Correlation between intervertebral disc degeneration and hyperuricemia / 中国组织工程研究

BACKGROUND:Hyperuricemia is a common metabolic disease,and the main clinical manifestation of patients with hyperuricemia is the formation of uric acid crystals leading to gout.Previous studies have only reported that uric acid crystals lead to intervertebral disc degeneration,but there are fewer studies on the correlation between hyperuricemia and intervertebral disc degeneration. OBJECTIVE:To retrospectively analyze the characteristics of intervertebral disc degeneration in patients with hyperuricemia and the correlation between serum uric acid level and intervertebral disc degeneration. METHODS:A retrospective analysis was performed in all patients diagnosed with intervertebral disc degeneration admitted at the Department of Orthopedics,the Affiliated Hospital of Southwest Medical University from January 2021 to December 2022.There were 97 hyperuricemia patients in the hyperuricemia group and 194 non-hyperuricemia patients in the control group according to sex and age in a ratio of 1:2.Blood uric acid test results were collected,and Pfirrmann scoring was performed for the degree of disc degeneration in patients based on the whole spinal MRI images.The difference in the degree of disc degeneration between the two groups was compared,and the correlation between the serum uric acid level and the degree of intervertebral disc degeneration was analyzed. RESULTS AND CONCLUSION:The Pfirrmann score in the hyperuricemia group was higher than that in the control group,and the total number of disc degeneration in the hyperuricemia group was also significantly higher than that in the control group(P<0.05).Spearman correlation analysis showed that the degree of disc degeneration in male patients was positively correlated with serum uric acid level at many spinal segments in the hyperuricemia group(C3/4:r=0.317,C4/5:r=0.333,C5/6:r=0.309,L2/3:r=0.443,P<0.05);the degree of disc degeneration in female patients was also positively correlated with serum uric acid level(C3/4:r=0.354,C4/5:r=0.388,C6/7:r=0.312,T7/8:r=0.282,T9/10:r=0.305,T11/12:r=0.277,L4/5:r=0.319,L5-S1:r=0.367,P<0.05).In the control group,there was no significant correlation between the degree of disc degeneration and serum uric acid level in male and female patients(P>0.05).To conclude,in patients with hyperuricemia,the higher serum uric acid level indicates the more serious intervertebral disc degeneration.Therefore,hyperuricemia is one of the risk factors for intervertebral disc degeneration.

Analyzing the morphologic characteristics of pedicle-facet joints in lumbar spondylolysis: correlation with spinopelvic parameters and its clinical relevance / 中华骨科杂志

Objective:To delineate the morphological features of pedicle-facet joints in lumbar spondylolysis patients, correlating these with spinopelvic parameters to explore their mechanisms and clinical implications.Methods:This study enrolled 121 patients with L 5 spondylolysis (IS group), 108 with L 4, 5 degenerative spondylolisthesis (DS group), and 100 with normal L 4, 5 but L 5S 1 lumbar disc herniation (NL group), who underwent radiography and multislice spiral CT from May 2020 to January 2023. Parameters including vertebral slip percentage (SP) and spinopelvic alignments, such as sacral slope and lumbar lordosis, were quantified using standing lateral lumbar radiographs. Morphological parameters of the L 4 and L 5 facet joints were measured on 3D reconstructed lumbar CT images, including the facet joint angle (FJA), pedicle-facet joint angle (PFA), facet joint osteoarthritis (OA), and facet joint tropism (FT). Results:The analysis revealed significant variances in SS and LL among the groups ( F=21.910, P<0.001; F=22.439, P<0.001). The IS group exhibited the highest SS and LL, followed by the DS and NL groups. Morphological assessments showed the largest L 4 FJA in the IS group, with progressive decreases in the DS and NL groups ( F=344.791, P<0.001). Conversely, L 4 PFA was greatest in the DS group ( F=193.725, P<0.001). Notably, L 4 OA was markedly more severe in the DS group compared to IS and NL groups ( H=467.925, P<0.001), with no significant disparity between IS and NL groups ( P>0.05). Correlation analyses within each cohort highlighted a negative association of sacral slope and lumbar lordosis with facet joint angles, yet a positive correlation with pedicle-facet joint angles both with statistical significance ( P<0.05). Furthermore, L 4 facet joint angles were consistently smaller than those at L 5, and L 4 pedicle-facet joint angles were larger than L 5 ( P<0.05). Osteoarthritis at L 5 was more pronounced in the IS group compared to L 4 ( Z=7.043, P<0.001), a trend inversely observed in the DS group ( Z=11.868, P<0.001), while the NL group showed no significant osteoarthritic variance between levels ( Z=0.556, P=0.578). Conclusion:Patients with lumbar spondylolysis demonstrate elevated sacral slope and lumbar lordosis, indicative of increased localized biomechanical stress in the lumbar spine. These alterations in the morphology of the pedicle-facet joints highlight the distinctive structural adaptations and potential strain distributions within this cohort.

