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Objective:To investigate effects of mesalazine(MS)on proliferation,apoptosis and inflammatory injury of cell model of ulcerative colitis(UC)induced by lipopolysaccharide(LPS),as well as transforming growth factor-β1(TGF-β1)/Smad signaling pathway effect in this study.Methods:Human colonic epithelial cells NCM-460 cultured in vitro were induced UC model by LPS,and divided into Con group(no treatment),LPS group(1 mg/L LPS),MS group(0.1,0.2,0.4 mg/L MS+1 mg/L LPS)and inhibitor group(10 μmol/L TGF-β1/Smad signaling pathway inhibitor LY2109761+0.2 mg/L MS+1 mg/L LPS).Cell morphology,proliferation,apoptosis and levels of inflammatory factors and TGF-β1/Smad pathway-related markers were examined by inverted microscope,EdU assay,Hoechst 33258 staining,ELISA and Western blot.Results:LPS treatment highly induced cell proliferation rate and Smad7 pro-tein level compared with Con group,while apoptotic cells,inflammatory factors TNF-α and IL-6,soluble interleukin-2 receptor(sIL-2R)release,as well as TGF-β1,p-Smad2,p-Smad3 protein expressions were increased;the above effects induced by LPS was reversed by MS in a dose-dependent manner(P<0.05).Compared with 0.2 mg/L MS group,NCM-460 cells proliferation rate and Smad7 expression were increased,while apoptotic cells,TNF-α and IL-6,sIL-2R releases,and TGF-β1,p-Smad2,p-Smad3 protein expressions were decreased(P<0.05).Conclusion:MS can attenuate LPS-induced apoptosis and inflammatory injury in NCM-460 cells,and this protection was possibly through suppressing TGF-β1/Smad signaling pathway.
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Accurate and efficient methods for identifying and tracking each animal in a group are needed to study complex behaviors and social interactions. Traditional tracking methods (e.g., marking each animal with dye or surgically implanting microchips) can be invasive and may have an impact on the social behavior being measured. To overcome these shortcomings, video-based methods for tracking unmarked animals, such as fruit flies and zebrafish, have been developed. However, tracking individual mice in a group remains a challenging problem because of their flexible body and complicated interaction patterns. In this study, we report the development of a multi-object tracker for mice that uses the Faster region-based convolutional neural network (R-CNN) deep learning algorithm with geometric transformations in combination with multi-camera/multi-image fusion technology. The system successfully tracked every individual in groups of unmarked mice and was applied to investigate chasing behavior. The proposed system constitutes a step forward in the noninvasive tracking of individual mice engaged in social behavior.
Subject(s)
Animals , Mice , Deep Learning , Zebrafish , Algorithms , Neural Networks, Computer , Social BehaviorABSTRACT
OBJECTIVE@#To investigate the effect of vitamin D binding protein (DBP) gene polymorphism on susceptibility and prognosis of severe acute pancreatitis (SAP).@*METHODS@#A prospective study was conducted. Eighty-three patients with SAP who were admitted to the department of general surgery of Tianjin Fifth Central Hospital from March 2018 to March 2021 were selected as the research objects, and 83 healthy people in the same period were selected as controls. Peripheral blood RNA was extracted and reverse transcribed into cDNA, and the genotype and allele frequency of DBP gene rs7041 locus were detected by fluorescence quantitative analyzer. Hardy-Weinberg equilibrium was used to test the genetic balance. On the day of admission, serum C-reactive protein (CRP) level was detected by scattering immunoturbidimetry, serum procalcitonin (PCT) level was detected by electrochemiluminescence, serum DBP level was detected by enzyme-linked immunosorbent assay (ELISA), and neutrophil to lymphocyte ratio (NLR) was calculated automatically by the instrument. The length of intensive care unit (ICU) stay, the length of hospital stay and prognosis during hospitalization of patients were statistically analyzed. Multivariate Logistic regression analysis was used to screen the influencing factors of SAP occurrence.