Bioceramic scaffolds with two-step internal/external modification of copper-containing polydopamine enhance antibacterial and alveolar bone regeneration capability / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Magnesium-doped calcium silicate (CS) bioceramic scaffolds have unique advantages in mandibular defect repair; however, they lack antibacterial properties to cope with the complex oral microbiome. Herein, for the first time, the CS scaffold was functionally modified with a novel copper-containing polydopamine (PDA(Cu2+‍)) rapid deposition method, to construct internally modified (*P), externally modified (@PDA), and dually modified (*P@PDA) scaffolds. The morphology, degradation behavior, and mechanical properties of the obtained scaffolds were evaluated in vitro. The results showed that the CS*P@PDA had a unique micro-/nano-structural surface and appreciable mechanical resistance. During the prolonged immersion stage, the release of copper ions from the CS*P@PDA scaffolds was rapid in the early stage and exhibited long-term sustained release. The in vitro evaluation revealed that the release behavior of copper ions ascribed an excellent antibacterial effect to the CS*P@PDA, while the scaffolds retained good cytocompatibility with improved osteogenesis and angiogenesis effects. Finally, the PDA(Cu2+)-modified scaffolds showed effective early bone regeneration in a critical-size rabbit mandibular defect model. Overall, it was indicated that considerable antibacterial property along with the enhancement of alveolar bone regeneration can be imparted to the scaffold by the two-step PDA(Cu2+) modification, and the convenience and wide applicability of this technique make it a promising strategy to avoid bacterial infections on implants.

Astragaloside IV plays a role in reducing radiation-induced liver inflammation in mice by inhibiting thioredoxin-interacting protein/nod-like receptor protein 3 signaling pathway.

OBJECTIVE: To investigate the efficacy of Astragaloside IV (AS-IV) on radiation-induced liver inflammation in mice. METHODS: The mice were divided into normal group, dimethyl sulfoxide solvent group, irradiation group (IR), irradiation + AS-IV (20 mg/kg) group (IR+AS-20) and irradiation + AS-IV (40 mg/kg) group (IR+AS-40). One month after intraperitoneal injection of AS-IV, the mice were irradiated with 8Gry Co60γ, the blood was collected for biochemical analysis, and the liver was collected for hematoxylin-eosin staining, immunofluorescence and electron microscopic observation, oxidative stress, and Western blot analysis. RESULTS: The AS-IV treatment significantly ameliorated the pathological morphology of liver and reduced the alanine aminotransferase and aspertate amino-transferase levels in serum induced by radiation; AS-IV treatment also significantly reduced the expression of inflammatory factors tumor necrosis factor alpha and interleukin 6 and antagonized malonaldehyde content and superoxide dismutase activity in liver caused by radiation; in addition, AS-IV treatment can significantly inhibited the positive expression of thioredoxin-interacting protein (TXNIP) and nod-like receptor protein 3 (NLRP3) inflammasome in liver tissue after radiation; The expression of TXNIP, NLRP3 inflammasome, apoptosis-associated speck-like protein containing a CARD, cysteinyl aspartate-specific proteinase 1 and interleukin 1beta in the AS-IV prevention group decreased significantly compared to the radiation group. CONCLUSIONS: These findings suggested that Co60γ radiation can cause structural and functional damage to the liver, which may be related to the NLRP3 mediated inflammatory pathway; AS-IV may play a protective role by inhibiting the TXNIP/NLRP3 inflammasome signaling pathway in the radiation-induced liver injury model.

