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1.
Article in English | WPRIM | ID: wpr-971481

ABSTRACT

A series of chemotherapeutic drugs that induce DNA damage, such as cisplatin (DDP), are standard clinical treatments for ovarian cancer, testicular cancer, and other diseases that lack effective targeted drug therapy. Drug resistance is one of the main factors limiting their application. Sensitizers can overcome the drug resistance of tumor cells, thereby enhancing the antitumor activity of chemotherapeutic drugs. In this study, we aimed to identify marketable drugs that could be potential chemotherapy sensitizers and explore the underlying mechanisms. We found that the alcohol withdrawal drug disulfiram (DSF) could significantly enhance the antitumor activity of DDP. JC-1 staining, propidium iodide (PI) staining, and western blotting confirmed that the combination of DSF and DDP could enhance the apoptosis of tumor cells. Subsequent RNA sequencing combined with Gene Set Enrichment Analysis (GSEA) pathway enrichment analysis and cell biology studies such as immunofluorescence suggested an underlying mechanism: DSF makes cells more vulnerable to DNA damage by inhibiting the Fanconi anemia (FA) repair pathway, exerting a sensitizing effect to DNA damaging agents including platinum chemotherapy drugs. Thus, our study illustrated the potential mechanism of action of DSF in enhancing the antitumor effect of DDP. This might provide an effective and safe solution for combating DDP resistance in clinical treatment.


Subject(s)
Female , Male , Humans , Cisplatin/pharmacology , Disulfiram/pharmacology , Testicular Neoplasms/drug therapy , Fanconi Anemia/drug therapy , Alcoholism/drug therapy , Drug Resistance, Neoplasm , Cell Line, Tumor , Substance Withdrawal Syndrome/drug therapy , Apoptosis , Antineoplastic Agents/therapeutic use , Cell Proliferation
2.
Article in Chinese | WPRIM | ID: wpr-985954

ABSTRACT

Objective: To investigate dose-response associations between fluid overload (FO) and hospital mortality in patients with sepsis. Methods: The current cohort study was prospective and multicenter. Data were derived from the China Critical Care Sepsis Trial, which was conducted from January 2013 to August 2014. Patients aged≥18 years who were admitted to intensive care units (ICUs) for at least 3 days were included. Fluid input/output, fluid balance, fluid overload (FO), and maximum FO (MFO) were calculated during the first 3 days of ICU admission. The patients were divided into three groups based on MFO values: MFO<5%L/kg, MFO 5%-10%L/kg, and MFO≥10% L/kg. Kaplan-Meier analysis was used to predict time to death in hospital in the three groups. Associations between MFO and in-hospital mortality were evaluated via multivariable Cox regression models with restricted cubic splines. Results: A total of 2 070 patients were included in the study, of which 1 339 were male and 731 were female, and the mean age was (62.6±17.9) years. Of 696 (33.6%) who died in hospital, 968 (46.8%) were in the MFO<5%L/kg group, 530 (25.6%) were in the MFO 5%-10%L/kg group, and 572 (27.6%) were in the MFO≥10%L/kg group. Deceased patients had significantly higher fluid input than surviving patients during the first 3 days [7 642.0 (2 874.3, 13 639.5) ml vs. 5 738.0 (1 489.0, 7 153.5)ml], and lower fluid output [4 086.0 (1 367.0, 6 354.5) ml vs. 6 130.0 (2 046.0, 11 762.0) ml]. The cumulative survival rates in the three groups gradually decreased with length of ICU stay, and they were 74.9% (725/968) in the MFO<5% L/kg group, 67.7% (359/530) in the MFO 5%-10%L/kg group, and 51.6% (295/572) in the MFO≥10%L/kg group. Compared with the MFO<5%L/kg group, the MFO≥10%L/kg group had a 49% increased risk of inhospital mortality (HR=1.49, 95%CI 1.28-1.73). For each 1% L/kg increase in MFO, the risk of in-hospital mortality increased by 7% (HR=1.07, 95% CI 1.05-1.09). There was a"J-shaped"non-linear association between MFO and in-hospital mortality with a nadir of 4.1% L/kg. Conclusion: Higher and lower optimum fluid balance levels were associated with an increased risk of in-hospital mortality, as reflected by the observed J-shaped non-linear association between fluid overload and inhospital mortality.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Hospital Mortality , Cohort Studies , Prospective Studies , Water-Electrolyte Imbalance , Sepsis , Intensive Care Units , Retrospective Studies
3.
Article in Chinese | WPRIM | ID: wpr-985943

