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Objective:To explore the establishment and application of ovarian cancer organoids.Methods:Fresh ovarian tumor tissues, obtaining from patients underwent surgery in the First Affiliated Hospital of Nanjing Medical University between October 2021 and March 2022, were collected, enzymatic degraded, digested, and embedded into matrigel to establish organoids. A total of 32 ovarian cancer samples were collected. Hematoxylin eosin (HE) staining and immunofluorescence (IF) procedure were used to verify the morphological structure of organoids and their expression of molecular markers. 3D cyto-live or dead assay was used to detecte the live or dead cells in organoids. Carboplatin with a concentration ranging from 5 to 80 μmol/L (5, 10, 20, 40, 80 μmol/L) was added to organoids to calculate the 50% inhibitory concentration (IC 50) in different organoids. Results:(1) Organoids from a total of 32 patients were established, of which 18 cases could be passaged stably in the long term in vitro, while 14 could be passaged in the short time. The average amplification time of long-term passage in vitro was over 3 months, and the longest reached 9 months. (2) In HE staining, significant nuclei atypia and local micropapillary structures were observed in organoids. IF staining revealed that ovarian cancer organoids expressed molecular markers similar to primary tumor tissues, such as Pan cytokeratin (Pan-CK), p53, paired box gene 8 (PAX8), and Wilms tumor gene 1 (WT1). (3) In 3D cyto-live or dead assay, a large number of apoptotic cells were observed inside and around the organoids after added carboplatin. The sensitivity to carboplatin varied in 18 organoids could amplify in the long term, with an average IC 50 of (29.5±15.8) μmol/L. Moreover, IC 50 values of 4 organoids derived from patients received neoadjuvant chemotherapy were much higher than the 14 organoids which did not received neoadjuvant chemotherapy [(48.7±11.3) μmol/L vs (24.0±12.1) μmol/L; t=3.429, P=0.022]. Conclusions:Organoids recapitulate ovarian cancers in vitro and could be stably passaged. Organoids derived from patients received neoadjuvant chemotherapy have higher resistance to carboplatin.
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Objective:To compare the efficacies of arthroscopic modified Brostr?m procedure combined with or without peroneal tendon debridement in the treatment of chronic lateral ankle instability (CLAI) concomitant with fibular tendinitis.Methods:A retrospective cohort analysis was conducted on the clinical data of 31 patients with CLAI concomitant with fibular tendinitis, who were treated in Beijing Tongren Hospital, Capital Medical University between March 2019 and December 2021. The patients included 17 males and 14 females, aged 16-57 years [(32.8±9.6)years]. The anterior drawer test and talar tilt test were positive in all patients preoperatively. Diagnosis was confirmed by physical examination and MRI, and calcaneofibular ligament rupture was excluded. Eleven patients received arthroscopic modified Brostr?m procedure combined with peroneal tendon debridement (modified Brostr?m procedure+tendon debridement group), and 20 underwent pure arthroscopic modified Brostr?m procedure (modified Brostr?m procedure group). The operation time, intraoperative blood loss and length of hospital stay were documented. The visual analogue score (VAS) in peroneal tendon area was assessed before operation and at postoperative 2, 6 and 12 weeks. The American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and foot and ankle outcome score (FAOS) were assessed before operation and at postoperative 6 and 12 weeks. The anterior drawer test was performed at the last follow-up. The foot and ankle ability measure (FAAM) score was assessed before operation and at the last follow-up. Postoperative wound healing and complications were also observed.Results:All the patients were followed up for 4-19 months [(11.3±3.5)months]. The operation time was (66.0±4.2)minutes in the modified Brostr?m procedure+tendon debridement group, which was significantly longer than (61.5±3.4)minutes in the modified Brostr?m procedure group ( P<0.05). There was no significant difference in intraoperative blood loss or length of hospital stay between the two groups (all P>0.05). Compared with the preoperation, the value of VAS was significantly lowered, and the values of AOFAS ankle-hindfoot score, FAOS and FAAM score were significantly increased at different postoperative timepoints (all P<0.01). No significant differences in the values of VAS, AOFAS ankle-hindfoot score, FAOS or FAAM score were seen between the two groups before operation (all P>0.05). The value of VAS was 3.0(3.0, 4.0) points in the modified Brostr?m procedure+tendon debridement group, being markedly different from 4.0(4.0, 4.0)points in the modified Brostr?m procedure group at 2 weeks postoperatively ( P<0.05). The value of VAS was 2.0(1.0, 3.0)points in the modified Brostr?m procedure+tendon debridement group, being markedly different from 3.0(2.3, 3.0)points in the modified Brostr?m procedure group at 6 weeks postoperatively ( P<0.05). At 12 weeks postoperatively, there was no significant difference in the value of VAS between the two groups ( P>0.05). There were no significant differences in the values of AOFAS ankle-hindfoot score and FAOS between the two groups at 6 or 12 weeks postoperatively (all P>0.05). The anterior drawer test was negative in all patients at the last follow-up. No significant difference was seen in the value of FAAM score between the two groups at the last follow-up ( P>0.05). All incisions were healed well in the first stage after operation, without the occurrence of joint infection, impaired joint motion, nerve injury or deep vein thrombosis. Conclusions:Arthroscopic modified Brostr?m procedure combined with or without peroneal tendon debridement can both improve the foot function in CLAI patients concomitant with fibular tendinitis. However, the combined treatment allows for early pain relief, without increasing the risk of complications, and can therefore contribute to a faster postoperative recovery.