Clinical analysis of 50 cases of tracheal bronchus in children / 中华全科医师杂志

The clinical data of 50 children with tracheal bronchus, 35 males and 15 females with a mean age of 1.3 months (9 days to 10 years), diagnosed by bronchoscopy in the First Affiliated Hospital of Xiamen University from July 2017 to September 2021 were collected, including gender, age, symptoms, signs, bronchoscopy manifestations, imaging manifestations, associated diseases, and outcomes. There were 26 cases (52%) of severe pneumonia, 14 cases (28%) of recurrent wheezing, 8 cases (16%) of recurrent cough, and 2 cases (4%) of foreign bodies. The clinical symptoms were cough in 45 cases (90%), phlegm in 37 cases (74%), asthma in 28 cases (56%), and fever in 25 cases (50%). The physical signs were wet rale in 33 cases (66%), dry rale in 24 cases (48%), shortness of breath in 23 cases (46%), and triple concave sign in 21 cases (42%). The site of occurrence of tracheal bronchi was the right wall of the lower segment of the trachea. All 50 patients underwent complete pulmonary imaging examinations, but the presence of tracheal bronchus was reported in only 3 cases (6%). There were 24 cases (48%) with other types of tracheal malformations, including 9 cases (18%) of single malacia, 6 cases (12%) of single tracheal stenosis, 1 case (2%) of external tracheal compression, and 8 cases (16%) of multiple tracheal malformations. There were other underlying diseases in 27 cases (54%), congenital heart disease was the most common (17 cases, 34%), followed by premature infants (9 cases, 18%). In addition, there were 3 cases (6%) of chromosomal diseases, esophageal atresia, tracheoesophageal fistula, and polydactyly. All children were discharged after anti-infection and bronchoscopy alveolar lavage. It is suggested that tracheobronchial malformation can cause infection, as well as other tracheal deformities such as tracheal softening and stenosis.

Demands for contracted family doctor service among un-contracted young and middle-aged residents in Shanghai Baoshan District / 中华全科医师杂志

Objective:To analyze the demands of contracted family doctor service among uncontracted young and middle-aged people in Shanghai Baoshan.Methods:An online questionnaire survey on demands of contracted family doctor service was conducted in June 2021 among 702 uncontracted residents aged 18-60 years from Shanghai Baoshan district selected by stratified random sampling method. The demands of contracted family doctor service, including digital health file, routine laboratory tests and imaging investigation;health promotion;service convenience; home service were surveyed, and the factors related the demands were analyzed with regression analysis.Results:The survey showed that the demands of service convenience (3.8(3.0, 5.0)) and home service (4.0(3.0, 5.0)) were higher, while those of digital health file (3.0(2.0, 5.0)) and health promotion (3.0(2.0, 5.0)) were relatively lower. There were significant differences in the demands of all five contracted services among residents with different gender, age, education level, household register and family income (all P<0.05); while for young residents with different types of medical insurance there was significant difference in demands of all contracted services except digital health file (all P<0.05). Logistic regression analysis indicated that female( OR=1.83, P<0.001), high educational level( OR=4.81, P=0.019), household registered in Shanghai( OR=1.80, P=0.004)had higher demand for service convenience; female gender( OR=1.68, P=0.001), high educational level( OR=4.56, P=0.023)had higher demand for home service demands. Conclusion:The demands for contracted family doctor services are different among the uncontracted young and middle-aged people in Baoshan district, while the service convenience is generally most demanded. The study indicates that the contracted family doctor service should be provided accordingly.

Left atrial automated functional myocardial imaging to identify patients with paroxysmal atrial fibrillation at high risk of stroke / 中华超声影像学杂志

Objective:To investigate the risk factors of non-valvular paroxysmal atrial fibrillation (NVPAF) with cerebral ischemic stroke(CIS) and analyze NVPAF by using left atrial automatic imaging (AFILA). Logistic regression model was established for left atrial(LA) function parameters.Methods:A total of 205 patients with NVPAF were included in the study and divided into the NVPAF group without ischemic stroke (154 patients) and the CIS group (51 patients). The clinical baseline data, blood biochemical results and AFILA ultrasound data of all patients were collected. Univariate analysis was performed to compare the above data between the two groups of patients. The independent risk factors were obtained by multivariate logistic regression analysis. Logistic regression model was compared with CHA2DS2-VASc scoring system in terms of area under ROC curve, sensitivity and specificity.Results:There were significant differences in age, CHA2DS2-VASc score, taking anticoagulant drugs, history of hypertension, diabetes and coronary heart disease, LAEF, S_R, S_CT, WBC, NEUT, HCY, UREA, NDD, NT-proBNP, Fibrinogen(Fib), Cardiac troponin I(cTnI) and NLR between the two groups (all P<0.05). The results of multifactor analysis showed that: age, hypertension, S_ CT, UREA, NLR, Fib and cTnI were independent risk factors associated with CIS in patients with paroxysmal atrial fibrillation[ OR value: 1.608 ( P=0.003), 3.821 ( P=0.019), 1.259 ( P=0.001), 1.326( P=0.001), 1.352 ( P=0.011), 1.502 ( P=0.042), 7.651( P=0.001)]. After adjusting for the age, sex and history of hypertension included in CHA2DS2-VASc score, S_CT significantly led to NVPAF complicated with stroke[ OR value 1.259 (1.095-1.447), P=0.001]. The diagnostic efficacy of Logistic regression model is better than that of CHA2DS2-VASc scoring (AUC of 0.931 vs 0.717, 95% CI: 0.896-0.967 vs 0.634-0.799, sensitivity of 0.883 vs 0.755, specificity of 0.849 vs 0.713, all P<0.001). Conclusions:Age, hypertension, S_CT, UREA, NLR, fibrinogen, cTnI are independently associated risk factors for patients with combined CIS; The diagnostic efficacy of Logistic regression model is better than that of CHA2DS2-VASc scoring model.And the sensitivity and specificity are high.