@*RESULTS@#The results of Hardy-Weinberg equilibrium test showed that the distribution of gene polymorphisms in the two groups of subjects conformed to the law of genetic equilibrium. The frequencies of TT genotype and T allele of DBP gene rs7041 locus in the patients of SAP group were significantly higher than those in the healthy control group [TT genotype: 34.94% (29/83) vs. 9.64% (8/83), T allele: 55.42% (92/166) vs. 38.55% (64/166), both P < 0.01], and the frequency of GT genotype was significantly lower than that in the healthy control group [40.96% (34/83) vs. 57.83% (48/83), P < 0.05]. There was no significant difference in the frequency of GG genotype between the healthy control group and SAP group [32.53% (27/83) vs. 24.10% (20/83), P > 0.05]. Further multivariate Logistic regression analysis showed that TT genotype [odds ratio (OR) = 2.831, 95% confidence interval (95%CI) was 1.582-5.067, P < 0.001] and T allele (OR = 2.533, 95%CI was 1.435-4.472, P < 0.001) of DBP gene rs7041 locus were independent risk factors for SAP in healthy people, while GT genotype was a protective factor for SAP (OR = 0.353, 95%CI was 0.143-0.868, P = 0.041). The levels of CRP, PCT, NLR and DBP in patients with TT genotype of DBP gene rs7041 locus were significantly higher than those in patients with GG/GT genotype on the day of admission in SAP group [CRP (mg/L): 43.25±13.25 vs. 31.86±12.83, PCT (μg/L): 1.53±0.24 vs. 1.21±0.20, NLR: 3.15±0.53 vs. 2.71±0.48, DBP (μg/L): 87.78±19.64 vs. 70.58±18.67, all P < 0.01]. The length of ICU stay in patients with TT genotype of DBP gene rs7041 locus in SAP group was significantly longer than that in patients with GG/GT genotype (days: 11.35±1.58 vs. 9.71±1.35, P < 0.01). The length of hospital stay of patients with TT genotype was longer than that of patients with GG/GT genotype (days: 23.41±3.64 vs. 23.17±3.57), and the in-hospital mortality was higher than that of patients with GG/GT genotype [34.48% (10/29) vs. 29.63% (16/54)], but the difference was not statistically significant (both P > 0.05).@*CONCLUSIONS@#The risk of SAP was significantly increased in patients with TT genotype of rs7041 locus of DBP gene, and the mechanism may be related to the increase of DBP expression. And carrying the TT genotype will prolong the ICU hospitalization time of SAP patients, but the effect on prognosis is not obvious.
Subject(s)
Humans , Polymorphism, Single Nucleotide , Prospective Studies , Vitamin D-Binding Protein/genetics , Acute Disease , Pancreatitis/genetics , Genotype , PrognosisABSTRACT
This article uses the "behavioural and social drivers of vaccination" model released by the World Health Organization (WHO) in 2022 to analyze influenza vaccine policy documents issued by the state and governments. This indicates that the current influenza vaccination policy in China has paid some attention to "publicity and mobilization", but it still pays insufficient attention to "vaccination convenience". It is recommended to continue to strengthen publicity and mobilization, explore ways to improve the convenience of vaccination, formulate corresponding plans to improve the convenience of vaccination, scientifically set vaccination rate targets, and encourage areas with conditions to carry out free vaccination projects for key populations.
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Rabies is a zoonosis caused by rabies virus for which no effective treatment is available.The main preventive measure is vaccination with human rabies vaccine before or after rabies exposure.With progress in science and technology,the production process of human rabies vaccine has continually advanced,thereby increasing vaccine quality,and providing a safer,more effective means of rabies prevention and control through increasing human resistance to rabies.New human rabies vac-cines have made breakthroughs in basic research and clinical research.However,the problems of poor vaccine compliance and low vaccination rates must urgently be addressed.China must actively explore effective coping strategies,accelerate the upda-ting of existing immunization procedures,effectively increase the rabies vaccination rate,and achieve the goal of eliminating ra-bies by 2030 as soon as possible.
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This article uses the "behavioural and social drivers of vaccination" model released by the World Health Organization (WHO) in 2022 to analyze influenza vaccine policy documents issued by the state and governments. This indicates that the current influenza vaccination policy in China has paid some attention to "publicity and mobilization", but it still pays insufficient attention to "vaccination convenience". It is recommended to continue to strengthen publicity and mobilization, explore ways to improve the convenience of vaccination, formulate corresponding plans to improve the convenience of vaccination, scientifically set vaccination rate targets, and encourage areas with conditions to carry out free vaccination projects for key populations.