Intervention effect of low temperature plasma air purifier in highway toll booths / 环境与职业医学

Background The serious air pollution of highway toll booths poses a high occupational exposure risk to toll collectors. It is urgent to develop purification methods suitable for airborne particles and microbial pathogens in highway toll booths. Objective To verify the purification effect of low temperature plasma air purifiers on airborne particles and microbes in highway toll booths. Methods Based on controlled-intervention design, we selected three toll booths in an expressway toll station as on-site experimental locations for 6 d (no-intervention period: the low-temperature plasma purifier was turned off in the first three days; intervention period: the purifier was turned on from 9:00 to 17:00 in the following three days). The indoor and outdoor PM2.5 and PM10 concentrations were continuously monitored during the study. At 9:00, 12:00, and 17:00 of every day during the experiment, indoor and outdoor air samples were collected to analyze the concentration of airborne culturable colonies with a plankton sampler. Airborne particle samples were collected in the outermost exit continuously from 9:00 to 17:00 every day during the experiment using a medium flow particulate sampler, and the species and relative abundance of fungi and bacteria contained in the samples were analyzed by gene sequencing. Independent-sample t test was used to compare the concentration of indoor PM2.5, PM10, and culturable colonies between the intervention period and the non-intervention period. α diversity analysis, β diversity analysis, and t test were used to compare the diversity and relative abundance of specific species of bacteria and fungi, as well as typical pathogenic bacteria and fungi in the samples between the non-intervention period and the intervention period to reflect the purification effect of low temperature plasma air purifier on airborne PM2.5, PM10, and microorganisms. Results During the intervention period, the mean indoor concentrations of PM2.5, PM10, and culturable colonies were lower than those of the no-intervention period (P<0.01 or P<0.001). The ratios of indoor to outdoor concentration (I/O) of PM2.5 and PM10 during the intervention period were significantly lower than those of the no-intervention period (P<0.001), except the I/O of culturable colonies. Compared with the average concentration at 9:00, the average cleaning rates at 12:00 and 17:00 for PM2.5 were 49.0% and 46.1%, for PM10 were 49.7% and 45.4%, for airborne culturable colonies were 50.8% and 49.9%, respectively. The β diversity analysis showed that there were significant differences in composition at the level of species of bacteria, and at the levels of genus and species of fungi between the intervention and the no-intervention periods. The relative abundances of 10 species of bacteria such as Lactobacillus and 7 species of fungi such as Torula in the intervention period were significantly lower than those in the non-intervention period, but the relative abundances of fungi such as unclassified_f_cladosporiaceae, trichomerium, and cercospora were higher (P<0.05). For typical pathogenic bacteria, the relative abundances of Lactobacillus and Clostridium_sensu_stricto_1 during the intervention period were 73.5% and 86.9% lower than those in the no-intervention period, and the relative abundance of Talaromyces was 53.5% lower (P<0.05). Conclusion Low temperature plasma air purifier has a good purification effect on indoor PM2.5, PM10, and culturable colonies in highway toll booths, and likely a limited effect on some fungi.

Clinical application of PARP inhibitors in breast cancer / 国际肿瘤学杂志

Poly adenosine diphosphate ribose polymerase (PARP) inhibitors lead to synthetic lethality in homologous recombination repair-deficient (HRD) tumors by inhibiting DNA damage repair. Two PARP inhibitors, olaparib and talazoparib, have been approved for the salvage treatment of breast cancer susceptibility gene (BRCA) mutation, human epidermal growth factor receptor 2 (HER2) negative advanced breast cancer, and adjuvant treatment of early breast cancer. PAPR inhibitor single agent shows good antitumor activity and controllable safety. A number of clinical studies on PAPR inhibitors combined with chemotherapy, radiotherapy, antiangiogenic therapy and immunotherapy are being carried out. The indications of PARP inhibitors also extend from BRCA mutation to HRD, from ovarian cancer and breast cancer to other solid tumors, promising to benefit more patients in the future.

Effects of orlistat on the viability of human gallbladder cancer cells / 中华消化外科杂志

Objective:To investigate the effects of orlistat on the viability of human gall-bladder cancer (GBC) cells.Methods:The experimental study was conducted. The human GBC NOZ cells with high expression of FSAN was screened out through in vitro cultivating human GBC-SD, SGC-996 and NOZ cells. The cell proliferation assay, clone formation assay and protein detection experiment were used to analysis of the effects of orlistat on the viability of human GBC cells. Cell grouping: NOZ cells cultured with medium were set as the control group, cultured with medium + 10 μmol/L orlistat were set as the low-dose orlistat group, cultured with medium + 100 μmol/L orlistat were set as the high-dose orlistat group, respectively. Observation indicators: (1) expression of FASN protein in human GBC cells; (2) effects of orlistat on the proliferation of human GBC NOZ cells; (3) effects of orlistat on apoptosis of human GBC NOZ cells. Measurement data with normal distribution were represented as Mean± SD, the ANOVA test was used for comparison between groups and the least significant difference method was used for pairwise comparison. Results:(1) Expression of FASN protein in human GBC cells. Results of western blot showed that the relative expression of FASN protein in human GBC NOZ, GBC-SD and SGC-996 cells was 0.57±0.06, 0.12±0.04 and 0.10±0.02, respectively, showing a significant difference among them ( F=115.67, P<0.05). There were significant differences between the NOZ cells and the GBC-SD or the SGC-996 cells ( P<0.05), and there was no significant difference between the GBC-SD cells and the SGC-996 cells ( P>0.05). (2) Effects of orlistat on the proliferation of human GBC NOZ cells. ① Results of cell proliferation assay showed that the absorbance value of NOZ cells was 2.34±0.12, 1.57±0.08 and 1.07±0.13 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a significant difference among them ( F=205.88, P<0.05). ② Results of clone formation assay showed that the number of NOZ cells clones was 257±23, 153±11 and 83±11 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a significant difference among them ( F=92.64, P<0.05). ③Results of western blot showed that the relative expression of Cyclin-D1 protein of NOZ cells was 2.31±0.10, 1.52±0.05 and 1.23±0.11 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a significant difference among them ( F=120.73, P<0.05). The relative expression of CDK-4 protein of NOZ cells was 1.58±0.04, 1.21±0.02 and 1.19±0.04 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a signifi-cant difference among them ( F=110.45, P<0.05). (3) Effects of orlistat on apoptosis of human GBC NOZ cells. Results of western blot showed that the relative expression of Bcl-2 protein of NOZ cells was 1.07±0.03, 0.36±0.03 and 0.15±0.02 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a significant difference among them ( F=1 242.93, P<0.05). The relative expression of Bax protein of NOZ cells was 0.51±0.03, 0.38±0.05 and 1.38±0.04 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a signifi-cant difference among them ( F=583.51, P<0.05). Conclusion:Orlistat can inhibit the growth of human GBC NOZ cells and promote their apoptosis.

