The role of PINK1/Parkin-mediated mitophagy in mechanical imbalance-induced endplate cartilage degeneration / 局解手术学杂志

Objective To detect the changes of mitophagy level in rats with endplate cartilage degeneration induced by spinal instability,and explore the role of PINK1/Parkin-mediated mitophagy in endplate cartilage and intervertebral disc degeneration.Methods The rat spinal instability model was established by surgically removing the superspinal and interspinal ligaments of L2 to L5,and cleaning the bilateral articular processes of the L2 to L5.Eighteen SD rats were divided into the normal group,the degenerative group,and the carbonyl cyanide 3-chlorophenylhydrazone(CCCP)group,with 6 rats in each group.The rats in the normal group had no special treatment,the rats in the degenerative group constructed a rat spinal instability model,and the rats in the CCCP group were injected with 5 μL of CCCP(10 μmol/L)in the intervertebral disc after the construction of spinal instability model.The changes of histomorphology in the endplate cartilage and intervertebral disc were abserved by HE staining,and the change of extracellular matrix of endplate cartilage was observed by safranin O-fast green staining.RT-PCR detected the mRNA expression of type Ⅱ collagen(COL-2A),aggrecan(ACAN),PINK1 and Parkin in each group.The changes of the protein expression levels of COL-2A,ACAN,PINK1,Parkin and mitochondrial membrane proteins of Tomm20 and Timm23 were detected by Western blot.Results Compared with the normal group,the intervertebral disc nucleus pulposus of rats in the degenerative group was significantly destroyed and the secretion of extracellular matrix of endplate chondrocytes decreased;while the structure of intervertebral discs for rats in the CCCP group was more intact,and the secretion of extracellular matrix of endplate chondrocytes was significantly increased compared with that in the degenerative group.Compared with the normal group,the expression of COL-2A and ACAN in endplate cartilage tissues of rats in the degenerative group were significantly down-regulated(P<0.05),the expression of mitochon-drial autophagy-related genes of PINK1 and Parkin were significantly decreased(P<0.05),and the expression of mitochondrial membrane proteins of Tomm20 and Timm23 were increased(P<0.05).Compared with the degenerative group,the expression of COL-2A,ACAN,PINKI and Parkin in the endplate cartilage tissue of rats in the CCCP group were significantly up-regulated(P<0.05),and the protein levels of Tomm20 and Timm23 were significantly down-regulated(P<0.05).Conclusion Rat spinal instability leads to a decrease level of mitophagy mediated by PINK1/Parkin signaling pathway in endplate cartilage,thereby inducing endplate cartilage and intervertebral disc degeneration,and the activation of mitophagy can significantly reduce endplate cartilage and intervertebral disc degeneration.

Two types of coumarins-specific enzymes complete the last missing steps in pyran- and furanocoumarins biosynthesis

Pyran- and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans, respectively, exhibiting diverse physiological and medical bioactivities. However, the biosynthetic mechanisms for their core structures remain poorly understood. Here we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in plants. These included three distinct P. praeruptorum prenyltransferases (PpPT1-3) responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors, and two novel CYP450 cyclases (PpDC and PpOC) crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran scaffolds. Biochemical analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring refactoring. The possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific mutagenesis. We identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic process. This study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process.

Estrogen upregulates DNA2 expression through the PI3K-AKT pathway in endometrial carcinoma / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Endometrial cancer is the most common gynecological malignancy, affecting up to 3% of women at some point during their lifetime (Morice et al., 2016; Li and Wang, 2021). Based on the pathogenesis and biological behavioral characteristics, endometrial cancer can be divided into estrogen-dependent (I) and non-estrogen-dependent (II) types (Ulrich, 2011). Type I accounts for approximately 80% of cases, of which the majority are endometrioid carcinomas, and the remaining are mucinous adenocarcinomas (Setiawan et al., 2013). It is generally recognized that long-term stimulation by high estrogen levels with the lack of progesterone antagonism is the most important risk factor; meanwhile, there is no definite conclusion on the specific pathogenesis. The incidence of endometrial cancer has been on the rise during the past two decades (Constantine et al., 2019; Gao et al., 2022; Luo et al., 2022). Moreover, the development of assisted reproductive technology and antiprogestin therapy following breast cancer surgery has elevated the risk of developing type I endometrial cancer to a certain extent (Vassard et al., 2019). Therefore, investigating the influence of estrogen in type I endometrial cancer may provide novel concepts for risk assessment and adjuvant therapy, and at the same time, provide a basis for research on new drugs to treat endometrial cancer.