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AIM: To compare the efficacy of 25-gauge(25G)vitrectomy combined with intraocular lens transciliary sulcus scleral suture fixation and sutureless scleral tunnel interlamellar fixation in the treatment of complete lens dislocation.METHODS: Retrospective case-control study. A total of 40 patients(40 eyes)diagnosed with complete lens luxation in the vitreous cavity in our hospital from May 2015 to September 2021 were selected, among which 21 eyes(suture group)underwent 25G vitrectomy combined with intraocular lens fixation via ciliary sulci scleral suture, and 19 eyes(sutureless group)underwent 25G vitrectomy combined with interlamellar scleral tunnel fixation of intraocular lens. The patients in both groups were followed up until 3mo after surgery to observe the operative time, best corrected visual acuity(BCVA), corneal endothelial cell count(CECC), central corneal thickness(CCT)and postoperative complications.RESULTS: The operation time was significantly shorter in the sutureless group than in the suture group(31.79±6.01min vs. 45.38±8.04min, P<0.001). BCVA in both groups was significantly improved after surgery(all P<0.05), and the BCVA(LogMAR)at 1wk after operation in the sutureless group was significantly better than that in the suture group(0.32±0.14 vs. 0.57±0.25, P<0.001). At 3mo after surgery, CECC in both groups was lower than that before surgery(all P<0.01). The CCT at 1wk after operation in the suture group was greater than that before operation and at 3mo after operation(all P<0.01), and there was no significant change in CCT before and after surgery in the sutureless group. During follow-up period, the total complication rate in the sutureless group was lower than that in the suture group(26% vs. 38%, P>0.05).CONCLUSION: 25G vitrectomy combined with intraocular lens sutureless scleral tunnel interlamellar fixation in the treatment of complete lens luxation has shorter operation time, faster postoperative visual acuity improvement and fewer postoperative complications.
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AIM: To compare the effect of different courses of budesonide nasal spray on the postoperative efficacy of endoscopic dacryocystorhinostomy.METHOD: Prospective study. A total of 90 patients(90 eyes)with chronic dacryocystitis who underwent endoscopic dacryocystorhinostomy in our hospital from January 2019 to April 2022 were selected, and they were randomly divided into three groups. In group A, 30 patients(30 eyes)continued to use budesonide nasal spray for 2mo after surgery; in group B, 30 patients(30 eyes)continued to use budesonide nasal spray for 3mo after surgery; in group C, 30 patients(30 eyes)continued to use budesonide nasal spray for 4mo after surgery. Follow-up for 6mo after surgery, Lund-Kenndey score, surgical efficacy and complications of the three groups were compared.RESULT: At 3, 4 and 6mo after surgery, the Lund-Kenndey score of group C was lower than that of group A(P<0.05), and there was no statistical difference between group C and group B(P>0.05). Following up to 6mo, the surgical efficacy of group C was better than that of group A, and the incidence of complications was lower than that of group A(P<0.05); There was no statistically significant difference in efficacy and complications between group C and group B(P>0.05).CONCLUSION: Budesonide combined with endoscopic dacryocystorhinostomy has acceptable efficacy in the treatment of chronic dacryocystitis. After 3mo of treatment, inflammation can be well controlled, which can reduce the occurrence of postoperative complications and improve the effective rate of surgery. However, increasing the treatment course cannot further improve the effective rate of surgery.
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This article reviews the relevant studies on the efficacy and safety of influenza, pneumococcal and COVID-19 vaccination among tumor patients worldwide in recent years. By combing and analyzing the retrieved literature, the results show that influenza and pneumococcal vaccination can significantly reduce the morbidity and hospitalization rate of infectious diseases in tumor patients, reduce the risk of cardiovascular events and death, and significantly improve survival prognosis. COVID-19 vaccination can also protect tumor patients, especially those who have completed full dose vaccination. Authoritative guidelines and consensuses worldwide all recommend that tumor patients receive influenza, pneumococcal and COVID-19 vaccines. We should carry out relevant researches, as well as take effective measures to strengthen patient education, so that tumor patients can fully experience the health protection brought by the vaccine to this specific group.
