Research progress and maturity assessment of continuous manufacturing of traditional Chinese medicine / 中国中药杂志

The pharmaceutical manufacturing model is gradually changing from intermittent manufacturing to continuous manufacturing and intelligent manufacturing. This paper briefly reviewed the supervision and research progress in continuous pharmaceutical manufacturing in China and abroad and described the definition and advantages of continuous pharmaceutical manufacturing. The continuous manufacturing of traditional Chinese medicine(TCM) at the current stage was summarized in the following three terms: the enhancement of the continuity of intermittent manufacturing operations, the integration of continuous equipment to improve physical continuity between units, and the application of advanced process control strategies to improve process continuity. To achieve continuous manufacturing of TCM, the corresponding key technologies, such as material property characterization, process modeling and simulation, process analysis technology, and system integration, were analyzed from the process and equipment, respectively. It was proposed that the continuous manufacturing equipment system should have the characteristics of high speed, high response, and high reliability, "three high(H~3)" for short. Considering the characteristics and current situation of TCM manufacturing, based on the two dimensions of product quality control and production efficiency, a maturity assessment model for continuous manufacturing of TCM, consisting of operation continuity, equipment continuity, process continuity, and quality control continuity, was proposed to provide references for the application of continuous manufacturing technology for TCM. The implementation of continuous manufacturing or the application of key continuous manufacturing technologies in TCM can help to systematically integrate advanced pharmaceutical technology elements and promote the uniformity of TCM quality and the improvement of production efficiency.

A prospective study of the perforator evaluation and eccentric design of anterolateral thigh flap based on superficial fascial perforators assisted by modified computed tomography angiography / 中华烧伤杂志

Objective: To explore the preoperative whole perforator evaluation and intraoperative eccentric design of anterolateral thigh flap (ALTF) based on superficial fascial perforators by modified computed tomography angiography (CTA), and the clinical effects were observed. Methods: A prospective observational study was adopted. Twelve patients with oral and maxillofacial tumors and 10 patients with open injury of the upper limb with large soft tissue defects were hospitalized in the Department of Hand & Microsurgery and Department of Oral & Maxillofacial Surgery of Affiliated Hospital of Binzhou Medical University from January 2021 to July 2022, with 12 males and 10 females, aged from 33 to 75 years, an average age of 56.6 years. The wounds of the patients with oral and maxillofacial tumors were reconstructed by ALTF after the extensive tumor resection and radical cervical lymph node dissection in the same stage; the wounds of the patients with skin and soft tissue defect on the upper limb were covered by ALTF in stage Ⅱ after debridement in stage Ⅰ. After debridement, the area of wound was 3.5 cm×3.5 cm-25.0 cm×10.0 cm and the area of the required flap area was 4.0 cm×4.0 cm-23.0 cm×13.0 cm. Modified CTA scan was performed on the donor site of ALTF before the operation, with the parameters of modified CTA being set to mainly reduce the tube voltage and tube current, and increase the contrast dose and the dual phase scan. The acquired image data were sent to GE AW 4.7 workstation and adopted the volume reconstruction function for visual reconstruction and evaluation of the whole perforator. The information of perforator and source artery was marked on the body surface before operation according to the above evaluation. During the operation, an eccentric flap centered on the visible superficial fascia whole perforator was designed and cut according to the desired flap area and shape. The donor sites of the flap were repaired by direct sutures or full-thickness skin grafts. The total radiation dose was compared between the modified CTA scan and the traditional CTA scan. The distribution of outlet point of perforator of double thighs, the length and direction of superficial fascia perforators based modified CTA were recorded. The type, number, and origin of the target perforator, distribution of of outlet point of perforator, and the diameter, course, and branch of the source artery observed before the operation were compared with those observed during the operation. The healing of donor site wound and the survival of flaps in recipient site were observed after operation. The texture and appearance of flap, oral and upper limb functions, and the functions of femoral donor sites were followed up. Results: The total radiation dose of modified CTA scan was lower than that of the traditional CTA scan. A total of 48 perforators of double thighs were observed, among which, 31 (64.6%) perforators went outward and downward, 9 (18.8%) perforators went inward and downward, 6 (12.5%) perforators went outward and upward, and 2 (4.2%) perforators went inward and upward, and the average length of superficial fascia perforators was 19.94 mm. The preoperative observed type, number, and source of the perforator, the distribution of the outlet point of the perforator, diameter, course, and branches of the source artery were basically consistent with the intraoperative exploration. The types of 15 septocutaneous (including musculoseptocutaneous) perforators and 10 musculocutaneous perforators observed before the operation was consistent with intraoperative exploration. The distance between the mark of the surface perforator point and the actual exit point of the perforator during operation was (0.38±0.11) mm. All flaps survived without vascular crisis. The donor site wounds of 5 cases of skin grafting and 17 cases of direct suturing wounds healed well. The postoperative follow-up was 2 months to 1 year, with an average of 8.2 months, the flaps were soft and slightly bloated; the function of diet and mouth closing was accessible in patients with oral and maxillofacial tumors, the speech function was mildly impaired in patients with tongue cancer, but they could complete basic oral communication; the wrist and elbow joints and forearm rotation function were not significantly limited in patients with upper limb soft tissue injuries; there was no obvious tightness in the donor sites, and the function of the hip and knee joints was not limited. Conclusions: The whole perforator and even the subcutaneous perforator of the donor site of ALTF can be evaluated by modified CTA, and the flap can be used in oral or maxillofacial reconstruction and repair of skin and soft tissue defects of upper limbs to achieve good results. By clarifying the type, number, and source of the perforator, the distribution of the outlet point of the perforator, diameter, course, and branches of the source artery before the operation, the eccentric design of the ALTF based on the superficial fascia perforator was realized. This study has strong guiding value.