Morphological characteristics of L 4, 5 facet joints in degenerative lumbar spondylolisthesis / 中华骨科杂志

Objective:To observe the morphological characteristics of L 4, 5 facet joints in patients with degenerative lumbar spondylolisthesis (DLS) of different spinopelvic types based on Roussouly classification. Methods:We retrospectively analyzed 142 patients with DLS who visited the department of orthopaedics in the Affiliated Hospital of Southwest Medical University from August 2018 to May 2022. There were 33 males aged 65.0±10.7 years and 109 females aged 61.8±9.6 years. The following morphological parameters of the L 4, 5 facet joint were measured on the CT images: facet joint angle (FJA), pedicle facet angle (PFA), facet joint tropism (FT) and facet joint osteoarthritis (OA) degree; the sacral slope (SS), lumbar lordosis (LL) and percentage of L 4 slip distance (SDP) were measured on preoperative standing neutral lumbar radiographs. According to the Roussouly classification, the patients were divided into four groups (type I, type II, type III, and type IV). The differences of morphological parameters of the facet joints and SDP were compared among the four groups, and the correlation between the FJA and PFA was analyzed. Results:There were 142 patients, including 28 type I, 50 type II, 43 type III, and 21 type IV according to the Roussouly classification. The SDPs of type I, type II, type III, and type IV were 19.1%±3.4%, 18.6%±3.9%, 21.7%±3.9%, 25.0%±2.4%, respectively. Except for types I and II, there were statistically significant differences in pairwise comparison among all other types ( P<0.05). The FJAs in type I and type II (31.4°±6.3°, 35.2°±6.8°) were larger than those in type III (28.4°±5.6°) and type IV (23.4°±4.5°), and the FJA in type III was larger than that in type IV. Conversely, the FJA in type I was smaller than that in type II. These differences were statistically significant ( P<0.05). The PFAs in type I and type II (113.9°±4.9°, 111.3°±5.6°) were smaller than those in type III (116.3°±4.4°) and type IV (121.8°±3.5°), and the PFA in type III was smaller than that in type IV, while, the PFA in type I was larger than that in type II. These differences were statistically significant ( P<0.05). The degree of OA in both type I and type II was lower than that in type III and type IV, with statistically significant differences ( P<0.05). However, there were no statistically significant differences in the degree of OA between type I and type II and between type III and type IV ( P> 0.05). Additionally, there were no statistically significant differences ( F=0.40, P=0.752) in the FT values among type I, type II, type III, and type IV (5.8°±2.3°, 5.6°±2.4°, 6.1°±1.8°, 5.9°±1.9°). Pearson correlation analysis showed that FJA was negatively correlated with PFA ( r=-0.68, P<0.001). Conclusion:In the slip segment of DLS, the facet joint morphology was part of the joint configuration in different spinopelvic types, not just the result of joint remodeling after DLS. Morphological characteristics of the facet joints and DLS interacted with each other.

Genetic variations in four geographical isolates of Gohieria fusca based on cytochrome b and internal transcribed spacer genes / 中国血吸虫病防治杂志