Subject(s)
Humans , Influenza, Human/prevention & control , COVID-19 Vaccines , COVID-19/prevention & control , Influenza Vaccines/therapeutic use , Vaccination , Pneumococcal Vaccines/therapeutic use , Streptococcus pneumoniae , NeoplasmsABSTRACT
Objective: To investigate the association between the response to repeated negative HIV testing and the risk sexual behaviors in men who have sex with men (MSM) in Chengdu. Methods: A total of 610 MSM were recruited by convenience sampling method through Chengdu Tongle Health Consultation Service Centre from March to May 2022. Data were collected from the MSM through questionnaire survey, including the demographic characteristics, sexual behaviors in the past 6 months, the response to rerpeated negative HIV testing. Univariate and multivariate logistic regression models were conducted to analyze the association between the response to repeated negative HIV testing and risk sexual behavior. Results: A total of 579 (94.9%) participants participated in the questionnaire survey and 354 (61.1%) subjects were included in the study.For the negative HIV testing, some MSM believed that they had taken effective protection measures (17.03±2.20), some believed that they were lucky (7.50±1.87) and some believed that they were at low risk (8.87±3.62). Multivariate logistic regression model showed that protected sexual behavior was negatively associated with group sex (aOR=0.80, 95%CI: 0.67-0.95), lucky was positively associated with casual sex (aOR=1.20, 95%CI: 1.06-1.35), inconsistent condom use (aOR=1.21, 95%CI: 1.06-1.37), group sex (aOR=1.26, 95%CI: 1.00-1.60), and multiple sexual partners (aOR=1.24, 95%CI: 1.09-1.42) and low risk perception was positively associated with multiple sexual partners only (aOR=1.08, 95%CI: 1.01-1.15). Conclusions: There were high levels of recognition of protected sexual behavior and lucky dimensions in response to repeated negative HIV testing and well risk perception in MSM in Chengdu. In HIV testing and counseling services, intervention and risk warning should be strengthened in MSM who believed that they are lucky to improve their awareness of safe sex and reduce the negative effects of fluke mind.
Subject(s)
Male , Humans , Homosexuality, Male , HIV Infections/prevention & control , Sexual and Gender Minorities , Sexual Behavior , HIV Testing , Logistic ModelsABSTRACT
Objective:To investigate the short-term clinical efficacy of laparo-gastroscopic esophagectomy (LGE).Methods:The retrospective and descriptive study was conducted. The clini-copathological data of 11 patients with esophageal cancer who underwent LGE in the Zhongshan Hospital of Fudan University from June 2020 to October 2021 were collected. There were 8 males and 3 females, aged (68±4)years. Sorted by operation time, the sentinel lymph nodes navigation (SLN) was performed since the sixth patient in the cohort, and abdominal surgery and neck surgery were performed simultaneously to complete LGE. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Follow-up was conducted using outpatient examination or telephone interview to detect death of patients during postoperative 30 days. Patients were followed up during postoperative 30 days. Measurement data with normal distribution were represented as Mean± SD, and count data were described as absolute numbers. Results:(1) Surgical situations. Of the 11 patients, 5 cases received SLN with satisfactory visualization, 6 cases did not receive SLN, 1 case terminated the operation as sentinel lymph nodes biopsy showing positive results and the rest of 10 cases completed LGE successfully without conversion to thoracotomy. The operation time and tumor diameter of the 10 patients completing LGE was (204±27)minutes and (2.5±1.0)cm, respec-tively. (2) Postoperative situations. Of the 10 patients completing LGE, 2 cases had pulmonary complications after surgery and recovered well with symptomatic treatment, and none of patient had anastomotic leakage or other serious complication. Results of postoperative histopathological examination showed squamous cell carcinoma in the 10 patients completing LGE. Nine patients were classified as T1b?3N0M0 stage and 1 patient was classified as T1bN1M0 stage. Ten patients completing LGE had R 0 resection and the number of lymph nodes dissected was 14±4. There were 3 cases with nerve bundle invasion, 2 cases with vascular invasion and 5 cases without nerve bundle and vascular invasion. The postoperative treatment time at intensive care unit and duration of hospital stay of the 10 patients completing LGE were (4.0±2.4)days and (7.2±1.5)days. (3) Follow-up. The 10 patients completing LGE were followed up and none of them died during the postoperative 30 days. Conclusions:LGE is safe and feasible. Combined with SLN can guarantee the oncology effect of surgery.
