Development and validation of prognostic nomogram for malignant pleural mesothelioma / 中华肿瘤杂志

Objective: To development the prognostic nomogram for malignant pleural mesothelioma (MPM). Methods: Two hundred and ten patients pathologically confirmed as MPM were enrolled in this retrospective study from 2007 to 2020 in the People's Hospital of Chuxiong Yi Autonomous Prefecture, the First and Third Affiliated Hospital of Kunming Medical University, and divided into training (n=112) and test (n=98) sets according to the admission time. The observation factors included demography, symptoms, history, clinical score and stage, blood cell and biochemistry, tumor markers, pathology and treatment. The Cox proportional risk model was used to analyze the prognostic factors of 112 patients in the training set. According to the results of multivariate Cox regression analysis, the prognostic prediction nomogram was established. C-Index and calibration curve were used to evaluate the model's discrimination and consistency in raining and test sets, respectively. Patients were stratified according to the median risk score of nomogram in the training set. Log rank test was performed to compare the survival differences between the high and low risk groups in the two sets. Results: The median overall survival (OS) of 210 MPM patients was 384 days (IQR=472 days), and the 6-month, 1-year, 2-year, and 3-year survival rates were 75.7%, 52.6%, 19.7%, and 13.0%, respectively. Cox multivariate regression analysis showed that residence (HR=2.127, 95% CI: 1.154-3.920), serum albumin (HR=1.583, 95% CI: 1.017-2.464), clinical stage (stage Ⅳ: HR=3.073, 95% CI: 1.366-6.910) and the chemotherapy (HR=0.476, 95% CI: 0.292-0.777) were independent prognostic factors for MPM patients. The C-index of the nomogram established based on the results of Cox multivariate regression analysis in the training and test sets were 0.662 and 0.613, respectively. Calibration curves for both the training and test sets showed moderate consistency between the predicted and actual survival probabilities of MPM patients at 6 months, 1 year, and 2 years. The low-risk group had better outcomes than the high-risk group in both training (P=0.001) and test (P=0.003) sets. Conclusion: The survival prediction nomogram established based on routine clinical indicators of MPM patients provides a reliable tool for prognostic prediction and risk stratification.

Application of our self-made Kirschner wire connecting rod in difficult extraction of intramedullary implants / 中华创伤骨科杂志

Objective:To report the application of our self-made Kirschner wire connecting rod combined with a conventional intramedullary nail extractor in difficult extraction of intramedullary devices.Methods:From January 2012 to August 2017, 10 patients with a hard-to-remove intramedullary device were treated at Department of Orthopaedics, The Fifth Hospital Affiliated to Xinjiang Medical University. They were 7 males and 3 females with a mean age of (40.0±9.0) years. In cases where no relevant extractor was available for the intramedullary device or it was impossible to connect the extractor connecting rod to the tail of the intramedullary device, the Kirschner wire was bent and pulled through the screw hole or the hole newly drilled at the tail of the intramedullary device to be tied or fixed with a conventional extractor connecting rod to form an effective connection. Next, our self-made Kirschner wire connecting rod was used to pull out the intramedullary device. In this cohort, 7 intramedullary nails in the tibia, 1 femoral intramedullary nail, 1 humeral intramedullary nail, and 1 tibial elastic nail were removed. The difficult extraction was due to "cold welding" of the tail cap of the intramedullary nail in 3 cases, mismatch between the screw rod of the extractor and the tail screw hole of the intramedullary nail in 4 cases, and unavailability of relevant removal tools in 3 cases. The time for intramedullary device removal, blood loss and postoperative adverse reactions were recorded.Results:Of this cohort, 9 patients underwent simple removal of the intramedullary device and 1 patient replacement of the intramedullary device. The total time for removal of an intramedullary device was (2.3±0.8) h, ranging from 1.0 to 3.2 h. The amount of blood loss was (159.0±61.0) mL, ranging from 80 to 250 mL. The follow-up was (14.5±2.2) months, ranging from 11 to 18 months. There was no infection or fracture associated with implant removal.Conclusion:Application of our self-made Kirschner wire connecting rod in combination with a conventional intramedullary nail extractor is an easy operation to successfully extract hard-to-remove intramedullary implants, requiring no more special instruments.

Fixation with a retrograde pubic ramus intramedullary nail for anterior pelvic ring fractures / 中华创伤骨科杂志

