Objective To explore the potential mechanism of proguanil on the proliferation and apoptosis of bladder cancer cells.Methods 253J cells were randomly divided into control group(normal treatment),proguanil group(42.06 μmol·L-1 proguanil),pcDNA group(transfected with pcDNA+42.06 μmol·L-1 proguanil),FADS2 group[transfected fatty acid desaturase gene 2(FADS2)+42.06 μmol·L-1 proguanil],si-NC(transfection si-NC),si-FADS2(transfection si-FADS2),Ferrostatin-1 group(transfected with si-FADS2+10 μmol·L-1 ferrostatin-1).Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)assay was used to detect mRNA expression of related genes;Western blot assay was used to detect the expression of each protein;apoptosis was detected by TdT mediated dUDP nick end labeling(Tunel)assay;5-ethynyl-2'-deoxyuridine(EdU)assay to detect cell proliferation;the Transwell assay measures the ability of cells to migrate;Fe2+levels were determined by kit method;DCFH-DA probe was used to detect ROS levels.Results The mRNA levels of FADS2 in control group,proguanil group,pcDNA group and FADS2 group were 1.00±0.11,0.47±0.09,0.49±0.06 and 2.09±0.21,respectively;cell proliferation rate were(100.00±3.50)％,(54.31±4.90)％,(56.46±5.17)％and(78.76±6.50)％,respectively;the apoptosis rate were(3.92±0.53)％,(28.79±3.30)％,(27.20±2.90)％and(7.34±0.68)％,respectively;the migration number were 132.70±9.81,70.10±5.05,68.70±537 and 101.80±11.25,respectively;Fe2+level were(100.00±8.14)％,(201.33±17.84)％,(192.38±21.34)％and(116.70±10.90)％,respectively;GPX4 protein relative expression level were 0.77±0.05,0.31±0.05,0.34±0.05 and 0.68±0.06,respectively.The above indexes in proguanil group were compared with those in control group,the above indexes in FADS2 group were compared with those in pcDNA group,all the differences were statistically significant(all P＜0.05).The ROS levels of si-NC,si-FADS2 and Ferrostatin-1 groups were 9.72±1.18,40.94±5.63 and 13.77±1.40,respectively.Compared the si-FADS2 group with the si-NC group,Ferrostatin-1 group compared with si-FADS2 group,ROS level were significantly different(all P＜0.05).Conclusion Proguanil can induce the apoptosis of bladder cancer cells by inhibiting FADS2 expression mediated by oxidation-reduction driven ferroptosis pathway.

OBJECTIVE: To evaluate the early clinical efficacy of robot-assisted percutaneous short-segment bone cement-augmented pedicle screw fixation in the treatment of stageⅡ-Ⅲ Kümmell disease. METHODS: The clinical data of 20 patients with stageⅡ-Ⅲ Kümmell's disease who underwent robot-assisted percutaneous bone cement-augmented pedicle screw fixation between June 2017 and January 2021 were retrospectively analyzed. There were 4 males and 16 females, aged from 60 to 81 years old with an average age of (69.1±8.3) years. There were 9 cases of stageⅡand 11 cases of stage Ⅲ, all of which were single vertebral lesions, including 3 cases of T₁₁, 5 cases of T₁₂, 8 cases of L₁, 3 cases of L₂, and 1 case of L₃. These patients did not exhibit symptoms of spinal cord injury. The operation time, intraoperative blood loss, and complications were recorded. The position of pedicle screws and the filling and leakage of bone cement in gaps were observed using postoperative CT 2D reconstruction. The data of the visual analogue scale (VAS), Oswestry disability index (ODI), kyphosis Cobb angle, wedge angle of the diseased vertebra, and anterior and posterior vertebral height on lateral radiographs were statistically analyzed preoperatively, 1 week postoperatively, and at the final follow-up. RESULTS: Twenty patients were followed up for 10 to 26 months, with an average follow-up of (16.0±5.1) months. All operations were successfully completed. The surgical duration ranged from 98 to 160 minutes, with an average of (122±24) minutes. The intraoperative blood loss ranged from 25 to 95 ml, with an average of (45±20) ml. There were no intraoperative vascular nerve injuries. A total of 120 screws were inserted in this group, including 111 screws at grade A and 9 screws at grade B according to the Gertzbein and Robbins scales. Postoperative CT indicated that the bone cement was well-filled in the diseased vertebra, and cement leakage occurred in 4 cases. Preoperative VAS and ODI were (6.05±0.18) points and (71.10±5.37)%, respectively, (2.05±0.14) points and (18.57±2.77)% at 1 week after operation, and (1.35±0.11) points and (15.71±2.12) % at final follow-up. There were significant differences between postoperative 1 week and preoperative, and between final follow-up and postoperative 1 week(P<0.01). Anterior and posterior vertebral height, kyphosis Cobb angle, and wedge angle of the diseased vertebra were(45.07±1.06)%, (82.02±2.11)%, (19.49±0.77) °, and (17.56±0.94) ° preoperatively, respectively, (77.00±0.99)%, (83.04±2.02)%, (7.34±0.56) °, and (6.15±0.52) ° at 1 week postoperatively, and (75.13±0.86)%, (82.39±0.45)%, (8.38±0.63) °, and (7.09±0.59) ° at the final follow-up. CONCLUSION Robot-assisted percutaneous short-segment bone cement-augmented pedicle screw fixation demonstrates satisfactory short-term efficacy in treating stageⅡ-Ⅲ Kümmell's disease as an effective minimally invasive alternative. However, longer operation times and strict patient selection criteria are necessary, and long-term follow-up is required to determine its lasting effectiveness.
Male ; Female ; Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Pedicle Screws ; Bone Cements ; Robotics ; Blood Loss, Surgical ; Retrospective Studies ; Spinal Fractures/surgery* ; Lumbar Vertebrae/injuries* ; Treatment Outcome ; Kyphosis ; Thoracic Vertebrae/injuries* ; Fracture Fixation, Internal