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Objective:To investigate the effect of the lactitol powder combined with piperacillin sodium and tazobactam sodium in patients with spontaneous bacterial peritonitis (SBP), and the influence on the body microenvironment.Methods:The clinical data of 135 patients with SBP from January 2017 to December 2019 in Huxi Hospital Affiliated Jining Medical College were retrospectively analyzed. Among them, 68 patients were treated with lactitol powder combined with piperacillin sodium and tazobactam sodium (observation group), 67 patients were treated with piperacillin sodium and tazobactam sodium (control group). The curative effect was compared between 2 groups. The recovery time of clinical symptoms and signs (disappearance time of abdominal pain, disappearance time of abdominal distension, disappearance time of abdominal tenderness, recovery time of body temperature and recovery time of ascites white blood cell), liver function indexes (alanine aminotransferase, ALT; total bilirubin; albumin; aspartate aminotransferase, AST), microcirculation indexes (haptoglobin; procalcitonin; interleukin-6, IL-6; neutrophil gelatinase-associated lipocalin, NGAL), intestinal mucosal permeability indexes (endotoxin, blood ammonia, diamine oxidase) and adverse reactions (diarrhea, nausea and skin itching) were recorded.Results:The total effective rate in observation group was significantly higher than that in control group: 95.59% (65/68) vs. 82.09% (55/67), and there was statistical difference ( P<0.05). The disappearance time of abdominal pain, disappearance time of abdominal distension, disappearance time of abdominal tenderness, recovery time of body temperature and recovery time of ascites white blood cell in observation group were significantly shorter than those in control group: (6.15±1.34) d vs. (8.26±1.19) d, (5.34±1.29) d vs. (7.18±1.35) d, (7.59±1.65) d vs. (9.86±1.80) d, (5.28±1.20) d vs. (6.39±1.12) d and (10.87±2.25) d vs. (12.18±1.67) d, and there were statistical differences ( P<0.01). The ALT, total bilirubin, AST, haptoglobin, procalcitonin, IL-6, NGAL, endotoxin, blood ammonia and diamine oxidase 1 and 2 weeks after treatment in observation group were significantly lower than those in control group, and there were statistical differences ( P<0.01); there was no statistical difference in albumin between 2 groups ( P>0.05). There was no statistical difference in incidence of adverse reactions between2 groups ( P>0.05). Conclusions:The lactitol powder combined with piperacillin sodium and tazobactam sodium for SBP patients can more significantly improve the liver function and intestinal mucosal permeability, and promote the body microenvironment and the recovery of symptoms.
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@#AIM: To evaluate efficacy, safety and complications of 25G vitrectomy, phacoemulsification combined with intrascleral fixated intraocular lens(IOL)implantation for treatment of lens luxation.<p>METHODS: Totally 20 patients(20 eyes)with complete lens luxation and the hardness of lens nucleus was grade 3 or above who underwent 25G vitrectomy, phacoemulsification combined with intrascleral fixated IOL implantation between May 2018 and December 2020 were analyzed retrospectively. The uncorrected visual acuity, best corrected visual acuity, intraocular pressure, the count of corneal endothelium cell, central corneal thickness and complications were observed. <p>RESULTS: The uncorrected visual acuity and best corrected visual acuity after operation were improved than those before treatment(<i>P</i><0.05). The number of corneal endothelial cells in the central part of cornea after operation was lower than that before operation(<i>P</i> >0.05). There was no significant difference in central corneal thickness 2wk after operation compared with that before operation(<i>P</i> >0.05). There were 3 cases of low intraocular pressure and 2 cases of high intraocular pressure, but they all returned to normal at the end of follow-up. The IOL were all centered and there were no obvious eccentricity and inclination. No other complications such as vitreous hemorrhage and retinal detachment occurred.<p>CONCLUSION: 25G vitrectomy, phacoemulsification combined with intrascleral fixated IOL implantation is a fast, safe and simple method for the treatment of complete lens luxation.
