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Objective:Based on Web of Science database, this study aimed to explore the current status, research hotspots and development trends of countries regarding clinical management of osteoporotic fractures using bibliometrics and visualized analysis.Methods:We collected literatures in the field of clinical management of osteoporotic fractures included in Web of Science database, and applied bibliometrics to analyze the publication dates, countries, institutions, journals, authors, highly cited literatures and research hotspots. Visualization was drawn by VOSviewer software.Results:Analysis of the 2 508 articles revealed 3 types of data. (1) The analysis of basic information of the literature showed that: ①The country with the largest number of publications was the United States, which published 672 articles, followed by the United Kingdom and Canada, and China ranked fourth; ②The top three authors in the number of publications were Kanis JA, Cooper C and McCloskey EV respectively; ③The institution with the highest number of publications was the University of Sheffield, UK, followed by the University of Southampton, UK and the University of Toronto, Canada. (2) Network visualization of highly cited literatures showed that 118 highly cited literatures were mainly divided into 5 clusters, which were related to osteoporotic fracture diagnosis, treatment, medication adherence, management consensus and strategies of preventing refracture. (3) Temporal overlay visualization of research hotspots showed that early research mainly focused on traditional therapeutic drugs, and current research hotspots were mainly molecular targeted drugs, trabecular bone score and fracture liaison services.Conclusion:This study shows that the research activity of clinical management of osteoporotic fractures is increasing worldwide, and there is still a huge gap between China and Europe or the United States. Current research hotspots and development trends mainly focus on molecular targeted drugs, osteoporotic fracture treatment concepts, emerging fracture risk assessment tools, and fracture prevention and management models.
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Objective:To evaluate the post-marketing safety and immunogenicity of a 23-valent pneumococcal polysaccharide vaccine (PPV23).Methods:From September 2020 to June 2021, a clinical trial of single-dose PPV23 was conducted in people ≥3 years old in Centers for Disease Control and Prevention of Guizhou, Hunan and Fujian provinces. Blood samples were collects from the subjects before and 30 d after vaccination. ELISA was used to quantitatively detect IgG antibodies against capsular polysaccharides of 23 Streptococcus pneumoniae serotypes in serum samples. The adverse events (AEs) were monitored within 7 d after vaccination. Results:A total of 409 subjects were enrolled and included in safety analysis. Except for one with antibody level inversion, the other 408 participants were included in immunogenicity analysis. The levels of antibodies against the 23 Streptococcus pneumoniae serotypes were all increased after vaccination by an average of 4.24 folds. The two-fold growth rates of the antibodies ranged from 51.72% to 96.81% with a total two-fold growth rate of 78.59%. The overall rate of AEs was 27.14% (111/409). Local AEs were mainly pain, induration, redness and swollen. No serious adverse events related to vaccination occurred. Conclusions:This study preliminarily demonstrated the good immunogenicity and safety of PPV23 vaccine.
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Objective:To develop a grading prediction model of traumatic hemorrhage volume based on deep learning and assist in predicting traumatic hemorrhage volume.Methods:A retrospective observational study was conducted based on the experimental data of pig gunshot wounds in the time-effect assessment database for experiments on war-traumatized animals constructed by the General Hospital of the Chinese People's Liberation Army. The hemorrhage volume data of the study population were extracted, and the animals were divided into 0-300 mL, 301-600 mL, and > 600 mL groups according to the hemorrhage volume. Using vital signs indexes as the predictive variables and hemorrhage volume grading as the outcome variable, trauma hemorrhage volume grading prediction models were developed based on four traditional machine learning and ten deep learning methods. Using laboratory test indexes as predictive variables and hemorrhage volume grading as outcome variables, trauma hemorrhage volume grading prediction models were developed based on the above fourteen methods. The effect of the two groups of models was evaluated by accuracy and area under the receiver operator characteristic curve (AUC), and the optimal models in the two groups were mixed to obtain hybrid model 1. Feature selection was conducted according to the genetic algorithm, and hybrid model 2 was constructed according to the best feature combination. Finally, hybrid model 2 was deployed in the animal experiment database system.Results:Ninety-six traumatic animals in the database were enrolled, including 27 pigs in the 0-300 mL group, 40 in the 301-600 mL group, and 29 in the > 600 mL group. Among the fourteen models based on vital signs indexes, fully convolutional network (FCN) model was the best [accuracy: 60.0%, AUC and 95% confidence interval (95% CI) was 0.699 (0.671-0.727)]. Among the fourteen models based on laboratory test indexes, recurrent neural network (RNN) model was the best [accuracy: 68.9%, AUC (95% CI) was 0.845 (0.829-0.860)]. After mixing the FCN and RNN models, the hybrid model 1, namely RNN-FCN model was obtained, and the performance of the model was improved [accuracy: 74.2%, AUC (95% CI) was 0.847 (0.833-0.862)]. Feature selection was carried out by genetic algorithm, and the hybrid model 2, namely RNN-FCN* model, was constructed according to the selected feature combination, which further improved the model performance [accuracy: 80.5%, AUC (95% CI) was 0.880 (0.868-0.893)]. The hybrid model 2 contained ten indexes, including mean arterial pressure (MAP), hematocrit (HCT), platelet count (PLT), lactic acid, arterial partial pressure of carbon dioxide (PaCO 2), Total CO 2, blood sodium, anion gap (AG), fibrinogen (FIB), international normalized ratio (INR). Finally, the RNN-FCN* model was deployed in the database system, which realized automatic, continuous, efficient, intelligent, and grading prediction of hemorrhage volume in traumatic animals. Conclusion:Based on deep learning, a grading prediction model of traumatic hemorrhage volume was developed and deployed in the information system to realize the intelligent grading prediction of traumatic animal hemorrhage volume.