ABSTRACT

To evaluate the predictive value of early warning scores for intensive care unit (ICU) admission in patients with coronavirus disease 2019 (COVID-19). For COVID-19 patients who were admitted to Shijiazhuang People's Hospital from January 2021 to February 2021, national early warning score (NEWS), national early warning score 2 (NEWS2), rapid emergency medicine score (REMS), quick sepsis-related organ failure (qSOFA), altered consciousness, blood urea nitrogen, respiratory rate, blood pressure, and age-65 (CURB-65) were used to evaluate the inpatient condition and the predictive value for ICU admission. A total of 368 patients were included, and 32 patients (8.7%) were transferred to the ICU. The median age was 49.0 (34.0,61.0) years. The scores of NEWS, NEWS2, REMS, and CURB-65 were 1 (0, 2), 1 (0, 2), 4 (2, 6) and 0 (0, 1), respectively. The receiver operating characteristic (ROC) cure (AUC) was used to evaluate the predictive value in detecting patients who are at risk of being transferred to the ICU. Area under the ROC AUC of NEWS was 0.756, sensitivity 65.6%, and specificity 71.3%. ROC AUC of NEWS2 was 0.732, sensitivity 62.5%, and specificity 61.3%. ROC AUC of REMS was 0.787, sensitivity 84.4%, and specificity 64.6%. ROC AUC of CURB-65 was 0.814, sensitivity 81.3%, and specificity 76.8%. The predictive value of NEWS and NEWS2 combined with age were significantly improved. The ROC AUC of NEWS combined with age was 0.885, sensitivity 85.1%, and specificity 75.0%. The ROC AUC of NEWS2 combined with age was 0.883, sensitivity 84.2%, and specificity 75.0%. NEWS and NEWS2 combined with age can be used as a predictive tool for whether COVID-19 patients will be admitted to the ICU.


Subject(s)
Humans , Middle Aged , Aged , COVID-19 , Retrospective Studies , Hospitalization , Intensive Care Units , ROC Curve , Prognosis , Hospital Mortality
4.
Article in Chinese | WPRIM | ID: wpr-994755

ABSTRACT

Objective:To construct an evaluation scale for post competence of family doctors based on knowledge-skill-management model.Methods:The evaluation dimensions and indicators for post competency of family doctors were preliminarily developed through literature review, internal group meeting and brainstorming, and in-depth interviews of experts. And 16 experts in the fields of general practice and health management were invited for 2 rounds of Delphi consultation from December 2020 to April 2021. A competency evaluation scale for family doctors based on the dimensions of knowledge, skills and management was finally constructed.Results:The age of the experts was (47.9±7.3) years with a working experience of (24.6±7.8) years. The Cronbach′s α of the questionnaires was 0.891 and the KMO was 0.844. The positive coefficients for 2 rounds of expert consultation were 100%; the familiarity level of experts was 0.86 and authority level was 0.89 in the first round consultation, and those were 0.84 and 0.90 in the second round consultation. After 2 rounds of consultation, the coordination coefficient of expert opinions in the knowledge and skill dimensions was>0.5, and that in the management dimension and overall evaluation system was>0.3. After discussion 2 indicators were deleted in the first round of consultation. The finally constructed family doctor post competency evaluation scale included 3 dimensions, 8 secondary indicators and 61 tertiary indicators. Conclusion:Through the Delphi consultation, we have successfully constructed an evaluation scale for post competence of family doctors based on the three dimensions of knowledge, skills and management.

5.
Article in Chinese | WPRIM | ID: wpr-994744

ABSTRACT

Objective:To analyze the clinical knowledge and training needs of general practitioners from subjective perception and objective assessment, and to analyze their relationship.Methods:A survey was conducted among general practitioners from community health service centers in Shanghai Changning district from September to December 2020. Based on the general practitioner competency indicator system designed by the project team, 17 clinical knowledge competency evaluation indicators were developed through expert consultation, and used for subjective perception and objective assessment of clinical knowledge and learning needs among general practitioners. The influencing factors of objective assessment scores were analyzed, and the relationship between subjective perception and objective assessment scores was analyzed using the four quadrant method.Results:A total of 136 general practitioners participated in the study with the mean age of (39.25±5.90) years, most of whom were attending physician (67.65%, 92/136) and had undergraduate education (88.20%, 122/136). The average daily application frequency score was (1.55±0.21), and the training needs score was (1.65±0.09) for 17 clinical knowledge items; the average objective evaluation score was (74.21±14.0) points. The older the age ( OR=1.25, 95% CI:1.14-1.37), the higher the educational level ( OR=2.11, 95% CI:1.57-2.83), and the longer the working years ( OR=1.16, 95% CI:1.04-1.30) were significantly correlated with the higher objective evaluation scores (all P<0.05). The objective evaluation scores of endocrine diseases such as diabetes, cerebrovascular diseases and respiratory diseases are the highest, and the daily application frequency and learning needs are high (the first quadrant); The objective evaluation scores of common orthopedic diseases, common psychological diseases, and planned immunity indicators were relatively low, but their daily application frequency and learning needs were relatively high (second quadrant). The objective evaluation scores of indicators such as common malignant tumors, common dermatology diseases and health problems, and common ENT diseases were low, and the daily application frequency and learning needs were also low (the third quadrant). The objective evaluation scores of indicators such as hospice and palliative care are relatively high, but their daily application frequency and training needs are relatively low (listed in the fourth quadrant). Conclusions:The clinical knowledge levels of general practitioners are correlated with age, education level, and years of practice. There is a certain overlap between the objective evaluation results of clinical knowledge and the frequency of knowledge usage and training needs of general practitioners, and a targeted training mechanism should be established.