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Objective: To evaluate the performance of point-of-care testing for cervical cancer and precancerous lesions screening. Methods: In September 2020, 197 and 273 women were selected by using simple random sampling method from "self-sampling" cohort and "physician-sampling" cohort established in Xiangyuan county, Shanxi Province, China, respectively. Cervical exfoliated cells were collected by women themselves or gynecologists. All samples were detected by POCT and women with positive result were directly referred for colposcopy. Subsequently, all the samples were detected by careHPV and PCR test. Colposcopy and punch biopsy were performed for women with POCT negative but careHPV or PCR test positive at another visit. Using histopathological diagnosis as the gold standard, we calculated sensitivity, specificity and drew the receiver operating characteristic (ROC) curves. The accuracy of POCT was analyzed and compared to that of careHPV and conventional PCR test in cervical cancer and precancerous lesions screening. Results: The median (Q1 , Q3) age of 470 women was 51 (45, 57) years old. Based on self-sampling, the sensitivity and specificity of POCT for CIN2+ were 100.00% (95%CI: 56.56%-100.00%) and 28.95% (95%CI: 22.97%-35.76%), respectively. Compared with POCT, POCT HPV16/18 test had similar sensitivity and higher specificity of 89.47% (95%CI: 84.30%-93.08%). Self-sampling POCT HPV16/18 test had an AUC of 0.947 (95%CI:0.910-0.985), which was higher than that of careHPV and PCR test. Physician-sampling POCT test had 100.00% sensitivity (95%CI: 64.57%-100.00%) and 55.85% specificity (95%CI: 49.83%-61.70%) for detecting CIN2+. POCT HPV16/18 test had lower sensitivity (71.43%, 95%CI: 35.90%-91.76%) and higher specificity (92.45%, 95%CI: 88.63%-95.06%). POCT HPV16/18 test generally showed similar AUC on both self-collected samples and clinician-collected samples (0.947 vs 0.819, P=0.217). Conclusion: POCT HPV16/18 test is an effective method with relatively high sensitivity and specificity for cervical cancer screening.
Subject(s)
Female , Humans , Pregnancy , Uterine Cervical Dysplasia/diagnosis , Colposcopy , Early Detection of Cancer/methods , Human papillomavirus 16/genetics , Human papillomavirus 18 , Mass Screening/methods , Papillomaviridae , Papillomavirus Infections/diagnosis , Point-of-Care Testing , Sensitivity and Specificity , Uterine Cervical NeoplasmsABSTRACT
This paper reviews the domestic and foreign studies published in 2020 on the application of influenza vaccine in populations at high risk. The importance of influenza vaccination in population at high risk has been proved by larger sample, multicentre, high-quality evidence-based studies. Influenza vaccination is the most cost-effective measure to prevent influenza. However, the coverage rate of influenza vaccine is very low in China, it is necessary to strengthen the health education to promote influenza vaccination in different populations. It is recommended to give influenza vaccination to the population in whom influenza vaccination has been proven safe and effective before influenza season. Research of the safety, efficiency and cost-effectiveness of influenza vaccine should be accelerated for the populations in whom such data are lacking or insufficient.
Subject(s)
Humans , China , Costs and Cost Analysis , Influenza Vaccines/adverse effects , Influenza, Human/prevention & control , VaccinationABSTRACT
Objective: To understand the current situation regarding pediatric off-label use of drugs recommendations in Chinese clinical practice guidelines and to make recommendations for standardized reporting format regarding off-label use of drugs for children. Methods: This cross-sectional study was carried out by systematically searching the databases for Chinese guideline consensus articles published in journals between 2018 and 2020 and extracting recommendations regarding off-label use of drugs from those articles. The essential characteristics of the included guidelines, the ranking of off-label drug types, the order of drug information, the type of off-label drug use, and the percentage of citation studies on which the recommendations were based were analyzed. Results: Among 108 studies that included Chinese off-label guidelines and consensus, 364 recommendations on pediatric off-label use of drugs were included. The Chinese Medical Association published the most, 48 out of the 108 studies (44.4%), and of those 14 studies (13.0%) were on infectious and parasitic diseases. Of the 364 recommendations on off-label use of drugs, the most commonly addressed drugs were 16 recommendations (4.4%) for cyclosporine A, 11 recommendations (3.0%) for methotrexate , and 11 recommendations (3.0%) for fentanyl. The most commonly addressed drug categories were as follows: 68 recommendations (18.6%) were immune system drugs, 66 recommendations (18.1%) were anti-infectives, and 56 recommendations (15.4%) were oncology drugs. The most commonly addressed drug information accounts were as follows: 364 recommendations (100.0%) were indications, 204 recommendations (56.0%) were dosages, and 198 recommendations (54.4%) were the route of administration. Based on the instructions approved by the Chinese Food and Drug Administration, the main forms of the off-label drug were as follows: 175 recommendations (48.1%) were unapproved indications, 127 recommendations (34.9%) were unapproved populations, and 72 recommendations (19.8%) were unapproved ages. Only 129 recommendations (35.4%) were cited, mainly including clinical guidelines (48 studies, 23.4%), reviews (22 studies, 10.7%), and pediatric randomized controlled trials (22 studies, 10.7%). Conclusions: Off-label use of drugs is commonly recommended in pediatric guidelines and consensus documents written by Chinese authors. However, the reporting of the recommendations varies widely, and the quality of the supporting evidence is poor.