Objective:To explore the clinical efficacy of a retrograde pubic ramus intramedullary nail (RPRIN) in the treatment of anterior pelvic ring fractures.Methods:A retrospective study was conducted to analyze the 14 patients with anterior pelvic ring fracture who had been treated and followed up at Department of Traumatic Surgery, Tongji Hospital From June 2020 to February 2021. There were 10 males and 4 females with an age of (44.8±12.5) years. By the AO/OTA classification for pelvic fractures, 5 cases were type 61-A, 4 cases 61-B, and 5 cases type 61-C; by the Nakatani classification, 1 case belonged to unilateral zone Ⅰ fracture, 5 cases to unilateral zone Ⅱ fracture, 2 cases to unilateral zone Ⅲ fracture, 3 cases to right zone Ⅱ and left zone Ⅲ fracture, 2 cases to zone Ⅲ fracture on both left and right sides, and 1 case to zone Ⅱ fracture on both sides. The time from injury to operation was (7.8±1.8) days. All the anterior pelvic ring fractures were fixated with a RPRIN. The time and fluoroscopic frequency for placement of every single RPRIN, quality of fracture reduction, and pelvic function and incidence of postoperative complications at the last follow-up were recorded.Results:A total of 18 RPRINs were placed in the 14 patients. For placement of each RPRIN, the time was (35.9±8.6) min, and the fluoroscopic frequency (22.8±1.9) times. No complications such as infection occurred at any surgical incision after RPRIN placement. According to the Matta scoring, the quality of postoperative fracture reduction was assessed as excellent in 7 cases, as good in 5 cases and as fair in 2 cases. The 14 patients were followed up for (18.1+1.5) months. Their X-ray and CT images of the pelvis at the last follow-up showed that the fractures healed well and the intramedullary nails were placed in the cortical bone of the anterior ring of the pelvis. According to the Majeed scoring at the last follow-up, the pelvic function was assessed as excellent in 10 cases, as good in 3 cases and as fair in 1 case. One patient reported discomfort during squatting 2 months after operation but the symptom improved 3 months later without any special treatment. No patient experienced such complications as displacement or slippage of RPRIN, or pain at the insertion site.Conclusion:RPRIN is effective in the treatment of anterior pelvic ring fractures, showing advantages of small surgical incision, limited intraoperative fluoroscopy and short operation time.

Shoulder arthroscopic treatment of avulsion fracture of humeral greater tuberosity with double-row suture bridge / 中华创伤骨科杂志

Objective:To evaluate the shoulder arthroscopic treatment of avulsion fracture of humeral greater tuberosity with double-row suture bridge.Methods:Retrospectively analyzed were the 13 avulsion fractures of humeral greater tuberosity which had been treated by shoulder arthroscopic double-row suture bridge at Bone and Joint Department, Guangzhou Liwan District Orthopedic Hospital from March, 2018 to March, 2020. There were 6 males and 7 females, with an average ages of 52.3 years (from 35 to 69 years). According to the Mutch classification, all the fractures of humeral greater tuberosity were attributed to the avulsion type. Of them, 3 were simple avulsion fractures of humeral greater tuberosity and 10 were complicated with shoulder anterior dislocation which was reduced manually before operation. There were 3 obsolete avulsion fractures of humeral greater tuberosity. Regular clinic and X-ray follow-ups were carried out. At the final follow-up, the pain, range of motion (ROM) and stability of the shoulder joint were assessed using visual analogue scale (VAS), American shoulder elbow scores (ASES), and Korean shoulder scores (KSS).Results:All the patients were followed up for an average of 12.3 months (from 10 to 16 months) postoperatively. No infection or shoulder instability was observed. At the final follow-up, the abduction and elevation averaged 164.6° (from 135° to 180°), the lateral external rotation 62.7° (from 40° to 80°), the internal rotation touch back test T10 level (from L2 to T6), the VAS 0.65 (from 0 to 2.5), the ASES 90.5 (from 78 to 100), and the KSS 91.5 (from 84 to 100).Conclusion:Shoulder arthroscopic treatment of avulsion fracture of humeral greater tuberosity with double-row suture bridge is minimally invasive and allows for repair of combined injury, leading to quick postoperative recovery.

The Etiological Study of Three Hunter Syndrome Families in Southern China / 中山大学学报(医学科学版)

ObjectiveTo reveal the molecular pathogenesis of Hunter syndrome in three families in southern China and to clarify the correlation between phenotype and genotype， so as to lay a foundation for future prenatal or preimplantation genetic diagnosis. MethodsOn the basis of initial clinical diagnosis and pedigree analysis， qualitative detection of glycosaminoglycans in urine was performed first， and then anticoagulant blood samples were collected from the children and their relatives. DNA was extracted and the IDS gene sequence was analyzed by PCR and Sanger sequencing. Various methods such as RT-PCR and bioinformatics analysis were used to identify the pathogenicity of the new variants. ResultsThe urine test results of the patients in the three families were all strongly positive（++）. Probands were all male， with hemizygous mutations in IDS gene from their mothers， and the mutation sites were c.615_622delCATACAGT， c.847_848delGT and IVS7 ds+1 G>A， respectively. The cross-species conservation analysis showed that the amino acid of IDS gene mutation site was highly conserved during species evolution. Compared with the normal protein， mutant proteins exhibited significant differences in the predicted results of advanced structure. The variants identified in the three families were classified as pathogenic by ACMG criteria. ConclusionsThe three probands were diagnosed with Hunter syndrome. The c.615_622del（p.Il206Valfs*18）， c.847_848del（p.Val283Alafs*57） and IVS7 ds+1 G>A （p.G336Dfs*12） of IDS gene are all novel pathogenic mutations， which are the underlying causes of morbidity in children. This study has further enriched the mutation spectrum of IDS gene.