Effects of genistein supplementation on the characteristics of human sperm during liquid storage

Cryopreservation, the most popular way to preserve human sperm, led to a significant decline in sperm motility. Here, we tried to introduce a new method to store sperm without freezing. Different concentrations of genistein were added to liquid preserved sperm. We investigated the effects of supplementation on sperm total antioxidative capacity (T-AOC), glutathione(GSH), methane dicarboxylic aldehyde (MDA), acrosomal enzyme activity, and fertilization ability of sperm. The effects of liquid storage and cryopreservation on sperm parameters were also compared. IVF medium supplemented with genistein (20µmol L-1 ) maintained sperm motility for up to 11 days. The addition of genistein led to a decrease in reactive oxygen species (ROS) generation that demonstrated an effective improvement in sperm motility and decreased the MDA production and maintained the GSH content and enhanced the oxidative stress resistance ability of the sperm during liquid storage. The storage sperm were used for intracytoplasmic sperm injection(ICSI) into human oocytes and activated oocytes successfully. Sperm stored in liquid medium containing genistein was superior to sperm stored in liquid nitrogen in terms of antioxidant stress and fertilization ability. We confirmed that genistein could be used as an antioxidant for the liquid storage of sperm. Sperm stored in an IVF medium with genistein could avoid cryodamage, which may become an alternative option in assisted reproduction technology. (Afr J Reprod Health 2022; 26[7]: 72-82)

Effects of nedaplatin combined with docetaxel on serum tumor markers and T lymphocyte subsets in patients with ovarian epithelial carcinoma / 中国基层医药

Objective:To investigate the effects of nedaplatin combined with docetaxel on serum tumor markers and T lymphocyte subsets in patients with epithelial ovarian cancer.Methods:Ninety-two patients with epithelial ovarian cancer who received treatment from March 2016 to December 2017 were included in this study. They were randomly assigned to undergo nedaplatin combined with docetaxel (observation group, n = 46) or cisplatin combined with paclitaxel (control group, n = 46). Both groups received two 21-day courses of treatment. Serum tumor marker level, T lymphocyte subset level, clinical efficacy, incidence of adverse reactions, and 2-year survival rate were compared between the two groups. Results:After treatment, serum cancer antigen 125 (CA125), cancer antigen 199 (CA199), and carcinoembryonic antigen (CEA) levels were (45.84 ± 22.46) U/mL, (35.13 ± 15.03) U/mL, (16.21 ± 3.20) U/mL, respectively in the control group and they were (28.33 ± 20.11) U/mL, (14.82 ± 10.11) U/mL, (5.16 ± 1.33) U/mL, respectively in the observation group. After treatment, CA125, CA199, and CEA levels in each group were significantly decreased compared with before treatment. After treatment, CA125, CA199, and CEA levels were significantly lower in the observation group than in the control group ( t = 3.94, 7.61, 21.63, all P < 0.05). After treatment, the numbers of CD3 +, CD4 +, CD8 + cells in the control group were (16.22 ± 3.12)%, (15.20 ± 1.46)%, (29.21 ± 5.17)%, respectively, and they were (31.22 ± 4.11)%, (24.99 ± 1.71)%, (24.25 ± 4.45)% respectively in the observation group. After treatment, the numbers of CD3 + and CD4 + cells in the observation group were significantly higher than those in the control group ( t = 19.72, 29.53, both P < 0.05). After treatment, the number of CD8 + cells in the observation group was significantly lower than that in the control group ( t = 4.93, P < 0.05). Total response rate was significantly higher in the observation group than in the control group [78.26% (36/46) vs. 58.70% (27/46), χ2 = 4.08, P < 0.05]. The incidence of adverse reactions was significantly lower in the observation group than in the control group [23.91% (11/46) vs. 45.65% (21/46), χ2 = 4.79, P < 0.05]. The 2-year survival rate was significantly higher in the observation group than in the control group [43.48% (20/46) vs. 23.91% (11/46), χ2 = 3.94, P < 0.05]. Conclusion:Nedaplatin combined with docetaxel is highly effective on epithelial ovarian cancer. The combined therapy can greatly reduce serum CA125, CA199, and CEA levels but has no great effects on T lymphocyte subsets. It can increase the survival rate but has no serious adverse reactions.