Objective To investigate the genetic diversity and genetic differentiation of different geographical isolates of Gohieria fusca.. Methods G. fusca isolates were sampled from Wuhu (WH), Bengbu (BB) and Bozhou cities (BZ) of Anhui Province and Jiaxing City of Zhejiang Province (JX). Mitochondrial cytochrome b (Cytb) and ribosomal internal transcribed spacer (ITS) genes were amplified in WH, BB, BZ and JX isolates of G. fusca using PCR assay. The gene sequences were edited and aligned using the software Chromas 2 and DNASTAR 1.00, and the haplotype, haplotype diversity (Hd) and nucleotide polymorphism (Pi) of each isolate were calculated using the software DnaSP 5.10.00. The genetic differentiation among isolates (Fst) and gene flow value (Nm) were estimated using the software MEGA 10.2, and a phylogenetic tree was built. Tests of neutrality and analysis of molecular variance (AMOVA) were performed using the software Arlequin 3.1 and a haplotype network was built based on the Median-Joining network using the software Network 10.2. Results PCR assay showed that the sizes of the Cytb and ITS genes were 372 bp and 1 301 to 1 320 bp, respectively. All four isolates of G. fusca presented high genetic diversity based on mitochondrial Cytb and ITS genes (Hd = 0.804, Pi = 0.006 91). AMOVA showed genetic differentiation among geographical isolates of G. fusca (Fst = 0.202 40, P < 0.05), and the genetic variation was mainly caused by intra-population variations (79.76%). Gene flow analysis showed a high level of gene flow among G. fusca isolates (Nm > 1). Tests of neutrality based on Cytb gene measured a Tajima’s D value of −1.796 31 (P < 0.05) and a Fu’s FS value of −3.293 98 (P < 0.05) in WH isolate of G. fusca, indicating population expansion in WH isolate of G. fusca. Haplotype network analysis and phylogenetic analysis revealed no remarkable geographical distribution pattern among different geographical isolates of G. fusca. All four isolates of G. fusca presented high genetic diversity (Hd = 0.985, Pi = 0.011 97). AMOVA showed moderate level of genetic differentiation between four isolates (Fst = 0.104 62, P < 0.05). The tests of neutrality based on ITS genes measured a Tajima’s D value of −6.088 20 and a Fu’s FS value of −1.935 99 (both P > 0.05) in the whole isolate of G. fusca, indicating no obviously population expansion. Conclusions The four geographical isolates of G. fusca have high genetic diversity and remarkable genetic differentiation. Since a high level of gene flow is detected among different geographical isolates of G. fusca, no obvious geographical distribution pattern of G. fusca is found.

New strategies for the treatment of carcinoma of unknown primary / 中华肿瘤杂志

Carcinoma of unknown primary (CUP) is a kind of metastatic tumor whose primary origin cannot be identified after adequate examination and evaluation. The main treatment modality of CUP is empiric chemotherapy, and the median overall survival time is less than 1 year. Compared with immunohistochemistry, novel method based on gene expression profiling have improved the sensitivity and specificity of CUP detection, but its guiding value for treatment is still controversial. The approval of immune checkpoint inhibitors and pan-cancer antitumor agents has improved the prognosis of patients with CUP, and targeted therapy and immunotherapy based on specific molecular characteristics are the main directions of future research. Given the high heterogeneity and unique clinicopathological characteristics of CUP, "basket trial" is more suitable for clinical trial design in CUP.

Overexpressed SIRT6 ameliorates doxorubicin-induced cardiotoxicity and potentiates the therapeutic efficacy through metabolic remodeling

Since the utilization of anthracyclines in cancer therapy, severe cardiotoxicity has become a major obstacle. The major challenge in treating cancer patients with anthracyclines is minimizing cardiotoxicity without compromising antitumor efficacy. Herein, histone deacetylase SIRT6 expression was reduced in plasma of patients treated with anthracyclines-based chemotherapy regimens. Furthermore, overexpression of SIRT6 alleviated doxorubicin-induced cytotoxicity in cardiomyocytes, and potentiated cytotoxicity of doxorubicin in multiple cancer cell lines. Moreover, SIRT6 overexpression ameliorated doxorubicin-induced cardiotoxicity and potentiated antitumor efficacy of doxorubicin in mice, suggesting that SIRT6 overexpression could be an adjunctive therapeutic strategy during doxorubicin treatment. Mechanistically, doxorubicin-impaired mitochondria led to decreased mitochondrial respiration and ATP production. And SIRT6 enhanced mitochondrial biogenesis and mitophagy by deacetylating and inhibiting Sgk1. Thus, SIRT6 overexpression coordinated metabolic remodeling from glycolysis to mitochondrial respiration during doxorubicin treatment, which was more conducive to cardiomyocyte metabolism, thus protecting cardiomyocytes but not cancer cells against doxorubicin-induced energy deficiency. In addition, ellagic acid, a natural compound that activates SIRT6, alleviated doxorubicin-induced cardiotoxicity and enhanced doxorubicin-mediated tumor regression in tumor-bearing mice. These findings provide a preclinical rationale for preventing cardiotoxicity by activating SIRT6 in cancer patients undergoing chemotherapy, but also advancing the understanding of the crucial role of SIRT6 in mitochondrial homeostasis.

