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OBJECTIVE To establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of bepotastine and hydroxychloroquine concentrations in human breast milk and apply it in clinical practice. METHODS The milk samples (50 μL) were precipitated with 200 μL methanol containing the internal standard (100 ng/mL chloroquine), and the supernatant was taken for analysis after vortexing and centrifugation. The separation was performed on a Waters ACQUITY UPLC HSS T3 column with mobile phase consisted of 0.1% formic acid-10 mmol/L ammonium acetate solution (phase A) and methanol (phase B) at gradient elution of 0.35 mL/min. The injection volume was 2 μL, and the analysis time was 4 min. The detection of the analytes was performed by electrospray ionization in positive mode by multiple reaction monitoring with the transition of m/z 388.9→201.9 (bepotastine), m/z 336.3→247.1 (hydroxychloroquine), and m/z 320.2→247.2 (chloroquine). The established LC-MS/MS method was researched in methodology and used to determine the drug concentrations in the breast milk of 1 case of lactating patient. RESULTS The linear range of bepotastine was 2-200 ng/mL( r=0.999), and hydroxychloroquine was 50-1 000 ng/mL (r=0.998). The intra-assay and inter-assay precisions were both ≤15%, and the accuracy, extraction recovery, matrix effect, and stability all met the acceptance criteria for bioanalytical method validation. The concentration result of bepotastine and hydroxychloroquine in the breast milk of the lactating patient showed, after 2 h and 14 h, the concentrations of bepotastine in the breast milk of the patient were 34.95 ng/mL and 5.72 ng/mL; those of hydroxychloroquine were 211.92 ng/mL and 104.18 ng/mL, respectively. The relative infant doses were 1.83% and 0.56%, respectively. CONCLUSIONS The established method is simple, rapid, and sensitive. It is suitable for simultaneous determination of bepotastine and hydroxychloroquine concentrations in human milk and can provide reference for safe drug use during lactation.
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OBJECTIVE To establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of bepotastine and hydroxychloroquine concentrations in human breast milk and apply it in clinical practice. METHODS The milk samples (50 μL) were precipitated with 200 μL methanol containing the internal standard (100 ng/mL chloroquine), and the supernatant was taken for analysis after vortexing and centrifugation. The separation was performed on a Waters ACQUITY UPLC HSS T3 column with mobile phase consisted of 0.1% formic acid-10 mmol/L ammonium acetate solution (phase A) and methanol (phase B) at gradient elution of 0.35 mL/min. The injection volume was 2 μL, and the analysis time was 4 min. The detection of the analytes was performed by electrospray ionization in positive mode by multiple reaction monitoring with the transition of m/z 388.9→201.9 (bepotastine), m/z 336.3→247.1 (hydroxychloroquine), and m/z 320.2→247.2 (chloroquine). The established LC-MS/MS method was researched in methodology and used to determine the drug concentrations in the breast milk of 1 case of lactating patient. RESULTS The linear range of bepotastine was 2-200 ng/mL( r=0.999), and hydroxychloroquine was 50-1 000 ng/mL (r=0.998). The intra-assay and inter-assay precisions were both ≤15%, and the accuracy, extraction recovery, matrix effect, and stability all met the acceptance criteria for bioanalytical method validation. The concentration result of bepotastine and hydroxychloroquine in the breast milk of the lactating patient showed, after 2 h and 14 h, the concentrations of bepotastine in the breast milk of the patient were 34.95 ng/mL and 5.72 ng/mL; those of hydroxychloroquine were 211.92 ng/mL and 104.18 ng/mL, respectively. The relative infant doses were 1.83% and 0.56%, respectively. CONCLUSIONS The established method is simple, rapid, and sensitive. It is suitable for simultaneous determination of bepotastine and hydroxychloroquine concentrations in human milk and can provide reference for safe drug use during lactation.