Factors influencing bilirubin elevation and its correlation with UGT1A1 gene polymorphism in the early postoperative period of transjugular intrahepatic portosystemic shunt / 中华肝脏病杂志

Objective: To investigate the factors influencing total bilirubin elevation and its correlation with UGT1A1 gene polymorphism in the early postoperative period of transjugular intrahepatic portosystemic shunt (TIPS). Methods: 104 cases with portal hypertension and esophageal variceal hemorrhage (EVB) treated with elective TIPS treatment were selected as the study subjects and were divided into a bilirubin-elevated group and a normal bilirubin group according to the total bilirubin elevation level during the early postoperative period. Univariate analysis and logistic regression were used to analyze the factors influencing total bilirubin elevation in the early postoperative period. PCR amplification and first-generation sequencing technology were used to detect the polymorphic loci of the UGT1A1 gene promoter TATA box, enhancer c.-3279 T > G, c.211G > A, and c.686C > A. Logistic regression was used to analyze the correlation of four locus alleles and genotypes with elevated total bilirubin in the early postoperative period. Results: Among the 104 cases, 47 patients were in the bilirubin elevated group, including 35 males (74.5%) and 12 females (25.5%), aged (50.72 ± 12.56) years. There were 57 cases in the normal bilirubin group, including 42 males (73.7%) and 15 females (26.3%), aged (51.63 ± 11.10) years. There was no statistically significant difference in age (t = -0.391, P = 0.697) and gender (χ(2) = 0.008, P = 0.928) between the two groups of patients. Univariate analysis revealed that preoperative alanine transaminase (ALT) level (χ(2) = 5.954, P = 0.015), total bilirubin level (χ(2) = 16.638, P < 0.001), MELD score (χ(2) = 10.054, P = 0.018), Child-Pugh score (χ(2) = 6.844, P = 0.022), and postoperative portal vein branch development (χ(2) = 6.738, P = 0.034) were statistically significantly different between the two groups. Logistic regression analysis showed that preoperative ALT level, total bilirubin level, and portal vein branch development after TIPS were correlated with the elevated total bilirubin in the early postoperative period. The polymorphism of the c.211G > A locus of the UGT1A1 gene correlation had elevated total bilirubin in the early postoperative period of TIPS. The risk of elevated total bilirubin was increased in the population carrying allele A (P = 0.001, OR = 4.049) in the early postoperative period. Allelic polymorphisms in the TATA box promoter region and enhancer c.-3279 T > G and c.686C > A had no statistically significant difference between the bilirubin-elevated group and the normal bilirubin group. Conclusion: The preoperative ALT level, total bilirubin level, and portal vein branch development are correlated with the elevated total bilirubin in early postoperative patients. The polymorphisms of the UGT1A1 gene and enhancer c.211G > A are correlated with the occurrence of elevated total bilirubin in the early postoperative period of TIPS. Allele A carrier may have a higher risk of elevated total bilirubin in the early postoperative period.

Manufacturing classification system for oral solid dosage forms of traditional Chinese medicines(Ⅲ): classification of granule dissolving behaviors / 中国中药杂志