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

OBJECTIVE: To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study. METHODS: A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 community older adults. After the baseline survey, the last follow-up was March 31, 2021 with an average 8.13 years of follow-up. Cox proportional hazard model was used to estimate the hazard ratios (HR) with 95% CI for cardiovascular disease (CVD) death and all-cause death in associations with baseline lipid indicators. RESULTS: A total of 4499 participants were recruited, and the mean levels of uric acid, body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol (TC), triglyceride, and low-density lipoprotein cholesterol (LDL-C) showed an upward trend with the increasing remnant cholesterol (RC) quarters (P_trend < 0.05), while the downward trend was found in high-density lipoprotein cholesterol (HDL-C). During the total 36,596 person-years follow-up, the CVD mortality and all-cause mortality during an average 8.13 years of follow-up was 3.87% (95% CI: 3.30%-4.43%) and 14.83% (95% CI: 13.79%-15.86%) with 174 CVD death participants and 667 all-cause death participants. After adjusting for confounders, the higher level of TC (HR = 0.854, 95% CI: 0.730-0.997), LDL-C (HR = 0.817, 95% CI: 0.680-0.982) and HDL-C (HR = 0.443, 95% CI: 0.271-0.724) were associated with lower risk of CVD death, and the higher level of HDL-C (HR = 0.637, 95% CI: 0.501-0.810) were associated with lower risk of all-cause death. The higher level of RC (HR = 1.276, 95% CI: 1.010-1.613) increase the risk of CVD death. Compared with the normal lipid group, TC ≥ 6.20 mmol/L group and LDL-C ≥ 4.10 mmol/L group were no longer associated with lower risk of CVD death, while RC ≥ 0.80 mmol/L group was still associated with higher risk of CVD death. In normal lipid group, the higher levels of TC, LDL-C and HDL-C were related with lower CVD death. CONCLUSIONS In community older adults, higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range. Higher RC was associated with higher CVD mortality, which may be a better lipid indicator for estimating the CVD death risk in older adults.

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

With the aging process of population in the society, the prevalence of cardiovascular diseases (CVD) in China is increasing continuously and the number of dental patients with CVD is increasing gradually too. Due to the lack of guidelines for dental patients with CVD in our country, how to implement standardized preoperative evaluation and perioperative risk prevention remains a problem to be solved for dentists at present. The present expert consensus was reached by combining the clinical experiences of the expert group of the Fifth General Dentistry Special Committee, Chinese Stomatological Association and respiratory and cardiology experts in diagnosis and treatment for CVD patients, and by systematically summarizing the relevant international guidelines and literature regarding the relationship between CVD and oral diseases and the diagnosis and treatment of dental patients with heart failure, hypertension and antithrombotic therapy. The consensus aims to provide, for the dental clinicians, the criteria on diagnosis and treatment of CVD in dental patients in China so as to reduce the risk and complications, and finally to improve the treatment levels of dental patients with CVD in China.
Cardiovascular Diseases/prevention & control* ; China/epidemiology* ; Consensus ; Dental Care ; Humans ; Oral Medicine

BACKGROUND: The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults. METHODS: Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 μg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 μg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose. RESULTS: In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-μg vaccine (n = 24), 10-μg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-μg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-μg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-μg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-μg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses. CONCLUSIONS: Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-μg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial. TRIAL REGISTRATION http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).
Adult ; COVID-19 ; COVID-19 Vaccines ; Double-Blind Method ; Humans ; SARS-CoV-2 ; Vaccines, Inactivated/adverse effects*