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Objective:To explore the efficacy and safety of dual drug regimen in the treatment of Hantavirus hemorrhagic fever with renal syndrome with upper gastrointestinal bleeding.Methods:Sixty patients with hantavirus hemorrhagic fever with renal syndrome and upper gastrointestinal bleeding admitted to the Eighth Medical Center of the 301 Hospital from January 2020 to January 2022 were selected as the research objects. They were randomly divided into the control group (30 cases) and the observation group (30 cases). They were treated with omeprazole and omeprazole combined with octreotide respectively for 72 hours. The clinical efficacy, hemostasis time, hospital stay, hemoglobin, serum glucagon levels, adverse reactions and rebleeding rate were compared between the two groups.Results:The total effective rate of clinical treatment in the observation group was 93.33%(28/30), significantly better than 76.67%(23/30) in the control group, with a statistically significant difference ( P<0.05). The hemostasis time and hospitalization time in the observation group were significantly shorter than those in the control group (all P<0.05). After treatment, the hemoglobin level in both groups was higher than that before treatment, and the serum glucagon level was lower than that before treatment, the difference was statistically significant (all P<0.05); After treatment, the hemoglobin level in the observation group was higher than that in the control group, and the serum glucagon level was lower than that in the control group (all P<0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (all P>0.05). The 48 hour rebleeding rate in the observation group was 3.33%(1/30), lower than the 26.67%(8/30) in the control group, with a statistically significant difference ( P<0.05). Conclusions:The dual drug regimen for Hantavirus hemorrhagic fever with renal syndrome with upper gastrointestinal bleeding can effectively control the bleeding symptoms, improve the hemostasis effect, lower the serum glucagon level, reduce the risk of rebleeding, and its safety is worthy of recognition.
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Objective:To explore the diagnostic value of 3D-arterial spin labeling (ASL) and digital subtraction angiography (DSA) in the occlusion and collateral circulation (CC) of patients with acute ischemic stroke (AIS).Methods:From January 2019 to June 2020, 53 cases of AIS patients with middle cerebral artery (MCA) occlusion in Langfang Hospital of Traditional Chinese Medicine were selected as the research objects. All patients underwent DSA and 3D ASL examination. According to the gold standard of DSA, the diagnostic value of proximal intra-arterial signal (IAS) in 3D-ASL was observed, and the clinical value of distal IAS in the diagnosis of lateral CC was observed. Univariate and multivariate logistic regression were used to identify risk factors for poor outcome in AIS patients.Results:There were 31 cases with good collateral circulation judged by DSA. Taking DSA as the gold standard, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of digital IAS in diagnosing CC status were 93.55%, 81.82%, 87.88%, 90.00% and 88.68%, respectively. The National Institutes of Health Stroke Scale (NIHSS) score of patients with good CC assessed by 3D-ASL was lower than that of patients with poor CC at admission, and the good prognosis rate at discharge was higher than that of patients with poor CC, with statistically significant difference (all P<0.05). There was no significant difference in clinical data between patients with good CC and those with poor CC, such as gender, age, history of atrial fibrillation, hypertension, diabetes, smoking, drinking, onset to treatment time, treatment methods, etc (all P>0.05). Univariate and multivariate analysis showed that poor CC assessed by ASL was a risk factor for poor prognosis in AIS patients ( OR=5.897, P<0.05). Conclusions:The proximal and distal IAS of 3D-ASL can provide important diagnostic clues for detecting arterial occlusion and collateral perfusion in patients with AIS, and the detection of CC by ASL is of great value for prognosis.
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Objective:To explore the relationship between self-perceptions of aging and cognitive function, and the mediating and moderating effect of loneliness among them.Methods:A multi-stage stratified sampling was conducted in Jinzhou from September to November 2021, and 318 community-based elderly were included.General data questionnaire, the brief ageing perceptions questionnaire (BAPQ), UCLA loneliness scale(UCLA-LS) and mini-mental state examination (MMSE) were applied to all subjects.IBM SPSS 25.0 software was used to conduct independent sample t-test, analysis of variance and Pearson correlation analysis, and Bootstrap program of AMOS 22.0 was used to analyze the mediation effect.The model in SPSSAU on-line analysis program was used to test the moderating effect. Results:The average scores of self-perceptions of aging, loneliness and cognitive function were (44.85±12.48), (41.70±8.73) and (24.87±3.40) respectively.And 65 of 318 subjects had cognitive impairment, and the detection rate was 20.44%(65/318). Self-perceptions of aging, loneliness and cognitive function scores were significantly correlated between each other(all P<0.05). Self-perceptions of aging had a negative effect on cognitive function ( β=-0.467, P<0.01). Self-perceptions of aging had a positive effect on loneliness ( β=0.585, P<0.01). Loneliness had a negative effect on cognitive function ( β=-0.234, P<0.01). The indirect standardization effect of loneliness between self-perceptions of aging and cognitive function was -0.137, and the mediating effect accounted for 22.68% of the total effect.Loneliness played a moderating role between self-perceptions of aging and cognitive function ( β=-0.114, t=-2.26, P=0.025). Conclusion:Self-perceptions of aging and loneliness can predict the cognitive function in the elderly, and loneliness plays a mediating role between self-perceptions of aging and cognitive function.Early detection of negative senility emotion and loneliness of the elderly will play a positive role in preventing the occurrence of cognitive impairment.
