PHP. The most common pathological factor in the population was plantar fasciitis. Some existing research studies had found a correlation between calcaneal spurs and plantar fasciitis, and this study had found the correlation in Chinese population. It is invaluable not only to understand the relationship between different types of plantar calcaneal spurs and plantar fasciitis but also to identify the most appropriate treatment strategies. A total of 71 patients with calcaneal spurs were chosen from the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University. All 71 patients had completed X-rays and MRI scans; then, surgeons had removed their plantar calcaneal spurs. After surgery, all patients were followed up for 12 months; their prognosis was tested by the VAS and AOFAS scores. Type II (29, 40.8%) had the highest incidence in Chinese population, followed with type I (24, 33.8%) and type III (18, 25.4%). Preoperative VAS scores showed that type II (7.72 ± 1.10) was significantly higher than the other two types (P < 0.001). Postoperative VAS scores of type II were higher than those of type I and type III (P < 0.001). Postoperative AOFAS scores of type II were the lowest (P < 0.001). Researchers had proved that type II was more likely to cause PF.

The effect of vascular endothelial growth factor (VEGF) on mouse condylar articular cartilage cultured in vitro.

In this study, we explored the direct effect of vascular endothelial growth factor (VEGF) on temporomandibular joint osteoarthritis (TMJ-OA) by analyzing the transformation of mouse condylar cartilage treated in vitro with various concentrations of VEGF. Tissue samples from 126 condyles of four-week-old male C57 mice were randomly divided into 21 groups and treated with VEGF (0 ng/mL, 100 ng/mL, 500 ng/mL, 1 µg/mL, or 2 µg/mL). Furthermore, the samples were treated at different time points (1 d, 2 d, 4 d, and 7 d) and stained with hematoxylin and eosin (HE) and Safranin O and Fast Green stains to observe their morphology. The Mankin score was used to evaluate changes to the condylar cartilage tissues, and immunohistochemistry was performed to observe the expressions of VEGF receptor 2 (VEGFR2), matrix metallopeptidase 9 (MMP9), matrix metallopeptidase 13 (MMP13), and tumor necrosis factor-related activation-induced cytokine (TRANCE). An HE staining analysis revealed that the experimental groups treated with VEGF exhibited the destruction of their condylar cartilage and a proliferation of their hypertrophic cells, in comparison to the control group. Safranin O and Fast Green staining showed that the experimental groups had decreased levels of proteoglycan and degenerative changes in their condylar cartilage. The Mankin score of the samples increased with increasing concentration and treatment time of VEGF, and the differences between the groups were statistically significant (P < 0.05). Immunohistochemistry demonstrated that the expression levels of VEGFR2, MMP9, MMP13, and TRANCE significantly increased in the experimental groups, in comparison to those in the control group, suggesting that VEGF promoted TMJ-OA in mice in vitro.

[Shaoyangzhugu Formula regulates p19Arf-p53-p21Cip1 signaling pathway to ameliorate cartilage degeneration in aged cynomolgus monkeys with knee osteoarthritis].

OBJECTIVE: To study the effect of Shaoyangzhugu (SYZG) Formula (a formula consisting of 9 traditional Chinese drugs) in delaying the degeneration of articular cartilage and the role p19Arf-p53-p21Cip1 signaling pathway in mediating this effect. METHOD: Thirteen aged cynomolgus monkeys with degenerative knee joints were selected based on X-ray findings, and one of them was randomly selected for pathological observation. The other monkeys were randomized equally into SYZG Formula group (treated with SYZG decoction), ammonia moxime group and saline group. All the monkeys were sacrificed after 8 weeks of treatment with intragastric administration of the drugs or saline. The pathology in the knee joint articular cartilage was observed and the mRNA and protein expressions of p19Arf, p53, and p21Cip1 in the articular cartilage were detected using RT-qPCR and Western blotting. RESULTS: The pathological findings of the articular cartilage in old cynomolgus monkeys were consistent with the characteristics of knee osteoarthritis (KOA). Mankin scores of the cynomolgus monkeys were 7.38∓0.52 in SYZG Formula group, 7.88∓0.83 in ammonia moxime group, and 8.38∓0.74 in saline group, showing a significant difference between SYZG Formula group and saline group (P<0.05). The expressions of p19Arf, p53, and p21Cip1 were the lowest in SYZG Formula group and the highest in saline group with significant differences among the 3 groups (P<0.05). CONCLUSION: SYZG Formula can delay chondrocyte senescence by regulating p19Arf-p53-p21Cip1 signaling pathway to delay articular cartilage degeneration in aged cynomolgus monkeys.

Hyperbaric Oxygenation Protects Against Ischemia-Reperfusion Injury in Transplanted Rat Kidneys by Triggering Autophagy and Inhibiting Inflammatory Response.

BACKGROUND Ischemia-reperfusion injury (IRI) is a clinically common pathologic process defined as the inability to improve neuronal function. This study aimed to investigate the pathological mechanism of IRI and to explore effects of hyperbaric oxygenation (HBO) on autophagy and inflammatory response in IRI. MATERIAL AND METHODS Ninety Sprague-Dawley (SD) rats were randomly divided into a Sham group, a kidney transplant group (Trans), and a kidney transplant plus HBO treatment group (Trans+HBO). The kidney was harvested from the donor and transplanted to recipient rats according to a previously reported study. Rats were anesthetized using pentobarbital-natrium, and the kidney was resected and fixed in 4% paraformaldehyde. Serum creatinine (Scr) was detected using an automatic biochemical analyzer. The interleukin-6 (IL-6) level was assessed using enzyme-linked immunosorbent assay (ELISA). LC-3 was examined using indirect immunofluorescence assay and immunochemistry assay. LC-3 mRNA levels were analyzed using real-time PCR (RT-PCR). RESULTS The kidney transplant IRI model was successfully established. Scr and IL-6 levels were significantly increased in the Trans group (P<0.05). HBO significantly enhanced Scr and IL-6 levels. Scr was positively correlated with IL-6 levels (r-0.607, P<0.05). HBO increased LC-3 protein and mRNA expression in kidney-transplanted rats compared to the Sham and Trans group (P<0.05). Moreover, immunofluorescence assay also showed that LC-3 protein mainly distributes along renal tubular epithelial cells in a linear manner. CONCLUSIONS Autophagy dysfunction and inflammatory response after renal transplantation play important roles in processes of IRI. HBO treatment protects against the renal injury of IRI in renal tissues at the early stage, which may be triggered by the IL-6 pathway.

[Three dimensional finite element analysis of the influence of stress on occlusal surface of the mandibular first molar].

PURPOSE: Use of three-dimensional finite element to analyze stress distribution and transient displacement of mandibular first molar both at the occlusal surface level, to investigate the biomechanical basis of vertical root fracture occurring in the mesial root. METHODS: Mimics finite element software was used to build the horizontal and tilt abrasion of the mandibular first permanent molar. Each status was then divided into 4 kinds of wearing degree and 8 models were then established including sliced 1, sliced 2, sliced 3, sliced 4 and miter 5°,miter10°,miter15°,miter20° respectively. 200 N of bite force was loaded on the occlusal surface using MSC. Marc nonlinear finite element analysis software was used to investigate the distribution of stress and transient displacement. RESULTS: When distal tipping angle of the abrasion plane of mandibular first molar increased from 5° to 15°, the angle between instant displacement contours and tooth long axis become smaller, the mesial root suffered from the biggest stress concentration and thus the possibility of longitudinal root fracture increased. CONCLUSIONS: When the abrasion plane of mandibular first molar tilted distally, the possibility of the mesial root longitudinal fracture increased.