Objective To summarize the practice experience of establishing a stable abdominal heart transplantation model combined with tail vein injection in mice. Methods In the preliminary experiment, 50 pairs of donor and recipient Kunming mice received isotransplantation, 40 pairs of donor and recipient C57BL/6J mice underwent isotransplantation. In the formal experiment, 10 pairs of donor and recipient C57BL/6J mice received isotransplantation, 30 pairs of Balb/c mice as the donor and C57BL/6J mice as the recipient received allotransplantation. The time of each step of the heart transplantation (including harvesting and dressing of the donor heart, vascular anastomosis of the recipient, etc.) was recorded. The duration of transplanted heart beat and the survival time of the recipient was observed daily after operation. The time required for tail vein injection in the transplanted mice was recorded. Pathological examination of the transplanted heart was performed at 30 d after isotransplantation (n=5) and 7 d after allotransplantation (n=5). Results In the formal experiment, the success rate of heart transplantation was 90%. The harvesting and dressing time of donor heart was (13.9±0.6) min. The cold ischemia time of the recipient was (14.2±1.2) min. The vascular anastomosis time was (34.2±3.1) min. The total operation time was (86.6±5.4) min. Postoperatively, the transplanted heart of the mice undergoing isotransplantation survived longer than 100 d. Pathological examination at postoperative 30 d demonstrated only a slight amount of inflammatory cell infiltration. The survival time of the mice receiving allotransplantation was (7.2±0.5) d due to rejection reaction. At postoperative 7 d, pathological examination showed a large quantity of inflammatory cells infiltrating into the myocardium, manifested with acute cellular rejection. The success rate reached 90% after over 200 times of tail vein injection. Conclusions In this study, a stable mouse abdominal heart transplantation model is successfully established. The mouse models in the preliminary experiment can be utilized for tail vein injection.

Objective To explore the distribution of genetic structure of Y-SNP and Y-STR genetic markers in different ethnic groups and its application in forensic science. Methods SNaPshot minisequencing was used to detect the polymorphisms of 12 Y-SNP loci in 439 males from 6 ethnic groups, including Guangxi Han, Guangxi Jing, Guangxi Miao, Guangxi Yao, Guangxi Zhuang and Guangxi Dong. DNATyperTM Y26 kit was used to multiplex-amplify 26 Y-STR loci. The PCR products were analyzed by 3130xl genetic analyzer. The network analysis of Y-STR haplotype under the same Y-SNP haplogroup was analyzed by Network 5.0 software. Results Six haplogroups defined by 12 Y-SNP loci were detected in 6 ethnic groups, and 362 haplotypes were detected in 26 Y-STR loci. The haplotype diversity was 0.996 6. In the C haplogroup, the samples from Guangxi Yao, Guangxi Zhuang and Guangxi Dong were clustered on different branches; in the O1 haplogroup, those from Guangxi Zhuang, Guangxi Miao and Guangxi Jing were relatively independent and clustered separately; in the O2 haplogroup, some samples from Guangxi Miao and Guangxi Yao were gathered in a cluster. Conclusion Based on the Y-STR network analysis of samples with identical haplogroup of Y-SNP, some ethnic groups can be preliminarily distinguished, which could be used to infer male suspects' ethnic group through detecting their genetic markers left in the crime scene.
China ; Chromosomes, Human, Y ; Ethnicity ; Genetics, Population ; Haplotypes ; Humans ; Male ; Microsatellite Repeats

BACKGROUND: Unicompartment knee arthroplasty (UKA) is gradually applied in the treatment of knee osteoarthritis, and the management of perioperative blood loss is a hot spot in clinical research. It is very important to control perioperative blood loss and changes in hemoglobin level for postoperative rapid recovery. OBJECTIVE: To investigate the changes in the blood-related indexes during the management of perioperative blood loss in UKA, so as to provide technical reference and data reference for clinical application. METHODS: Clinical data 70 patients undergoing UKA at the Department of Bone and Joint of Guangdong Provincial Hospital of Chinese Medicine from January to December 2015 were analyzed retrospectively, and received the management of perioperative blood loss. The operation time, intraoperative blood loss, postoperative drainage volume, total blood loss and rate of blood transfusion were recorded; the preoperative hemoglobin, albumin, coagulation indexes, D-dimer, erythrocyte sedimentation rate and C-reactive protein were investigated. The effect of operation on the postoperative blood loss and drainage volume was analyzed. RESULTS AND CONCLUSION: (1) The operation time was (89.36±19.89) minutes, intraoperative blood loss was (39.71±23.64) mL, postoperative drainage volume was (56.21±34.21) mL, and rate of autologous blood transfusion was 0. (2) The operation time exerted no effect on the intraoperative blood loss (P=0.685 7), but affected on the postoperative drainage volume (P=0.021 6). (3) The total postoperative blood loss was little, and the blood loss did not differ significantly at 3 hours, 1, 3 and 7 days postoperatively (P > 0.05). (4) There was a slight decline in hemoglobin on days 1-3 after surgery, and then returned slowly; the erythrocyte sedimentation rate and C-reactive protein increased rapidly within 1 day after surgery and declined within 1-3 days; the D-dimer rapidly increased on day 1 after surgery, then rapidly decreased on days 1-3, and then slowly increased on days 3-7; the plasma total protein and albumin were stable and fluctuated in the normal range within 1-3 days. (5) These results suggest that the UKA had short operation time, few total blood loss and slight fluctuation, and the blood-related indexes exhibit different fluctuations. Moreover, the preoperative management of blood loss can reduce the total blood loss and rate of blood transfusion..