Research progress on the role and clinical application of Siglecs in tumor immunity / 细胞与分子免疫学杂志

Lectins are proteins responsible for recognizing the signals of sugar molecules in the body. Sialic acid-binding immunoglobulin-like lectins (Siglecs) regulate the innate and adaptive immune responses in the tumor microenvironment by recognizing the glycan structure containing sialic acid and mediating downstream signals through immune receptor tyrosine inhibitory motifs. In recent years, a variety of tumor treatment strategies targeting the sialic acid-Siglecs axis have been introduced, including sialoglycoprotein-mediated drug delivery and antibody mediated inhibition of Siglecs from recognizing tumor surface ligands. In the future, by combining with glycoprotein nanotherapy, antibody therapy and gene therapy, Siglecs can be used to accurately locate tumor targets and release the anti-tumor immunity, so as to achieve the purpose of effective cure of tumors.

Clinical characteristics and prognosis of patients with therapy-related myelodysplastic syndrome and acute myeloid leukemia arising from malignant tumors / 中华血液学杂志

Objective: To investigate the clinical characteristics, cytogenetics, molecular biology, treatment, and prognosis of patients with therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML) secondary to malignancies. Methods: The clinical data of 86 patients with t-MDS/AML in West China Hospital of Sichuan University between January 2010 and April 2023 were retrospectively analyzed. The clinical characteristics, primary tumor types, and tumor-related therapies were analyzed. Results: The study enrolled a total of 86 patients with t-MDS/AML, including 67 patients with t-AML, including 1 patient with M(0), 6 with M(1), 27 with M(2), 9 with M(3), 12 with M(4), 10 with M(5), 1 with M(6), and 1 with M(7). Sixty-two patients could be genetically stratified, with a median overall survival (OS) of 36 (95% CI 22-52) months for 20 (29.9%) patients in the low-risk group and 6 (95% CI 3-9) months for 10 (14.9%) in the intermediate-risk group. The median OS time was 8 (95% CI 1-15) months in 32 (47.8%) patients in the high-risk group. For patients with non-acute promyelocytic leukemia (APL) and AML, the median OS of the low-risk group was 27 (95% CI 18-36) months, which was significantly longer than that of the non-low-risk group (χ(2)=5.534, P=0.019). All 9 APL cases were treated according to the initial treatment, and the median OS was not reached, and the 1-, 2-, and 3-year OS rates were 100.0%, (75.0±6.2) %, and (75.0±6.2) % respectively. Of the 58 patients with non-APL t-AML (89.7%), 52 received chemotherapy, and 16 achieved complete remission (30.8%) after the first induction chemotherapy. The 1-, 2-, and 3-year OS rates of the non-APL t-AML group were (42.0 ± 6.6) %, (22.9±5.7) %, and (13.4±4.7) %, respectively. The median OS of patients who achieved remission was 24 (95% CI 18-30) months, and the median OS of those who did not achieve remission was 6 (95% CI 3-9) months (χ(2)=10.170, P=0.001). Bone marrow CR was achieved in 7 (53.8%) of 13 patients treated with vineclar-containing chemotherapy, with a median OS of 12 (95% CI 9-15) months, which was not significantly different from that of vineclar-containing chemotherapy (χ(2)=0.600, P=0.437). In 19 patients with t-MDS, the 1-, 2-, and 3-year OS rates were (46.8±11.6) %, (17.5±9.1) %, and (11.7±9.1) % with a median OS of 12 (95% CI 7-17) months, which was not significantly different from that in t-AML (χ(2)=0.232, P=0.630) . Conclusions: Breast cancer, bowel cancer, and other primary tumors are common in patients with t-MDS/AML, which have a higher risk of adverse genetics. Patients with APL had a high induction remission rate and a good long-term prognosis, whereas patients without APL had a low remission rate and a poor long-term prognosis.