6.
Article in Chinese | WPRIM | ID: wpr-994741

ABSTRACT

The integration of regional medical centers and community health service centers is an effective way to improve the professional ability of general practitioners in post-practice training. Its major advantage lies in the establishment of a regional general practitioner ability improvement system integrating assessment, practice and teaching under the unified health administrative department. This article introduces the path of general practitioner post-training developed by Shanghai Tongren Hospital in forms of a regional medical center combined with the community health service center under the "integrated dual-drives" model, which was carried out in Shanghai Changning District; and its preliminary accomplishment is also discussed. It may provide reference for regional medical centers to improve the ability of general practitioners through practice-driven and teaching-driven.

7.
Article in Chinese | WPRIM | ID: wpr-989998

ABSTRACT

Infantile spasms (IS) is one of the most prevalent epileptic encephalopathies in infants and toddlers.The primary clinical features are episodes of spastic spasms, and an electroencephalogram may exhibit hypsarrhythmia features.The majority of patients have a poor prognosis, exhibiting uncontrolled seizures, conversion to other seizure types, as well as intellectual and motor developmental impairments.With the advancement of neurosurgery, genetics, and neuroimaging, various studies have been conducted on the etiologies and pathogenesis of IS; as a result, the prognosis of IS has substantially improved.This article introduced the prognosis of IS and the contributing factors affecting the prognosis.

8.
Article in Chinese | WPRIM | ID: wpr-989851

ABSTRACT

Objective:To investigate the indication, effectiveness, tolerance, and safety of levosimendan in patients with acute heart failure (AHF) in 20 hospitals in Beijing, China.Methods:This prospective, observational, and multicenter study consecutively enrolled AHF patients who were treated with levosimendan at 20 hospitals in Beijing from April 2020 to March 2022. Baseline demographics, laboratory parameters, clinical presentation, concomitant diseases and medications were collected. After initiation of levosimendan, levosimendan administration, laboratory parameter pre- and post-administration, symptoms improvement, and adverse events were also collected.Results:Totally 800 AHF patients were included, 67% of whom were male, aged (65 ±17) years, 50% of whom had ischemic heart disease, and the left ventricular ejection fraction (LVEF) was (36±11)%. The dose of levosimendan was (11.84 ±2.11) mg and the mean infusion time was (1 450±307) min. Dyspnea was improved in 83.4% of AHF patients at 24 h after treatment. The level of B-type natriuretic peptide (BNP) significantly decreased from 689 (406-1509) pg/mL to 410 (156-697) pg/mL in all patients at 24-72 h after treatment ( P<0.001), and the level of N-terminal pro-brain natriuretic peptide (NT-pro BNP) decreased from 6910 (3 715-13 914) pg/mL to 2 851 (1 288-6 191) pg/mL ( P<0.001). Meanwhile, LVEF level also improved significantly [(40±11)% vs. (36±11)%, P<0.001]. During levosimendan administration, adverse events occurred in 74 (9.3%) patients, including hypotension (5.9%), arrhythmia (1.9%), and other symptoms (1.1%). Among them, 7 patients ( 2 patients with hypotension and 5 patients with ventricular tachycardia) interrupted levosimendan administration. Conclusions:The use of levosimendan is safe, and can improve symptoms reduce BNP or NT-pro BNP levels and increase LVEF level in AHF patients.