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Objective:To analyze the diagnostic performance of contrast-enhanced ultrasound (CEUS) in the diagnosis of papillary thyroid carcinoma (PTC) and related parameters in the diagnosis of cervical lymph node metastasis.Methods:The clinical data of 130 patients who underwent ultrasonography in Ningbo Hospital of Traditional Chinese Medicine from Jan. 2019 to Jan. 2022 were retrospectively analyzed. All patients received contrast-enhanced ultrasonography and postoperative pathological examination. According to the pathological diagnosis of benign and malignant tumors, they were divided into PTC group and benign nodule group. In the PTC group, there were 46 males and 40 females, aging 51.79±5.01 years old, ranging from 32 to 63 years old; In the nodule group, there were 25 males and 19 females, aging 52.05±4.89 years old, ranging from 33 to 64 years old. According to the presence or absence of cervical LNM, they were divided into a metastasis group of 31 cases, 17 males and 14 females; age (51.69±6.14 years), ranging from 36 to 63 years; 55 cases in the non-transfer group, 29 males and 26 females, aging (51.75±6.18) years, ranging from 36 to 62 years. Comparative analysis of different nodule properties, presence or absence of LNM, different lesion diameters in imaging manifestations and time-intensity curve (time-intensity curve, TIC) parameters differences, measurement data between groups were conducted by independent sample t test, count data between groups were compared by χ2. The receiver operating characteristic curve (receiver operating characteristic, ROC) was drawn to evaluate the diagnostic performance of TIC parameters for cervical LNM. Results:The proportion of PTC nodules with low enhancement, irregular enhancement, heterogeneous enhancement, unclear lesion boundary, and perfusion defect (72.09%, 87.21%, 88.64%, 69.77%, 70.93%) was significantly higher than that of benign nodules (38.64%, 11.36%) %, 27.27%, 77.27%, 27.27%) ( χ2=13.67, 70.75, 49.69, 25.92, 18.24, P<0.05) ; PTC nodule peak intensity (peak intensity, PI), TIC area under the curve (area under curve, AUC) was significantly lower than that of benign nodules (14.86±2.11dB vs 23.94±3.51dB, 985.14±105.31dB·s vs 1621.14±182.61dB·s) ; time to peak (TTP) was significantly higher than that of benign nodules ( 44.82±5.01s vs 36.95±4.18s) ( t=18.39, 21.36, 8.94, P<0.05) ; there was no significant difference in mean transit time (MTT) ( P>0.05) ; AUC was significantly higher than that of the non-metastatic group (16.86±2.09) dB vs (13.73±1.42) dB, (1163.54±131.41) dB·s vs (884.59±93.25) dB·s ( t=8.25, 11.46, P<0.05) ; The PI and AUC of PTC patients with lesion diameter ≤1.5 cm were significantly lower than those of patients with lesion diameter > 1.5 cm (11.56±1.94) dB vs (15.93±2.46) dB, (876.97±100.21) dB·s vs (1020.09±125.41) dB·s ( t=8.39, 5.34, P< 0.05), there was no significant difference in terms of TTP or MTT ( P>0.05) ; the AUC of PI in the diagnosis of cervical lymph node metastasis in PTC patients was 0.888 (95% CI: 0.807-0.969), the sensitivity was 90.91%, and the specificity was 77.42%; The AUC for the diagnosis of cervical lymph node metastasis in PTC patients was 0.972 (95% CI: 0.943-1.000), with a sensitivity of 87.10% and a specificity of 96.36%. Conclusion:The CEUS manifestations of PTC nodules are mostly irregular and heterogeneous low-enhancement, and the TIC-related parameters of PTC nodules and benign nodules are significantly different, and TIC-related parameters have good diagnostic efficiency for patients with cervical lymph node metastasis.
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Objective:To investigate the clinical characteristics and short-term follow-up outcomes of primary nephrotic syndrome (PNS) children infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the Omicron variant outbreak in Shanghai, and to provide a reliable reference for clinicians in the diagnosis and treatment.Methods:It was a case-control study. The clinical data of children with PNS (PNS group) who were diagnosed and followed-up up to 1 year in the nephrology department of four children's medical centers in Shanghai, and the children (control group) who had no underlying diseases and were infected with SARS-CoV-2 in Shanghai Jinshan Public Health Center, including the data when they were infected with SARS-CoV-2, were retrospectively analyzed.Results:(1) From March 30th to April 13th, 2022, 6 PNS children in Shanghai were infected with SARS-CoV-2, including 5 boys and 1 girl. The median age was 4.5 (2.0, 11.0) years old. And 30 children were matched by sex, age and disease type as control group, including 20 males and 10 females. The median age was 4.5 (2.0, 9.0) years. There were no significant differences between the PNS group and the control group in clinical symptoms (including fever duration), treatment regimens, vaccine doses and virus clearance time (all P>0.05). (2) The 6 children with PNS included 3 cases of steroid-sensitive type, 3 cases of steroid-resistant type, 2 cases of minimal change disease, 2 cases of focal segmental glomerulosclerosis and 2 cases with no renal biopsy. Before SARS-CoV-2 infection, their primary disease-PNS were stable, and urine protein was negative, four of them were under maintenance treatment with oral steroids or immunosuppressive drugs. At the time of SARS-CoV-2 infection, the symptoms of all of the 6 cases were mild, no severe, critical or fatal cases, and they were all cured and discharged from hospital through medical isolation observation or symptomatic treatment of infections. (3) Five cases of them still had discomfort symptoms such as cough, anorexia, and fatigue after being discharged from the hospital, which lasted for about 1 week. Within 1 year of follow-up, none of the children have suffered from "recurrent positive PCR results" or "secondary infection" of the SARS-CoV-2. (4) Among them, 4 cases of PNS relapsed after SARS-CoV-2 infection, timely addition of steroids was effective, their urine protein quickly turned negative, and there was no recurrence after 1 year of follow-up. (5) Before infection with SARS-CoV-2, the levels of immunoglobulin IgG were lower than the normal reference value in the 4 cases with PNS recurrence. Conclusions:During the Omicron variant outbreak in Shanghai, the infection of SARS-CoV-2 in children with PNS are resulted in high transmission among household contacts. Most of them have mild symptoms and good prognosis. PNS is prone to relapse after SARS-CoV-2 infection, and steroid therapy is effective and safe for these relapse. IgG may be a potential marker for the prognosis of PNS children infected with SARS-CoV-2.