Association between posterior tibial slope and tibial torsion angle and recurrent patellar dislocation based on the full-length CT of the lower limbs / 解剖学报

Objective To measure and compare the lateral posterior tibial slope (LPTS) , medial posterior tibial slope ( MPTS) and tibial torsion angle ( TTA) between the patients of recuiTent patellar dislocation and the heathy people, and to analyze the correlation between LPTS, MPTS and TTA and the risk factors of recuiTent patellar dislocation. Methods A total of 33 patients (44 knees) with recuiTent patellar dislocation in our hospital from July 2019 to June 2021 were selected and listed as the stud)' group. Twenty-three subjects (46 knees) who were suspected iliac vascular and lower limb vascular diseases during the same period were selected and listed as the control group. All the enrolled researchers had fulllength CT scans date of the lower limbs. Three-dimensional models were reconstructed using Mimics 21. 0 software and then imported into 3-matic software. The LPTS, MPTS and TTA were measured and compared between the two groups. Results In the study group, the LPTS, MPTS and TTA were (7. 69} 1. 42) ° , ( 10. 06} 1. 71) ° , ( 36. 42}8. 13 ) ° , respectively while the control group, the LPTS, MPTS and TTA were ( 8. 42 } 1. 65 ) ° , ( 10. 44 } 0. 86 ) ° , ( 25. 77} 3. 90 ) ° , respectively. There were no signiiicant differences in the LPTS, MPTS and TTA between different genders and sides both in the stud)' group and the control group ( P > 0. 0 5 ) . Compared with the control group, the LPTS in the stud)' group was smaller, and the difference was statistically significant (P0. 05). Compared with the control group, the TTA in the stud)' group was higher, and the difference was statistically significant (P< 0. 0 5 ) . Compared with the control group, the LPTS and MPTS in the study group were significant asymmetry, and the difference was statistically significant ( P < 0 . 0 5 ). Conclusion The lateral posterior tibial slope of patients with recurrent patellar dislocation is significantly smaller than that in the healthy people, while there is no significant difference in the medial posterior tibial slope; The tibial torsion angle of patients with recurrent patellar dislocation is significantly larger than in the healthy people; The lateral posterior tibial slope and tibial torsion angle have certain correlation with recurrent patellar dislocation, which can conduct the diagnosis of recurrent patellar dislocation.

Cardioprotective mechanism of SGLT2 inhibitor against myocardial infarction is through reduction of autosis

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular mortality in patients with diabetes mellitus but the protective mechanism remains elusive. Here we demonstrated that the SGLT2 inhibitor, Empagliflozin (EMPA), suppresses cardiomyocytes autosis (autophagic cell death) to confer cardioprotective effects. Using myocardial infarction (MI) mouse models with and without diabetes mellitus, EMPA treatment significantly reduced infarct size, and myocardial fibrosis, thereby leading to improved cardiac function and survival. In the context of ischemia and nutritional glucose deprivation where autosis is already highly stimulated, EMPA directly inhibits the activity of the Na+/H+ exchanger 1 (NHE1) in the cardiomyocytes to regulate excessive autophagy. Knockdown of NHE1 significantly rescued glucose deprivation-induced autosis. In contrast, overexpression of NHE1 aggravated the cardiomyocytes death in response to starvation, which was effectively rescued by EMPA treatment. Furthermore, in vitro and in vivo analysis of NHE1 and Beclin 1 knockout mice validated that EMPA's cardioprotective effects are at least in part through downregulation of autophagic flux. These findings provide new insights for drug development, specifically targeting NHE1 and autosis for ventricular remodeling and heart failure after MI in both diabetic and non-diabetic patients.