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Objective:To investigate the clinical efficacy of liraglutide combined with metformin in the treatment of type 2 diabetes mellitus in overweight or obese patients.Methods:The clinical data of 120 overweight or obese patients with type 2 diabetes mellitus admitted to Bayannur Hospital from January 2020 to June 2021 was retrospectively analyzed. They were divided into study and control groups ( n = 60/group) according to different treatments. The study group was treated with liraglutide combined with metformin, and the control group was treated with metformin alone. All patients were treated for 12 weeks. Clinical efficacy was compared between the two groups. Results:After treatment, body mass, body mass index, fasting blood glucose, 2-hour postprandial blood glucose, glycated hemoglobin, total cholesterol, triglyceride, low-density lipoprotein cholesterol, visceral fat area, and insulin resistance index in the study group were (71.51 ± 10.12) kg, (25.98 ± 2.63) kg/m 2, (6.09 ± 0.99) mmol/L, (9.08 ± 2.39) mmol/L, (6.75 ± 1.13)%, (4.43 ± 0.88) mmol/L, (1.76 ± 0.68) mmol/L, (2.29 ± 0.90) mmol/L, (108.21 ± 26.46) cm 2 and (3.57 ± 1.45), respectively, which were significantly lower than (75.57 ± 7.11) kg, (27.91 ± 2.46) kg/m 2, (7.02 ± 0.95) mmol/L, (11.26 ± 2.86) mmol/L, (7.28 ± 1.04)%, (5.24 ± 1.11) mmol/L, (2.19 ± 0.70) mmol/L, (2.86 ± 0.97) mmol/L, (118.32 ± 28.63) cm 2, and (4.28 ± 2.07) respectively in the control group ( t = 2.54, 4.15, 5.23, 4.53, 2.66, 4.45, 3.43, 3.39, 2.01, 2.19, all P < 0.05). High-density lipoprotein cholesterol in the study group was significantly higher than that in the control group [(1.55 ± 0.28) mmol/L vs. (1.20 ± 0.32) mmol/L, t = -6.38, P < 0.05]. The grade of nonalcoholic fatty liver disease in the study group was significantly superior to that in the control group ( Z =-2.16, P < 0.05). Conclusion:Liraglutide combined with metformin can effectively improve blood glucose and lipid levels, and reduce insulin resistance, body weight, visceral adipose tissue and liver hepatocellular fatty deposits in overweight or obese patients with type 2 diabetes mellitus.
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AIM: To explore the progress of clinical trials for ophthalmic drugs in China in 2022 and discuss its changes with 2014 to 2021, thus providing the latest data reference for the development of new drug and the implementation of clinical trials, and a basis for decision-making.METHODS: In this cross-sectional study, we retrieved the drug clinical trials registration and information disclosure platform of National Medical Products Administration database. Drug clinical trials for eye diseases registered from January 1 to December 31, 2022 were included. Number(proportion)was used to describe the characteristics of clinical trials for ophthalmic drug, the indication, the trial phase, the efficacy and the geographical distribution.RESULTS:A total of 55 clinical trials for ophthalmic drug were included, which accounted for 1.66% of all clinical trials, showing a steady growth trend. Main drug type was chemical drugs with the highest proportion of 58.18%. The top three indications with the most clinical trials were age-related macular degeneration, myopia and dry eye. Two gene drugs emerged in 2022, and 7 drugs carried out ≥2 trials, of which atropine sulfate and recombinant anti-vascular endothelial growth factor(VEGF)humanized monoclonal antibody were the most(7 and 5 respectively). Most trials were in phase I and phase III stages, accounting for 36.36% and 27.27% respectively. The median start-up time of phase I trials in 2022 was 2.72(0.77, 3.47)mo, which was significantly shorter than 3.87(3.00, 6.30)mo of 2014～2021(Z=-2.630, P=0.009), and there were no significant differences between BE, phase II, III, IV comparing with 2014～2021(P>0.05).CONCLUSIONS: In 2022, the number and implementation efficiency of clinical trials for ophthalmic drugs in China increased steadily. The indications are mainly fundus disease, myopia and dry eye. Most new drugs are in the early stage of research and development or close to market. Gene therapy drugs began to emerge.
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Objective@#To understand the current status of main professional work in independent school health departments of Chinese centers for disease control and prevention, so as to provide reference and suggestions for the further development of school health work in China.@*Methods@#Electronic questionnaire was used to collect the basic work of school health, the monitoring work, the intervention action of common diseases and the development of health intervention among students in independent school health departments of centers for disease control and prevention in China.@*Results@#Among the 357 institutions that have set up independent school health departments, the implementation rates of school mental health work, safety emergency and risk avoidance health intervention were low, which were 11.8% and 11.5%, respectively. Relying on the project "national monitoring and intervention of common diseases and health influencing factors of students", the overall implementation of health monitoring in schools nationwide was successful, but the overall implementation rate of students nutritional status monitoring and "healthy parents action" were low, accounting for 44.5% and 24.4%, respectively. At the same time, there were still as many as 27.2% institutions that had not carried out the intervention action for common diseases of students which advocated in the monitoring program. The failure rate of county level institutions was higher than that of provincial level and prefecture level institutions, and the failure rate of the central and western institutions was much higher than that of the eastern institutions; the difference was statistically significant( χ 2=30.1, 41.6, P <0.05).@*Conclusion@#We should increase support including policy preference, fund guarantee, technical guidance and so on for the school health work of disease control institutions at the grass roots level and in economically underdeveloped areas, so as to ensure the healthy growth of children and adolescents in all respects.