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Objective:To evaluate the safety and feasibility of neoadjuvant chemotherapy (NACT) combined with radical surgery for elderly patients with locally advanced gastric cancer (LAGC).Methods:One hundred and fourty eight patients with LAGC after NACT and gastrectomy between 2012 and 2020 were retrospectively reviewed. They were divided into two groups: (1) <65 years old (111 cases) and (2) ≥65 years old (37 cases) and their clinicopathological and prognostic data were compared.Results:There was no significant difference between the two groups in the incidence of hematological complications such as anemia ( χ2=0.235, P=0.628), leukopenia ( χ2=0.613, P=0.434), neutropenia ( χ2=0.011, P=0.918) and thrombocytopenia ( χ2=0.253, P=0.615) and non-hematological complications such as nausea ( χ2=0.092, P=0.762), vomiting ( χ2=0.166, P=0.683), diarrhea ( χ2=0.015, P=0.902) and mucositis ( χ2=0.199, P=0.766) due to NACT. There were no statistical differences between the older patients and the younger in operation duration ( t=0.270, P=0.604), intraoperative bleeding ( t=1.140, P=0.250) and R 0 resection rate ( χ2=0.105, P=0.750). The incidence of postoperative complications was 25.2% and 37.8% in the younger patients and the olders ( χ2=2.172, P=0.141). Pleural effusion ( χ2=7.007, P=0.008) and pulmonary infection ( χ2=10.204, P=0.001) was significantly higher in the older patients than in the youngers. The 3-year progression-free survival rate ( t=0.494, P=0.482) and 3-year overall survival rate ( t=0.013, P=0.908) were comparable between the two groups. Conclusions:NACT combined with radical surgery is safe and effective in elderly patients with LAGC, except for higher perioperative pulmonary-related complications.
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The paper summarizes the clinical and follow-up data of percutaneous endoscopic gastrostomy (PEG) in three infants with chronic kidney disease to explore the safety and reliability of using PEG to improve the growth and development, and nutritional status. During follow-up, the weight and height of case 1 and 3 were obviously improved. Case 2 was followed up for 3 months, due to dying of cardiac arrest, and the infant's height and weight were not significantly improved. Serum albumin and prealbumin improved in 3 cases after PEG. No PEG-related infection occurred in 3 infants.
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Objective:To investigate the safety and feasibility of the CHESS endoscpic ruler (CHESS ruler), and the consistency between the measured values and the interpretation values by endoscopic physician experience.Methods:From January 2021 to January 2022, a total of 105 liver cirrhosis patients with portal hypertension were prospectively enrolled from General Hospital, Xixia Branch Hospital, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region (29 cases), and the First People′s Hospital of Yinchuan (25 cases), General Hospital of Ningxia Medical University (18 cases), Wuzhong People′s Hospital (10 cases), the Fifth People′s Hospital of Ningxia Hui Autonomous Region (10 cases), Shizuishan Second People′s Hospital (6 cases), Yinchuan Second People′s Hospital (5 cases), and Zhongwei People′s Hospital (2 cases) 8 hospitals. The clinical characteristics of all the patients, including gender, age, nationality, etiolog of liver cirrhosis, and Child-Pugh classification of liver function were recorded. A big gastroesophageal varices was defined as diameter of varices ≥5 mm. Endoscopist (associated chief physician) performed gastroscopy according to the routine gastroscopy procedures, and the diameter of the biggest esophageal varices was measured by experience and images were collected, and then objective measurement was with the CHESS ruler and images were collected. The diameter of esophageal varices of 10 randomly selected patients (random number table method) was determined by 6 endoscopists (attending physician or associated chief physician) with experience or measured by CHESS ruler. Kappa test was used to test the consistency in the diameter of esophageal varices between measured values by CHESS ruler and the interpretation values by endoscopic physician experience.Results:Among 105 liver cirrhosis patients with portal hypertension, male 65 cases and female 40 cases, aged (54.8±12.2) years old, Han nationality 82 cases, Hui nationality 21 cases and Mongolian nationality 2 cases. The etiology of liver cirrhosis included chronic hepatitis B (79 cases), alcoholic liver disease (7 cases), autoimmune hepatitis (7 cases), chronic hepatitis C (2 cases), and other etiology (10 cases). Liver function of 32 cases was Child-Pugh A, Child-Pugh B 57 cases, and Child-Pugh C 16 cases. All 105 liver cirrhosis patients with cirrhotic portal hypertension were successfully measured the diameter of gastroesophageal varices by CHESS ruler, and the success rate of application of CHESS ruler was 100.0% (105/105). The procedure time from the CHESS ruler into the body to the exit of the body after measurement was (3.50±2.55) min. No complications happened in all the patients during measurement. Among 105 liver cirrhosis patients with cirrhotic portal hypertension, 96 cases (91.4%) were recognized as big gastroesophageal varices by the endoscopists. Totally 93 cases (88.6%) were considered as big gastroesophageal varices by CHESS ruler. Eight cases were recognized as big gastroesophageal varices by the endoscopist, however not by the CHESS ruler; 5 cases were recognized as big gastroesophageal varices by the CHESS ruler, but not by the endoscopists; 4 cases were not recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler; 88 cases were recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler. The missed diagnostic rate of big gastroesophageal varices by the endoscopists experience was 5.4% (5/93), and the Kappa value of consistency coefficient between the measurement by the CHESS ruler and the interpretation by endoscopists experience was 0.31 (95% confidence interval 0.03 to 0.60). The overall Kappa value of consistency coefficient by 6 endoscopists measured by CHESS ruler in big gastroesophageal varices diagnosis was 0.77 (95% confidence interval 0.61 to 0.93).Conclusion:As an objective measurement tool, CHESS ruler can make up for the deficiency of subjective judgment by endoscopists, accurately measure the diameter of gastroesophageal varices, and is highly feasible and safe.