The effects of functional electric stimulation and upper limb cycle training on upper limb motor function and daily living activities post-stroke / 中华物理医学与康复杂志

Objective:To explore the effect of combining functional electric stimulation (FES) with upper limb cycle training in rehabilitating upper limb motor function and ability in the activities of daily living after a stroke.Methods:Sixty hemiplegic stroke survivors were randomly divided into an experimental group and a control group. In addition to conventional rehabilitation therapy, the experimental group underwent 20 minutes of MOTOmed upper limb cycle training every day while receiving FES. The control group received only the 20 minutes of cycle training. Before and after 4 weeks, Brunnstrom staging was used to quantify hand and upper extremity functioning. The Fulg-Meyer assessment upper extremity scale (FMA-UE) and the modified Barthel index (MBI) were also used before the training and after 1, 2, 3 and 4 weeks of the treatments.Results:After 4 weeks of treatment, significant differences were observed in the average BS scores of both groups compared with before the intervention. The average hand and upper limb stages of the experimental group were significantly better than the control group′s averages. Significant improvement was also observed in the average FMA-UE and MBI scores of both groups after only one week, with significantly greater improvement in the experimental group.Conclusions:Supplementing upper limb cycle training with FES can significantly improve the upper limb motor function and ability in the activities of daily living of stroke survivors. It is more effective than the MOTOmed exercise alone.

Metabolic regulation mechanism of Aconiti Radix Cocta extract in rats based on / 中草药·英文版

Objective: To establish a metabonomics research technique based on the combination of

Overexpression of NAT10 induced platinum drugs resistance in breast cancer cell / 中华肿瘤杂志

Objective: To observe the platinum drugs resistance effect of N-acetyltransferase 10 (NAT10) overexpression in breast cancer cell line and elucidate the underlining mechanisms. Methods: The experiment was divided into wild-type (MCF-7 wild-type cells without any treatment) group, NAT10 overexpression group (H-NAT10 plasmid transfected into MCF-7 cells) and NAT10 knockdown group (SH-NAT10 plasmid transfected into MCF-7 cells). The invasion was detected by Transwell array, the interaction between NAT10 and PARP1 was detected by co-immunoprecipitation. The impact of NAT10 overexpression or knockdown on the acetylation level of PARP1 and its half-life was also determined. Immunostaining and IP array were used to detect the recruitment of DNA damage repair protein by acetylated PARP1. Flow cytometry was used to detect the cell apoptosis. Results: Transwell invasion assay showed that the number of cell invasion was 483.00±46.90 in the NAT10 overexpression group, 469.00±40.50 in the NAT10 knockdown group, and 445.00±35.50 in the MCF-7 wild-type cells, and the differences were not statistically significant (P>0.05). In the presence of 10 μmol/L oxaliplatin, the number of cell invasion was 502.00±45.60 in the NAT10 overexpression group and 105.00±20.50 in the NAT10 knockdown group, both statistically significant (P<0.05) compared with 219.00±31.50 in wild-type cells. In the presence of 10 μmol/L oxaliplatin, NAT10 overexpression enhanced the binding of PARP1 to NAT10 compared with wild-type cells, whereas the use of the NAT10 inhibitor Remodelin inhibited the mutual binding of the two. Overexpression of NAT10 induced PARP1 acetylation followed by increased PARP1 binding to XRCC1, and knockdown of NAT10 expression reduced PARP1 binding to XRCC1. Overexpression of NAT10 enhanced PARP1 binding to LIG3, while knockdown of NAT10 expression decreased PARP1 binding to LIG3. In 10 μmol/L oxaliplatin-treated cells, the γH2AX expression level was 0.38±0.02 in NAT10 overexpressing cells and 1.36±0.15 in NAT10 knockdown cells, both statistically significant (P<0.05) compared with 1.00±0.00 in wild-type cells. In 10 μmol/L oxaliplatin treated cells, the apoptosis rate was (6.54±0.68)% in the NAT10 overexpression group and (12.98±2.54)% in the NAT10 knockdown group, both of which were statistically significant (P<0.05) compared with (9.67±0.37)% in wild-type cells. Conclusion: NAT10 overexpression enhances the binding of NAT10 to PARP1 and promotes the acetylation of PARP1, which in turn prolongs the half-life of PARP1, thus enhancing PARP1 recruitment of DNA damage repair related proteins to the damage sites, promoting DNA damage repair and ultimately the survival of breast cancer cells.