Application of the combined use of curriculum ideological and political education and CDIO mode in the cultivation of stomatological top-notch innovative personnel / 中华医学教育探索杂志

Objective:To explore the teaching effect of the combined use of curriculum ideological and political education and CDIO (connective, design, implement, operate) mode in the cultivation of stomatological top-notch innovative personnel.Methods:The research subjects were undergraduate students from School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, who participated in stomatological top-notch innovative personnel training program in 2018 and 2019. CDIO was applied to control group, the combined use of curriculum ideological and political education and CDIO mode was applied to experimental group. After the training, the students' research and innovation capacity was examined and the teaching efficiency of these two models was reflected by the students' questionnaire. SPSS 20.0 software was used for t test. Results:In terms of research and innovation capacity, students scored significantly better in professional English, concluding report, papers publishing, and field defense in experimental group than in control group [(22.43±0.61) vs. (18.49±0.77), (22.48±0.32) vs. (19.05±0.53), (23.69±0.33) vs. (21.89±0.52), and (22.78±0.48) vs. (20.43±0.56), respectively, P<0.05]. The students in experimental group highly agreed with the teaching efficiency of the combined use of curriculum ideological and political education and CDIO mode. Conclusion:The combined use of curriculum ideological and political education and CDIO mode could enhance subjective initiative, sense of identity, sense of pride, sense of belonging, cultivation of multi-dimensional ability, thus helping to form a novel system of stomatological top-notch innovative personnel training.

Comparison of video laryngoscopy versus conventional laryngoscopy for tracheal intubation in neonatal resuscitation / 中国新生儿科杂志

Objective:To compare the clinical value of video laryngoscopy and conventional laryngoscopy for tracheal intubation in neonatal resuscitation.Methods:From July 2018, 100 cases of premature or asphyxia infants born in our hospital requiring tracheal intubation were enrolled. The infants were randomly assigned into video laryngoscopy group and conventional laryngoscopy group with 50 cases in each group. The time needed for intubation, the first time success rate and complications associated with intubation were compared between the two groups.Results:The time needed for intubation (21.7±2.7)s vs.(23.7±1.8)s and the first time success rate [98.0% (49/50) vs. 86.0% (43/50)] were significantly better in the video laryngoscopy group than the conventional laryngoscopy group ( P<0.05). The incidence of intubation complications showed no significant difference between the two groups ( P>0.05). Conclusions:Using video laryngoscopy, the time needed for tracheal intubation is shorter and the first time success rate is higher, without more complications. Video laryngoscopy can be safely used in tracheal intubation of neonatal resuscitation.

Chemotherapy initiation with single-course methotrexate alone or combined with dactinomycin versus multi-course methotrexate for low-risk gestational trophoblastic neoplasia: a multi-centric randomized clinical trial / 医学前沿

We aimed to evaluate the effectiveness and safety of single-course initial regimens in patients with low-risk gestational trophoblastic neoplasia (GTN). In this trial (NCT01823315), 276 patients were analyzed. Patients were allocated to three initiated regimens: single-course methotrexate (MTX), single-course MTX + dactinomycin (ACTD), and multi-course MTX (control arm). The primary endpoint was the complete remission (CR) rate by initial drug(s). The primary CR rate was 64.4% with multi-course MTX in the control arm. For the single-course MTX arm, the CR rate was 35.8% by one course; it increased to 59.3% after subsequent multi-course MTX, with non-inferiority to the control (difference -5.1%,95% confidence interval (CI) -19.4% to 9.2%, P = 0.014). After further treatment with multi-course ACTD, the CR rate (93.3%) was similar to that of the control (95.2%, P = 0.577). For the single-course MTX + ACTD arm, the CR rate was 46.7% by one course, which increased to 89.1% after subsequent multi-course, with non-inferiority (difference 24.7%, 95% CI 12.8%-36.6%, P < 0.001) to the control. It was similar to the CR rate by MTX and further ACTD in the control arm (89.1% vs. 95.2%, P =0.135). Four patients experienced recurrence, with no death, during the 2-year follow-up. We demonstrated that chemotherapy initiation with single-course MTX may be an alternative regimen for patients with low-risk GTN.