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Cervical cancer is a gynecological malignant tumor with a high incidence in the world. With the insidious onset and lack of obvious symptoms and signs in the early stage, 13% of cervical cancer patients are diagnosed in the advanced stage of the disease, and the 5-year survival rate of metastatic cervical cancer is only 16.5%. So far, surgery and radiotherapy/chemotherapy are still the basic means for the treatment of cervical cancer. However, with the emergence of toxicity, drug resistance, and other side effects, there are still some limitations in the clinical application of these therapies. In recent years, natural compounds represented by polysaccharides have been found to have a significant anti-cervical cancer effect, which has attracted extensive attention from researchers in China and abroad. Widely distributed in the roots, stems, leaves, flowers, and fruits of higher plants, plant-based polysaccharides are important components of natural polysaccharides, as well as multimers with a complex structure and biological response regulators, which have been widely studied in the fields of cancer, cardiovascular, endocrine, and other diseases. This study reviewed the research on the anti-cervical cancer effect and mechanism of natural plant-derived polysaccharides by consulting the literature in the past 20 years to bring breakthroughs in the research and development of anti-cervical cancer new drugs. Through the literature review, the results indicated that natural plant-derived polysaccharides could exert anti-tumor effects by inhibiting cell proliferation, promoting apoptosis, inhibiting invasion and migration, promoting autophagy, arresting cell cycle of cervical cancer cells, regulating epithelial-mesenchymal transition (EMT), resisting oxidative stress, inhibiting tumor angiogenesis, improving immunomodulatory activity, and regulating signaling pathways. It should be noted that in the current research on natural plant-derived polysaccharides against cervical cancer, the bioavailability of some natural polysaccharides is low and a considerable proportion of the research is limited to the in vitro experiment. Therefore, it is urgent to carry out more clinical experimental studies on the anti-cervical cancer of natural plant-based polysaccharides to obtain a more reliable theoretical and practical basis.
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Objective: To explore the short-term efficacy and safety of dapagliflozin in children with hereditary proteinuric kidney disease. Methods: This was a prospective cohort study. From August 2020 to December 2021, 23 children with hereditary kidney disease from Children's Hospital of Fudan University were enrolled. Patients received dapagliflozin 5 mg/d (weight≤30 kg) or initial dose 5 mg/d for 1 week, then 10 mg/d (weight>30 kg) and the dose of angiotensin converting enzyme inhibitors was stable during treatment. Clinical data including demographic parameters, primary diagnosis, estimated glomerular filtration rate (eGFR), 24 h proteinuria and characteristics in the follow-up were collected. The primary outcome was the change in 24 h proteinuria at 12 (±2) weeks, secondary outcomes included changes of 24 h proteinuria at 24 (±2) weeks, eGFR at both 12 (±2) and 24 (±2) weeks. The data were analysed by using mixed linear model. Results: Totally 23 patients were enrolled, including 16 males and 7 females. The age was (10.8±2.9) years. The primary diseases were Alport syndrome (12 cases), Dent disease (5 cases), proteinuria (4 cases), and focal segmental glomerulosclerosis (2 cases) respectively. Primary outcome showed that 24 h proteinuria decreased from baseline at 12 (±2) weeks during treatment (1.75 (1.46, 2.20) vs. 1.84 (1.14, 2.54) g/m2, P<0.05). Secondary outcomes showed that there was no significant difference in 24 h urine protein at 24 (±2) weeks (P>0.05). eGFR decreased slightly at 12 (±2) weeks ((107±21) vs. (112±28) ml/(min·1.73m2), P<0.05), and there was no significant difference at 24 (±2) weeks (P>0.05). Serum albumin increased at 12 (±2) and 24 (±2) weeks following the treatment ((39±8) vs. (37±8) g/L, (38±7) vs. (37±8) g/L, both P<0.05). No hypoglycemia event was reported during the treatment. Conclusion: The dapagliflozin had therapeutic effects on decreasing proteinuria and increasing serum albumin in short-term treatment in children with hereditary proteinuric kidney disease, no hypoglycemia or serious adverse events were observed.
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Feminino , Masculino , Humanos , Criança , Adolescente , Estudos Prospectivos , Nefrite Hereditária , Proteinúria/tratamento farmacológico , Albumina SéricaRESUMO
Visually induced motion sickness(VIMS)is the major barrier to be broken in the development of virtual reality(VR)technology,which seriously affects the progress in the VR industry.Therefore,the detection and evaluation of VIMS has become a hot research topic nowadays.We review the progress in physiological assessment of VIMS in VR based on several physiological indicators,including electroencephalogram(EEG),postural sway,eye movements,heart rate variability,and skin electrical signals,and summarize the available therapies,aiming to provide an outlook on the future research directions of VIMS.