9.
International Journal of Surgery ; (12): 49-55,C3,C4, 2023.
Article in Chinese | WPRIM | ID: wpr-989404

ABSTRACT

Objective:Three-dimensional simulation modeling technology was used to conduct three-dimensional reconstruction, classification and measurement for the anatomic structures of colorectal canal, tumor and key blood vessels in patients with rectal cancer before operation. And the accuracy of the data and information obtained for the prediction of anastomotic tension, important types of vascular variant, positioning of anatomical landmarks, etc. in laparoscopic-assisted radical resection of rectal cancer, and the guiding effect of operation was evaluated.Methods:The clinical data of 50 patients with laparoscopic-assisted radical resection of rectal cancer treated in the General Surgery Department, Beijing Ditan Hospital Capital Medical University from January 2019 to February 2021 were analyzed retrospectively, including 31 males and 19 females, aged from 42 to 83 years old, with an average age of (62.72 ±15.21) years. The patients were divided into two groups according to whether the patients underwent three-dimensional simulation reconstruction before operation. The patients who underwent abdomen pelvic enhancement CT and further three-dimensional reconstruction before surgery were taken as reconstruction group ( n=24), and the patients who were only routinely performed abdomen pelvic enhancement CT before operation were taken as control group ( n=26). For the patients in the reconstruction group, the CT images were modeled by Mimics software before operation, and the key data such as the length of colorectal and tumor, the correlation length of rigid structure of pelvic wall, the length of inferior mesenteric artery (IMA) from the bifurcation point of left and right arteria iliaca communis, the type and proportion of IMA variation, the length of left colonic artery (LCA) from the beginning of IMA and the distance between LCA and IMV were measured, and the consistency correlation coefficient (CCC) was analyzed with the actual data obtained during operation. And then the accuracy of three-dimensional simulation modeling technology for surgical guidance was evaluated. MedCalc 19.0 software was used for statistical analysis. Results:In the reconstruction group, regarding the data of each dimension of the model (intestinal tract, pelvic cavity, blood vessels) and the corresponding structural measurements during the operation, the consistent correlation coefficient (CCC) evaluation was more than 0.9. One case was predicted to have free splenic flexure of colon and one case actually had free splenic flexure of colon. The prediction accuracy was 100%. The IMA variants in the reconstruction group were divided into 4 types, all of which were verified by operation. Compared with the control group, the operation time ( P=0.011) and the location time (IMA, P=0.043; LCA, P=0.007; IMV, P=0.034) of each vessel in the reconstruction group were shorter, and the amount of intraoperative blood loss was less ( P=0.017). Conclusion:The application of three-dimensional simulation modeling technology before operation is helpful for the operator to accurately predict the intraoperative anastomotic tension, the type of IMA variation and the related diameter length, based on which the accurate operation plan can be made to guide the operation.

10.
Article in Chinese | WPRIM | ID: wpr-986967

ABSTRACT

OBJECTIVE@#To evaluate the correlation of magnetic resonance (MR) T2-weighted image (T2WI) signal characteristics of adenomyosis and the efficacy of high-intensity focused ultrasound (HIFU) ablation.@*METHODS@#Based on the presence or absence of patchy hyperintense foci on preoperative MR T2WI, the patients with adenomyosis undergoing HIFU treatment were divided into homogeneous signal group and heterogeneous signal group, and the heterogeneous group was further divided into heterogeneous hypointense group and heterogeneous isointense group according to signal intensity of the lesions. The patients in heterogeneous signal group were matched with the patients in the homogeneous group at a 1:1 ratio using the propensity score matching, and similarly, the patients in the heterogeneous hypointense group were matched with those in the heterogeneous isointense group at a 1:1 ratio. The non-perfused volume ratio (NPVR) and relief of dysmenorrhea were used to assess the therapeutic efficacy in the 4 groups.@*RESULTS@#A total of 299 patients were enrolled, who had a median preoperative dysmenorrhea score of 7.0 (6.0, 8.0) and a median NPVR of 53.5% (35.4, 70.1)%. After propensity score matching, the NPVR in homogeneous signal group was significantly higher than that in heterogeneous signal group [(60.3 ± 21.8)% vs (44.6±21.6)%, P < 0.05]. At 3, 6 and 12 months after HIFU, dysmenorrhea relief rates were higher in homogeneous signal group than in heterogeneous signal group, and the difference was statistically significant at 12 months (91.1% vs 76.8%, P < 0.05). The NPVR of heterogeneous hypointense group was higher than that of heterogeneous isointense group [(54.0±22.0) % vs (47.3± 22.9) %, P < 0.05]. At 6 months after HIFU, dysmenorrhea relief rate was significantly higher in heterogeneous hypointense group than in heterogeneous isointense group (91.5% vs 80.9%, P < 0.05).@*CONCLUSION@#The signal characteristics of adenomyosis on T2WI are closely related with the outcome of HIFU ablation, and its efficacy is better for homogeneous than for heterogeneous adenomyosis, and better for heterogeneous hypointense adenomyosis than for heterogeneous isointense adenomyosis.


Subject(s)
Female , Humans , Adenomyosis/pathology , Dysmenorrhea , Cohort Studies , Propensity Score , High-Intensity Focused Ultrasound Ablation/methods , Treatment Outcome
11.
Article in Chinese | WPRIM | ID: wpr-971080

ABSTRACT

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune inflammatory disease of the central nervous system, and little is known about its immune mechanism at present. There is a lack of disease-related biomarkers in cerebrospinal fluid except anti-NMDAR antibody, which leads to delayed diagnosis and treatment in some patients. Therefore, there has been an increasing number of studies on related cytokines in recent years to assess whether they can be used as new biomarkers for evaluating disease conditions and assisting diagnosis and treatment. Current studies have shown that some cytokines may be associated with the progression of anti-NMDAR encephalitis, and this article reviews the research advances in such cytokines associated with anti-NMDAR encephalitis.