Advances in the structure and function of chitosanase / 生物工程学报

Chitosanases represent a class of glycoside hydrolases with high catalytic activity on chitosan but nearly no activity on chitin. Chitosanases can convert high molecular weight chitosan into functional chitooligosaccharides with low molecular weight. In recent years, remarkable progress has been made in the research on chitosanases. This review summarizes and discusses its biochemical properties, crystal structures, catalytic mechanisms, and protein engineering, highlighting the preparation of pure chitooligosaccharides by enzymatic hydrolysis. This review may advance the understandings on the mechanism of chitosanases and promote its industrial applications.

Inhibitory effect of gamma-secretase inhibitor on retinal neovascularization and regulative mechanism of Notch1 signal pathway / 中华实验眼科杂志

Objective:To investigate the inhibitory effect and underlying mechanism of gamma-secretase inhibitor blocking Notch1 signaling on retinal neovascularization caused by oxygen-induced retinopathy (OIR) in mice.Methods:To establish the OIR model, 7-day-old pups of C57BL/6J mice were exposed to 75% oxygen together with their mother until postnatal day (P)12.On P12, the mice were transferred to room air.All the mice were randomly divided into three groups, OIR group as control group, OIR+ DAPT group and OIR+ DMSO group receiving 1 μl intravitreal injection of gamma-secretase inhibitor (DAPT, 10 mmol/L) and 1∶20 DMSO dilution respectively.The right eye was taken as experimental eye.The mice were euthanized on P17 and the eyes were harvested to obtain retinas for further investigation.The total proteins were extracted from the retinas.The relative expression levels of Notch1 signal pathway and its downstream Hes1, the markers of M1 phenotype inducible nitric oxide synthase (iNOS) and M2 phenotype arginase-1 (Arg-1) microglia were measured by western blot.Retinal flat mounts were made and the retinal vessels were stained with isolectin B4 (IB4) to investigate the relative retinal neovascularization areas which was calculated as the ratio of neovascularization area/retinal area.The mumber of the neovascular endothelium cells beyond the inner limiting membrane was observed by hematoxylin-eosin staining.The use and care of animals complied with ARVO statement.This study protocol was approved by the Animal Ethics Committee of Guangdong Provincial People's Hospital (No.KY-Z-2021-2015-01).Results:The relative protein expression levels of Notch1 and Hes1 in OIR+ DAPT group, OIR group, and OIR+ DMSO group were 0.68±0.06 and 0.70±0.08, 1.00±0.00 and 1.00±0.00, 1.03±0.08 and 1.02±0.07, respectively, with statistically significant differences among them ( F=70.62, 53.65; both at P<0.01). Compared with the OIR group and OIR+ DMSO group, the expressions of Notch1 and Hes1 were significantly reduced in OIR+ DAPT group (all at P<0.01). The relative protein expression levels of iNOS and Arg-1 in OIR+ DAPT group, OIR group, and OIR+ DMSO group were 0.74±0.07 and 1.49±0.12, 1.00±0.00 and 1.00±0.00, 1.04±0.10 and 0.94±0.07, respectively, showing statistically significant differences ( F=31.63, 89.32; both at P<0.01). Compared with OIR group and OIR+ DMSO group, the expression of iNOS in OIR+ DAPT group was significantly reduced, and the expression of Arg-1 was significantly increased (all at P<0.01). The relative neovascularization area and the number of neovascular endothelium cells beyond the inner limiting membrane in OIR+ DAPT group, OIR group, and OIR+ DMSO group were (8.82±2.71)% and 38.17±3.29, (22.32±5.34)% and 60.83±5.11, (20.27±3.36)% and 58.67±4.75, respectively, showing statistically significant differences ( F=33.72, 39.44; both at P<0.01). The relative neovascularization area and the number of neovascular endothelium cells in OIR+ DAPT group were significantly reduced in comparison with OIR group and OIR+ DMSO group (all at P<0.01). Conclusions:Intravitreal injection of DAPT can inhibit the retinal neovascularization in OIR mice through blocking Notch1 signaling activation and promoting retinal microglia polarization from M1 to M2 phenotype.

Sacral osteotomy combined with triangular osteosynthesis in the treatment of malunion or nonunion of vertically displaced pelvic fractures / 中华骨科杂志