Solubility is an important sensory quality attribute of traditional Chinese medicine(TCM) granules. In this paper, 90 batches of granules(30 batches of TCM formula granules, 30 batches of Chinese patent medicine granules and 30 batches of Japanese Kampo granules) were used as the research objects. The turbidity sensor was used to characterize the turbidity curve of the granule dissolution process. The classification system of granule dissolution behaviors was constructed from three dimensions: dissolution degree, equilibrium time, and dissolution mechanism. According to the equilibrium time, the granule dissolution rates were divided into three categories : faster(<100 s), general(101-300 s) and slow(>301 s). According to the turbidity curve profile, the granule dissolution mechanisms were classified into dissolution-controlled type(α-type), dispersion-controlled type(β-type), and dispersion-controlled type followed by dissolution-controlled type(γ-type). The proportion of TCM formula granules, Chinese patent medicine granules and Japanese Kampo granules with complete dissolution or slight turbidity at the end of dissolution was 46.7%, 96.7%, and 10.0%. The proportion of TCM formula granules, Chinese patent medicine granules, and Japanese Kampo granules with faster dissolution rates(<100 s) was 23.3%, 26.7%, and 40.0%. The average dissolution rate of Japanese Kampo granules was faster than that of TCM formula granules, and it was slightly faster than the average dissolution rate of Chinese patent medicine granules. The dissolution mechanism of Chinese patent medicine granules was mainly α-type, while that of Japanese Kampo granules was mainly β-type, and the three types of dissolution mechanisms of TCM formula granules accounted for a relatively average. The purpose of improving the solubility and dispersion of granules can be achieved by combining the comprehensive application of various functional excipients with the small dosage of Japanese Kampo granules and the wide addition scope of excipients. In the process of transforming TCM compound prescriptions into formulas, there is still much room for innovation in formula excipients and process optimization.

Intelligent co-design of material, process, and equipment for manufacturing high-quality traditional Chinese medicine preparations / 中国中药杂志

In the context of Pharma 4.0, the design tools that support the pharmaceutical Quality by Design(QbD) are iterating fast toward intelligent or smart design. The conventional development methods for traditional Chinese medicine(TCM) preparations have the limitations such as over dependence on experience, low dimensions for the designed experiment parameters, poor compatibility between the process and equipment, and high trial-and-error cost during process scale-up. Therefore, this paper innovatively proposed the intelligent co-design involving material, process, and equipment for manufacturing high-quality TCM preparations, and introduced the design philosophy, targets, tools, and applications with TCM oral solid dosage(OSD) as an example. In terms of design philosophy, the pharmaceutical design tetrahedron composed of critical material attributes, critical process parameters, critical equipment attributes, and critical quality attributes was developed. The design targets were put forward based on the product performance classification system. The design tools involve a design platform that contains several modules, such a as the iTCM material database, the processing route classification system, the system modeling and simulation, and reliability-based optimization. The roles of different modules in obtaining essential and universal design knowledge of the key common manufacturing units were introduced. At last, the applications of the co-design methodology involving material, process, and equipment in the high shear wet granulation process development and the improvement of the dissolving or dispersion capability of TCM formula granules are illustrated. The research on advanced pharmaceutical design theory and methodology will help enhance the efficiency and reliability of drug development, improve the product quality, and promote the innovation of high-end TCM products across the industry.

Application of Optical Genome Mapping Technology in Detecting Complex Chromosomal Rearrangement / 中山大学学报(医学科学版)

ObjectiveTo investigate the application of optical genome mapping （OGM） technology in detecting complex chromosomal rearrangement. MethodsWe recruited five patients who were diagnosed as complex chromosomal rearrangement at the Reproductive Medicine Center of the Sixth Affiliated Hospital of Sun Yat-sen University from January 2022 to June 2023. They underwent OGM， nanopore sequencing and pre-implantation genetic testing （PGT）. The results were compared with the results of karyotype and chromosomal microarray analysis （CMA）/ copy number variation sequencing （CNV-Seq）. ResultsOGM could detect translocation， invert inversion， and triplet translocation， which were consistent with the results of OGM and CMA/ CNV-Seq. But OGM could not detect Robertsonian translocation. ConclusionBecause of its ultra-long reads， OGM realizes the detection across repetitive regions， and it has great advantages when applied in patients with complex chromosome rearrangement or uncertain karyotype analysis. It can accurately locate breakpoints.

Multimodality-based super-resolution reconstruction for routine brain magnetic resonance images / 南方医科大学学报

OBJECTIVE@#To propose a multi-modality-based super-resolution synthesis model for reconstruction of routine brain magnetic resonance images (MRI) with a low resolution and a high thickness into high-resolution images.@*METHODS@#Based on real paired low-high resolution MRI data (2D T1, 2D T2 FLAIR and 3D T1), a structure-constrained image mapping network was used to extract important features from the images with different modalities including the whole T1 and subcortical regions of T2 FLAIR to reconstruct T1 images with higher resolutions. The gray scale intensity and structural similarities between the super-resolution images and high-resolution images were used to enhance the reconstruction performance. We used the anatomical information acquired from segment maps of the super-resolution T1 image and the ground truth by a segmentation tool as a significant constraint for adaptive learning of the intrinsic tissue structure characteristics of the brain to improve the reconstruction performance of the model.@*RESULTS@#Our method showed the performance on the testing dataset than other methods with an average PSNR of 33.11 and SSIM of 0.996. The anatomical structure of the brain including the sulcus, gyrus, and subcortex were all reconstructed clearly using the proposed method, which also greatly enhanced the precision of MSCSR for brain volume measurement.@*CONCLUSION@#The proposed MSCSR model shows excellent performance for reconstructing super-resolution brain MR images based on the information of brain tissue structure and multimodality MR images.