Role of hippocampal REV-ERBα in postoperative cognitive dysfunction in rats / 中华麻醉学杂志

Objective:To evaluate the role of hippocampal REV-ERBα in postoperative cognitive dysfunction in rats.Methods:Thirty-two SPF healthy male Sprague-Dawley rats, aged 12-14 weeks, weighing 360-380 g, were divided into 4 groups ( n=8 each) using a random number table method: control group (group C), surgery group (group S), surgery + dimethyl sulfoxide (DMSO) group (group SD), and surgery + SR9009 group (group SS). Exploratory laparotomy was performed under sevoflurane anesthesia in S, SD and SS groups.Normal saline containing 0.1% DMSO was injected into hippocampal CA1 area at 1 h before laparotomy, with 2 μl on each side in group SD, and REV-ERBα agonist SR9009 (in normal saline containing 0.1% DMSO) was injected into hippocampal CA1 area at 1 h before laparotomy, with 2 μl on each side in group S+ SR9009.Morris water maze test was performed at 1 and 3 days after operation.Rats were sacrificed at 1 h after the end of Morris water maze test on day 3 after surgery, and the hippocampal tissues were obtained for determination of the expression of REV-ERBα, Brain and Muscle ARNT-Like 1 (BMAL1) protein, synaptophysin (SYN), postsynaptic density (PSD)-95 protein and N-methyl-D-aspartate receptor 2B subunit (GRIN2B) (by Western blot) and microscopic examination of the morphology of hippocampal neurons and Nissl bodies (by Nissl staining), and the viable neurons were counted. Results:Compared with group C, the percentage of time of staying at the target quadrant was significantly decreased, and the number of crossing platform was reduced on days 1 and 3 after exploratory laparotomy, the expression of REV-ERBα, BMAL1, PSD95, SYN and GRIN2B was down-regulated, and the number of viable neurons was decreased in group S and group SD ( P<0.05). Compared with group S and group SD, the percentage of time of staying at the target quadrant and the number of crossing platform were significantly increased on days 1 and 3 after exploratory laparotomy, the expression of REV-ERBα and PSD95 was up-regulated, the number of viable neurons was increased ( P<0.05), and no significant change was found in the expression of BMAL1, SYN and GRIN2B in group SS ( P>0.05). There was no significant difference in the indexes mentioned above between group S and group SD ( P>0.05). Conclusions:Activation of REV-ERBα can improve postoperative cognitive dysfunction, and the mechanism may be related to up-regulation of PSD95 expression in hippocampus and reduction of neuronal damage in rats.

Path analysis of the influence of professional values and self-concept of nursing professional on academic burnout of nursing students / 中国实用护理杂志

Objective:To investigate the academic burnout level of nursing interns, and to analyze the influence path of nursing professional self-concept and professional values on the academic burnout of nursing interns.Methods:From September to December 2021, 204 nursing students who practiced for 6 months in the First Affiliated Hospital of Anhui Medical University were surveyed using the College Student Learning Burnout Scale, the Nursing Professional Self-Concept Scale and the Nursing Professional Values Scale. Structural equation modeling using AMOS 23.0.Results:The total score of academic burnout was (52.37 ± 11.60), which was in the middle level. The results of correlation analysis showed that the nurses' professional values were negatively correlated with depression, misbehavior, and low sense of achievement ( r=-0.253, -0.256, -0.406), and the differences were statistically significant ( P<0.01). Nursing professional self-concept was negatively correlated with depression, misbehavior, and low sense of achievement ( r=-0.466, -0.414, -0.525), and the differences were statistically significant ( P<0.01). Intern nursing students' nursing occupational self-concept had a partial mediating effect on their professional values and academic burnout, and the mediating effect accounted for 48.57% of the total effect. Conclusions:Professional values of nursing students can directly affect academic burnout, and also indirectly affect them through nursing professional self-concept.

Graphene oxide disrupted mitochondrial homeostasis through inducing intracellular redox deviation and autophagy-lysosomal network dysfunction in SH-SY5Y cells.