Objective:To investigate the clinical therapy of sacral osteotomy combined with lumbopelvic distraction triangular osteosynthesis for malunion and nonunion of type C longitudinally displaced sacral fracture.Methods:A retrospective study of 9 patients with malunion and nonunion of type C pelvic fractures who had been treated with sacral osteotomy combined with triangular osteosynthesis from April 2015 to January 2020 were analyzed. They were 5 men and 4 women, with an average age of 30.67±10.06 (range 14-45 years). AO/OTA classification at initial pelvic fracture, 8 cases were type C1.3 and one was type C3.3. The period from injury to surgery was 12.8±18.92 months (range 3-60 months). The cranial displacement of one side of the pelvis was 3.8±0.57 cm (range 2.5-4.1 cm). Sacral osteotomy and triangular osteosynthesis were used in all nine patients, combined with osteotomy or no osteotomy of the superior and inferior branches of the anterior ring pubis. The degree of longitudinal displacement of one side of the pelvis was assessed by making a vertical line gap between the acetabular apex on both sides and the central axis of the sacrum on the X-ray of the pelvis. The Majeed scoring and visual analogue scale (VAS) were evaluated preoperatively and at the last follow-up to assess the therapeutic effect of the patients.Results:In all 9 patients, except for 1 case of postoperative pelvic residual displacement 1.5 cm (preoperative 3.2 cm difference compared with the healthy side), the other 8 patients had a postoperative bilateral difference of 0.1-0.7 cm. All the patients were followed up for 12.00±9.95 months. At the last follow-up, the Majeed score of pelvic fracture increased from 44.0(33.5, 76.0) points preoperatively to 91.0(80.5, 92.5) points. The difference before and after operation was statistically significant ( Z=2.67, P<0.001), and the gait was significantly improved. And the VAS score for pain decreased from 6.00±1.41 points preoperatively to 1.22±0.97 points. The difference before and after operation was statistically significant ( t=8.73, P<0.001). None had complications like infection, plate broken, screw loosening, iatrogenic nerve or blood vessel injury, etc. Conclusion:Sacral osteotomy combined with lumbopelvic distraction triangular osteosynthesis for the treatment of pelvic malunion and nonunion caused by sacral fracture can correct pelvic deformity, prolong limb length, and reconstruct the stability of pelvic ring with good clinical results.

Multi-omics analysis of regulating effects of hyperoside on lipid metabolism in high-fat diet mice / 生理学报

The aim of this study was to explore the regulating effects of hyperoside (Hyp) on lipid metabolism in high-fat diet mice. The high-fat diet mouse model was established by high-fat diet induction. After 5 weeks of Hyp intragastric administration in high-fat diet mice, the serum lipid levels before and after Hyp administration were measured by the corresponding kits. The tissue structure of mouse liver was observed by HE staining before and after Hyp administration. The changes of intestinal flora and transcriptome were measured by Illumina platforms. Liquid chromatography-mass spectrometry (LC-MS) was used to determine non-targeted metabolites. The results showed that Hyp significantly reduced lipid levels in the high-fat diet mice and effectively restored the external morphology and internal structure of liver tissue. Hyp changed the species composition of the intestinal flora in high-fat diet mice, increased the abundance of beneficial flora such as Ruminococcus, and decreased the abundance of harmful flora such as Sutterella. Combined multi-omics analysis revealed that the effect of retinoic acid on lipid metabolism was significant in the high-fat diet mice treated with Hyp, while the increase of retinoic acid content was significantly negatively correlated with the expression of genes such as cyp1a2 and ugt1a6b, positively correlated with AF12 abundance, and significantly negatively correlated with unidentified_Desulfovibrionaceae abundance. These results suggest that Hyp may modulate the abundance of AF12, unidentified_Desulfovibrionaceae and inhibit the expression of genes such as cyp1a2 and ugt1a6b, thus increasing the content of retinoic acid and regulating lipid metabolism in the high-fat diet mice.

MiR-744-5p inhibits the proliferation, invasion, and migration of clear-cell renal cell carcinoma cells by targeting CCND1 / 南方医科大学学报

OBJECTIVE@#To explore the role of miR-744-5p/CCND1 axis in clear-cell renal cell carcinoma (ccRCC).@*METHODS@#We examined the expression levels of miR-744-5p in 65 pairs of ccRCC and adjacent tissue specimens and in 5 ccRCC cell lines and human renal tubular epithelial (HK2) cells using qRT-PCR. The ccRCC cell lines 786-O and OSRC2 were transfected with miR-744-5p mimic, CCND1 mimic, or their negative control mimics, and the changes in cell proliferation, migration, and invasion were evaluated with CCK-8, wound healing, and Transwell assays. The downstream target molecules of miR-744-5p were predicted by bioinformatics analysis, and the expression level of CCND1 in ccRCC cells was verified by qRT-PCR and Western blotting. The relationship between miR-744-5p and CCND1 was further validated by dual luciferase reporter assay, and the role of the miR-744-5p/CCND1 axis in ccRCC was explored by rescue experiments.@*RESULTS@#MiR-744-5p was significantly downregulated in ccRCC tissues and cell lines (all P < 0.05), and its overexpression inhibited the proliferation, migration, and invasion of ccRCC cells (all P < 0.05). Bioinformatics analysis and dual luciferase reporter assay showed that CCND1 was a downstream target of miR-744-5p. The results of rescue experiments showed that upregulation of CCND1 could partially reverse the inhibitory effect of miR-744-5p overexpression on ccRCC cell proliferation, migration, and invasion (all P < 0.05).@*CONCLUSION@#MiR-744-5p inhibits the malignant phenotype of ccRCC cells by targeting CCND1, and the miR-744-5p/CCND1 axis may be a novel target for diagnosis and treatment of ccRCC.