Design of combined lower limb elastic compression device and comparative study with elastic bandage / 中国骨伤

OBJECTIVE@#To compared with the modified Robert Jones bandage of 3M elastic bandage, to evaluate the fitness, convenience, safety and comfort of the modular combination lower limb elastic compression device.@*METHODS@#Forty healthy adult college students, including 28 males and 12 females, aged 16 to 25 (20.3±2.2) years old and weighing 40 to 81 (60.4±20.2) kg, were randomly divided into two groups with 40 samples in each group. According to the body surface parameters of Chinese lower limbs and guided by the concept of modularization, a group of modular combined lower limb elastic compression device was designed. Each module was combined to evaluate the fitness of the modular combined compression device in thelength and circumference of the lower limbs. The left and right lower limbs were randomly paired and divided into groups, with 40 samples in each group. The convenience of the operation time, adjustment times and required time were compared between two groups. The safety of the two groups after 24 hours of application of pressure injury was compared. The subjective pain feeling changes within 24 hours were recorded by visual analogue scale (VAS) to evaluate the comfort.@*RESULTS@#The device was composed of several elastic compression outer lining modules with different length and width of 15 cm, an inner lining module for buffering, positioning and attaching the main body, and an elastic ankle compression module. The length of the elastic compression outer lining module covers the circumference of the human lower limbs. The length of a single outer lining module increased from 15 cm to 80 cm every 5 cm interval, and the length of a single inner lining module increased from 62 cm to 83 cm every 3 cm interval. After the modules were selected and combined, the length and circumference of the lower limbs can reach 100% fitness. The operation time of the first placement(118.23±7.33) s and re operation(60.08±5.88) s of experimental group were significantly shorter than those of control group (164.68±8.93) s and re operation (131.23±7.91) s. The adjustment times (3) and operation time (3.50±0.71) s of experimental group were significantly shorter than those of control group(11)and operation time(139.00±5.66) s (@*CONCLUSION@#The modular combined elastic compression device has good fitness, better placement and flexible adjustment, convenience and safety, and better comfort than modified Robert Jones bandage of 3M elastic bandage.

Research progress on joint replacement for hemiplegic femoral neck fracture / 中国骨伤

With China's aging society, the number of patients with hemiplegia caused by cerebrovascular accident is increasing gradually. The risk of hip fracture in the first year after the onset of this kind of patients is 4 times higher than that of ordinary people, and most of them occur in the side of hemiplegia. For senile femoral neck fracture, artificial joint replacement is almost the first choice of treatment, with mature operation technology and good curative effect. At present, it is considered that if the muscle strength of hemiplegic side can reach grade III after cerebral vascular accident, hip arthroplasty can be the first choice for hemiplegic patients with hemiplegic femoral neck fracture. However, the situation of hemiplegic patients is different from that of ordinary people. The hemiplegic limbs may have muscle atrophy, muscle strength imbalance, osteoporosis and other problems, which brings difficulties to the formulation of surgical plan. This paper mainly discusses the choice of surgical approach, the use of total hip arthroplasty or hemiarthroplasty, the use of cemented prosthesis or cementless prosthesis, and how to reduce the incidence of postoperative dislocation The purpose is to provide more reference evidence for orthopedic doctors in clinical decision-making.

Evaluation and classification of dissolution behavior and capability of Chinese medicine granules based on an inline turbidity sensor / 中国中药杂志

In this paper, the inline turbidity sensor technology was used to quantify the turbidity of the solution during the dissolution of Chinese medicine granules. The probe measurement position and the magnetic stirring speed were optimized. As a result, the stirring speed was 400 r·min~(-1), and the probe position was at 1/4 of the diameter of the beaker. The measurement results were accurate and reliable. Totally 105 batches of commercially available Chinese medicine granules were collected and dissolved according to the requirements of the Chinese Pharmacopoeia. At the time point of 5 min, 57 batches of granules were completely dissolved, and the corresponding turbidity values ranged between 0-70 FTU; 32 batches of granules showed a slight turbidity, and the corresponding turbidity values ranged between 70-350 FTU; 14 batches of granule solution were turbid, and the corresponding turbidity values ranged between 350-2 000 FTU; two batches of granule solution were heavily turbid, and the corresponding turbidity values were >2 000 FTU. Among the above results, the number of batches in line with the pharmacopoeia dissolution requirement was 84.76%, and the dissolution of some granules still needed to be improved. The turbidity sensor recorded the change curve of turbidity value over time(solubility behavior curve). The degree of important of disintegration and dissolution during the dissolution process showed disintegration > dissolution, disintegration≈dissolution, disintegration < dissolution. The dissolution behavior of the granules can be classified into three categories. The analysis of the mechanism in the process of granule solubility provides a basis for product process improvement.