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Anorectal malignant melanoma (ARMM) is a rare malignant melanoma arising from mucosa in anorectal area. Symptoms and signs of ARMM are not specific, causing high misdiagnosis rate in this disease. Cornerstone treatment of ARMM is radical excision. Although more systematic therapy including target therapy and immunotherapy have been applied to ARMM, as the understanding of ARMM deepens. The overall prognosis of ARMM is still poor due to the lack of accurate clinical classification and staging standards.
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Objective@#To explore the features of imatinib mesylate (IM) plasma concentration during adjuvant therapy and clinical factors associated with IM plasma concentration in patients with high risk gastrointestinal stromal tumors (GIST), and to determine whether IM plasma concentration <1100 μg/L influences the efficacy of adjuvant therapy.@*Methods@#A retrospective case control study method was used. Case inclusion criteria: (1) complete resection of lesion and GIST confirmed by pathology; (2) high risk classified according to modified National Institutes of Health classification system (2008); (3) administration of IM 400 mg/d for at least 1 month; (4) not taking the medication likely affecting IM pharmacokinetic, such as rifampicin, dilantin, and carbamazepine, within 1 month before blood collection. Data of GIST patients who visited GIST Disease - Oriented Outpatient, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 2015 to December 2018 were retrospectively analyzed. After taking IM for 22-26 hours, 5 ml of peripheral venous blood was collected into EDTA anticoagulant tube. IM plasma concentration was detected by using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Patients were divided into <1100 μg/L group and ≥1100 μg/L group according to plasma concentration. Linear regression was used to analyze the relevance between clinical features and IM plasma concentration. Parameters with normal distribution were analyzed by Pearson correlation coefficient, and parameters with non-normal distribution were analyzed by Spearman correlation. Kaplan-Meier survival curves and COX regression model were used for survival analysis.@*Results@#Among the 85 patients enrolled in the study, 49 patients (57.6%) were male and 36 (42.4%) were female, with mean age of (51.9±11.0) years. The body mass index was (22.5±2.9) kg/m2 and body surface area was (1.6±0.2) m2. Thirty patients received gene test, including 23 patients with c-Kit exon 11 mutation, 4 with c-Kit exon 9 mutation, 1 with c-Kit exon 11 and 17 mutation and 2 without c-Kit or PDGFRA gene mutation. The mean IM plasma concentration was (1391.4±631.3) μg/L, and there were 32 patients with plasma concentration <1100 μg/L and 53 patients with plasma concentration ≥1100 μg/L. There were no statistically significant differences between the two groups in gender, age, body mass index, body surface area, hematological examination (white blood cells, albumin, alanine aminotransferase, aspartate aminotransferase and serum creatinine), tumor location, tumor size, mitotic counts, duration of adjuvant therapy and methods of operation (all P>0.05). Positive correlation between IM plasma concentration and serum creatinine was observed in linear regression analysis (r=0.297, P=0.007), but there were no correlations between IM plasma concentration and age (r=0.044, P=0.686), body mass index (r=0.066, P=0.547), body surface area (r=-0.010, P=0.924), white blood cells (r=-0.080, P=0.478), albumin (r=-0.065, P=0.563), alanine aminotransferase (r=0.114, P=0.308), aspartate aminotransferase (r=0.170, P=0.127) and duration of adjuvant therapy (ρ=0.060, P=0.586). There was no statistically significant difference in IM plasma concentration between patients with different genders (t=0.336, P=0.738) and patients with different surgical methods (F=0.888, P=0.451). Up to March 1, 2019. the median follow-up time was 30 (range 4-49) months. Tumor recurrence was detected in two patients with plasma concentration <1100 μg/L and two with plasma concentration ≥1100 μg/L. One recurrent patient with plasma concentration <1100 μg/L was detected to harbor c-Kit exon 11 and exon 17 mutations, and the other did not receive gene detection. Two recurrent patients with plasma concentration ≥1100 μg/L were both detected to harbor c-Kit exon 9 mutation. The 3-year relapse-free survival rate was 96.4% in the cohort, 96.2% in patients with plasma concentration <1100 μg/L, and 96.6% in patients with plasma concentration ≥1100 μg/L. No significant difference in relapse-free survival was observed between the two groups (P=0.204). Univariate Cox analysis showed that IM plasma concentration <1100 μg/L was not a risk factor for patients with high risk GIST (HR=0.238, 95% CI: 0.022-2.637, P=0.242).