Design, synthesis and antiplatelet activity evaluation of novel quinoxaline antagonists of protease activated receptor 4 (PAR4) / 药学学报

Twenty-five compounds of novel quinoxaline-based scaffold with antiplatelet activity were designed and synthesized on the basis of previous quinoxaline analogues, and the structures were confirmed by 1H NMR, 13C NMR, and MS. The antiplatelet activity was evaluated, structure-activity relationship (SAR) study was summarized and the selectivity of PAR4 was confirmed by calcium mobilization assays. It was indicated that compound 14a, 14g, 13i, 13p showed moderate activity against PAR4, especially, the activity of compound 14g (IC50 = 0.26 μmol·L-1) was 6.7 times than the lead compound A (IC50 = 1.73 μmol·L-1). Therefore, 2,3-dihydro-[1,4]dioxino[2,3-g]quinoxaline and [1,3]dioxolo[4,5-g]quinoxaline derivatives are promising compounds for the discovery of novel antiplatelet agents. It is worthy of further research to develop highly effective and selective PAR4 antagonists.

Preliminary study of MRI features of cerebral amyloid angiopathy-related inflammation / 中华放射学杂志

Objective:To explore the MRI features of cerebral amyloid angiopathy-related inflammation (CAA-ri).Methods:The clinical and imaging data of 12 patients with CAA-ri diagnosed in Affiliated Guizhou Aviation Industry Cor Ltd No 300 Hospital of Zunyi Medical University (9 cases), Xingyi People′s Hospital (2 cases) and Anshun people′s Hospital (1 case) from June 2013 to June 2020 were analyzed retrospectively. There were 3 females and 9 males, aged from 57 to 89 years old, with an average age of 71±10 years. The twelve patients included 5 cases with probable CAA-ri and 7 cases with possible CAA-ri. The duration of the disease ranged from 30 minutes to 2 years. One patient has ApoE ε4/ε4 gene overexpressed. All the 12 patients underwent MRI, including susceptibility weighted imaging in 12 cases, DWI in 10 cases, contrast enhanced MRI (CE-MRI) in 9 cases, MRS in 3 cases, MRA in 7 cases, and perfusion-weighted imaging in 1 case.Results:Imaging features of CAA-ri included encephalopathic, tumoral, classical cerebral amyloid angiopathy(CAA) manifestations. Twelve cases of encephalopathic manifestations showed patchy white matter hyperintensity (WMH) involving U-shaped fibers on T 2 weighted fluid-attenuated inversion recovery sequence (FLAIR), usually asymmetric,with various degree of mass effect, no diffusion restriction on DWI and no enhancement on CE-MRI. One case showed a single tumoral lesion with irregular enhancement on CE-MRI. The classic CAA findings included hemorrhagic lesions (microhemorrhage in 8 cases, lobar hemorrhage in 6 cases, subarachnoid hemorrhage in 3 cases, iron deposition on the brain surface in 7 cases) and ischemic lesions (microinfarction in 1 case, enlarged perivascular space and interlobar space in 4 cases). Follow-up showed lesions absorption and/or new lesion formation in 5 cases. Conclusions:The MRI features of CAA-ri are mainly patchy WMH involving U-shaped fibers on T 2 FLAIR, usually asymmetric, with wandering and alternating features, and inconsistency with clinical manifestations.

Herbalogical study on historical evolution of collection, processing and efficacy of Citri Exocarpium Rubrum and Citri Grandis Exocarpium / 中国中药杂志