Key technologies and applications of industrial big data in manufacturing of Chinese medicine / 中国中药杂志

Along with the striding of the Chinese medicine(CM) manufacturing toward the Industry 4.0, some digital factories have accumulated lightweight industrial big data, which become part of the enterprise assets. These digital assets possess the possibility of solving the problems within the CM production system, like the Sigma gap and the poverty of manufacturing knowledge. From the holistic perspective, a three-tiered architecture of CM industrial big data is put forward, and it consists of the data integration layer, the data analysis layer and the application scenarios layer. In data integration layer, sensing of CM critical quality attributes is the key technology for big data collection. In data analysis and mining layer, the self-developed iTCM algorithm library and model library are introduced to facilitate the implementation of the model lifecycle methodologies, including process model development, model validation, model configuration and model maintenance. The CM quality transfer structure is closely related with the connection mode of multiple production units. The system modeling technologies, such as the partition-integration modeling method, the expanding modeling method and path modeling method, are key to mapping the structure of real manufacturing system. It is pointed out that advance modeling approaches that combine the first-principles driven and data driven technologies are promising in the future. At last, real-world applications of CM industrial big data in manufacturing of injections, oral solid dosages, and formula particles are presented. It is shown that the industrial big data can help process diagnosis, quality forming mechanism interpretations, real time release testing method development and intelligent product formulation design. As renewable resources, the CM industrial big data enable the manufacturing knowledge accumulation and product quality improvement, laying the foundation of intelligent manufacturing.

Correlation analysis of plasma N-terminal pro-brain natriuretic peptide, p-selectin and type 2 diabetes mellitus complicated with acute coronary syndrome / 解放军医学杂志

[Abstract] Objective To investigate the relationship between plasma N-terminal pro-brain natriuretic peptide (NT-pro-BNP), P-selectin (PS) and type 2 diabetes mellitus (T2DM) patients with acute coronary syndrome (ACS). Methods Two hundred and twenty-eight patients with chest pain, admitted in the Department of Cardiology of Langfang Traditional Chinese Medicine Hospital and the Affiliated Hospital of North China University of Science and Technology from July 2017 to April 2018, were selected in present study, including 32 patients with T2DM, 124 patients with ACS, and 72 patients with T2DM complicated with ACS (DA group). ELISA was performed to detect the levels of plasma NT-pro-BNP and PS, and venous blood was taken on an empty stomach to complete a general biochemical project. Based on the results of coronary angiography performed by using Judkins method, the Gensini score was used to evaluate the degree of coronary stenosis. The general clinical data of the 3 groups were compared, and logistic regression was performed to analyze the risk factors for ACS in patients with T2DM. Results No statistical difference existed in gender, history of hypertension, smoking, body mass index, age, and creatinine among the three groups; The levels of low-density lipoprotein cholesterol and triglyceride were higher in DA group [(3.16±0.98)mmol/L and (2.21±1.36)mmol/L] than in T2DM and ACS group [(2.83±0.91)mmol/L, (1.65±1.05)mmol/L and (2.84±0.92)mmol/L, (1.68±0.97)mmol/L] with significant difference (P<0.05). The left ventricular ejection fraction was lower in DA group (58.97±7.35)% than in T2DM and ACS groups [(63.48±7.37)% and (61.26±7.68)%, respectively] with statistically significant difference (P<0.01). The PS was higher in DA group (48.30±13.61)ng/L than in ACS group (38.87±9.12)ng/L, and in ACS group than in T2DM group (21.46±12.30)ng/L; The C-reactive protein was higher in DA group [(27.63±11.87)mg/L] than in ACS group (20.21±9.32)mg/L, and in ACS group than in T2DM group [(10.30±4.22)mg/L]; The NT-pro-BNP M(Q1, Q3) was higher in DA group [419(154, 1350)pg/ml] than in ACS group [120(43, 416)pg/ml], and in ACS group than in T2DM group [22(12, 54)pg/ml]; The Gensini scores was higher in DA group (138.39±88.31) than in ACS group (82.12±63.08), and in ACS group than in T2DM group (39.98±32.12), all the differences listed above were statistically significant (P<0.01). It had been confirmed by multivariate logistic regression analysis that the levels of PS and high-sensitivity C-reactive protein were the risk factors for ACS in patients with DM, their OR estimates were 1.138 (95%CI 1.089-1.990, P<0.01) and 1.656 (95%CI 1.189~2.307, P<0.01), respectively. Conclusion High levels of PS and high-sensitivity C-reactive protein are the independent risk factors for ACS in patients with T2DM. NT-pro-BNP was not associated with ACS in patients with T2DM.