Improving Acetabular Component Positioning in Supine Direct Anterior Total Hip Arthroplasty with a Transparency Template: A Novel, Simple, and Cost-effective Technique / 대한고관절학회지

Purpose@#A novel and simple method to ensure accurate acetabular component anteversion and inclination intraoperatively with the use of a transparency template is described. @*Materials and Methods@#Patients who underwent total hip arthroplasty (THA) via direct anterior approach (DAA) from June 2019 to January 2020 were included. A transparency template that can be placed over the image intensifier monitor to allow surgeons an accurate reading of the acetabular component position intraoperatively was designed, developed and utilized to determine effectiveness. The first template consists of two perpendicular lines indicating the “trans-ischial line” and the “pubic symphysis/coccyx”. The second template consist of a line indicating 45。inclination and parallel lines of corresponding distances apart required to achieve 20。anteversion based on Lewinnek’s formula: version=sin-1 (D1/D2), where D1: minor axis and D2: major axis of the component. This template was used throughout the acetabular part of the surgery, from reaming to impaction of component. Postoperative acetabular inclination, anteversion, surgical duration, length of stay, as well as complications were recorded. @*Results@#Twenty-six patients were included in this study. Mean postoperative acetabular cup inclination was 43.46±3.09。and mean version was 19.98±2.89。. A total of 21 patients (80.8%) fell within the Callanan safe zone and all 26 patients (100%) were within the Lewinnek safe zone. @*Conclusion@#The transparency template is a simple, reproducible, and effective tool with a minimal learning curve and no requirement for expensive equipment. This template has the potential to assist surgeons, especially those who are less experienced with DAA THA, in obtaining better postoperative radiographic outcomes.

Research Progress of Breath Sound Analysis in Children with Bronchial Asthma / 中国医学科学院学报

Bronchial asthma is a common chronic respiratory disease,and its diagnosis is mainly based on symptoms,signs,and pulmonary function test.Wheezing is a major symptom of asthma attack,which shows no obvious sign in the early stage while appears after the disease has progressed.Therefore,bronchial asthma is difficult to be detected in early stages,which often leads to worsening of the disease conditions.Pulmonary function test can effectively monitor upper and lower airway abnormalities and is currently the main means for monitoring asthma.However,its accuracy is highly dependent on patient's motivation and cooperation,which obviously limits the scope of application,especially for preschoolers and infants.Hence,there is an urgent need for a new technology with the function of long-term breath sound monitoring and automatic breathing detection to overcome the existing clinical deficiencies.Breath sound analysis emerges in the era of medical artificial intelligence,which can digitally process and convert the collected respiratory sounds by using a variety of different methods to form characteristic signal parameters and model the relationship between parameters and diseases.As we know,breath sounds are closely related to airway changes,and thus the detection and analysis of the sounds can provide reliable clinical information for the progress and control evaluation of asthma.This review mainly summaries the research progress of respiratory sound analysis in recent years,hoping to provide reference for further research.

Application and prospect of organoid culture in cancer / 中国药理学通报

At present, the traditional models for cancer research include the 2D cell model, human tumor xenograft model and animal model. With the deepening of research, the traditional tumor model is unable to meet the needs of researchers. Organoid model is derived from the surgical specimens of tumor patients, which can completely preserve the histological and genomic characteristics of tumor. It can be used in the research of tumor pathogenesis, drug screening, personalized treatment of patients, etc. Compared with traditional model, it has the advantages of short modeling time, economic benefits and closer-ness to the characteristics of the original tumor. This paper mainly focuses on the research status of organoid technology in tumor, the application of organoid model in treatment, and the advantages of organoid model compared with traditional model, so as to provide reference for the follow-up research.