Subject(s)
Child , Humans , China , Consensus , Cross-Sectional Studies , Off-Label Use , Pharmaceutical PreparationsABSTRACT
OBJECTIVE@#To analyze the independent risk factors of long-term ischemic stroke and establish a nomogram for predicting the long-term risks in elderly patients with obstructive sleep apnea (OSA).@*METHODS@#This multicenter prospective cohort study was conducted from January, 2015 to October, 2017 among consecutive elderly patients (≥60 years) with newly diagnosed OSA without a history of cardio-cerebrovascular diseases and loss of important clinical indicators. The follow-up outcome was the occurrence of ischemic stroke. The baseline demographic and clinical data, sleep parameters, laboratory and ultrasound results were collected from all the patients, who were randomized into the modeling group (n=856) and validation group (n=258) at a 3∶1 ratio. LASSO regression was used for variable reduction and dimension screening, and the risk score prediction model of ischemic stroke was established based on Cox proportional hazard regression.@*RESULTS@#In the total of 1141 patients enrolled in this study, 58 (5.08%) patients experienced ischemic stroke during the median follow-up of 42 months (range 41-54 months). The cumulative incidence of ischemic stroke was 5.14% in the model group and 4.91% in the verification group (P < 0.05). Age (HR=3.44, 95% CI: 2.38- 7.77), fasting blood glucose (FPG) (HR=2.13, 95% CI: 1.22-3.72), internal diameter of the ascending aorta (HR=2.60, 95% CI: 1.0- 4.47), left atrial anteroposterior diameter (HR=1.98, 95% CI: 1.75-2.25) and minimum oxygen saturation (LSpO2) (HR=1.57, 95% CI: 1.20-1.93) were identified as independent risk factors for ischemic stroke (P < 0.05 or 0.01). A long-term ischemic stroke risk score model was constructed based the regression coefficient ratios of these 5 risk variables. Before and after the application of the Bootstrap method, the AUC of the cohort risk score model was 0.84 (95% CI: 0.78- 0.90) and 0.85 (95% CI: 0.78- 0.89) in the model group and was 0.83 (95% CI: 0.73-0.93) and 0.82 (95%CI: 0.72-0.90) in the verification group, respectively, suggesting a good prediction efficiency and high robustness of the model. At the best clinical cutoff point, the cumulative incidence of ischemic stroke was significantly higher in the high-risk group than in the low-risk group (P=0.021).@*CONCLUSION@#This model can help to identify high-risk OSA patients for early interventions of the risks of ischemic stroke associated with OSA.
Subject(s)
Aged , Humans , Middle Aged , Ischemic Stroke , Prospective Studies , Risk Factors , Sleep , Sleep Apnea, Obstructive/complications , Stroke/complicationsABSTRACT
Objective:To investigate the therapeutic effect of exosomes divided from bone marrow mesenchymal stem cell (BMSC) on pancreatic cancer in vivo through regulation of tumor-associated macrophages (TAM) polarization.Methods:Ten male C57BL/6 mice weighing approximately 20 g, ages 4 weeks, were used for BMSC exosomes extraction and PKH26 labelling. Thirty female SPF BALB/c-nu/nu nude mice weighing approximately (18.56±0.85) g, ages 4-6 weeks, were adopted for pancreatic carcinoma models. The models were randomly divided into 3 groups with 10 in each: control group (injected with PBS through tail vein), portal vein treatment group (injected with exosomes in PBS through portal vein), tail vein treatment group (injected with exosomes in PBS through tail vein). After the models were executive 8 weeks later, the percentage of PKH26 positive-exosomes in pancreas tissue was quantified by flow cytometry technique. The volume of the primary pancreatic tumor, the tumor volume of inhibitory rate, the number of metastatic nodule, and the ascitic fluid were assess. Also, the weight of liver and the tumor weight were evaluated. The expression of M1 and M2 macrophage-activate biomarkers and the content of pancreatic cancer marker B7-H4 tumor carbohydrate antigen 199 in peripheral blood was detected. Moreover, the expression of Survivin and matrix metalloproteinase-9 (MMP-9) in pancreatic cancer tissue cells was also detected.Results:There was no significant difference for the tumor volume of inhibitory rate between portal vein treatment group (72.4±21.6)% and tail vein treatment group (70.1±20.7)% ( t=0.24, P=0.811). Compared with control group, the volume of the primary pancreatic tumor, the weight of liver, the tumor weight, the number and rate of liver metastatic nodule, the ascitic fluid, and the number of other metastatic nodule were totally lower in the 2 treatment groups with significant difference (all P<0.05). Compared with the control group, iNOS and CD68 in portal vein treatment group and tail vein treatment group were increased, while Arginase, CD206, B7-H4, tumor carbohydrate antigen 199, Survivin and matrix metalloprotein-9 were decreased, with statistically significant differences (all P<0.05). Conclusion:Exosomes derived from BMSC can inhibit the polarization of TAM to the M2 phenotype and induce their polarization to the M1 phenotype, thereby suppressing the proliferation, invasion and migration of pancreatic cancer.