Limited open reduction and intramedullary fixation for the treatment of refractory femoral subtrochanteric fractures / 中国骨伤

OBJECTIVE@#To explore the surgical technique and clinical effect of limited open reduction and intramedullary fixation assisted with orthopedic traction bed for the treatment of femoral subtrochanteric fractures.@*METHODS@#From July 2015 to October 2017, 12 patients with femoral subtrochanteric fractures were treated including 9 males and 3 females with an average age of 44 years old ranging from 33 to 67 years old. Among them, 10 cases were on the left trochanter and 2 on the right, and there were 8 cases of highly fall injury and 4 cases of traffic accident injury. All patients received operation at 2 to 5 days after injury. According to the Seinsheimer classification, 8 cases were type IIIA, 2 were type IIIB and 2 were type IV, and all cases were closed injury. The patients were placed on the orthopedic traction bed for trial closed reduction to maintain proper traction before operation. Under C-arm X-ray fluoroscopy, it was advisable to take the fracture end of the main bone block without obvious shortening and shifting. Then limited incision and lengthened InterTan intramedullary nailing were performed, and the Sanders traumatic hip score was used to evaluate the postoperative efficacy.@*RESULTS@#All 12 patients were followed up from 6 to 24 months with an average of 12 months. All cases were received bone healing at 3 to 6 months with an average time of 4 months. According to the Sanders grades, the results were excellent in 9 cases, good in 2 cases and medium in 1 case. Infection, breakage of internal fixation loosening and adverse complications such as malunion were not appeared in all the cases.@*CONCLUSIONS@#Limited open reduction assisted with traction bed can be effective to solve the problem of the intraoperative reduction in the complex subtrochanteric fractures, which could save operation time and decrease bleeding. Combined with intramedullary fixation, this method could acquire good counterpoint and stability for the fracture end, and provide a method for the treatment of refractory subtrochanteric fractures.

Magnetic resonance imaging features and differential diagnosis of multiple gliomas / 医学研究生学报

Objective The magnetic resonance imaging (MRI) patterns of multiple gliomas are insufficiently understood because the related studies are rarely reported and mostly with small-size samples. This article summarizes the MR manifestations of multiple gliomas, analyzes their imaging features and proposes some diagnostic ideas. Methods We retrospectively reviewed 303 cases of diffuse glioma pathologically confirmed in our hospital from January 2014 to December 2018, including 240 cases of solitary (79.2%) and 63 cases of multiple gliomas (20.8%). We analyzed the MRI manifestations, summarized the MRI patterns, and investigated the differential diagnosis of multiple gliomas. Results According to the growth patterns, 4 of the 63 cases of multiple gliomas were classified as multicentric and the other 59 as multifocal glioma, and of the 59 cases of multifocal glioma, 35 spread along the white matter fiber bundle, 24 along the subependymal and small vessel space, 6 along the meningia-subarachnoid space, and 41 in a mode of direct invasion. The manifestations of cortical involvement included cortical tubers (37.2% [16/43]), multiple cortical tubers with high-intensity signals on T2WI, diffuse cortical swelling (44.2% [19/43]), frontal cortical swelling with high-intensity signals on T2FLAIR, and enhancement along the cortex (37.2% [16/43]). Interfocal heterogeneity was observed in 45 of 63 cases (71.4%). The imaging features of the lesions were classified into 5 types: metastasis (69.8%), granulomatosis (4.8%), abscess (12.7%), encephalitis (6.3%) and metabolic encephalopathy (6.3%). Conclusion The specific MRI presentations of multiple gliomas are cortical involvement and interfocal heterogeneity. The 5 MRI features of multiple gliomas may help improve the differential diagnosis of the lesions.

An improved method for in vivo electroporation of morpholinos into the adult zebrafish retina / 生理学报

In vivo electroporation of morpholinos (MOs) into the retina of adult zebrafish is an efficient method to study gene function related to retinal disease and regeneration. However, the currently reported methods are complicated with low MO transfer efficiency and high probability to cause collateral damage. The present study was aimed to optimize the existing MO electroporation methods. Two major changes were made to MO electroporation procedure in zebrafish retina. One was to coat the inner side of the electrode with ultrasonic gel. The other was to replace the commonly used round electrode with novel rectangular one. The results showed that the use of ultrasonic gel reduced collateral damage caused by retinal electroporation and simplified the experimental procedure. The rectangular electrode significantly increased transfection efficiency of MO electroporation. In particular, knocking down the expression of Ascl1a in the retina by using our method significantly inhibited the generation of retinal progenitor cells. These results suggest our method is the optimization of the current MO electroporation methods and may be a better alternative for relevant researchers.