Chemical Composition Analysis of Antibacterial and Anti-inflammatory Functions of Volatile Oils from Pelargonium graveolens L'Herit / 中国生物化学与分子生物学报

The components of volatile oils are generally complex, and they often have the functions of divergent dissolving surface, insecticidal and antibacterial. However, there are few reports on bacteriostasis, anti-inflammation and antioxidation roles of volatile oils of Pelargonium graveolens L'Herit. The volatile oil of Pelargonium graveolens L’Herit. was extracted by steam distillation, and GC-MS and peak area normalization analysis showed that it mainly contained 30 compounds, and the identified components accounted for 90.26% of the total peak area. The volatile oil of Pelargonium graveolens L'Herit. has a certain inhibitory effect on Candida albicans and Staphylococcus aureus, especially on Candida albicans. The diameter of the bacteriostatic zone is 15.55±1.53 mm by using the oxford cup method. Dexamethasone and low, middle and high doses of volatile oils of Pelargonium graveolens L'Herit. were given after the RAW264. 7 cell inflammatory model and was induced by lipopolysaccharide (LPS = 10.0 μg/mL). ELISA assays showed that it could effectively reduce the expression of IL-1β and TNF-α in inflammatory cells, and the effect of high doses was similar to that of IL-1β and TNF-α in the dexamethasone group. GC-MS was successfully used to determine and identify the chemical constituents of volatile oils from Pelargonium graveolens L'Herit. in this study. We show that the volatile oil of Pelargonium graveolens L'Herit. had certain bacteriostatic activity and effectively reduces the secretion of IL-1β and TNF-α by inflammatory cells. It provides an experimental basis for the development and utilization of volatile oils from Pelargonium graveolens L'Herit.

Effect of Qizhi Zhenwutang in Improving Renal Interstitial Fibrosis and Its Mechanism on Unilateral Ureteral Obstruction in Rats / 中国实验方剂学杂志

Objective:To explore the effect of Qizhu Zhenwutang on renal interstitial fibrosis in rats ligated with unilateral ureter， transforming growth factor-β1 （TGF-β1）/Smads and oxidative stress. Method:A total of 30 male SD rats were randomly divided into sham operation group， model group， high-dose group， low-dose group and irbesartan group （n=6）. The left ureter ligation was performed in the model group and the treatment group. In the sham operation group， the ureter was not ligated， only the ureter was separated， and the abdominal cavity was closed. Rats in each group were given drugs by gavage on the next day after operation. Sham operation group and model group were given aseptic distilled water 10 mL·kg-1 by gavage， high-dose Qizhizhenwu Tang group was given 22.2 g·kg-1 by gavage， low-dose group was given 11.1 g·kg-1 by gavage， and irbesartan group was given 0.02 g·kg-1 by gavage. Rats in each group were sacrificed on the 14th day after operation， 24-hour urine was collected before sampling， and the total amount of 24 hour urine protein （24 h-Upr） was detected. Blood samples were collected from the abdominal aorta to detect serum creatinine（SCr） and blood urea nitrogen （BUN）. The tissues were stained with htoxylin eosin （HE） and Masson， and the pathological changes were observed under light microscope， immunohistochemical method was used to detect α-SMA， FN and Col-Ⅰ expressions. Western blot method was used to detect the expressions of TGF-β1， Smad3， p-Smad3 and NOX4. Result:Compared with sham group， SCr， BUN and collagen volume fraction （CVF），24 h-Upr in model group were all increased （P<0.05， P<0.01）. The expressions of α-SMA， Col-Ⅰ， FN， TGF-β1， p-Smad3， NOX4 were higher （P<0.05）. Compared with the model group， SCr， BUN and CVF were lower in high-dose group and irbesartan group （P<0.05）. 24 h-Upr was lower in high-dose group （P<0.05）， the expressions of α-SMA， Col-Ⅰ， FN， TGF-β1， Smad3， p-Smad3， NOX4 in traditional Chinese medicine treatment group were less （P<0.05）. Conclusion:Qizhi Zhenwutang can reduce the urinary protein of UUO rats， protect the renal function， and inhibit the occurrence and development of renal interstitial fibrosis， the mechanism may be related to the inhibition of TGF-β1/Smads signaling pathway and oxidative stress response.