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OBJECTIVE@#To evaluate the clinical features, laboratory and imaging results, treatment and outcomes of eosinophilic fasciitis (EF) and assess the value of ultrasound in the diagnosis of EF.@*METHODS@#We retrospectively analyzed the clinical data of 45 patients with EF treated in our center from January 1, 2006 to February 28, 2022. The consistency between the diagnoses of EF based on ultrasound and MRI findings was assessed.@*RESULTS@#In the 45 EF patients (male/female ratio 3.5:1), the age of onset ranged from 16 to 64 years with a mean disease course of 22.6 months. The average time from symptom onset to diagnosis was 16 months. The most common possible trigger of the disease was vigorous exercise (10/45), causing symmetrical lesions in the limbs, most commonly in the forearms (86.7%) and lower legs (80%). Clinical features of EF included subcutaneous swelling and induration (95.6%), arthralgia and arthritis (55.6%), groove sign (42.2%), hand joint contractures (42.2%), skin pigmentation (37.8%), and peau d'orange appearance (13.3%). Eosinophilia was found in 31 patients (68.9%). Hypergammaglobulinemia was seen in 23/44 (52.3%) and positive antinuclear antibodies in 9 (20%) of the patients. Twentyone of the patients were treated with high-dose methylprednisolone (≥200 mg daily for 3 to 5 consecutive days), and compared with the patients who did not receive this treatment, these patients more frequently experienced relapse before admission, had more extensive involvement, and had a higher rate of hypergammaglobulinemia without fever, but these differences were not statistically significant. Of the 31 patients (68.9%) with follow-up data (for a median of 3.2 years [range 0.2-15.9]), complete remission was achieved in 12 (38.7%) patients, and the accumulative complete remission rate was 44.1% at 5.5 years. No specific baseline characteristics or immunosuppressants were found to correlate with the treatment response. A total of 26 patients underwent both ultrasound and MRI examination, and the Kappa value of the diagnostic results between ultrasound and MRI was 0.91.@*CONCLUSION@#EF is characterized by symmetrical subcutaneous swelling and induration in the limbs, accompanied by eosinophilia and hypergammaglobulinemia. Glucocorticoid is effective for treating EF. Ultrasound examination can identify thickening of subcutaneous fascia for an early diagnosis of EF.
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Humanos , Femenino , Masculino , Lactante , Preescolar , Estudios Retrospectivos , Hipergammaglobulinemia , Eosinofilia , Ultrasonografía , Mano , Contractura , Resultado del TratamientoRESUMEN
Hypoxia, as an important hallmark of the tumor microenvironment, is a major cause of oxidative stress and plays a central role in various malignant tumors, including glioblastoma. Elevated reactive oxygen species (ROS) in a hypoxic microenvironment promote glioblastoma progression; however, the underlying mechanism has not been clarified. Herein, we found that hypoxia promoted ROS production, and the proliferation, migration, and invasion of glioblastoma cells, while this promotion was restrained by ROS scavengers N-acetyl-L-cysteine (NAC) and diphenyleneiodonium chloride (DPI). Hypoxia-induced ROS activated hypoxia-inducible factor-1α (HIF-1α) signaling, which enhanced cell migration and invasion by epithelial-mesenchymal transition (EMT). Furthermore, the induction of serine protease inhibitor family E member 1 (SERPINE1) was ROS-dependent under hypoxia, and HIF-1α mediated SERPINE1 increase induced by ROS via binding to the SERPINE1 promoter region, thereby facilitating glioblastoma migration and invasion. Taken together, our data revealed that hypoxia-induced ROS reinforce the hypoxic adaptation of glioblastoma by driving the HIF-1α-SERPINE1 signaling pathway, and that targeting ROS may be a promising therapeutic strategy for glioblastoma.
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Humanos , Hipoxia de la Célula , Línea Celular Tumoral , Glioblastoma/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Inhibidor 1 de Activador Plasminogénico/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Microambiente Tumoral , Neoplasias Encefálicas/patologíaRESUMEN
Objective To master the changes of foodborne disease pathogen spectrum in Yichang during 2014-2020, and to understand the impact of the toilet revolution on the pathogen spectrum of foodborne diseases in Yichang. Methods The basic information on the cases of foodborne diseases in Yichang from 2014 to 2020 was collected. The fecal specimens were collected to detect pathogens, including Salmonella , Vibrio parahaemolyticus, Shigella, and diarrheogenic Escherichia coli and Norovirus. The distribution of foodborne pathogenic bacteria in food was obtained from the surveillance project report of food microorganisms and their pathogenic factors in Yichang. From 2017 to 2020, water samples from the Yangtze River were collected from May to October with frequent intestinal diseases to detect pathogenic bacteria of foodborne diseases. Results The monitoring results of foodborne diseases showed that the detection rate of norovirus increased to 6.12% year by year from 2015 to 2017, and plummeted to 0.43% in 2018, with a statistically significant difference (χ2＝60.962，P2＝106.47，P2＝44.036 , P<0.05). Conclusion The toilet revolution can reduce the detection rate of pathogens of foodborne diseases in Yichang and reduce the detection rate of Salmonella in Yangtze River water, but it has little impact on the composition of foodborne disease pathogen spectrum.