Dose-dense paclitaxel plus carboplatin in combination with trastuzumab neoadjuvant versus standard adjuvant therapy in human epidermal growth factor receptor-2 positive and hormone receptor negative breast cancer: a prospective cohort study / 中华肿瘤杂志

Objective: To provide survival evidence of anthracycline-free neoadjuvant chemotherapy for patients with stages Ⅱ-Ⅲ human epidermal growth factor receptor-2 (HER-2) positive and hormone receptor (HR) negative breast cancer. Methods: The prospective cohort study was conducted at the Department of Medical Oncology of Cancer Hospital, Chinese Academy of Medical Sciences. Patients with HER-2 positive and HR negative breast cancer in stages Ⅱ-Ⅲ were enrolled to receive neoadjuvant therapy (NAT) of dose-dense paclitaxel (175 mg/m(2)) plus carboplatin (AUC=4.0) biweekly for 6 cycles in combination with trastuzumab (PCbH), and matched patients who received standard adjuvant therapy of physicians' choice were recruited for survival and safety comparison. Results: From July 2013 to November 2019, 166 patients were included (neoadjuvant 51, adjuvant 115). Compared with those who received adjuvant therapy, patients receiving NAT were younger (<35 years: 19.6% vs 5.2%, P=0.014), had larger tumors (T3: 62.7% vs 7.8%, P<0.001) and more advanced diseases (stage ⅡA: 2.0% vs 41.7%, P<0.001). Patients in the neoadjuvant group all received surgery, and 96 (83.5%) in the adjuvant group received anthracycline-and-taxane-containing regimens. A total of 98 patients (49 pairs) were matched, and the covariates between the two groups were acceptably balanced. Within a median follow-up of 46.5 (range, 14-87) months, the 4-year recurrence-free survival (RFS) rate among patients who received NAT was 73.3% (95% CI: 59.0%-87.6%), versus 80.6% (95% CI: 67.9%-93.3%) among those in the adjuvant group without statistical difference (P=0.418). A similar result was observed for the 4-year overall survival (OS) [neoadjuvant versus adjuvant: 91.5% (95% CI: 81.7%-100.0%) vs 97.8% (95% CI: 93.5%-100.0%), P=0.314]. Compared with standard adjuvant therapy, PCbH was related to less neutropenia and better cardiac safety. Conclusions: These results support the consideration of anthracycline-free neoadjuvant chemotherapy combined with anti-HER-2 therapy for patients with stages Ⅱ-Ⅲ HER-2-positive and HR-negative breast cancer. Optimized regimens with both efficacy and safety are needed and to be further investigated.

Dose-dense paclitaxel plus carboplatin in combination with trastuzumab neoadjuvant versus standard adjuvant therapy in human epidermal growth factor receptor-2 positive and hormone receptor negative breast cancer: a prospective cohort study / 中华肿瘤杂志

Objective: To provide survival evidence of anthracycline-free neoadjuvant chemotherapy for patients with stages Ⅱ-Ⅲ human epidermal growth factor receptor-2 (HER-2) positive and hormone receptor (HR) negative breast cancer. Methods: The prospective cohort study was conducted at the Department of Medical Oncology of Cancer Hospital, Chinese Academy of Medical Sciences. Patients with HER-2 positive and HR negative breast cancer in stages Ⅱ-Ⅲ were enrolled to receive neoadjuvant therapy (NAT) of dose-dense paclitaxel (175 mg/m(2)) plus carboplatin (AUC=4.0) biweekly for 6 cycles in combination with trastuzumab (PCbH), and matched patients who received standard adjuvant therapy of physicians' choice were recruited for survival and safety comparison. Results: From July 2013 to November 2019, 166 patients were included (neoadjuvant 51, adjuvant 115). Compared with those who received adjuvant therapy, patients receiving NAT were younger (<35 years: 19.6% vs 5.2%, P=0.014), had larger tumors (T3: 62.7% vs 7.8%, P<0.001) and more advanced diseases (stage ⅡA: 2.0% vs 41.7%, P<0.001). Patients in the neoadjuvant group all received surgery, and 96 (83.5%) in the adjuvant group received anthracycline-and-taxane-containing regimens. A total of 98 patients (49 pairs) were matched, and the covariates between the two groups were acceptably balanced. Within a median follow-up of 46.5 (range, 14-87) months, the 4-year recurrence-free survival (RFS) rate among patients who received NAT was 73.3% (95% CI: 59.0%-87.6%), versus 80.6% (95% CI: 67.9%-93.3%) among those in the adjuvant group without statistical difference (P=0.418). A similar result was observed for the 4-year overall survival (OS) [neoadjuvant versus adjuvant: 91.5% (95% CI: 81.7%-100.0%) vs 97.8% (95% CI: 93.5%-100.0%), P=0.314]. Compared with standard adjuvant therapy, PCbH was related to less neutropenia and better cardiac safety. Conclusions: These results support the consideration of anthracycline-free neoadjuvant chemotherapy combined with anti-HER-2 therapy for patients with stages Ⅱ-Ⅲ HER-2-positive and HR-negative breast cancer. Optimized regimens with both efficacy and safety are needed and to be further investigated.

Application of target controlled infusion mode based on precision anesthesia concept in cardiac surgery anesthesia / 局解手术学杂志

Objective To explore the effect and safety of target controlled infusion mode based on precision anesthesia concept in cardiac surgery anesthesia.Methods A total of 100 patients underwent cardiac surgery in our hospital were selected as the research subjects,and they were randomly divided into the control group and the observation group,with 50 cases in each group.The surgical types,surgical related indicators,dosage of anesthetic drugs,and complications of the two groups were compared.Results There was no statistically significant difference in the proportions of patients who underwent coronary artery bypass surgery,valve surgery,macrovascular surgery,artial septal defect repair surgery,or other types of surgery between the two groups(P>0.05).There were statistically significant differences in the surgical time,bleeding volume,infusion volume,proportion of cardiopulmonary bypass,times of postoperative analgesic drug use and mechanical ventilation duration between the two groups(P<0.05).The usage of various anesthetic drugs in the observation group was lower than that in the control group,with statistically significant difference(P<0.05).The incidence of complication in the observation group was lower than that in the control group,and the difference was statistically significant(P<0.05).Conclusion The target controlled infusion mode based on precision anesthesia concept can be used for cardiac surgery anesthesia to reduce the dosage of anesthetic drugs and postoperative complications,and improve the anesthesia effect and surgical safety.