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@#AIM: To investigate the prognostic value of DIP endoscopic scoring system for simultaneous operation of chronic dacryocystitis complicated with sinusitis.METHODS: From January 2018 to February 2021, 96 patients(96 eyes)with chronic dacryocystitis complicated with sinusitis who underwent nasal endoscopic sinus surgery and dacryocystorhinostomy were enrolled in a prospective single-blind study. Patients were examined by nasal endoscopy and recorded video to get DIP endoscopic score before operation. The patients were followed-up for 6mo, and the curative effect was based on the results of the last follow-up. The receiver operating characteristic curve(ROC curve)was drawn according to DIP endoscopic scoring system and postoperative curative effect, and the value of DIP endoscopic scoring system in predicting the prognosis of nasal endoscopic sinus surgery combined with dacryocystorhinostomy was evaluated. According to the best cutoff value obtained by ROC curve analysis, patients were analyzed in subgroups, and the age and sex constituent ratio of two groups were compared. RESULTS: Among the 96 eyes with chronic dacryocystitis complicated with sinusitis, 86 eyes(90%)were cured, 4 eyes(4%)were improved, and 6 eyes(6%)were invalid. ROC curve analysis showed that the area under the ROC curve(AUC)of DIP endoscopic score for predicting the curative effect of nasal endoscopic sinus surgery combined with dacryocystorhinostomy was 0.905. When Yoden index reached its peak, the DIP endoscopy score was 16.5 as the best cutoff value. At the same time, the sensitivity was 80.0% and the specificity was 86.0%. In the subgroup analysis, there was no significant difference in age and sex constituent ratio between the two groups(<i>P</i>>0.05); The surgical efficiency of patients with DIP endoscopic score <16.5 was better than the patients with DIP endoscopic score ≥16.5(<i>P</i><0.05).CONCLUSION: DIP endoscopic scoring system has a good predictive value for the prognosis of endoscopic of transnasal endoscopic sinus opening combined with dacryocystorhinostomy.
ABSTRACT
Many people affected by fragile X syndrome (FXS) and autism spectrum disorders have sensory processing deficits, such as hypersensitivity to auditory, tactile, and visual stimuli. Like FXS in humans, loss of Fmr1 in rodents also cause sensory, behavioral, and cognitive deficits. However, the neural mechanisms underlying sensory impairment, especially vision impairment, remain unclear. It remains elusive whether the visual processing deficits originate from corrupted inputs, impaired perception in the primary sensory cortex, or altered integration in the higher cortex, and there is no effective treatment. In this study, we used a genetic knockout mouse model (Fmr1KO), in vivo imaging, and behavioral measurements to show that the loss of Fmr1 impaired signal processing in the primary visual cortex (V1). Specifically, Fmr1KO mice showed enhanced responses to low-intensity stimuli but normal responses to high-intensity stimuli. This abnormality was accompanied by enhancements in local network connectivity in V1 microcircuits and increased dendritic complexity of V1 neurons. These effects were ameliorated by the acute application of GABAA receptor activators, which enhanced the activity of inhibitory neurons, or by reintroducing Fmr1 gene expression in knockout V1 neurons in both juvenile and young-adult mice. Overall, V1 plays an important role in the visual abnormalities of Fmr1KO mice and it could be possible to rescue the sensory disturbances in developed FXS and autism patients.