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Objective:To explore the pupil size distribution of the Chinese myopic population under different mesopic conditions, and to analyze the possible influencing factors.Methods:A cross-sectional study was conducted.Two hundred and fourteen myopic patients (428 eyes) who underwent refractive surgery in Tianjin Eye Hospital from December 2018 to April 2019 were randomly selected.The patients were 17 to 45 years old, with an average age of (22.62±4.88) years old.The patients were divided into astigmatism <-1.5 D group (372 eyes) and astigmatism ≥-1.5 D group (56 eyes) according to their astigmatism measurements.The low mesopic pupil size (LMPS) (0.2 lx) was measured with the infrared Colvard pupillometer, and the high mesopic pupil size (HMPS) (6-12 lx) was obtained through the anterior Pentacam segment analyzer.The pupil size was compared between both eyes, different sexes and different astigmatism measurements.The relationship between pupil size and possible influencing factors, such as age, sex, spherical equivalent, spherical diopter, cylinder diopter, axis, mean keratometry(Km), and central cornea thickness was analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Tianjin Eye Hospital (No.201912). Written informed consent was obtained from each subject or their guardians.Results:The pupil sizes measured by the Colvard pupillometer and Pentacam were (6.806±0.776)mm and (3.312±0.540)mm, respectively.The pupil size of male subjects was (6.692±0.754)mm, which was larger than (6.668±0.792)mm of females, showing a statistically significant difference ( t=2.935, P=0.004). Under the high mesopic condition, the pupil size of astigmatism ≥-1.5 D group was lower than that of astigmatism <-1.5 D group, with a statistically significant difference ( t=2.611, P=0.009). Under the low mesopic condition, pupil size was negatively correlated with age and Km ( r=-0.213, -0.210; both at P<0.001). Under the high mesopic condition, pupil size was weakly positively correlated with cylinder power ( r=0.124, P=0.010) and was weakly negatively correlated with Km ( r=-0.142, P=0.003). The multiple linear regression analysis revealed that the LMPS=0.659×HMPS-0.019×age-0.084×Km+ 8.662.About 28% of pupil size under low mesopic conditions could be predicted by Pentacam.LMPS of ≤7 mm could be better predicted when the results were below 3.6 mm. Conclusions:Age and corneal curvature are influencing factors of mesopic pupil size.Older people with steep curvature have a smaller pupil.At high mesopic conditions, astigmatism affects pupil size.Pentacam measurements can predict LMPS to some degree but are not a substitute for dark-adapted pupil diameter.
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Objective:To evaluate and summarize the best evidence related to the management of cancer-related fatigue in children with leukemia and provide an evidence-based basis for clinical practice.Methods:The search for the relevant guidelines and evidence synthesis from UpToDate, JBI, Cochrane Library, Registered Nurses′ Association of Ontario, Guidelines International Network, National Institute for Health and Clinical Excellence, National Guideline Clearinghouse, YiMaiTong Guideline Network, National Comprehensive Cancer Network, PubMed, CINAHL, EMbase, China National Knowledge Infrastructure, Wanfang, China Biology Medicine from January 1st, 2012 to May 1st, 2022. Two researchers evaluated the quality of the literature independently according to the unified standard and extracted the best evidence.Results:A total of 13 literatures were extracted, including three clinical practice guidelines, two evidence summaries and eight systematic reviews. Finally, 22 pieces of evidence were summarized, involving six aspects which were environmental management, cancer-related fatigue assessment, exercise management, adventure therapy, sleep management and psychosocial interventions.Conclusions:Best evidence for the management of cancer-related fatigue in children with leukemia, which should be used in conjunction with the environment, the child's age, physical ability, medical condition and psychological acceptability to develop an individualized symptom management plan to improve the quality of care and the child′s quality of life.
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Objective:To investigate the effect of resveratrol on apoptosis of ovarian cancer cells and its molecular mechanism, and to find a potential new target for the treatment of ovarian cancer.Methods:Ovarian cancer SKOV-3 cells were divided into control group and resveratrol group.The survival rate of SKOV-3 cells treated with resveratrol was measured by MTT assay. 24 h after resveratrol intervention in SKOV-3 cells, Western blot was used to detect the expression of Bcl-2, Bax, Caspase-3, HMGB1, TLR4 and NF-?B. Ovarian cancer SKOV-3 cells were transfected with si-NC, si-HMGB1, Rb1+pcDNA3.1 or Rb1+pcDNA3.1-HMGB1, and the sensitivity of cells to resveratrol was detected by MTT assay. The transfected cells were treated with resveratrol and apoptosis was detected by flow cytometry.Results:Resveratrol could inhibit the growth of ovarian cancer SKOV-3 cells, and the higher the concentration of resveratrol, the more significant the inhibitory effect. The expression level of HMGB1 in control cells and resveratrol group was 1.24±0.15 and 0.86±0.11, respectively. 25μM resveratrol inhibited HMGB1 protein level ( P<0.01) . The sensitivity to resveratrol was increased after HMGB1 was downregulated, and the apoptosis of SKOV-3 cells was promoted. HMGB1 overexpression increased the resistance to resveratrol and inhibited the apoptosis of SKOV-3 cells. TLR4 expression quantity control and resveratrol cells were 0.98±0.12 and 0.63±0.08, amount of NF-?B expression were 1.21±0.14 and 0.45±0.07, 25 μM resveratrol could cut TLR4 and NF-?B protein levels. Conclusions:Resveratrol can promote apoptosis of ovarian cancer SKOV-3 cells. This mechanism may be related to the down-regulation of HMGB1/TLR4/NF-?B, which provides a basis for resveratrol treatment of ovarian cancer.