In ancient times, the original plants of Citri Exocarpium Rubrum and Citri Grandis Exocarpium had experienced succession and change, including tangerine(Citrus reticulata), pomelo(C. grandis), and Huazhou pomelo(C. grandis 'Tomentosa'), a specific cultivar of C. grandis produced in Huazhou, Guangdong. Before the Qing Dynasty, tangerine was the main original plant, while Huazhou pomelo came to the fore in the Qing Dynasty. In the 1950 s and 1960 s, the producing area of Huazhou pomelo was destroyed, and thus it had to be supplemented with pomelo. From then on, C. grandis 'Tomentosa' and C. grandis were both listed as the original plants of Citri Grandis Exocarpium in the Chinese Pharmacopoeia. This paper reviewed the historical evolution of the collection, processing, and efficacy of Citri Exocarpium Rubrum and Citri Grandis Exocarpium. The research showed that:(1)The harvest time of the original plants of Citri Grandis Exocarpium and Citri Grandis Exocarpium had changed from maturity to immaturity. The collection and processing of Citri Exocarpium Rubrum was first recorded in the Illustrated Classics of Materia Medica in the Song Dynasty. During the Ming and Qing Dynasties, the mesocarp of Citri Exocarpium Rubrum needed to be removed completely, and Citri Grandis Exocarpium from C. grandis 'Tomentosa' was processed into different specifications such as seven-piece, five-piece, and single piece. Furthermore, processed young fruits of Huazhou pomelo appeared.(2)Citri Exocarpium Rubrum and Citri Grandis Exocarpium were processed with carp skin for the first time in the Master Lei's Discourse on Medicinal Processing. It was suggested that carp skin might be helpful for eliminating bones stuck in throat. During the Song, Jin, and Yuan Dynasties, some other processing methods such as ba-king, stir-frying, and salt-processing appeared. Honey, soil, ginger juice, and alum were firstly used as adjuvants for the processing in the Ming and Qing Dynasties. Citri Exocarpium Rubrum was mainly prepared with salt in order to improve the effect of lowering Qi, while it was unnecessary for Citri Grandis Exocarpium from C. grandis 'Tomentosa' because of its obvious effect of lowering Qi and eliminating phlegm. The stir-frying and honey-frying methods helped reduce the strong effect of Citri Grandis Exocarpium from C. grandis 'Tomentosa'.(3)According to the application of Citri Exocarpium Rubrum and Citri Grandis Exocarpium in history, their medicinal use began in Han and Tang Dynasties, developed in Song, Jin, and Yuan Dynasties, and matured in Ming and Qing Dynasties. Citri Grandis Exocarpium from C. grandis 'Tomentosa' was originally applied in Ming and Qing Dynasties, and it still plays an important in role treating COVID-19 nowadays. Moreover, Citri Grandis Exocarpium from C. grandis had cold medicinal property, while Citri Grandis Exocarpium from C. grandis 'Tomentosa' had warm medicinal property, and thus they should not be treated the same. At present, Huazhou pomelo has a certain production scale. Therefore, it is recommended that in the next edition of Chinese Pharmacopoeia, only C. grandis 'Tomentosa' should be included as the original plant of Citri Grandis Exocarpium, and C. grandis should be deleted. The results are conducive to the further development and utilization of Citri Exocarpium Rubrum and Citri Grandis Exocarpium, and support the rational use of Citri Grandis Exocarpium and its processed products.

Lumbopelvic fixation using sacral ala-iliac screw for sacral fractures / 中华骨科杂志

Objective:To investigate clinical effects of lumbopelvic fixation and triangular osteosynthesis using sacral ala-iliac screws for the treatment of sacral fractures.Methods:The data of 12 patients with sacral fractures treated with lumbopelvic fixation and triangular osteosynthesis using sacral ala-iliac screws from December 2019 to June 2020 were retrospectively analyzed. There were 3 males and 9 females with an average age of 32.6±15.0 years (range, 13-52 years); causes of injury: 11 fall injuries and 1 traffic injury. The Denis classification of sacrum fracture: 4 cases of type II and 8 cases of type III. AO (Tile-Muller) classification: 4 cases of type C1.3, 8 cases of type C3.3; of the 8 cases of C3.3 fractures, Roy-Camille and Strange-Vognsen classification: 2 cases of type II, 6 cases of type III. According to the scoring system of Gibbons sacral nerve injury, there were 6 cases of scored 3 and 2 cases of scored 4; 4 cases of C1.3 fractures had no nerve injury. The time from injury to operation was 6 to 32 days, with an average of 19.3±9.2 days. After the vital signs were stabilized, laminectomy and decompression of sacral nerve roots, fracture reduction, lumbopelvic fixation and triangular osteosynthesis using sacral ala-ilac screws were performed. The fixation method of the anterior ring was determined according to the injury. The postoperative fracture reduction quality was evaluated according to Matta criteria. The clinical function and neurological function were evaluated according to the Majeed scoring system and Gibbons sacral nerve injury scoring system at the last follow-up.Results:Twelve patients were operated smoothly. 8 cases of C3.3 fractures were fixed by lumbopelvic fixation, of which 6 cases of U-shaped fractures were fixed by transverse rods due tolongitudinal separation displacement; Four cases of C1.3 used triangular osteosynthesis and transverse fixation in 3 cases with sacroiliac screws, and 1 case with sacral local plate. Six patients with anterior ring injury were fixed with steel plate in 4 cases, INFIX in 1 case and pubic branch screw in 1 case. All patients were followed up for 6 to 12 months, with an average of 7.3±1.7 months. Postoperative Matta standard evaluation: excellent in 7 cases; good in 4 cases; fair in 1 case. Majeed score at the last follow-up: excellent in 6 cases, good in 5 cases, and fair in 1 case. One of 2 cases of rectal and bladder dysfunction patients completely recovered, the other was found partial rupture of the nerve roots of sacrum 1 and 2 during operation, whose muscle strength below the calf was still reduced; 6 cases of preoperative muscle strength loss below the calf were significantly improved, among which 4 patients recovered completely, and 2 patients had lower limb sensory impairment; the Gibbons score improved by an average of 1.8±0.7 points (preoperative average 3.2 points, postoperative average 1.4 points). X-ray examinations were performed 3 to 6 months after the operation showed that the fractures were all healed. During the follow-up period, no complications such as fat liquefaction, infection, wound healing, and screw protrusion discomfort were found.1 case of S 2AI screw penetrated the outer plate of the ilium, and there was no pelvic tilt and unequal length deformity of the lower limbs. One patient took out the internal fixation 6 months after the operation due to lower back discomfort. At the last follow-up, all patients had no internal fractures or loss of fracture reduction. Conclusion:Lumbopelvic fixation and triangular osteosynthesis using sacral ala-iliac screws for the treatment of sacral fractures are reliable, with less trauma and lower incidence of complications; and the clinical results are satisfactory.