@*Conclusions@#IM plasma concentration of adjuvant therapy in patients with high risk GIST varies with individual. Patients with higher level of serum creatinine are more likely to have a higher plasma concentration. A blood drug concentration standard of less than 1100 μg/L for advanced GIST patients may not influence the prognosis of patients with high risk GIST.
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Bariatric surgery is an effective method for the treatment of obesity and type 2 diabetes mellitus. Morbidly obese patients usually have metabolic syndromes, as such, surgeons need to choose the reasonable surgical methods for patients according to their individuality and particularity. Hiatal hernia is a very common disease prevalent in obese patients and could induce gastroesophageal reflux, which increases the difficulty of bariatric surgery and proposes higher demands on choice of surgical methods to surgeons. It is important to recognize the presence of the hiatal hernia preoperatively and choose a more effective procedure of bariatric surgery to decrease the incidence of postoperative complications.
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Bariatric surgery is an effective method for the treatment of obesity and type 2 diabetes mellitus.Morbidly obese patients usually have metabolic syndromes,as such,surgeons need to choose the reasonable surgical methods for patients according to their individuality and particularity.Hiatal hernia is a very common disease prevalent in obese patients and could induce gastroesophageal reflux,which increases the difficulty of bariatric surgery and proposes higher demands on choice of surgical methods to surgeons.It is important to recognize the presence of the hiatal hernia preoperatively and choose a more effective procedure of bariatric surgery to decrease the incidence of postoperative complications.
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Objective To investigate the clinical efficacy and safety of domestic imatinib in the treatment of gastrointestinal stromal tumor (GIST). Methods Clinicopathological and follow-up data of GIST patients who received domestic imatinib treatment from January 2014 to December 2017 in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were analyzed retrospectively. The treatment efficacy and adverse reactions were analyzed. Results A total of 35 patients included 20 males and 15 females with a median age of 53 years old (28-79 years old). Among all the patients, 25 with primary GIST underwent complete resection, in which 20 cases were classified as high risk and 5 as moderate risk according to the risk stratification. Of the remaining 10 recurrent/metastatic or unresectable GIST patients, 6 cases had metastasis in liver, 2 cases had metastasis in peritoneum, 1 case had extensive abdominal and pelvic metastasis, and the other 1 case was initially unresectable. The follow-up data of all the 35 patients were available, with a median follow-up time of 25 months (4-49 months). Twenty-five primary patients with complete resection received adjuvant therapy with a median time of 14 months (4-44 months). The median time of follow-up was 25 months (4-49 months), and none of the primary patients was detected with recurrence or metastasis of GIST. Meanwhile, of the 10 patients with recurrent/metastatic or unresectableGIST, the median time of medicine-taking was 24 months (3-49 months). Seven of 10 patients received imatinib monotherapy, including 5 cases of partial remission and 2 cases of stable disease. The other 3 patients with localized progression received complete resection along with imatinib therapy. All the 10 patients achieved durable clinical benefit. Twenty-seven patients (77.1％) experienced adverse events, and only 1 case (2.9 ％) had grade 3 adverse events. Conclusion Domestic imatinib is effective and safe for patients who received adjuvant therapy after complete resection of primary GIST as well as those with recurrent/metastatic or unresectable GIST, but it remains to be further confirmed by large samples of prospective studies.