Graphene oxide (GO) nanomaterials have significant advantages for drug delivery and electrode materials in neural science, however, their exposure risks to the central nervous system (CNS) and toxicity concerns are also increased. The current studies of GO-induced neurotoxicity remain still ambiguous, let alone the mechanism of how complicated GO chemistry affects its biological behavior with neural cells. In this study, we characterized the commercially available GO in detail and investigated its biological adverse effects using cultured SH-SY5Y cells. We found that ultrasonic processing in medium changed the oxidation status and surface reactivity on the planar surface of GO due to its hydration activity, causing lipid peroxidation and cell membrane damage. Subsequently, ROS-disrupted mitochondrial homeostasis, resulting from the activation of NOX2 signaling, was observed following GO internalization. The autophagy-lysosomal network was initiated as a defensive reaction to obliterate oxidative damaged mitochondria and foreign nanomaterials, which was ineffective due to reduced lysosomal degradation capacity. These sequential cellular responses exacerbated mitochondrial stress, leading to apoptotic cell death. These data highlight the importance of the structure-related activity of GO on its biological properties and provide an in-depth understanding of how GO-derived cellular redox signaling induces mitochondrion-related cascades that modulate cell functionality and survival.

MicroRNA miR-92a-3p regulates breast cancer cell proliferation and metastasis via regulating B-cell translocation gene 2 (BTG2).

MicroRNAs (miRNAs) dysregulation contributes to tumorigenesis, and it is reported that abnormal miR-92a-3p expression participates in multiple cancers' occurrence and progression. This study focuses on miR-92a-3p's functions and regulatory mechanism in breast cancer (BC). The current study proved miR-92a-3p expression was enhanced in BC tissues and cells, and its high expression was related to increased TNM stage and larger tumor size of BC patients. Functionally, transfection of miR-92a-3p mimics facilitated BC cell proliferation and metastasis, yet transfection of miR-92a-3p inhibitors functioned oppositely. In addition, BTG2 was verified as a direct miR-92a-3p target in BC cells. This research indicated that miR-92a-3p facilitates BC cell proliferation and metastasis through repressing BTG2 expression.

Cognition analysis of doctor-patient relationship from the perspective of medical students / 中华医学教育探索杂志

Objective:Based on the current medical environment, to learn about cognition status of doctor-patient relationship among medical students and analyze causes of the tension between doctors and patients.Methods:Using the self-designed questionnaire "Clinical Medical Students' Cognition Survey on Occupational Status and Doctor-Patient Relationship", a cross-sectional survey was conducted on 527 medical students from 5-year and 7-year clinical program in Batch 2014 in a medical university in Heilongjiang Province. The survey mainly analyzed the causes of the tension between doctors and patients from the level of medical staff, patients and their families, hospitals and society. SPSS 22.0 was used for descriptive statistics and chi-square test.Results:The results showed that 93.7% of the medical students believed that the current doctor-patient relationship was not harmonious. There were cognitive differences among medical students in different gender ( P=0.029), first contact clinical grade ( P=0.003) and professional identity ( P<0.001). Conclusion:Medical students have a poor evaluation towards the current doctor-patient relationship. In order to construct harmonious doctor-patient relationship in the future, we can try to take measures such as carrying out relevant courses of doctor-patient communication, improving the medical students' communication skills and enhancing their professional identity.

Efficacy and safety of ibrutinib in treatment of chronic lymphocytic leukemia / 白血病·淋巴瘤