Observation on the long-term efficacy of posterior atlantoaxial fixation without fusion for the treat-ment of fresh type Ⅱ odontoid fractures / 中国脊柱脊髓杂志

Objectives:To observe the long-term efficacy of posterior atlantoaxial fixation without fusion for the treatment of fresh type Ⅱ odontoid fractures.Methods:Retrospective analysis of the clinical data of 22 patients with fresh type Ⅱ odontoid fractures who underwent posterior atlantoaxial fixation without fusion at the Affiliated Hospital of Southwest Medical University from June 2006 to December 2017 and were followed up for more than 5 years was conducted.Among the patients,there were 19 males and 3 females,aged 19-58 years old(average of 40.9±10.5 years old)at the time of fracture;17 cases were with no displacement or mild displacement(displacement≤2mm),and 5 cases were with obvious displacement(displacement＞2mm).The visual analog scale(VAS)of neck pain,neck disability index(NDI),and grade of American Spinal Injury Association(ASIA)were compared between before operation,before removal of fixations,and at final follow-up,respec-tively.The neck stiffness severity of the patients was compared between before removal of fixations and at fi-nal follow-up using the method proposed by Landells et al.X-ray,multiplanar reconstruction CT,and func-tional CT were used to evaluate postoperative fracture healing,stability of atlantoaxial joint,degeneration grade of atlanto-odontoid and lateral atlantoaxial joints,and range of motion of the atlantoaxial joint.Correlation analysis was further performed to explore the factors that affect the rotational motion of atlantoaxial joint at fi-nal follow-up.Results:All the patients were removed for implants at 11.0±2.7 months after fixation surgery,and were followed up for 7.9±2.0 years.The median VAS scores before surgery,before removal of fixations,and at final follow-up were 6.5(6.0,7.0)points,1.0(1.0,2.0)points,and 1.0(1.0,1.0)points,respectively.The VAS score before the removal of fixations was significantly lower than that before surgery(P＜0.05),which was not statistically different from that at the final follow-up(P＞0.05).The median NDI before surgery,before the removal of fixations,and at final follow-up were 28.5(26.5,32.0),3.5(3.0,5.0),and 2.0(2.0,3.0),respectively.The NDI before the removal of fixations was significantly reduced compared with before surgery(P＜0.05),and it further decreased at the final follow-up(P＜0.05).Before the removal of fixations and at final follow-up,3 patients who had spinal cord injury achieved 1 level improvement of ASIA grade compared to before surgery.There was no statistically significant difference in ASIA grade between before surgery,before the removal of fixations,and at final follow-up(P＞0.05).At final follow-up,the proportion of patients with severe neck stiff-ness was significantly lower than that before the removal of fixations(36.4％vs.77.3％,P＜0.05).All the pa-tients had fracture healing before the removal of fixations,and no implants breakage or fixation displacement was found.And at the final follow-up,no atlantoaxial instability was observed.At the final follow-up,the degeneration of the atlanto-odontoid joint worsened compared with before removal of fixations(P＜0.05),and there was no statistically significant difference in the degeneration grade of the lateral atlantoaxial joints com-pared with before removal of fixations(P＞0.05).At the final follow-up,the range of motions in flexion-exten-sion and rotation of the atlantoaxial joint were 2.0°(0.9°,3.0°)and 5.4°(3.7°,9.5°),respectively.The correla-tion analysis showed that there was negative correlations between the degree of fracture displacement and the degeneration grade of the atlanto-odontoid joint and the rotational activity of the atlantoaxial joint in long-term follow-up(r=-0.381,P=0.038;r=-0.584,P=0.001).Conclusions:The treatment of fresh type Ⅱodontoid process fractures using posterior atlantoaxial fixation without fusion can achieve satisfactory long-term clinical results,but the range of motion of the atlantoaxial joint cannot be preserved well in the long term,which is related to the severe fracture displacement and progressive degeneration of the atlanto-odontoid joint.

Capabilities and mechanisms of microalgae on nutrients and florfenicol removing from marine aquaculture wastewater.