Subject(s)
Humans , Cytokines , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/therapy , Biomarkers
12.
Article in Chinese | WPRIM | ID: wpr-970585

ABSTRACT

In observational studies, herbal prescriptions are usually studied in the form of "similar prescriptions". At present, the classification of prescriptions is mainly based on clinical experience judgment, but there are some problems in manual judgment, such as lack of unified criteria, labor consumption, and difficulty in verification. In the construction of a database of integrated traditional Chinese and western medicine for the treatment of coronavirus disease 2019(COVID-19), our research group tried to classify real-world herbal prescriptions using a similarity matching algorithm. The main steps include 78 target prescriptions are determined in advance; four levels of importance labeling shall be carried out for the drugs of each target prescription; the combination, format conversion, and standardization of drug names of the prescriptions to be identified in the herbal medicine database; calculate the similarity between the prescriptions to be identified and each target prescription one by one; prescription discrimination is performed based on the preset criteria; remove the name of the prescriptions with "large prescriptions cover the small". Through the similarity matching algorithm, 87.49% of the real prescriptions in the herbal medicine database of this study can be identified, which preliminarily proves that this method can complete the classification of herbal prescriptions. However, this method does not consider the influence of herbal dosage on the results, and there is no recognized standard for the weight of drug importance and criteria, so there are some limitations, which need to be further explored and improved in future research.


Subject(s)
Humans , COVID-19 , Algorithms , Databases, Factual , Prescriptions , Plant Extracts
13.
Article in Chinese | WPRIM | ID: wpr-970450

ABSTRACT

We provided the palliative care of a multiple disciplinary team care mode to a patient diagnosed with advanced head and neck cancer and her caregivers.People-centered integrated health services were provided according to the specific needs and preferences of individuals.The team-based palliative care relieved the suffering and improved the quality of life of the patient and that of her family who were facing challenges associated with life-threatening illness.


Subject(s)
Humans , Female , Palliative Care , Quality of Life , Head and Neck Neoplasms/therapy
14.
Chinese Journal of Pediatrics ; (12): 256-260, 2023.
Article in Chinese | WPRIM | ID: wpr-970277

ABSTRACT

Objective: To explore the related factors of negative conversion time (NCT) of nucleic acid in children with COVID-19. Methods: A retrospective cohort study was conducted. A total of 225 children who were diagnosed with COVID-19 and admitted to Changxing Branch of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from April 3rd to May 31st 2022 were enrolled in the study. The infection age, gender, viral load, basic disease, clinical symptoms and information of accompanying caregivers were retrospectively analyzed. According to age, the children were divided into<3 years of age group and 3-<18 years of age group. According to the viral nucleic acid test results, the children were divided into positive accompanying caregiver group and negative accompanying caregiver group. Comparisons between groups were performed using Mann-Whitney U test or Chi-square test. Multivariate Logistic regression analysis was used to analyze the related factors of NCT of nucleic acid in children with COVID-19. Results: Among the 225 patients (120 boys and 105 girls) of age 2.8 (1.3, 6.2) years, 119 children <3 years and 106 children 3-<18 years of age, 19 cases were diagnosed with moderate COVID-19, and the other 206 cases were diagnosed with mild COVID-19. There were 141 patients in the positive accompanying caregiver group and 84 patients in the negative accompanying caregiver group.Patients 3-<18 years of age had a shorter NCT (5 (3, 7) vs.7 (4, 9) d, Z=-4.17, P<0.001) compared with patients <3 years of age. Patients in the negative accompanying caregiver group had a shorter NCT (5 (3, 7) vs.6 (4, 9) d,Z=-2.89,P=0.004) compared with patients in the positive accompanying caregiver group. Multivariate Logistic regression analysis showed that anorexia was associated with NCT of nucleic acid (OR=3.74,95%CI 1.69-8.31, P=0.001). Conclusion: Accompanying caregiver with positive nucleic acid test may prolong NCT of nucleic acid, and decreased appetite may be associated with prolonged NCT of nucleic acid in children with COVID-19.


Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Male , Young Adult , China/epidemiology , COVID-19/genetics , Nucleic Acids , Retrospective Studies
15.
Article in Chinese | WPRIM | ID: wpr-969910

ABSTRACT

Objective: To estimate the latent period and incubation period of Omicron variant infections and analyze associated factors. Methods: From January 1 to June 30, 2022, 467 infected persons and 335 confirmed cases in five local Omicron variant outbreaks in China were selected as the study subjects. The latent period and incubation period were estimated by using log-normal distribution and gamma distribution models, and the associated factors were analyzed by using the accelerated failure time model (AFT). Results: The median (Q1, Q3) age of 467 Omicron infections including 253 males (54.18%) was 26 (20, 39) years old. There were 132 asymptomatic infections (28.27%) and 335 (71.73%) symptomatic infections. The mean latent period of 467 Omicron infections was 2.65 (95%CI: 2.53-2.78) days, and 98% of infections were positive for nucleic acid detection within 6.37 (95%CI: 5.86-6.82) days after infection. The mean incubation period of 335 symptomatic infections was 3.40 (95%CI: 3.25-3.57) days, and 97% of them developed clinical symptoms within 6.80 (95%CI: 6.34-7.22) days after infection. The results of the AFT model analysis showed that compared with the group aged 18~49 years old, the latent period [exp(β)=1.36 (95%CI: 1.16-1.60), P<0.001] and incubation period [exp(β)=1.24 (95%CI: 1.07-1.45), P=0.006] of infections aged 0~17 year old were also prolonged. The latent period [exp(β)=1.38 (95%CI: 1.17-1.63), P<0.001] and the incubation period [exp(β)=1.26 (95%CI: 1.06-1.48), P=0.007] of infections aged 50 years old and above were also prolonged. Conclusion: The latent period and incubation period of most Omicron infections are within 7 days, and age may be the influencing factor of the latent period and incubation period.

16.
Acta Pharmaceutica Sinica B ; (6): 2955-2962, 2023.
Article in English | WPRIM | ID: wpr-982891

ABSTRACT

Deubiquitinating enzymes (DUBs) or deubiquitinases facilitate the escape of multiple proteins from ubiquitin‒proteasome degradation and are critical for regulating protein expression levels in vivo. Therefore, dissecting the underlying mechanism of DUB recognition is needed to advance the development of drugs related to DUB signaling pathways. To data, extensive studies on the ubiquitin chain specificity of DUBs have been reported, but substrate protein recognition is still not clearly understood. As a breakthrough, the scaffolding role may be significant to substrate protein selectivity. From this perspective, we systematically characterized the scaffolding proteins and complexes contributing to DUB substrate selectivity. Furthermore, we proposed a deubiquitination complex platform (DCP) as a potentially generic mechanism for DUB substrate recognition based on known examples, which might fill the gaps in the understanding of DUB substrate specificity.

17.
Article in Chinese | WPRIM | ID: wpr-981726

ABSTRACT

OBJECTIVE@#To observe the analgesic effect of Tuina by pressing and kneading the Huantiao (GB30) acupoint on rats with chronic constriction injury (CCI) and to explore the analgesic mechanism of Tuina on sciatica rats.@*METHODS@#Thirty-two SPF male SD rats weighing 180 to 220 g were randomly divided into fore groups:blank group (without any treatment), sham group (only exposed without sciatic nerve ligating), model group (sciatic nerve ligating) and Tuina group (manual intervention after lsciatic nerve ligating). The CCI model was prepared by ligating the right sciatic nerve of the rats, on the third day of modeling, the rats in the Tuina group were given pressing and kneading the Huantiao (GB30) point for 14 days, and the changes of paw withdrawal threshold(PWT), paw withdrawal latency(PWL) were measured before and on the 1st, 3rd, 7th, 10th, 14th and 17th days after modeling. The changes of sciatic functional index(SFI) were measured before and on the 1st and 17th day after modeling. The morphological changes of the sciatic nerve were observed by hematoxylin-eosin(HE) staining;and the differences in NF-κB protein expression in the right dorsal horn of the spinal cord of rats were detected.@*RESULTS@#Following modeling, there was no significant difference in PWT, PWL and SFI between the blank group and the sham group (P>0.05), but the PWT, PWL and SFI of the model group and the Tuina group decreased significantly (P<0.01). After manual intervention, the pain threshold of rats in Tuina group increased. On the 8th day of manual intervention (the 10th day after modeling), PWT in Tuina group increased significantly compared with that in model group (P<0.01). On the 5th day of manual intervention (the 7th day after modeling), the PWL of the massage group was significantly higher than that of the model group (P<0.01). The pain threshold of rats in Tuina group continued to rise with the continuous manipulation intervention. After 14 days of manipulative intervention, the sciatic nerve function index of rats in the Tuina group increased significantly(P<0.01). Compared with the blank group and sham group, the myelinated nerve fibers of sciatic nerve in the model group were disordered and the density of axons and myelin sheath was uneven. Compared with the model group, the nerve fibers of rats in the Tuina group were gradually continuous and the axons and myelin sheath were more uniform than those in the model group. Compared with the blank group and sham group, the expression of NF-κB protein in the right spinal dorsal horn of the model group was significantly increased(P<0.01). Compared with the model group, the expression of NF-κB protein in the right spinal dorsal horn of rats in Tuina group decreased significantly(P<0.01).@*CONCLUSION@#Pressing and kneading the Huantiao (GB30) point restores nerve fiber alignment;and improves the PWT、PWL and SFI in the CCI model by decreasing NF-κB p65 protein expression in the spinal dorsal horn. There fore, Tuina demmstrates an analgesic effect and improves the gait of rats with sciatica.