Objective:To investigate the clinical efficacy and safety of ibrutinib in treatment of chronic lymphocytic leukemia (CLL).Methods:The clinical data of 68 patients with CLL in Fujian Medical University Union Hospital from May 1998 to October 2019 were retrospectively analyzed, including 39 cases receiving ibrutinib as the first therapy, 20 cases receiving ibrutinib as the second therapy, and 9 cases receiving ibrutinib as the second and above therapy. The clinical characteristics, IGHV gene mutation, the short-term therapeutic efficacy and survival of patients with stratified chromosomal karyotype were analyzed; the adverse events were also analyzed.Results:The median follow-up time was 53.2 months until May 2020. The objective remission rate (ORR) was 83.8% (57/68), including 8 cases (11.8%) of complete remission, 49 cases (72.1%) of partial remission, 5 cases (7.4%) of the stable disease, 6 cases (8.8%) of progression of the disease. The ORR of patients without IGHVmutation was higher than that of those with IGHV mutation [93.3% (28/30) vs. 76.3% (29/38), χ2=33.656, P<0.05]; the ORR of patients with low risk and low-moderate risk International Prognostic Index (IPI) score was higher than that of those with moderate-high risk and high risk [90.6% (29/32) vs. 77.8% (28/36), χ2=7.248, P = 0.007], and differences in the ORR of patients stratified by other factors were not statistically significant (all P > 0.05). Among 68 patients, 31 cases (45.6%) had adverse reactions and they insistently received the treatment; 26 cases (38.2%) had grade1-2 adverse reactions, 5 cases (7.4%) had grade 3 and above adverse reactions; 2 cases (2.9%) had drug withdrawal because of adverse reactions. The median progression-free survival (PFS) time and overall survival (OS) time of CLL patients treated with ibrutinib had not been reached. The 5-year PFS rate of patients with IGHV mutation was higher than that of patients with IGHV non-mutation (100.0% vs.72.1%, P = 0.020), the 5-year PFS rate of patients with normal chromosome karyotype was higher than that of those with abnormal chromosome karyotype (100.0% vs.74.3%, P = 0.019). Conclusion:Ibrutinib is effective and safe in treatment of CLL patients.

Effect of intensive intervention for improving the referral rate among preschoolers with vision abnormalities / 中国学校卫生

Objective@#To explore effect of intensive intervention for improving the referral rate of children with visual refractive disorders, and to provide a reference for myopia prevention and control of children and adolescents.@*Methods@#A total of 4 464 preschool children were selected from Zhuanqiao county, Minghang district in Shanghai for the eyesight investigation during April to June in 2019. Stratified random cluster sampling method was used to divide 1 724 children into intervention group and (896) control group (828) depending on the type of kindergartens. The intervention group was provied with an intensive intervention, including children s vision health assessment, parental self management guidance for children s eye care, and community based eye care services, while the control group carried out routine intervention measures.@*Results@#In 2019, the incidence of visual and primary refractive screen abnormalities in preschoolers of Zhuanqiao community was 38.62%. The incidence of naked eye vision abnormalities was 4.40%, the incidence of myopia risk group, hyperopia risk group and astigmatism risk group was 37.10%, 2.20%, and 6.10 %, respectively. After the intervention, the referral rate of the intervention group (68.75%) was significantly higher than that of the control group (17.15%)( χ 2=465.09, P <0.01). The differences between two groups were statistically significant in choosing the hospital for treatment ( χ 2=10.01, 51.51, 15.40, 27.79, 19.96, 24.24, P <0.01).@*Conclusion@#The vision and refractive status of preschoolers worths further attention. Intensive intervention can improve the referral rate for children with screened vision abnormalities, which facilitates the prevention and early diagnosis of vision problems among preschoolers.

Global burden of periodontal disease and its relation with socioeconomic development during 1990-2019 / 浙江大学学报·医学版

To analyze the global burden of periodontal disease and its relation with socioeconomic development. Data of global disability-adjusted life year (DALY) due to periodontal disease and human development index (HDI) from 1990 to 2019 were obtained from Global Health Data Exchange (GHDx) and human development reports. The trend of the global burden of periodontal disease from 1990 to 2019 was described. The correlation between age-standardized DALY rates and HDI were examined in 2019, and between-country periodontal disease burden inequality from 1990 to 2019 was measured using health-related Gini coefficients and concentration indexes. From 1990 to 2019, the global DALY rate due to periodontal disease increased from 78.63 to 85.48, and the epidemiological burden did not increase significantly. Statistical differences were found across different HDI categories for age-standardized DALY rates of periodontal disease ( 44.315, <0.01) in 2019. Linear regression analysis also revealed a negative correlation between age-standardized DALY rate of periodontal disease and HDI ( = -0.417, <0.01) . Gini coefficients decreased from 0.361 to 0.281 and concentration indexes fell from 0.0339 to -0.0538 between 1990 and 2019. The global burden of periodontal disease did not increase between 1990 and 2019, though the socioeconomic-associated inequality still existed. The burden of periodontal disease was more concentrated in less developed countries, and the socioeconomic-associated inequality has increased since 2000.