The regulations governing the discharge of marine aquaculture wastewater are becoming increasingly stringent, and the problems of nitrogen and phosphorus pollution and antibiotic residues in wastewater are serious. Microalgae-based treatment with the dual benefits of wastewater purification and microalgae resource recycling was regarded as the most promising technology in aquaculture wastewater treatment. Isochrysis galbana and Chlorella sp. were chosen to investigate antibiotic and nutrient removal mechanisms from aquaculture wastewater. FLO addition stimulated microalgae growth at low FLO concentrations (0.1 and 1 mg/L) but inhibited growth at 10 mg/L. The removal efficiency of DIN by Chlorella sp. and I. galbana after 7 days of cultivation was 66.4% and 25.8%, respectively. Linear curves were obtained between DIN concentration and cultivation duration, remove constant (k) increased as FLO concentration increased from 0 to 10 mg/L, and the highest value of k was obtained in both the Chlorella sp. and I. galbana groups at 10 mg/L. DIP concentrations in FLO-contained simulated aquaculture wastewater decreased sharply with the cultivation of Chlorella sp. and I. galbana, and DIP removal rate increased as FLO concentration increased. When the initial concentration of FLO was 0.1 mg/L, biodegradation by I. galbana accounted for 86.67% of FLO removal. In contrast, FLO removal with biodegradation and biosorption by Chlorella sp. was 89.74% and 3.72%, respectively. Furthermore, Chlorella sp. grown in MPBR demonstrated superior capability for antibiotic-containing marine aquaculture wastewater purification, with average removal rates of DIN and DIP of 81.2% and 100%, respectively. The high removal rate is related to membranes which can improve microalgae performance by decoupling SRT and HRT. For microalgae-based aquaculture wastewater, ammonia was the most crucial nitrogen source, followed by nitrate. These findings serve as a theoretical foundation for developing microalgae-based aquaculture wastewater treatment technology and eliminating antibiotics in aquaculture.

Genetic susceptibility genes and clinical features of early-onset breast cancer / 国际肿瘤学杂志

Objective:To explore the germline mutation frequency of genetic susceptibility genes and clinical characteristics in early-onset breast cancer (onset age ≤35 years) in China.Methods:Clinical information and peripheral blood of 150 patients aged 35 and younger diagnosed with breast cancer in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from January 1, 2015 to December 31, 2019 were collected. Then DNA was extracted to detect germline mutations in breast cancer susceptibility gene (BRCA) 1, BRCA2, ataxia telangiectasia mutated (ATM) , partner and localizer of BRCA2 (PALB2) , tumor protein 53 (TP53) and cell cycle checkpoint kinase 2 (CHEK2) genes. Mutations were interpreted as pathogenic, likely pathogenic, uncertain significance, likely benign and benign according to the classification criteria and guidelines for genetic variation. Patients were divided into mutation group ( n=18) and non-mutation group ( n=132) according to the presence or absence of pathogenic or probable pathogenic germline mutations, and the χ2 test was used to analyze the relationships between genetic susceptibility gene mutations and clinicopathological characteristics. Results:Eighteen pathogenic or likely pathogenic germline mutations were detected in 150 patients with early-onset breast cancer, for an overall mutation frequency of 12.0%. Among them, there were 8 (5.3%) BRCA2 mutation, 7 (4.7%) BRCA1 mutation, 1 (0.7%) PALB2 mutation, and 2 (1.3%) TP53 mutation. There were no pathogenic or likely pathogenic variants in ATM and CHEK2 genes. The mutation type was dominated by frameshift mutation (9/18, 50.0%) , followed by nonsense mutation (7/18, 38.9%) , missense mutation (1/18, 5.6%) and splice acceptor mutation (1/18, 5.6%) . Among the molecular subtypes of 18 mutation carriers, 9 cases were Luminal B, 6 cases were triple negative breast cancer (TNBC) , 2 cases were Luminal A, and only 1 case was human epidermal growth factor receptor-2 (HER-2) amplification. Among them, 8 BRCA2 mutation carriers were Luminal type, and 6 of 7 BRCA1 mutation carriers were TNBC type. There were no statistical differences in family history of breast cancer ( P=0.343) , estrogen receptor (ER) status ( χ2=0.16, P=0.688) , HER-2 status ( χ2=2.89, P=0.089) , molecular subtype ( χ2=1.99, P=0.575) , and initial diagnosis TNM stage ( χ2=2.49, P=0.115) between the mutation group and the non-mutation group. Conclusion:The patients with early-onset breast cancer have high frequency of germline mutations. It is recommended that patients with early-onset breast cancer undergo genetic counseling and multigene testing.

The development of questionnaire on the willingness of nursing staff to volunteer to serve the disabled elderly and its reliability and validity test / 中国实用护理杂志

Objective:To develop a questionnaire for voluntary care of the disabled elderly based on the theory of planned behavior, and test its reliability and validity.Methods:With the theory of planned behavior as the theoretical framework, a questionnaire entry pool was formed on the basis of extensive reading of domestic and foreign literatures and semi-structured interviews, and the questionnaire items were screened by Delphi method. From July to August 2020, 350 nursing staff from 10 hospitals in Suzhou were selected by convenience sampling method, and the reliability and validity of the questionnaire were tested, and the formal questionnaire was finally formed.Results:Totally 350 questionnaires were distributed in this study, and 330 copies of effective questionnaires were recovered, with an effective recovery rate of 94.29%. This questionnaire included a total of 26 items in 4 dimensions, including attitude, subjective norms, perceived behavioral control and behavioral intention. Cronbach′s α coefficient was 0.977, split-half reliability was 0.906, test-retest reliability was 0.84, the content validity index (CVI) of total questionnaire was 0.97, item-level CVI value was 0.88 to 1.00. Four exploratory factors were extracted, and cumulative contribution rate was 80.03%.Conclusions:The questionnaire has good reliability and validity, which can well explain and predict the willingness of nursing staff to volunteer for the disabled elderly, and can also provide incentive basis for policy makers and managers.