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Humanos , Enjoo devido ao Movimento/diagnóstico , Realidade Virtual , Frequência CardíacaRESUMO
Objective:To explore the real maternal and infant care experience and needs of spouses of puerperal women, so as to provide a basis for improving maternal and infant care capacity and participation of spouses and promoting maternal and infant health.Methods:Guided by dyadic coping theory, the semi-structured interviews were conducted among 18 spouses of puerperal women who gave birth at the First Affiliated Hospital of Soochow University from July to September 2022 using the phenomenological research method, and the recording data were analyzed by Colaizzi phenomenon analytical method.Results:Three themes were extracted, including positive experience of maternal and infant care of spouses of puerperal women (positive psychological emotions, adjustment of perceptions and behaviors, understanding of social support), negative experience of maternal and infant care of spouses of puerperal women (negative psychological emotions, poor care competence, imbalance during life and work), diversified needs for maternal and infant care of spouses of puerperal women (the need for multidimensional knowledge and skills, the suggestion of building continuous health education platform, the expectation of support from family).Conclusions:Medical staff should provide the spouses of puerperal women with diversified maternal and infant care and professional continuing nursing according to their experience and needs. Meanwhile, the family support system should be improved to enhance their sense of competence and participation in maternal and infant care and promote maternal and infant health.
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OBJECTIVE To evaluate the efficacy and safety of antibody-drug conjugates (ADC) in the treatment of breast cancer, so as to provide an evidence-based reference for clinical medication. METHODS Retrieved from CNKI, Wanfang database, VIP, PubMed, the Cochrane Library, Embase, and Web of Science, randomized controlled trials (RCTs) about trastuzumab emtansine, trastuzumab deruxtecan and sacituzumab govitecan (trial group) versus chemotherapy or other anti-tumor drugs (control group), were collected during the inception to April 2023. After screening the literature, extracting data, and evaluating the quality of the literature, a meta-analysis was conducted by using RevMan 5.4.1 software. RESULTS A total of 8 RCTs were included, with a total of 5 577 patients. The results of the meta-analysis showed that the progression-free survival (PFS) [HR=0.76, 95%CI (0.69, 0.83), P<0.000 01], overall survival (OS) [HR=0.87, 95%CI (0.81, 0.93), P<0.000 1], and clinical benefit rate (CBR) [OR=2.70, 95%CI (1.15, 6.33), P=0.02] of the trial group were significantly higher than control group. There was no statistically significant difference in objective response rate (ORR) between the two groups [OR=2.34, 95%CI (0.59, 9.33), P=0.23]. The results of subgroup analysis showed that the PFS of HER2-positive patients and HER2-negative patients, and the OS of HER2-positive patients in the trial group were significantly higher than control group (P<0.05). The incidence of anemia and increase of aspartic acid transaminase (AST) in the trial group was significantly higher than control group (P<0.05). The results of sensitivity analysis showed that the results obtained with PFS, OS, and ORR as indicators were relatively robust, while the results obtained with CBR as indicators lacked robustness. CONCLUSIONS ADC drugs have significant effects on breast cancer, but will increase the risk of anemia and elevated AST.
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Maternal diabetes not only affects the mother′s own health but also has a significant influence on offspring.Adverse prenatal and intrauterine condition can influence fetal kidney development, which may increase the risk of kidney disease in the adulthood.This article reveiws the impact of maternal diabetes on kidney structure and function.Maternal diabetes can increase the risk of congenital anomalies of the kidney and urinary tract(CAKUT)and impair early and long-term renal function of offspring.In addition, this article reveiws the research progress of the potential mechanisms of how maternal diabetes affects kidney development including oxidative stress, key signal pathway changes of kidney development and epigenetic changes.
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In recent years, rituximab(RTX) has been increasingly used in the treatment of refractory primary nephrotic syndrome in children, and has achieved positive effects.Experimental evidence suggests that RTX may exert its therapeutic effects by directly acting on B cells and T cells, interfering with the interaction between B cells and T cells, and directly protecting podocytes.However, the number of studies on the mechanism of RTX in the treatment of nephrotic syndrome is limited and there is no definitive evidence, so there is no consensus in the academic community.This article summarizes experimental research results and reasonable speculations put forward by many scholars in recent years, and summarizes the significance of the research on the mechanism of RTX and the existing research gaps in this field, in order to provide theoretical guidance for the clinical application of RTX.
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Long non-coding RNAs (lncRNAs) play an important role in cancer metastasis. Exploring metastasis-associated lncRNAs and developing effective strategy for targeted regulation of lncRNA function in vivo are of utmost importance for the treatment of metastatic cancer, which however remains a big challenge. Herein, we identified a new functional lncRNA (denoted lncBCMA), which could stabilize the expression of eukaryotic translation elongation factor 1A1 (eEF1A1) via antagonizing its ubiquitination to promote triple-negative breast cancer (TNBC) growth and metastasis. Based on this regulatory mechanism, an endosomal pH-responsive nanoparticle (NP) platform was engineered for systemic lncBCMA siRNA (siBCMA) delivery. This NPs-mediated siBCMA delivery could effectively silence lncBCMA expression and promote eEF1A1 ubiquitination, thereby leading to a significant inhibition of TNBC tumor growth and metastasis. These findings show that lncBCMA could be used as a potential biomarker to predict the prognosis of TNBC patients and NPs-mediated lncBCMA silencing could be an effective strategy for metastatic TNBC treatment.