TRAF6/ERK/p38 pathway is involved in interleukin-17-mediated autophagy to promote osteoclast precursor cell differentiation / 浙江大学学报·医学版

To investigate the effects of interleukin (IL)-17-mediated autophagy on the TNF receptor associated factor (TRAF6)/extracellular signal-regulated kinase (ERK)/p38 pathway and osteoclast differentiation. Mouse bone marrow-derived macrophages (BMM) were cultured with a medium containing 30 ng/mL macrophage colony stimulating factor and 50 ng/mL receptor activator of nuclear factor-kappa B ligard (RANKL), and IL-17 (0.01, 0.1, 1.0, 10 ng/mL) was added for intervention (IL-17 group). Tartrate-resistant acid phosphatase (TRAP) staining was used to observe TRAP positive multinucleated cells; phalloidin fluorescent staining was used to detect actin ring circumference; toluidine blue staining was used to analyze bone resorption lacuna formation. To further examine the mechanism of the effect of IL-17-mediated autophagy on the differentiation of osteoclasts, the control group used RANKL medium to culture mouse macrophage RAW264.7 cells, while the IL-17 group was treated with IL-17 (0.01, 0.1, 1.0, /mL). Western blot was used to detect the expression of autophagy-related proteins Beclin-1, microtubule-associated protein 1 light chain 3 (LC3) and osteoclast-related proteins c-fos and nuclear factor of activated T cell 1 (NFATc1) after treatment with different concentrations of IL-17. The expression of LC3, NFATc1, TRAF6/ERK/p38 signaling pathway related proteins were detected in IL-17 and autophagy inhibitor 3-MA group. The number of TRAP positive multinucleated cells, the circumference of the actin ring and the area of bone resorption lacuna in IL-17 group treated with IL-17 (0.01, 0.1, were significantly higher than those in the control group. In IL-17 treated RAW264.7 cells, the expression of c-fos, NFATc1, Beclin-1, LC3, TRAF6, p-ERK, and p-p38 was all significantly up-regulated (all 0.05). After treatment with the autophagy inhibitor 3-MA, the expression levels of LC3, NFATc1, TRAF6, p-ERK, and p-p38 all decreased significantly (all 0.05). IL-17 can promote the expression of autophagy proteins and enhance the differentiation ability of osteoclast precursor cells, and the TRAF6/ERK/p38 signaling pathway may be involved in this process.

Effects of esketamine on myocardial injury and relationship with Nrf2/HO-1 signaling pathway in septic rats / 中华麻醉学杂志

Objective:To evaluate the effects of esketamine on myocardial injury and the relationship with nuclear factor-erythroid 2-related factor 2 (Nrf2) heme oxygenase-1 (HO-1) signaling pathway in septic rats.Methods:Thirty-two SPF healthy adult male Sprague-Dawley rats, weighing 200-230 g, were randomized into 4 groups ( n=8 each) using a random number table method: control group (group C), control plus esketamine group (group CE), sepsis group (group S) and sepsis plus esketamine group (group SE). Lipopolysaccharide (LPS) 10 mg/kg was intraperitoneally injected to establish the sepsis model.At 30 min after LPS or normal saline intraperitoneal injection, esketamine 10 mg/kg was intraperitoneally injected, and administration was repeated 12 h later in group SE and group CE.At 24 h after LPS injection, left ventricular ejection fraction (LVEF) was measured (using echocardiography), and serum cardiac troponin I (cTnI), brain natriuretic peptide (BNP), lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), tumor necrosis factor alpha (TNF-α) and high mobility group box-1 (HMGB1) concentrations were determined (by enzyme linked immunosorbent assay). Myocardial tissues were obtained for examination of pathological changes (by hematoxylin-eosin staining) and for determination of expression of Nrf2, HO-1 and transcription factor Bach 1 (BTB-CNC allogeneic 1). Results:Compared with group C, LVEF was significantly decreased, concentrations of cTnI, BNP, LDH, CK-MB, TNF-α and HMGB1 in serum were increased, expression of Nrf2 and HO-1 was down-regulated, and expression of Bach 1 was up-regulated ( P<0.05), and the significant pathological changes of myocardial tissues were found in S and SE groups.No significant change was found in the parameters mentioned above in group CE ( P>0.05). Compared with group S, LVEF was significantly increased, concentrations of cTnI, BNP, LDH, CK-MB, TNF-α and HMGB1 in serum were decreased, expression of Nrf2 and HO-1 was up-regulated, and expression of Bach 1 was down-regulated ( P<0.05), and the pathological changes of myocardium were significantly attenuated in group SE. Conclusion:Esketamine can reduce myocardial injury, and the mechanism may be related to activating Nrf2/HO-1 signaling pathway in septic rats.