Effect of Ultrashort Wave on Macrophage Polarization and Inflammatory Response after Spinal Cord Injury in Rats / 中国康复理论与实践

Objective To explore the effect of ultrashort wave on macrophage polarization and inflammation response after spinal cord injury in rats. Methods A total of 96 Sprague-Dawley rats were randomly divided into sham group, model group and ultrashort wave group, with 32 rats in each group. The spinal cord injury model was established by modified Allen's method in the model group and the ultrashort wave group. The ultrashort wave group received ultrashort wave since the first day after modeling. BBB score was applied to evaluate the locomotion recovery. HE staining was used to as-sess the injury area, while immunochemistry, real-time PCR and Western blotting were applied to measure the mRNA and protein expression of inducible nitric oxide synthase (iNOS), arginase-1 (Arg-1) and tumor necrosis factor-α (TNF-α). Results Compared with the model group, the BBB score increased (P<0.05), the expression of iNOS and TNF-α de-creased, and the expression of Arg-1 increased (P<0.05). Conclusion Ultrashort wave therapy may promote macrophage polarization from M1 to M2, inhibit inflammatory re-sponse and promote recovery after spinal cord injury in rats.

Protective Effect and Mechanism of Every-other-day Fasting on Rats with Spinal Cord Injury / 中国康复理论与实践

Objective To observe the effect of every-other-day fasting(EODF)on pathology and functional recovery of rats with spinal cord clip-compression injury,and to explore the related mechanism. Methods A total of 36 Sprague-Dawley rats were randomly assigned to groups A(sham operation),B(sham operation and EODF),C(spinal cord injury)and D(spinal cord injury and EODF)with nine rats in each group.The spinal cord injury rat model in T10was established by using medical aneurysm clip in latter two groups.The motor func-tion was assessed by Basso-Beattie-Bresnahan(BBB)score one day before and one day,two,four,six,eight,ten, twelve weeks after operation;and toluidine blue staining was performed for pathological observation at twelve weeks after operation.Another 180 Sprague-Dawley rats were randomly assigned in same way.The level of tu-mor necrosis factor-α(TNF-α)and interleukin-10(IL-10)were detected with ELISA six hours,twelve hours,one day,three days and seven days after operation. Results The BBB score reached lowest on the first day in groups C and D(P<0.05),and gradually increased with time,and were higher in group D than in group C eight weeks,ten weeks and twelve weeks after operation(P<0.05). The pathology in spinal cord was less in group D than in group C.Compared with group A,the level of serum TNF-α increased twelve hours after operation(P<0.05),peaked one day after operation,and returned back seven days after operation;the level of serum IL-10 increased at each time point after operation(P<0.05).Compared with group C,the level of serum TNF-α was lower in group D one day after operation(P<0.05);the level of se-rum IL-10 was not significantly different at each time point after operation(P>0.05). Conclusion Long-term EODF can promote the hind limb motor recovery in rats with spinal cord clip-compression inju-ry,and alleviate pathological damage.EODF might inhibit acute inflammatory reaction at acute stage of spinal cord injury,which may be correlated with its neuroprotective effect.

Analysis of efficacy of rituximab in treating primary focal segmental glomerulosclerosis in children / 医学研究生学报

Objective There are few studies on children with primary focal segmental glomerulosclerosis (FSGS) treated with rituximab (RTX).This study aimed to analyze the side effects and safety of the single dose of RTX in 10 children with primary FSGS, and further provide reference for the RTX treatment of FSGS . Methods We retrospectively analysed the clinical data of 10 FSGS children who hospitalized in the department of pediatrics in Nanjing General Hospital of Nanjing Military Area Command from April 2014 to August 2017.24 hours urinary protein, serum albumin, the count of circulating CD20+B cells and the RTX adverse reactions were analyzed after the treatment of RTX . Results From the 10 ca-ses, 6 cases were steroid-resistant nephrotic syndrome (SRNS), and 4 cases were frequently relapsing /steroid dependent nephrotic syn -drome (FRNS/SDNS).After single dose of RTX treatment , 5 cases achieved complete remission (CR), 2 partial remission (PR), and 3 non-remission (NR).Among the 6 cases of SRNS, 2, 1, 3 ca-ses achieved CR, PR, NR respectively; Among the 4 cases of FRNS/SDNS, CR was achieved in 3 patients, PR was achieved in 1 pa-tient.3 months after RTX treatment, urinary protein decreased from [2.41 (0.89-6.82) g/24 h] to [0.43 (0.05-1.1) g/24h], ser-um albumin increased from [31.60 (13.00-38.22) g/L] to [38.30 (27.18-53.20) g/L] .Adverse reactions occurred in 1 case in-cluding fever, chills, and chest tightness.These adverse reactions relieved after the decreased of RTX infusion speed .One developed severe pneumonia and proteinuria one month after RTX treatment .There was no increase in the number of infections in other children and no abnormalities in the respiratory tract , digestive tract, and nervous system during follow-up. Conclusion RTX treatment of primary FSGS has high security and has no serious adverse reactions .It is one of the effective treatments for children with FSGS .