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The software of 3D-Modeling(UG NX 10.0) was used to design a new external fixator model for proximal femoral fracture, and fresh femoral cadaver specimens were used to simulate experimental operation. The results showed that the external fixator designed with the proximal femoral locking plate shape can improve the accuracy of Kirschner wire penetration into the femoral neck, reduce fluoroscopic and soft tissue incision injuries, and make a good stability and is easy to operate, which has a certain value for patients with proximal femoral fracture, such as intolerant surgery and poor physical condition.
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Humanos , Placas Ósseas , Fixadores Externos , Fraturas do Fêmur/cirurgia , Fixação Interna de Fraturas/métodosRESUMO
Objective:To investigate the clinicopathological features and prognosis of patients with gastric gastrointestinal stromal tumor (GIST) combined with digestive tract cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 163 patients with gastric GIST who were admitted to the Union Hospital admitted to Tongji Medical College of Huazhong University of Science and Technology from January 2002 to December 2021 were collected. There were 606 males and 557 females, aged 59(range,20?94)years. Of the 1 163 patients, 129 cases with gastric GIST combined with other digestive tract cancer were divided into the combined group, and 1 034 cases with only gastric GIST were divided into the non-combined group. Observation indicators: (1) clinicopathological features of patients; (2) surgical situations and postoperative complications; (3) follow-up and survival of patients; (4) analysis of prognosis associated affecting factors. Follow-up was conducted using outpatient examination, telephone and online interview to detect survival of patients up to January 2022. The overall survival time was defined as the time from surgery to the last tine of follow-up or the outcome events, such as death of patient, loss of follow-up, etc. Measurement data with normal distribution were represented as Mean± SD, and measure-ment data with skewed distribution were represented as M(range). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Com-parison of ordinal data was conducted using the non-parameter Mann-Whitney U test. Kaplan-Meier method was used to draw survival curves and calculate survival rates, and Log-Rank test was used to conduct survival analysis. The COX proportional hazard model was used for univariate and multivariate analyses. Results:(1) Clinicopathological features of patients. Of the 129 patients in the combined group, there were 81 cases combined with gastric cancer, 39 cases combined with esophageal cancer, 8 cases combined with colon cancer and 1 case combined with rectal cancer. Gender (male, female), cases with age ≤60 years or>60 years, cases without or with clinical symp-toms before surgery, cases with tumor diameter of gastric GIST as<2 cm, 2?5 cm, 5?10 cm,>10 cm, cases with mitotic index as <5/50× high power field, 5?10/50× high power field, >10/50× high power field, cases with cell proliferation index of Ki-67 as ≤5% or >5%, cases classified as extremely low risk, low risk, medium risk and high risk of the modified national institutes of health (NIH) risk classification, cases with or without tumor necrosis of the gastric GIST, cases without or with adjuvant imatinib therapy, cases with the expression of DOG-1 detected by immunohistochemical staining as positive or negative, cases with the expression of CD34 as positive or negative were 92, 37, 30, 99, 9, 120, 114, 10, 3, 2, 126, 1, 2, 122, 2, 112, 8, 5, 4, 129, 0, 121, 8, 118, 3, 117, 12 in the combined group, versus 514, 520, 585, 449, 194, 840, 383, 360,201, 90, 799, 155, 80, 851, 143, 337, 308, 192, 197, 960, 74, 769, 265, 850, 80, 990, 44 in the non-combined group, showing significant differences in the above indicators between the two groups ( χ2=21.46, 51.11, 11.06, Z=?10.27, ?5.34, χ2=15.94, Z=?10.61, χ2=9.86, 24.10, 5.52, 6.37, P<0.05). Of the 1 163 patients, there were 12 cases of the combined group suspected diagnosed as gastric GIST before surgery and 1 case of the combined group dia-gnosed as gastric GIST by gastroscopy and pathological examination before surgery. The rest of 1 150 patients were diagnosed as gastric GIST by intraoperative exploration or postoperative pathological examination. (2) Surgical situations and postoperative complications. Of the 129 patients in the combined group, 72 cases underwent open surgery and 57 cases underwent laparoscopic or thoracoscopic surgery including 3 cases converted to open surgery. Of the 1 034 patients in the non-combined group,207 cases underwent endoscopic surgery, 371 cases underwent open surgery, and 456 cases underwent laparoscopic or thoracoscopic surgery including 8 cases converted to open surgery. Incidence of postoperative complications was 10.078%(13/129) in the combined group, versus 2.321%(24/1 034) in the non-combined group, showing a significant difference between the two groups ( χ2=22.40, P<0.05). (3) Follow-up and survival of patients. Of the 1 163 patients, 1 046 cases were followed up for 44(range, 