Effects of 3D-printed porous metal cup with hip dual-mobility revision system for reconstruction of severe acetabular ring defects in revision total hip arthroplasty / 中华骨科杂志

Objective:To prospectively analyze the early clinical effects of 3D-printed porous metal cup with hip dual-mobility revision (HDR) system in treating severe acetabular bone defects.Methods:A total of 17 patients with severe acetabular defects (15 patients in Allan-Gross type 4 and 2 patients in type 5; 2 patients in Paprosky type 2B, 4 patients in type 3A and 11 patients in type 3B) who underwent revision hip arthroplasty between July 2019 and May 2020 were analyzed. There were 7 males and 10 females (mean age 67.3±9.3 years; range 42-80 years). The average body mass index was 22.2±3.8 kg/m 2 (range 17.7-33.3 kg/m 2). The preoperative mean leg length discrepancy (LLD) was 42.9±31.1 mm (range 10-160 mm) . One patient presented positive Trendelenburg sign. The follow-up duration was 12.1±3.0 months (range 6-16 months). The clinical and radiographic hip scores in all patients were evaluated. Results:The mean Harris Hip Score (HHS) was 31.2±11.3 points at preoperatively, 63.5±10.0, 68.7±10.4 and 70.2±10.1 points at 3 days, 7 days and 1 month postoperatively. At the latest follow-up, HHS was increased to 81.6±7.0 points. The outer cup mean abduction angle was 48.1°±10.6° and the mean inclination angle was 10.8°±6.0° postoperatively. The inner cup mean abduction angle was 45.0°±6.2° and the mean inclination angle was 10.8°±3.7°. The mean LLD decreased to 11.1±3.8 mm (range: 0-15 mm) after surgery. At the latest follow-up, all acetabular components were radiologically stable without displacement. No osteolysis or absorption was observed. There was no infection, loosening or nerve injury in all cases.Conclusion:During short-term follow-up, the 3D-printed porous metal HDR system can effectively enhance the stability of implants with satisfied quality of life. It can provide a good result for the revision of total hip arthroplasty with severe acetabular defects.

The value of acute gastrointestinal injury grading combined with qSOFA score in the diagnosis of sepsis / 中华急诊医学杂志

Objective:To develop a prediction model of acute gastrointestinal injury (AGI) grading combined with qSOFA score for the diagnosis of sepsis, and evaluate its value.Methods:This was a prospective observational study. The patients with infection or suspected infection in the General Ward of Changshu Hospital Affiliated to Soochow University from September 2018 to September 2019 were included. Patients younger than 18 years, pregnant, abandoned treatment and died within 3 days after admission were excluded. Clinical characteristics, laboratory test results and AGI grading from 48 h before the infection to 24 h after the onset of infection were recorded. The patients were divided into the sepsis and non-sepsis groups according to whether they were diagnosed with sepsis. The patients were allocated randomly to a modeling cohort and a validation cohort with a ratio of 7:3. Univariate and multivariate logistic regression analyses were used to analyze the relevant risk factors for sepsis in the modeling cohort. Three types of diagnostic models were constructed in the modeling cohort: model A (qSOFA model), model B (the combined model of AGI grading and qSOFA score), and model C (the combined model of clinical parameters). The clinical usefulness of the diagnostic models was assessed by receiver operating characteristic curve (ROC), calibration curve and decision curve analysis (DCA) in the validation cohort. The nomograms were developed based on these models.Results:A total of 2 553 patients were enrolled in the study, 1 789 patients in the modeling cohort and 764 patients in the validation cohort. and 326 were diagnosed with sepsis. There was no statistical difference in the basic conditions of patients in the two groups. Univariate analysis showed that age, gender, the source of infection, temperature, heart rate, polypnea, changes in consciousness, severe edema, hyperglycemia, white blood cell, C-reactive protein and procalcitonin, hypotension, hypoxemia, acute oliguria, coagulation disorders, hyperlacticemia, capillary filling damage or piebaldskin, AGI grading and qSOFA score were significantly correlated with sepsis (all P<0.01). Multivariate logistic regression analysis showed that age ( OR=1.027, P<0.01), source of infection ( OR=2.809, P=0.03), hypotension ( OR=35.449, P<0.01), hypoxemia ( OR=57.018, P<0.01), and AGI grading ( OR=19.313, P<0.01) were significantly associated with sepsis. ROC analysis showed that the area under the curve (AUC) of model A, B and C were 0.784, 0.944 and 0.971 in the modeling cohort, and 0.832, 0.975 and 0.980 in the validation cohort, respectively. The sensitivities were 63.9%, 89.5% and 97.5% in the modeling cohort, and 72.7%, 90.9% and 96.6% in the validation cohort; and the specificities were 90.8%, 90.3% and 88.1% in the modeling cohort, and 92.2%, 94.5% and 92.8% in the validation cohort, respectively. AUC of model B and C were significantly higher than that of model A ( P<0.01). Model A in the validation cohort was poorly calibrated, with low accuracy and high risk of missed sepsis diagnosis ( P=0.044). The net benefits of model B and C were better than that of model A. Conclusions:AGI grading combined with qSOFA score has a high predictive value and accuracy in the diagnosis of sepsis.