One-stage total knee arthroplasty combined with open reduction and internal fixation for knee osteoarthritis complicated with tibial stress fracture / 中华创伤骨科杂志

Objective:To explore one-stage total knee arthroplasty (TKA) combined with open reduction and internal fixation (ORIF) for knee osteoarthritis complicated with tibial stress fracture.Methods:The 3 patients were retrospectively analyzed who had been treated for knee osteoarthritis complicated with tibial stress fracture at Department of Orthopedics, Ganzhou District People＇s Hospital from March 2018 to March 2020. They were all female, aged from 54 to 76 years (average, 66 years). There were 2 transverse fractures and one short oblique fracture; all of them had knee varus deformity. The Hospital for Special Surgery (HSS) scores averaged 37.6 (from 28 to 50) for the left knee and 28.3 (from 22 to 39) for the right knee. One-stage TKA was performed for the articular surface while ORIF for the right tibial stress fracture for all patients. Recorded were fracture union time, HSS knee score and range of articular motion.Results:The 3 patients were followed up for 25 to 44 months (average, 32 months).The fracture union time ranged from 4 to 7 months (average, 5 months). The last follow-ups revealed no such complications as prosthesis loosening, peri-prosthesis osteolysis or joint instability. Knee varus deformity was corrected in all patients. The HSS knee scores at the last follow-up averaged 89.6 (from 88 to 91) for the left knee and 88.3 (from 85 to 90) for the right knee.Conclusion:In the treatment of knee osteoarthritis complicated with tibial stress fracture, one-stage TKA combined with ORIF can restore the function of knee joint, leading to fine curative effects.

The theoretical analysis of clinical teachers' characteristics of teaching competency in applied undergraduate medical colleges and universities / 中华医学教育探索杂志

Starting from the importance of clinical teachers' teaching competency research, this study analyzes the educational goals of applied undergraduate medical colleges and universities for clinical teachers' teaching competence requirements; comparatively analyzes the competence characteristics of college teachers and Chinese clinicians; defines the teaching competency of clinical teachers. And 15 items of clinical teacher teaching competency characteristics of applied undergraduate medical colleges are obtained, and the current status of clinical teacher competence of the college is evaluated and analyzed by this model. The results show that the average scores of clinical teachers in the affiliated hospitals have met the requirements of the competency items, and the competencies are relatively good. Among them, the professional quality and professional competence evaluation items have higher scores, but the teaching research and reform and the scores of teaching design and implementation are relatively low, which shows that the teaching and research ability of clinicians is a short board of clinical teachers.

Application of transcatheter aortic valve replacement in elderly patients with native pure aortic regurgitation / 中国医师杂志

Objective:This study sought to investigate the feasibility, anatomical indications and operating points of transcatheter aortic valve replacement (TAVR) procedure in the treatment of pure aortic regurgitation (AR).Methods:The medical records of 4 elderly patients with pure AR who were treated in the cardiology department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from March 2020 to March 2021 were retrospectively analyzed. All patients were implanted with self-expandable valve stents via peripheral artery approach for TAVR treatment. The feasibility, anatomical indications and key points of TAVR were analyzed.Results:The 4 patients with pure AR who were carefully screened had an average age of 66 years, and all achieved TAVR treatment success without serious perioperative complications and death. Postoperative examination and follow-up data showed that cardiac functions and cardiac remodeling indexes were significantly improved.Conclusions:This exploratory study shows that TAVR is technically feasible and effective treatment option for selected elderly patients with native pure AR, which is worthy of further study.

Effects of NLRP3-mediated pyroptosis on olfaction dysfunction in allergic rhinitis / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the relationship between NLRP3-mediated pyroptosis and olfactory dysfunction (OD) in allergic rhinitis (AR), and to evaluate the therapeutic potential of CY-09, a selective NLRP3 inhibitor for OD. Methods: An AR mouse model was established with ovalbumin, and the olfactory function of AR mice was detected by the buried food pellet test. Mice with OD were intraperitoneally injected with CY-09 or saline. The activation of microglia and astrocytes in olfactory bulb was detected by immunohistochemistry. The expression level of pyroptosis associated protein was detected by Western blot. The level of pyroptosis associated proinflammatory factor mRNA was determined by real-time PCR. SPSS 24.0 software was used for statistical analysis. Results: After the test, ovalbumin successfully established AR mice model, in which 52.5% (21/40) of them showed OD. The number of activated microglia and astroglia in olfactory bulb tissue in OD group were more than those in non-OD group (all P<0.05). Compared with the control group, the expression of NLRP3, caspase-1 and gasdermin D (GSDMD) was significantly increased in the olfactory bulb of the OD group (all P<0.05). CY-09 could significantly reduce the level of NLRP3, caspase-1, GSDMD, IL-1β and IL-18 expression, and inhibite the activation of microglia and astrocytes in the olfactory bulb tissues (all P<0.05). Conclusion: NLRP3-mediated pyroptosis is closely related to the OD associated with AR. CY-09 could improve the olfactory function in AR mice, which may be related to blocking the NLRP3-mediated pyroptosis.