1?220)months, with the postoperative 5-year overall survival rate as 87.2%. The postoperative 5-year overall survival rate was 51.2% in the combined group, versus 91.4% in the non-combined group, showing a significant difference between the two groups ( χ2=169.07, P<0.05). (4) Analysis of prognosis associated affecting factors. Results of univariate analysis showed that gender, age, tumor diameter of gastric GIST as 2?5 cm, 5?10 cm and >10 cm, combined with other digestive tract cancer, mitotic index as >10/50× high power field and tumor necrosis of the gastric GIST were related factors affecting the postoperative 5-year overall survival rate of patients with gastric GIST ( hazard ratio=2.16, 2.27, 0.46, 0.57, 1.75, 7.58, 2.70, 1.80, 95% confidence intervals as 1.52?3.07, 1.60?3.22, 0.29?0.71, 0.34?0.94, 1.11?2.77, 5.29?10.85, 1.67?4.38, 1.08?2.98, P<0.05). Results of multivariate analysis showed that gender, age, tumor diameter of gastric GIST, combined with other digestive tract cancer and mitotic index were independent factors affecting the post-operative 5-year overall survival rate of patients with gastric GIST ( hazard ratio=1.91, 1.82, 2.10, 7.11, 2.75, 95% confidence intervals as 1.33?2.75, 1.27?2.62, 1.14?3.87, 4.58?11.04, 1.50?5.03, P<0.05). Conclusions:The tumor diameter of gastric GIST is short in patients combined with other digestive tract cancer, and the risk grade of modified NIH risk classification is lower. Gender, age, tumor diameter of gastric GIST, combined with other digestive tract cancer and mitotic index are independent factors affecting the postoperative 5-year overall survival rate of patients with gastric GIST.
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Objective:To investigate the diagnostic value of independent and combined subtests of the psychometric hepatic encephalopathy score (PHES) in mild hepatic encephalopathy(MHE) of patients with liver cirrhosis, so as to optimize the PHES.Methods:This was a prospective, multicenter and real-world study which was sponsored by the National Clinical Research Center of Infectious Diseases and the Portal Hypertension Consortium. Twenty-six hospitals from 13 provinces, autonomous regions and municipalities countrywide participated in this study, induding Tianjin Third Central Hospital, the Fourth People′s Hospital of Qinghai Province, the Second Affiliated Hospital of Baotou Medical College, the Third People′s Hospital of Taiyuan, the Fifth Medical Center of PLA General Hospital and so on. From October 2021 to February 2022, outpatients and hospitalized patients with liver cirrhosis and no obvious hepatic encephalopathy were consecutively enrolled. All patients received 5 PHES subjects in the same order: number connection test(NCT)-A, NCT-B, digit symbol test(DST), line tracing test(LTT) and serial dotting test(SDT), and the scores were calculated. The total score of PHES <-4 was taken as the cut-off value for diagnosing MHE. Compare the differences in each subtest between MHE group and non-MHE group. Receiver operating characteristic curve(ROC) and area under the curve(AUC) was performed to assess the diagnostic value of independent and combined subtests in MHE. Mann-Whitney U test and DeLong test were used for statistical analysis. Results:A total of 581 patients with liver cirrhosis were enrolled, 457 were diagnosed as MHE, and the incidence of MHE was 78.7%. The results of NCT-A, NCT-B, SDT, LTT, DST of MHE group were 60.00 s(47.01 s, 88.00 s), 90.45 s(69.32 s, 125.35 s), 74.00 s(57.65 s, 96.60 s), 74.72(60.00, 98.61) and 27.00(20.00, 36.00), respectively. Compared those of non-MHE group(34.00 s(29.15 s, 44.48 s), 50.00 s(40.98 s, 60.77 s), 50.00 s(41.07 s, 63.03 s), 46.23(38.55, 59.42) and 42.00(34.00, 50.75)), the differences were statistically significant( Z=12.37, 12.98, 9.83, 11.56, 10.66; all P<0.001). The AUC(95% confidence interval(95% CI)) of subtests of PHES NCT-B, NCT-A, LTT, DST and SDT alone in MHE diagnosis were 0.880(0.849 to 0.910), 0.862(0.828 to 0.896), 0.838(0.799 to 0.877), 0.812(0.772 to 0.851) and 0.788(0.743 to 0.832), respectively. The combination of 2 PHES subtests significantly increased the diagnostic efficacy. Among them the diagnostic efficacy of the combination of NCT-B and LTT was the best, the AUC(95% CI) was 0.924(0.902 to 0.947), the specificity was 91.9% and the sensitivity was 79.2%, which was better than a single PHES subtest (NCT-A, NCT-B, SDT, LTT and DST) and the combination of NCT-A and DST(AUC was 0.879, 95% CI0.847 to 0.910) which was recommended by guidelines on the management of hepatic encephalopathy in cirrhosis, the differences were statistically significant ( Z=3.78, 3.83, 5.57, 5.51, 5.38, 2.93; all P<0.01). Furthermore, compared between the combination of NCT-B and LTT and the combination of 3 subests of PHES, only the diagnostic efficacy of combination of NCT-B, LTT and SDT (AUC was 0.936, 95% CI 0.916 to 0.956) was better than that of the combination of NCT-B and LTT, the difference was statistically significant( Z=2.32, P=0.020). Conclusion:Based on the diagnostic efficacy and clinical feasibility of PHES subtests and their combinations, the combination of NCT-B and LTT is recommended for the diagnosis of MHE.