Research status and progress of hypoxia-inducible factor on the regulation of diabetic retinopathy / 中华眼底病杂志

The intervention therapy targeting vascular endothelial growth factor (VEGF) has become a specific and effective method for the treatment of diabetic retinopathy (DR). However, some patients did not respond or responded poorly to anti-VEGF therapy, and its effects of eliminating edema and improving vision appear to be unstable in the same patient. Hypoxia-inducible factor-1α (HIF-1α), an important upstream transcriptional regulator of VEGF, is an oxygen concentration-sensitive protein expressed in tissues under hypoxia. It can simultaneously target many downstream target genes except VEGF, such as placental growth factor and angiopoietin-like protein 4, to cause blood-retinal barrier damage and neovascularization, and thus participate in various pathological changes of DR to promote the occurrence and development of DR. Therefore, direct intervention of HIF-1α or targeting one or more downstream target genes regulated by HIF-1α to treat DR may have better efficacy. In the future, the development of effective and safe HIF inhibitors or anti-VEGF with HIF-1α other target gene inhibitors may have broader clinical application prospects.

Alkaloid constituents from the fruits of Flueggea virosa / 中国天然药物

Three new indole alkaloids, flueindolines A-C (1-3), along with nine known alkaloids (4-12), were isolated from the fruits of Flueggea virosa (Roxb. ex Willd.) Voigt. Compounds 1 and 2 are two new fused tricyclic indole alkaloids possessing an unusual pyrido[1, 2-a]indole framework, and 3 presents a rare spiro (pyrrolizidinyl-oxindole) backbone. Their structures with absolute configurations were elucidated by means of comprehensive spectroscopic analysis, chemical calculation, as well as X-ray crystallography. Chiral resolution and absolute configuration determination of the known compounds 4, 10, and 11 were reported for the first time. The hypothetical biogenetical pathways of 1-3 were herein also proposed.

Normativity of overview report of the systematic review of acupuncture and moxibustion at home and abroad based on PRIO-harms scale / 中国针灸

OBJECTIVE@#To evaluate and compare the normativity of overview report of systematic review (Overviews) of acupuncture and moxibustion at home and abroad so as to further improve the report quality of Overviews of acupuncture and moxibustion in China and provide reliable evidences.@*METHODS@#The articles relevant with Overviews of acupuncture and moxibustion at home and abroad were retrieved by computer from the databases of CNKI, VIP, Wanfang, China BioMedical Literature database (SinoMed), PubMed, Embase and Conchrane Library, dated from the time of establishment to February 12, 2019. The preferred reporting items for Overviews (PRIO-harms) was adopted to evaluate their normativity and make the comparison of the articles between China and foreign countries.@*RESULTS@#A total of 13 articles of Overviews of acupuncture and moxibustion were included, 9 articles of them were of Chinese version and the rest were of English version. The results of PRIO-harms indicated that the proportions of the item numbers related to adequate, partial and inadequate adherence of Chinese version were 3.7%, 63.8% and 32.5%, and those of English version were 12.0%, 57.4% and 30.6% respectively. The reports on the item 10 "additional search for primary studies", the item 12 "data items" and the item 26 "Dual/(co-)authorship" were inadequate adherence by 100% in the articles of both Chinese and English version.@*CONCLUSION@#The overall information of English article report is better than Chinese one, but the reports of either Chinese or English articles are not so satisfactory. It is suggested that the Overviews report should be in reference to the specification in PRIO-harms and the Chinese researchers should study the advantages of English article report and improve the normalization and report quality so as to obtain the high-quality evidences in evidence-based medicine.

MSAP analysis of DNA methylation between pogoston-type and patchouliol-type of Pogostemon cablin / 中草药

Objective: To analyze the DNA methylations between two chemical types of Pogostemon cablin using MSAP technique. Methods: Methylation sensitive amplification polymorphism (MSAP) technique was used to detect the DNA methylation degree of two chemical type and a total of 197 P. cablin samples. Results: The highest or higher values of the Shannon polymorphism index of the four types of MSAP locus information were produced in the five areas of Yangchun, Deqing, Gaozhou Datong, Lubu, and Guangning. It formed two branches with P. cablin Shipaiensis (Pogostone-type) and the rest (Patchouliol-type). The percentage of variation among the populations was 60.66%, which was far greater than that within the population. A total of 10 differential fragments were screened out, sequenced and analyzed, one of those belongs to the serine/threonine protein kinase family. Conclusion: The MSAP technique can be used to identify the different origins of P. cablin. The formation of different chemical types of P. cablinis closely related to its DNA methylation level, and further research is needed.