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Objective:To establish a risk prediction model of acute kidney injury in paraquat (PQ) poisoning patients.Methods:A retrospective observational cohort of adult patients with acute PQ poisoning between September 10, 2010 and January 16, 2020 from the Emergency Department of West China Hospital, Sichuan University were conducted. Data on demographics, clinical records, and laboratory results were collected from electronic medical record. The patients were divided into the AKI group and the non-AKI group according to whether AKI occurred during hospitalization. The patients were randomly divided into the training and validation groups (7:3). Multivariate logistic regression analysis was used to screen the independent risk factors of AKI and the nomogram was used to establish a prediction model. Receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the differentiation and calibration of the prediction model. Decision curve analysis (DCA) was used to evaluate the clinical validity of the prediction model.Results:A total of 718 patients were included in this study. AKI occurred in 323 (45%) patients in hospital and 378 (52.6%) patients died. The mortality rate of the AKI group was higher than that of the non-AKI group (72.8% vs. 36.2%, P < 0.05). Multivariate logistic regression analysis showed that the time from poisoning to treatment ( OR=1.018, 95% CI:1.006-1.030), white blood cell count ( OR=1.128, 95% CI: 1.084-1.173), aspartate aminotransferase ( OR=1.017, 95% CI:1.006-1.027), cystatin C ( OR=516.753, 95% CI: 99.337-2688.172), and PQ concentration ( OR=1.064, 95% CI:1.044-1.085) in blood on admission were independent risk factors of AKI in patients with PQ poisoning ( P<0.01). The area under the ROC curve was 0.943 (95% CI: 0.923-0.962) in the training cohort, and the sensitivity and specificity were 82.4% and 93.6%, respectively. The calibration curve showed optimal agreement between prediction by nomogram and actual observation. Decision curve and clinical impact curve analysis indicated that the nomogram conferred high clinical net benefit. Conclusions:The time from poisoning to treatment, white blood cell count, aspartate aminotransferase, cystatin C, and PQ concentration in blood on admission were independent risk factors of AKI. The predictive model based on the above indicators has high sensitivity and specificity in evaluating AKI after PQ poisoning. Whether this prediction model can be applied to other PQ poisoning patients needs to be further expanded for verification.
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The grading of evidence is an important factor in clinical decision-making. The current evidence grading system based on western medicine is limited in the clinical practice of traditional Chinese medicine （TCM）， therefore we propose the solutions to the development of grading system for TCM interventional evidence， following the international evidence grading standards， taking into considerations of the unique characteristics of TCM practice， based on the Grades of recommendation， assessment， development and evaluation （GARDE） evaluation system， and integrating with grading system regarding TCM classical literature and empirical evidence from modern famous doctors. The evidence from classical literature is suggested to be evaluated from three aspects including source of ancient medical records， comprehensive of treatment details， and the inheritance. The qualification of famous doctors， content integrity， and inheritance of experiences will be used to evaluate the evidence from famous doctors' experience. The multi-sourced evidence such as TCM classical literature， experience of modern famous doctors， and modern researches is mainly integrated in a qualitative way， and the overall level of evidence of TCM interventions will be graded consistently with the GRADE system based on modern research. The evidence from classical literature and modern famous doctors' experience will be assessed and considered as supplementary evidence， which will make the evaluation of clinical evidence more objectively and comprehensively， thereby guiding clinical practice further.
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Objective: JWH133, a cannabinoid type 2 receptor agonist, was tested for its ability to protect mice from bleomycin-induced pulmonary fibrosis. Methods: By using a random number generator, 24 C57BL/6J male mice were randomly divided into the control group, model group, JWH133 intervention group, and JWH133+a cannabinoid type-2 receptor antagonist (AM630) inhibitor group, with 6 mice in each group. A mouse pulmonary fibrosis model was established by tracheal instillation of bleomycin (5 mg/kg). Starting from the first day after modeling, the control group mice were intraperitoneally injected with 0.1 ml of 0.9% sodium chloride solution, and the model group mice were intraperitoneally injected with 0.1 ml of 0.9% sodium chloride solution. The JWH133 intervention group mice were intraperitoneally injected with 0.1 ml of JWH133 (2.5 mg/kg, dissolved in physiological saline), and the JWH133+AM630 antagonistic group mice were intraperitoneally injected with 0.1 ml of JWH133 (2.5 mg/kg) and AM630 (2.5 mg/kg). After 28 days, all mice were killed; the lung tissue was obtained, pathological changes were observed, and alveolar inflammation scores and Ashcroft scores were calculated. The content of type Ⅰ collagen in the lung tissue of the four groups of mice was measured using immunohistochemistry. The levels of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in the serum of the four groups of mice were measured using enzyme-linked immunosorbent assay (ELISA), and the content of hydroxyproline (HYP) in the lung tissue of the four groups of mice was measured. Western blotting was used to measure the protein expression levels of type Ⅲ collagen, α-smooth muscle actin (α-SMA), extracellular signal regulated kinase (ERK1/2), phosphorylated P-ERK1/2 (P-ERK1/2), and phosphorylated ribosome S6 kinase type 1 (P-p90RSK) in the lung tissue of mice in the four