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Objective:To explore the clinical features, diagnosis, treatment and prognosis of rectal neuroendocrine tumor with lymphatic metastasis.Method:There were 153 case who were diagnosed with RNET, among them, there were 10 patients(6.5%) with lymphatic metastasis in Affiliated Union Hospital, Tongji Medical College, Huazhong University of Science & Technology from January 2012 to December 2020, including 4 males and 6 females, aged from 32 to 71 years old, and the median age was 56.5 years.Results:Of the 10 patients, 3 had tumors < 1 cm in diameter, 4 had 1 to 2 cm, and 3 had > 2 cm. Preoperative CT examination was performed in 10 patients, of which 9 suggested lymphatic metastasis; preoperative MRI examination was performed in 7 patients, of which 6 suggested lymphatic metastasis. All patients were received radical resection, in which Miles operation was performed in 2 cases, Dixon operation in 6 cases, and additional Dixon operation after endoscopic submucosal dissection in 2 cases.All patients were followed up for 51 months (ranged from 14 to 118 months). Nine patients had no recurrence or metastasis, and one patient had abdominal metastasis 40 months after surgery and died after 31 months of comprehensive treatment.Conclusions:Lymphatic metastasis is rare in rectal neuroendocrine tumor. Imaging examination has important reference value for judging the status of lymphatic metastasis. For rectal neuroendocrine tumor with lymphatic metastasis, radical resection is effective.
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Objective:To investigate the distribution and antimicrobial resistance patterns of common pathogens in children with urinary tract infections in a single center in Shanghai, and to provide basis for the selection of empirical antibiotics in the clinical practice.Methods:The clinical data, urine culture and drug sensitivity tests results of children with urinary tract infections between 0 to 14 years admitted to the Children′s Hospital of Fudan University from January 2016 to December 2019 were retrospectively analyzed. According to the time of onset and the complicated factors, the patients were divided into different groups. The distributions and antimicrobial resistance patterns of common pathogens were compared among the groups. The chi-square test was used for statistical analysis.Results:Among the 1 832 children, 1 042 cases had positive urine culture, with the culture positive rate of 56.9%. The top five pathogens detected were Escherichia coli (375 strains, 36.0%), Enterococcus faecium (164 strains, 15.7%), Klebsiella pneumoniae (133 strains, 12.8%), Enterococcus faecalis (95 strains, 9.1%) and Pseudomonas aeruginosa (44 strains, 4.2%). The annual detection rates of gram-negative bacteria (65.3% to 72.9%) were always higher than those of gram-positive bacteria (22.6% to 30.1%). The distributions of pathogens among the years were not significantly different ( χ2 =27.79, P=0.146). In patients with complicated urinary tract infections, the detection rates of Pseudomonas aeruginosa (5.8%(40/688) vs 1.1%(4/354)) and fungi (6.5%(45/688) vs 1.7%(6/354)) were significantly higher than those in patients with simple urinary tract infections ( χ2=12.68 and 11.79, respectively, both P<0.050). Both of Escherichia coli and Klebsiella pneumoniae had the highest resistance rates to ampicillin, which were 87.2%(301/345) and 87.1%(115/132), respectively. The resistance rates of Escherichia coli to amikacin, nitrofurantoin, fosfomycin, cefmetazole, piperacillin/tazobactam, ertapenem, imipenem and meropenem were 1.4%(5/345), 6.1%(21/345), 6.1%(21/345), 8.3%(11/132), 11.6%(40/345), 6.4%(22/345), 4.6%(16/345) and 4.6%(16/345), respectively. The resistance rates of Klebsiella pneumoniae to these drugs were 6.1%(8/132), 37.9%(50/132), 15.2%(20/132), 23.2%(13/56), 26.5%(35/132), 23.5%(31/132), 17.4%(23/132) and 16.7%(22/132), respectively, which were all higher than those of Escherichia coli, and the differences were all statistically significant ( χ2=6.02, 76.17, 9.99, 7.94, 16.04, 28.29, 20.79 and 18.84, respectively, all P<0.050). The resistance rates of Pseudomonas aeruginosa to cefoperazone/sulbactam, piperacillin/tazobactam and ceftazidime were 6.8%(3/44), 4.5%(2/44) and 2.3%(1/44), respectively, while those to carbapenems, amikacin and ciprofloxacin were all 0(0/44). The resistance rate of Enterococcus faecium to ampicillin was 96.8%(153/158), while that of Enterococcus faecalis was 9.1%(8/88). There was no Enterococcus strain resistant to vancomycin, teicoplanin or linezolid. When dynamically comparing the trends of the antimicrobial resistance from 2016 to 2019, the resistance rates of Escherichia coli and Klebsiella pneumoniae to β-lactams (including carbapenems) antimicrobial agents had shown a downward trend. Conclusions:Gram-negative bacteria are still the main pathogens of urinary tract infections in children, with a downward trend of drug resistance rates to β-lactams (including carbapenems) antimicrobial agents.