Subject(s)
Rats , Male , Animals , Rats, Sprague-Dawley , Sciatica/therapy , NF-kappa B/metabolism , Acupuncture Points , Spinal Cord Dorsal Horn/metabolism , Spinal Cord , Massage
18.
Rev. bras. med. esporte ; 29: e2021_0333, 2023. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1387954

ABSTRACT

ABSTRACT Periodontal disease (PD) is an inflammatory oral disease and alveolar bone loss is the most important sign of PD. However, the effects of exercise on inflammatory factors and alveolar bone loss in individuals with PD have been little studied. This meta-analysis assesses the effect of physical exercise on alveolar bone loss (ABL) and the inflammatory profile of PD in animal models. Relevant studies published through July 2020 in PubMed, Medline, Embase and Web of Science were searched after developing a PICOS statement. Quality assessment and risk of bias were analyzed according to the SYRCLE protocol. A total of 52 references were retrieved, 4 of which were considered eligible for inclusion. A total of thirty-four male Wistar rats from the included studies were evaluated for alveolar bone loss and assessed for inflammatory profile. The results indicated that physical exercise could reduce alveolar bone loss (95% CI -2.85 to -0.82, p = 0.002) and the pro-inflammatory tumor necrosis factor-α (TNF-α) in serum or gingival tissue (95% CI -0.45 to -0.24, p < 0.00001). Inversely, exercise increased anti-inflammatory interleukin-10 (IL-10) in serum or gingival tissue (95% CI 0.28 to 0.69, p < 0.00001). However, one study reported a negative result in the expression of TNF-α and IL-10. Current evidence indicates that physical exercise contributes to ameliorate PD by reducing alveolar bone loss and inflammation in animal PD models, which suggests that moderate exercise can be implemented in clinical practice to maintain periodontal health. Level of Evidence I; Systematic Review and Meta-analysis


RESUMEN La enfermedad periodontal (EP) es una enfermedad inflamatoria oral y la pérdida de hueso alveolar es su signo más importante. Sin embargo, los efectos del ejercicio sobre los factores inflamatorios y la pérdida ósea alveolar en individuos con EP han sido poco estudiados. Este meta-análisis evalúa el efecto del ejercicio sobre la pérdida ósea alveolar (POA) y el perfil inflamatorio de la EP en modelos animales. Se llevaron a cabo estudios relevantes publicados hasta julio de 2020 en PubMed, Medline, Embase y Web of Science tras desarrollar la investigación con el método PICO. La evaluación de la calidad y el riesgo de sesgo se analizaron según el protocolo SYRCLE. Se recuperó un total de 52 referencias, cuatro de las cuales se consideraron elegibles para su inclusión. En un total de 34 ratas Wistar macho de los estudios incluidos se evaluó la pérdida de hueso alveolar y el perfil inflamatorio. Los resultados indicaron que el ejercicio puede reducir la pérdida de hueso alveolar (IC del 95%: -2,85 a -0,82; p = 0,002) y el factor de necrosis tumoral proinflamatorio-α (TNFα) en suero o tejido gingival (IC del 95%: -0,45 a -0,24; p < 0,00001). Por el contrario, el ejercicio aumentó la interleucina-10 (IL-10) antiinflamatoria en el suero o en el tejido gingival (IC del 95%: 0,28 a 0,69; p < 0,00001). Sin embargo, un estudio informó de un resultado negativo en la expresión de TNFα e IL-10. Las pruebas actuales indican que el ejercicio contribuye a mejorar la EP al reducir la pérdida de hueso alveolar y la inflamación en modelos animales de EP, lo que sugiere que se puede implementar el ejercicio moderado en la práctica clínica para mantener la salud periodontal. Nivel de Evidencia I; Revisión Sistemática y Meta-análisis.