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Objective To investigate the clinical characteristics,treatment strategies and curative effect of recurrence and metastasis of primary gastrointestinal stromal tumor (GIST) after complete resection along with adjuvant therapy with imatinib,and to analyze the risk factors of recurrence and metastasis after adjuvant therapy.Methods The demographic data,clinicopathological characteristics and follow-up data of 80 primary GIST patients who received adjuvant therapy with imatinib for at least 1-year duration and had already stopped taking imatinib from January 2005 to December 2017 in Union Hospital,Tongji Medical College,Huazhong University of Science and Technology were analyzed retrospectively.The survival analysis was performed using Kaplan-Meier approach.Univariate analysis was conducted using log-rank test.Multivariate analysis was produced by Cox regression model.Results Of the enrolled 80 patients,recurrence and metastasis were detected in 17 cases after completion of postoperative adjuvant therapy with imatinib,with a median recurrence time of 12 months.All the 17 patients showed no specific clinical manifestations.Liver metastasis,peritoneum metastasis and local recurrence were found in 9,5 and 3 cases,respectively.In the 17 patients with recurrence and metastasis,9 patients received imatinib monotherapy.Among the 9 patients,6 achieved partial responses,while 3 demonstrated stable disease,and secondary drug resistance was found in 7 patients during the follow-up period,with a median progression-free survival of 35 months (95％ CI:15-55 months) and median overall survival of 49 months (95％ CI:30-68 months).A total of 7 patients with recurrence and metastasis were treated with imatinib after operation and achieved satisfying tumor control,and secondary drug resistance was found in 4 patients during the follow-up period,with a median progression-free survival of 31 months (95％ CI:6-56 months) and fell short of median overall survival.The remaining 1 patient gave up treatment.Univariate analysis showed that tumor location (x2 =4.120,P =0.042),preoperative neutrophil-to-lymphocyte ratio (NLR) (x2 =7.513,P =0.006) and preoperative platelet-to-lymphocyte ratio (PLR) (x2 =6.575,P =0.010) were associated with recurrence and metastasis of GIST patients after completion of adjuvant therapy.Multivariate analysis revealed that tumor location (HR =3.787,95％ CI:1.126-12.732,x2 =4.631,P =0.031) was an independent prognostic factor for those patients.Conclusion GIST patients who are identified recurrence and metastasis after completion of adjuvant imatinib treatment show no specific clinical manifestations after stopping andjuvant therapy with imatinib.Compared with gastric GIST,non-gastric origin GIST has a higher risk of recurrence.Imatinib monotherapy and surgery combined with imatinib therapy are both effective in treating this subgroup of patients.
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Objective:To investigate the effect of c-fos on the proliferation and migration of oral squamous cell carcinoma and potential mechansism.Methods:The expression of c-fos,CyclinD1 and p16 in 60 oral squamous cell carcinoma samples and 60 oral mucosa tissue samples was examined by immunohistochemistry.HN6 and SCC9 cells were respectively transfected with siRNA-c-fos and siRNA-scramble,then were respectively divided into control group,siRNA-scramble group and siRNA-c-fos group.The mRNA and protein expressions of CyclinD1 and p16 were decteted,meanwhile cell proliferation and migration were tested.Results:Compared with the oral mucosa tissue samples,the expressions of CyclinD1 and c-fos were increased in the carcinoma samples,while the expression of p16 was reduced.Compared with control group,the expressions of CyclinD1 in siRNA-c-fos group were significantly reduced,while p16 enpression was increased,with the inhibition of cell proliferation and migration.Conclusion:c-fos may regulate pl6/CyclinD1 signaling pathways and promote the proliferation and migration of oral squamous cell carcinoma.
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Objective:To investigate the effects of IGF-1 and IL-1β on the proliferation and apoptosis of cultured human condylar chondrocytes( CCs) of temporomandibular joint( TMJ) . Methods:Cultured CCs were derived from human TMJ condylar cartilage tis-sue, and identified by immunocytochemistry staining. The cultured cells were divided into 6 groups:control group, IL-1β(10 μg/L) group and IL-1 group (10 μg/L) + IGF-1 group (0, 1, 10, 50 and 100 μg/L, respectively). The cell proliferation ability was de-tected by MTT assay. The cell cycle and apoptosis were detected by flow cytometry. The expression of apoptosis-associated factors Bcl-2, Bax and p38 MAPK/NF-κB proteins were detected by Western blot. Results:Type II collagen was positively expressed in cultured CCs. IL-1β treatment decreased cell proliferation, increased cell apoptosis with concomitant increase of the percentage of early apopto-sis and late apoptotic cells, increased Caspase-3 expression, decreased Bcl-2/Bax ratio, and increased the expression of p38 MAPK/NF-κB proteins. Whereas, with 1-100 μg/L IGF-1 pretreatment, the proliferation ability and Bcl-2/Bax ratio of the cells were in-creased(P<0. 05), the apoptotic cells were decreased, the expression of Caspase-3 and p38 MAPK/NF-κB proteins was decreased ( P<0. 05) in a dose-dependent manner. Conclusion:IGF-1 may inhibit IL-1β-induced cell apoptosis and attenuate the activation of p38 MAPK/NF-κB of human condylar chondrocytes.