groups. Real-time quantitative polymerase chain reaction was used to measure the expression levels of collagen Ⅰ, collagen Ⅲ, and α-SMA mRNA in the lung tissue of the four groups of mice. Results: Compared with the control group, the pathological changes in the lung tissue of the model group mice worsened, with an increase in alveolar inflammation score (3.833±0.408 vs. 0.833±0.408, P<0.05), an increase in Ashcroft score (7.333±0.516 vs. 2.000±0.633, P<0.05), an increase in type Ⅰ collagen absorbance value (0.065±0.008 vs. 0.018±0.006, P<0.05), an increase in inflammatory cell infiltration, and an increase in hydroxyproline levels [(1.551±0.051) μg/mg vs. (0.974±0.060) μg/mg, P<0.05]. Compared with the model group, the JWH133 intervention group showed reduced pathological changes in lung tissue, decreased alveolar inflammation score (1.833±0.408, P<0.05), decreased Ashcroft score (4.167±0.753, P<0.05), decreased type Ⅰ collagen absorbance value (0.032±0.004, P<0.05), reduced inflammatory cell infiltration, and decreased hydroxyproline levels [(1.148±0.055) μg/mg, P<0.05]. Compared with the JWH133 intervention group, the JWH133+AM630 antagonistic group showed more severe pathological changes in the lung tissue of mice, increased alveolar inflammation score and Ashcroft score, increased type Ⅰ collagen absorbance value, increased inflammatory cell infiltration, and increased hydroxyproline levels. Compared with the control group, the expression of α-SMA, type Ⅲ collagen, P-ERK1/2, and P-p90RSK proteins in the lung tissue of the model group mice increased, while the expression of type Ⅰ collagen, type Ⅲ collagen, and α-SMA mRNA increased. Compared with the model group, the protein expression of α-SMA (relative expression 0.60±0.17 vs. 1.34±0.19, P<0.05), type Ⅲ collagen (relative expression 0.52±0.09 vs. 1.35±0.14, P<0.05), P-ERK1/2 (relative expression 0.32±0.11 vs. 1.14±0.14, P<0.05), and P-p90RSK (relative expression 0.43±0.14 vs. 1.15±0.07, P<0.05) decreased in the JWH133 intervention group. The type Ⅰ collagen mRNA (2.190±0.362 vs. 5.078±0.792, P<0.05), type Ⅲ collagen mRNA (1.750±0.290 vs. 4.935±0.456, P<0.05), and α-SMA mRNA (1.588±0.060 vs. 5.192±0.506, P<0.05) decreased. Compared with the JWH133 intervention group, the JWH133+AM630 antagonistic group increased the expression of α-SMA, type Ⅲ collagen, P-ERK1/2, and P-p90RSK protein in the lung tissue of mice, and increased the expression of type Ⅲ collagen and α-SMA mRNA. Conclusion: In mice with bleomycin-induced pulmonary fibrosis, the cannabinoid type-2 receptor agonist JWH133 inhibited inflammation and improved extracellular matrix deposition, which alleviated lung fibrosis. The underlying mechanism of action may be related to the activation of the ERK1/2-RSK1 signaling pathway.
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Ratones , Masculino , Animales , Fibrosis Pulmonar/patología , Agonistas de Receptores de Cannabinoides/metabolismo , Colágeno Tipo I/farmacología , Colágeno Tipo III/farmacología , Hidroxiprolina/farmacología , Cloruro de Sodio/metabolismo , Ratones Endogámicos C57BL , Pulmón/patología , Cannabinoides/efectos adversos , Bleomicina/metabolismo , Colágeno/metabolismo , Inflamación/patología , ARN Mensajero/metabolismoRESUMEN
Objective: To summarize the clinical data and prognosis of children with Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) common genes. Methods: This was a retrospective cohort study.Clinical data of 56 children with Ph-like ALL common gene cases (Ph-like ALL positive group) treated from January 2017 to January 2022 in the First Affiliated Hospital of Zhengzhou University, Henan Children's Hospital, Henan Cancer's Hospital and Henan Provincial People's Hospital were collected, 69 children with other high-risk B cell acute lymphoblastic leukemia (B-ALL) at the same time and the same age were selected as the negative group. The clinical characteristics and prognosis of two groups were analyzed retrospectively. Comparisons between groups were performed using Mann-Whitney U test and χ2 test. Kaplan-Meier method was used for survival curve, Log-Rank test was used for univariate analysis, and the Cox regression model was used for multivariate prognosis analysis. Results: Among 56 Ph-like ALL positive patients, there were 30 males and 26 females, and 15 cases were over 10 years old. There were 69 patients in Ph-like ALL negative group. Compared with the negative group, the children in positive group were older (6.4 (4.2, 11.2) vs. 4.7 (2.8, 8.4) years), and hyperleukocytosis (≥50×109/L) was more common (25% (14/56) vs. 9% (6/69)), the differences were statistically significant (both P<0.05). In the Ph-like ALL positive group, 32 cases were positive for IK6 (1 case was co-expressed with IK6 and EBF1-PDGFRB), 24 cases were IK6-negative, of which 9 cases were CRLF2 positive (including 2 cases with P2RY8-CRLF2, 7 cases with CRLF2 high expression), 5 cases were PDGFRB rearrangement, 4 cases were ABL1 rearrangement, 4 cases were JAK2 rearrangement, 1 case was ABL2 rearrangement and 1 case was EPOR rearrangement. The follow-up time of Ph-like ALL positive group was 22 (12, 40) months, and 32 (20, 45) months for negative group. The 3-year overall survival (OS) rate of positive group was significantly lower than the negative group ((72±7) % vs. (86±5) %, χ2=4.59, P<0.05). Compared with the 24 IK6-negative patients, the 3-year event free survival (EFS) rate of 32 IK6 positive patients was higher, the difference was statistically significant ((88±9) % vs. (65±14) %, χ2=5.37, P<0.05). Multivariate Cox regression analysis showed that the bone marrow minimal residual disease (MRD) not turning negative at the end of first induction (HR=4.12, 95%CI 1.13-15.03) independent prognostic risk factor for patient with Ph-like ALL common genes. Conclusions: Children with Ph-like ALL common genes were older than other high-risk B-ALL patients at diagnosis, with high white blood cells and lower survival rate. The bone marrow MRD not turning negative at the end of first induction were independent prognostic risk factor for children with Ph-like ALL common gene.