Detection of a BRCA1 c.2013_2014ins GT variant an ethnic Han Chinese pedigree affected with breast cancer / 中华医学遗传学杂志

OBJECTIVE@#To detect potential variant in an ethical Han Chinese pedigree affected with breast cancer.@*METHODS@#The proband and her relatives were subjected to next-generation sequencing using a target capture sequencing kit containing 121 cancer-related genes. Candidate variants were selected by analysis of their type, frequency in population, and segregation with the phenotype. Candidate variant was verified by Sanger sequencing and TA cloning.@*RESULTS@#A c.2013_2014ins GT variant was detected in the BRCA1 gene among all breast cancer patients from this pedigree but not among healthy females. The variant was not recorded in the 1000 Genome Project database or the Exome Aggregation Consortium (ExAC) database. The frameshifting insertion was predicted to form an premature stop codon in gene transcript and can give rise to a truncated protein.@*CONCLUSION@#The BRCA1 c.2013_2014ins GT variant probably underlies the pathogenesis of breast cancer in this Chinese pedigree.

Comparison of two methods for the determination of sucrose octasulfate concentration in irinotecan hydrochloride liposomes / 药学学报

HPLC-RID and HPIC-CD methods were established for the determination of sucrose octasulfate content in irinotecan hydrochloride liposomes for injection. HPLC-RID: This method was performed on a Kromasil 100-5-NH2 column (250 mm×4.6 mm, 5 μm) with a mobile phase of 0.8 mol·L-1 ammonium sulfate buffer (pH 3.5)-acetonitrile (83∶17). The flow rate, column temperature and detector temperature were maintained at 1 mL·min-1, 30 ℃ and 30 ℃ respectively. HPIC-CD: This method was performed on an anion exchange column Dionex InPacTM AS11-HC (250 mm×4 mm, 9 μm) with an eluent of 30 mmol·L-1 sodium hydroxide solution. The flow rate was 1.5 mL·min-1, the column temperature was 30 ℃ and the detector temperature was 35 ℃. The HPLC-RID method and HPIC-CD method were validated with respects to specificity, limit of detection, limit of quantitation, linearity, precision, accuracy, stability and robustness and met the validation requirements. There were no significant differences between the HPIC-CD and HPLC-RID methods according to T-test analysis, both of which were applicable for the measurement of sucrose octasulfate concentration in irinotecan hydrochloride liposomes for injection. However, the HPLC-CD was better at the following aspects: higher detection sensitivity, simpler sample pretreatment, lower time and money spent, better environmental protection.

Role and mechanism of endoplasmic reticulum stress response induced by wear particles in osteolysis / 中国骨伤

OBJECTIVE@#To analyze the role of endoplasmic reticulum stress response in the development of osteoblast apoptosis and osteolysis in osteolytic bone tissue, and to explore the causes of artificial joint loosening, so as to provide new ideas and theoretical basis for the prevention and treatment of artificial joint loosening.@*METHODS@#The animal model of osteolysis induced by wear particles was established by mouse skull, and randomly divided into 4 groups, 7 rats in each group:group 1, blank control group;group 2, wear particles tial6v4 nano alloy powder (TiNPs) group;group 3, endoplasmic reticulum stress response positive control (TiNPs+Tg) group; group 4, endoplasmic reticulum stress response inhibitor (TiNPs+4-PBA) group. The pathological changes of osteolysis were observed by toluidine blue staining, HE staining and ALP staining;the expression of endoplasmic reticulum stress response marker protein was detected by Western Blotting;the apoptosis of osteoblasts in osteolytic skull tissue was detected by TUNEL and Caspase-3 immunohistochemistry.@*RESULTS@#Wear particles TiNPs can induce osteolysis in vitro, aggravate the infiltration of inflammatory cells and inhibit the differentiation and maturation of osteoblasts. At the same time, wear particles can also up regulate the markers of endoplasmic reticulum stress response and promote the apoptosis of osteoblasts in osteolytic bone tissue. After adding 4-PBA, an inhibitor of endoplasmic reticulum stress (4-PBA), on the basis of wear particles TiNPs, the symptoms of osteolysis were significantly relieved, bone erosion and inflammatory infiltration were significantly reduced, the differentiation and maturation of osteoblasts were improved, the number of apoptotic osteoblasts decreased sharply, and the expression of endoplasmic reticulum stress marker protein gradually decreased.@*CONCLUSION@#Endoplasmic reticulum stress is involved in the formation of osteolysis and plays an important role in the occurrence and development of osteolysis. At the same time, endoplasmic reticulum stress can be used as a new therapeutic target to provide new ideas and methods for clinical reversal or treatment of osteolysis and aseptic loosening.