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Objective:To explore the effect of siRNA targeting myeloid cell leukemia-1(Mcl-1)on the biological behavior of salivary adenoid cystic carcinoma cells.Methods:The chemically synthesized Mcl-1-siRNA was transfected into salivary adenoid cystic carci-noma SACC-2 cells.The expression levels of Mcl-1-mRNA and Mcl-1protein were examined by Real-time PCR and western blotting respectively.MTT assay,transwell chamber and flow cytometry were used to determine the effect of Mcl-1-siRNA on SACC-2 cell pro-liferation,migration and apoptosis.Results:Compared with the control group,liposome group and NC-siRNA group,SACC-2 cell proliferation rate of Mcl-1-siRNA group was obviously slowed down.48 h after transfection,the migration of SACC-2 cells in Mcl-1-siRNA group(39 ±9.0)were lower than that in control group(69 ±6.0).The apoptosis rate of Mcl-1-siRNA group(8.6%)was sig-nificantly higher than that in control group(1.9%).Conclusion:Silence Mcl-1 can inhibit cell proliferation and migration and pro-mote apoptosis of salivary adenoid cystic carcinoma cells.
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Objective Through investigation of children fluorosis illness,family households improved stoves and related life styles,to provide a scientific basis for sustainable control of endemic fluorosis.Methods In 2013,in Huishui County and Baiyun District,3 towns were selected in each county(district),and 3 villages were selected in each town.All 8-12 years old children in the school of these villages were checked dental fluorosis,which was diagnosed according to Dental Fluorosis Diagnosis (WS/T 208-2011); at the same time,10 families were selected to survey the situation of improved stoves and related life styles.Results Dental fluorosis detection rate of 8-12 years old children in Huishui and Baiyun were 2.75％ (23/836) and 2.26％ (11/487),which were all lower than 30％.Qualified rate of improved stoves and qualified stoves correct utilization rate were all 100.0％ (90/90).For human consumption,the correct rate of corn drying was 100.0％ (90/90) ; the correct rates of chili drying were 98.9％ (89/90) and 100.0％ (90/90).Conclusions The prevention effect is obvious,which has reached the control standards.We should continue to improve the long-term mechanism of comprehensive control measures,and to achieve substantial elimination of coal-burning endemic fluorosis.
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Objective:To explore the effects of cysteine-rich 6 1 (Cyr6 1 )on biological behavior of human adenoid cystic carcinoma ACC-LM and ACC2 cells.Methods:The chemically synthesized Cyr6 1-siRNA was transfected into ACC-LM and ACC2 cells.Cell proliferation was measured by the MTT method,the invasive ability was evaluated by Transwell chamber assay,and cell apoptosis was analyzed using flow cytometry by double staining with Annexin V and propidium iodide.Results:Cyr61-siRNA significantly down-regu-lated Cyr61 protein expression in ACC-LMand ACC2 cells.Cyr61-siRNA markedly inhibited the proliferation and invasion of the cells, however,there was no significant difference in cell apoptosis between Cyr6 1-siRNA and control groups.Conclusion:Cyr6 1 promote the proliferation and invasion of adenoid cystic cancer cells.
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OBJECTIVE: To establish a method for determining the entrapment efficiency of gemcitabine hydrochloride liposomes(GHL).METHODS: The liposome and the free gemcitabine hydrochloride were separated by ultrafiltration,and the content of free gemcitabine hydrochloride was determined by HPLC.The entrapment efficiency of gemcitabine hydrochloride liposomes was computed as well.RESULTS: The recovery rate in ultrafiltration methods was 97.8%～100.1% for blank substance versus 99.0%～100.1% for sample.The linear range of gemcitabine hydrochloride was 1.0～80.0 mg?L-1(r=0.999 3) and its average recovery rate was 98.7～101.2%,and its inter-day and intra-day RSD were all less than 3% and its average entrapment efficiency was 81.21%.CONCLUSION: The method is simple,accurate and applicable for the determination of the entrapment efficiency of gemcitabine hydrochloride liposomes.