RESUMO A doença periodontal (DP) é uma doença inflamatória oral e a perda óssea alveolar é seu sinal mais importante. No entanto, os efeitos do exercício sobre os fatores inflamatórios e a perda óssea alveolar em indivíduos com DP têm sido pouco estudados. Esta metanálise avalia o efeito do exercício físico sobre a perda óssea alveolar (POA) e o perfil inflamatório da DP em modelos animais. Estudos relevantes publicados até julho de 2020 em PubMed, Medline, Embase e Web of Science foram pesquisados depois de desenvolver a pesquisa com o método PICO. A avaliação da qualidade e o risco de viés foram analisados de acordo com o protocolo SYRCLE. Um total de 52 referências foram recuperadas, quatro das quais foram consideradas elegíveis para inclusão. Um total de 34 ratos Wistar machos dos estudos incluídos foram avaliados quanto à perda de osso alveolar e avaliados quanto ao perfil inflamatório. Os resultados indicaram que o exercício físico pode reduzir a perda de osso alveolar (IC 95% -2,85 a -0,82, p = 0,002) e o fator de necrose tumoral pró-inflamatório-α (TNFα) no soro ou tecido gengival (IC 95% -0,45 a -0,24, p < 0,00001). Inversamente, o exercício aumentou a interleucina-10 anti-inflamatória (IL-10) no soro ou no tecido gengival (IC 95% 0,28 a 0,69, p < 0,00001). Contudo, um estudo relatou resultado negativo na expressão de TNFα e IL-10. As evidências atuais indicam que o exercício físico contribui para melhorar a DP, reduzindo a perda de osso alveolar e a inflamação em modelos animais de DP, o que sugere que o exercício moderado pode ser implementado na prática clínica para manter a saúde periodontal. Nível de Evidência I; Revisão Sistemática e Metanálise.

19.
Article in Chinese | WPRIM | ID: wpr-981248

ABSTRACT

Objective To investigate the effect of human platelet-rich plasma-derived exosomes(PRP-exos)on the proliferation of Schwann cell(SC)cultured in vitro. Methods PRP-exos were extracted by polymerization-precipitation combined with ultracentrifugation.The morphology of PRP-exos was observed by transmission electron microscopy,and the concentration and particle size distribution of PRP-exos were determined by nanoparticle tracking analysis.Western blotting was employed to determine the expression of the marker proteins CD63,CD81,and CD9 on exosome surface and the platelet membrane glycoprotein CD41.The SCs of rats were isolated and cultured,and the expression of the SC marker S100β was detected by immunofluorescence staining.The fluorescently labeled PRP-exos were co-cultured with SCs in vitro for observation of their interaction.EdU assay was employed to detect the effect of PRP-exos on SC proliferation,and CCK-8 assay to detect the effects of PRP-exos at different concentrations(0,10,20,40,80,and 160 μg/ml)on SC proliferation. Results The extracted PRP-exos appeared as uniform saucer-shaped vesicles with the average particle size of(122.8±38.7)nm and the concentration of 3.5×1012 particles/ml.CD63,CD81,CD9,and CD41 were highly expressed on PRP-exos surface(P<0.001,P=0.025,P=0.004,and P=0.032).The isolated SCs expressed S100β,and PRP-exos could be taken up by SCs.PRP-exos of 40,80,and 160 μg/ml promoted the proliferation of SCs,and that of 40 μg/ml showed the best performance(all P<0.01). Conclusions High concentrations of PRP-exos can be extracted from PRP.PRP-exos can be taken up by SCs and promote the proliferation of SCs cultured in vitro.


Subject(s)
Humans , Rats , Animals , Exosomes/metabolism , Platelet-Rich Plasma , Schwann Cells , Coculture Techniques , Cell Proliferation , Cells, Cultured
20.
Yonsei Medical Journal ; : 259-268, 2023.
Article in English | WPRIM | ID: wpr-977429

ABSTRACT

Purpose@#We aimed to analyze the optimal timing of enteral nutrition (EN) in the treatment of sepsis and its effect on sepsis-associated acute kidney injury (SA-AKI.) Materials and Methods: The MIMIC-III database was employed to identify patients with sepsis who had received EN. With AKI as the primary outcome variable, receiver operating characteristic (ROC) curves were utilized to calculate the optimal cut-off time of early EN (EEN). Propensity score matching (PSM) was employed to control confounding effects. Logistic regressions and propensity score-based inverse probability of treatment weighting were utilized to assess the robustness of our findings. Comparisons within the EEN group were performed. @*Results@#2364 patients were included in our study. With 53 hours after intensive care units (ICU) admission as the cut-off time of EEN according to the ROC curve, 1212 patients were assigned to the EEN group and the other 1152 to the delayed EN group. The risk of SA-AKI was reduced in the EEN group (odds ratio 0.319, 95% confidence interval 0.245–0.413, p<0.001). The EEN patients received fewer volumes (mL) of intravenous fluid (IVF) during their ICU stay (3750 mL vs. 5513.23 mL, p<0.001). The mediating effect of IVF was significant (p<0.001 for the average causal mediation effect). No significant differences were found within the EEN group (0–48 hours vs. 48–53 hours), except that patients initiating EN within 48 hours spent fewer days in ICU and hospital. @*Conclusion@#EEN is associated with decreased risk of SA-AKI, and this beneficial effect may be proportionally mediated by IVF volume.

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