Prognostic analysis for diabetic pyogenic liver abscess patients in different levels of haemoglobin treated with percutaneous catheter drainage / 中国介入影像与治疗学

Objective: To compare the prognosis of diabetic pyogenic liver abscess (PLA) patients with different levels of haemoglobin (HbA1c) treated with percutaneous catheter drainage (PCD), and to identify the predictors for overall recovery time (ORT) after PCD. Methods: Thirty-three diabetic PLA patients underwent PCD were retrospectively reviewed and divided into three groups based on HbA1c level, including group A (HbA1c<7%, n=11), group B (7%≤HbA1c<9%, n=9) and group C (HbA1c≥9%, n=13). The clinical success rate of PCD, ORT and recurrence rate of PLA were compared. Predictors of ORT were analyzed via univariate analysis (Log-rank test) and Cox multi-factor regression analysis. Results: The clinical success rate of PCD for treating PLA was 100% (33/33), with the mean ORT of (24.30±11.60) days. The mean catheter removal time and follow-up time was (27.76±12.03) days and (11.02±6.51) months, respectively. There was no significant difference of recurrence rate of PLA among three groups (P=0.140). However, significant difference of ORT (P=0.002) was found among three groups. Univariate analysis and multivariate analysis indicated that septic shock (hazard ratio [HR]=0.320, 95%CI [0.131, 0.777], P=0.012) and HbA1c≥7% (HR=0.249, 95%CI [0.104, 0.594], P=0.002) were predictors for ORT. Conclusion: For diabetic PLA patients, the higher level of HbA1c, the longer the ORT. Septic shock and HbA1c are predictors for ORT.

A new attempt of re-mapping acupoint atlas in the rat / 针刺研究

OBJECTIVE: To try to re-map an acupoint atlas in vector mode in the experimental rat by using a new-generation drawing tool. METHODS: A total of 5 SD rats were used in the present study. In reference to the current acupoint locations and anatomical structure of rats as well as those of the human body, an acupoint atlas having a stereoscopic mode was re-mapped by using Adobe photoshop/illustrator CS6 imaging processing and drawing system. RESULTS: According to the skeletal structure and body surface landmarks, an acupoint atlas consisting of Shuigou (GV26), Baihui (GV20), Tianmen (i.e. Cuanzhu, BL2), Erjian (MA-H6), Dazhui (GV14), Feishu (BL13), Xinshu (BL15), Geshu (BL17), Jizhong (GV6), Pishu (BL20), Shenshu (BL23), Houhui (SI3), Huantiao (GB30), Houhai, Yanglingquan (GB34), Housanli (ST36), Zhaohai (KI6), Sanyinjiao (SP6), Genduan point, Shenmai (BL62), Taichong (LR3), Zhijian (foot), Yongquan (KI1), Guanyuan (CV4), Xiqian, Weijian, Shenque (CV8), Zhongwan (CV12), Qiansanli (LI10), Waiguan (SJ5), Neiguan (PC6), Quchi (CV6), Zhoujie (EX-UE1), Hegu (LI4), Zhijian (hand), Houxi (SI3), Shenmen (HT7), Taiyuan (LU9), Shaohai (HT3), Chize (LU5), Danzhong (CV17), and Chengjiang (CV24) which have been positioned in plane graph mode by Professor HUA Xing-bang and colleagues in 1991. The newly re-mapped acupoint atlas displayed more clearly in the anatomic locations relevant to the traditional one. CONCLUSION: A new acupoint atlas with 3 dimension image mode is accomplished in the rat, being more convenient and applicable for researchers to edit the relevant graph materials in paper writing, and playing a possibly useful guidance for the standardization of acupoint selection in experimental acupuncture researches.