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Masculino , Femenino , Humanos , Niño , Pronóstico , Cromosoma Filadelfia , Estudios Retrospectivos , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Neoplasia ResidualRESUMEN
Objective: To compare the volumetric changes of cervical disc herniation (CDH) after cervical microendoscopic laminoplasty(CMEL),expansive open-door laminoplasty (EOLP) and conservative treatment. Methods: A retrospective study was conducted involving 101 patients with cervical spondylotic myelopathy(CSM),at the Department of Orthopaedics,the First Affiliated Hospital of Zhengzhou University from April 2012 to April 2021. The patients included 52 males and 49 females with an age of (54.7±11.8) years(range:25 to 86 years). Among them, 35 patients accepted CMEL treatment,33 patients accepted EOLP treatment,while 33 patients accepted conservative treatment. Volume data of CDH were measured by three-dimensional analysis of the initial and follow-up MRI images. The absorption rate and reprotrusion rate of CDH were calculated. The happening of resorption or reprotrusion was defined when the ratio was greater than 5%. The clinical outcomes and quality of life were evaluated by the Japanese Orthopaedic Association (JOA) score and the neck disability index (NDI).Quantitative data was analyzed by one-way ANOVA with post LSD-t test (multiple comparison) or Kruskal-Wallis test. Categorical data was analyzed by χ2test. Results: The follow-up time of the CMEL group,EOLP group and the conservative treatment group were (27.6±18.8)months,(21.6±6.9)months and(24.9±16.3)months respectively with no significant difference(P>0.05). Changes of CDH volume in patients:(1) There were 96 CDH of 35 patients in the CMEL group,among which 78 showed absorption. The absorption frequency was 81.3%(78/96) and the absorption rate was ranged 5.9% to 90.9%;9 CDH showed reprotrusion,the reprotrusion frequency was 9.4% (9/96) and the reprotrusion rate was 5.9% to 13.3%;(2) There were 94 CDH of 33 patients in the EOLP group,of which 45 showed absorption. The absorption prevalence was 47.9% (45/94) and the absorption rate was 5.0% to 26.7%;20 CDH showed reprotruded,with the reprotrusion frequency of 21.3% (20/94) and the reprotrusion rate was 5.8% to 28.3%;(3) There were 102 CDH in 33 patients of the conservative group. Among them, 5 showed absorption. The absorption frequency was 4.9% (5/102),and the absorption rate was 7.2% to 14.3%;58 CDH showed reprotruded with the re-protrusion ratio of 56.9% (58/102) and the re-protrusion rate was 5.4% to 174.1%. The absorption ratio and reprotrusion ratio of the CMEL group were statistically different from EOLP group or the conservative group (P<0.01).The absorption ratio and reprotrusion ratio of the EOLP group was different from conservative group (P<0.01). In terms of clinical outcomes, the excellent/good rate of the JOA score and NDI scores in the CMEL group were different from that of conservative group (P<0.01) but not from that of the EOLP group(P>0.05). Conclusions: CMEL is an effective method for the treatment of CSM,making CDH easier to resorption compared to the EOLP or conservative treatment,thus making a better decompression effect on the nerves. This study enlightened on a new strategy for the clinical treatment of CSM.
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Objective: To investigate the clinical, pathological and immunophenotypic features, molecular biology and prognosis of fibrin-associated large B-cell lymphoma (LBCL-FA) in various sites. Methods: Six cases of LBCL-FA diagnosed from April 2016 to November 2021 at the Beijing Friendship Hospital, Capital Medical University, Beijing, China and the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China were collected. The cases were divided into atrial myxoma and cyst-related groups. Clinical characteristics, pathological morphology, immunophenotype, Epstein Barr virus infection status, B-cell gene rearrangement and fluorescence in situ hybridization of MYC, bcl-2, bcl-6 were summarized. Results: The patients' mean age was 60 years. All of them were male. Three cases occurred in atrial myxoma background, while the others were in cyst-related background, including adrenal gland, abdominal cavity and subdura. All cases showed tumor cells located in pink fibrin clot. However, three cyst-related cases showed the cyst wall with obviously fibrosis and inflammatory cells. All cases tested were non germinal center B cell origin, positive for PD-L1, EBER and EBNA2, and were negative for MYC, bcl-2 and bcl-6 rearrangements, except one case with MYC, bcl-2 and bcl-6 amplification. All of the 5 cases showed monoclonal rearrangement of the Ig gene using PCR based analysis. The patients had detailed follow-ups of 9-120 months, were treated surgically without radiotherapy or chemotherapy, and had long-term disease-free survivals. Conclusions: LBCL-FA is a group of rare diseases occurring in various sites, with predilection in the context of atrial myxoma and cyst-related lesions. Cyst-related lesions with obvious chronic inflammatory background show more scarcity of lymphoid cells and obvious degeneration, which are easy to be missed or misdiagnosed. LBCL-FA overall has a good prognosis with the potential for cure by surgery alone and postoperative chemotherapy may not be necessary.