Efficacy and safety of aspirin for venous thromboembolism after total knee arthroplasty / 中国组织工程研究

BACKGROUND: The best prevention strategy for venous thrombosis (VTE) is currently controversial, especially for patients with high risk of total knee arthroplasty. There are no fully safe, effective and inexpensive thrombus prevention drugs. OBJECTIVE: To study the efficacy and safety of aspirin in preventing venous thrombosis after total knee arthroplasty. METHODS: 300 patients undergoing primary unilateral total knee arthroplasty from September 2014 to December 2016 were randomly divided into two groups: conventional anticoagulation group and risk stratification group (n=150 per group), including 88 males and 212 females at the age of 49-85 years old. The conventional anticoagulation group received low molecular weight heparin for prevention and treatment. Risk stratification group was stratified according to the risk of venous thrombosis. 64 patients with low risk were treated with aspirin and 86 patients with high risk were treated with low molecular weight heparin. Complications were analyzed within 90 days after surgery, including deep venous thrombosis, pulmonary embolism, wound infection, bleeding and death. RESULTS AND CONCLUSION: (1) Complications occurred in 39 cases (13%) within 90 days after follow-up. The total incidence of symptomatic deep vein thrombosis complications was 2% in 6 cases, and 19 cases (6.33%) had wound complications. There were 3 cases (2%) of symptomatic deep vein thrombosis in conventional anticoagulation group and 3 cases (2%) in risk stratification group. (2) The incidence of symptomatic deep vein thrombosis, proximal deep vein thrombosis and distal deep vein thrombosis and pulmonary embolism were 1.56% (1 case), 1.56% (1 case), 4.68% (3 cases), and 0% respectively in patients treated with aspirin. The incidence of symptomatic deep vein thrombosis, proximal deep vein thrombosis and distal deep vein thrombosis and pulmonary embolism in patients receiving low molecular weight heparin were 2.12% (5 cases), 0.85% (2 cases), 5.08% (12 cases) and 0.42% (1 case), respectively. There was no significant difference between the two groups (P > 0.05). (3) There were 11 cases of wound complications in the conventional anticoagulation group and 8 cases in the risk stratification group (χ2 = 506, P = 0.318). (4) The incidences of wound-related complications (wound delayed healing, superficial wound infection and deep wound infection) were 1.56% (1 case), 0% and 1.56% (1 case) respectively in patients receiving aspirin, and 5.51% (13 cases), 1.27% (3 cases) and 0.42% (1 case) in patients receiving low molecular weight heparin. (5) Results suggested that aspirin and low molecular weight heparin can effectively prevent the occurrence of deep vein thrombosis. For low-risk patients, aspirin multi-mode thrombosis prevention is safe and effective.

A modified working tube can reduce bone cement Ieakage in the treatment of osteoporotic vertebraI compression fracture / 中国组织工程研究

BACKGROUND: Vertebroplasty is an effective treatment for osteoporotic vertebral compression fractures (OVCF), but it is nagged by bone cement leakage. OBJECTIVE: To summarize the clinical outcome of modified self-making working tube in percutaneous vertebroplasty (PVP) for treatment of thoracolumbar OVCF. METHODS: Modified PVP working tube was designed to have a lateral gap at the sleeve tail, which could control the cement diffuse direction though rotating the working tube. Totally 121 thoracolumbar OVCF patients were enrolled, including 49 males and 72 females, aged 62-90 years, and then divided into two groups: 59 patients were treated with modified PVP in test group, and the other 62 patients experienced conventional PVP in control group. In the test group, a lateral gap instead of the conventional gap at the sleeve tail was made to control the direction of bone cement injection by rotating the sleeve. The visual analogue scale scores were compared before and after operation; radiographic examination was performed to detect bone cement leakage at 1 day postoperatively. RESULTS AND CONCLUSION: There were significant differences between the preoperative and postoperative visual analogue scale scores in the two groups (P < 0.05), but there was no significant difference between the two groups. There were 3 cases of bone cement leakage in the test group and 10 cases of bone cement leakage in the control group. Modified PVP working tube had significant lower rate of bone cement leakage than traditional PVP(14.9% vs.4.6%,P<0.05).Therefore,the modified PVP working tube is an effective tool to decrease the incidence of bone cement leakage in the treatment of thoracolumbar OVCF.