Objective To investigate the anti-inflammatory effects of Bupi Yichang Pills on mice with experimental colitis and its potential mechanism of action.Methods Dextran sulfate sodium(DSS)was used to model the experimental colitis,and low-,medium-and high-doses of Bupi Yichang Pills(1.5,3.0,6.0 g·kg-1·d-1)and Mesalazine(300 mg·kg-1·d-1)were fed at the same time.Mice were observed for general behavior and weighed.Hematoxylin-eosin staining was used to observe the pathological injury of colonic tissues.qPCR and ELISA were used to detect the levels of inflammatory cytokines(TNF-α,IL-1β,IL-6,IL-10,IL-35 and TGF-β1),qPCR and Western Blot were used to detect the mRNA and protein levels of glucose transporters and glycolytic kinases.Results Low-,medium-and high-doses of Bupi Yichang Pills significantly down-regulated disease activity index in colitis mice(P＜0.05,P＜0.01).The body mass and colon length were significantly increased,while colon mass,colon mass index and unit colon mass index were significantly reduced(P＜0.05,P＜0.01),and ulcer formation and inflammatory cell infiltration in colonic tissue were significantly improved.In addition,medium-and high-doses of Bupi Yichang Pills significantly down-regulated the mRNA levels and concentrations of pro-inflammatory cytokines including TNF-α,IL-1β and IL-6(P＜0.01),while significantly up-regulated the mRNA levels and concentrations of anti-inflammatory cytokines such as IL-10,IL-35 and TGF-β1(P＜0.01).We further found that high-dose of Bupi Yichang Pills significantly down-regulated the mRNA and protein expressions of glucose transporters(Glut1,Glut2,Glut4)and glycolytic kinases(HK2,Aldolase A,PKM2)in colonic tissue(P＜0.01).Conclusions Bupi Yichang Pills effectively alleviates DSS-induced experimental colitis,and its specific mechanism of action is related to the improvement of glycolytic metabolic pathways and the regulation of inflammatory cytokine expression.

Objective:To construct a risk prediction model for infection with Klebsiella pneumonia (KP) for patients with severe acute pancreatitis (SAP).Methods:Retrospective analysis was done on the clinical data of 109 SAP patients who were admitted to Shanghai General Hospital, between March 2016 and December 2021. Patients were classified into infection group ( n=25) and non-infection group ( n=84) based on the presence or absence of KP infection, and the clinical characteristics of the two groups were compared. The least absolute shrinkage and selection operator (LASSO) algorithm was used to reduce the dimension of the variables with statistical significance in univariate analysis. A nomogram prediction model was created by incorporating the optimized features from the LASSO regression model into the multivariate logistic regression analysis. Receiver operating characteristic curve (ROC) was drawn and the area under curve (AUC) was calculated; and consistency index (C-index) were used to assess the prediction model's diagnostic ability. Results:A total of 25 strains of KP were isolated from 109 patients with SAP, of which 21(84.0%) had multi-drug resistance. 20 risk factors (SOFA score, APACHEⅡ score, Ranson score, MCTSI score, mechanical ventilation time, fasting time, duration of indwelling of the peritoneal drainage tube, duration of deep vein indwelling, number of invasive procedures, without or with surgical intervention, without or with endoscopic retrograde cholangiopancreatography (ERCP), types of high-level antibiotics used, digestion disorders, abnormalities in blood coagulation, metabolic acidosis, pancreatic necrosis, intra-abdominal hemorrhage, intra-abdominal hypertension, length of ICU stay and total length of hospital stay) were found to be associated with KP infection in SAP patients by univariate analysis. The four variables (APACHEⅡ score, duration of indwelling of the peritoneal drainage tube, types of high-level antibiotics used, and total length of hospital stay) were extracted after reduced by LASSO regression. These four variables were found to be risk factors for KP infection in SAP patients by multiple logistic regression analysis (all P value <0.05). Nomogram prediction model for KP infection in SAP was established based on the four variables above. The verification results of the model showed that the C-index of the model was 0.939, and the AUC was 0.939 (95% CI 0.888-0.991), indicating that the nomogram model had relatively accurate prediction ability. Conclusions:This prediction model establishes integrated the basic clinical data of patients, which could facilitate the risk prediction for KP infection in patients with SAP and thus help to formulate better therapeutic plans for patients.

Objective:To explore the effectiveness of Acute Care of the Elderly(ACE)model and its existing problems in the clinical practice for older adults with acute clinical conditions.Methods:Using the random number table method, a random number sequence was generated, and the patients admitted to the Department of Geriatrics of Shenzhen Nanshan Hospital due to acute diseases From January 2019 to September 2021 were enrolled in the ACE model intervention group(160 cases)and the control group(77 cases)in a 2: 1 ratio.The inclusion criteria were based on disease severity, frailty assessment, and activity of daily living(ADL)assessment.The intervention time was 1-3 weeks.Outcomes of the patients include ADL, hospitalization days, hospitalization expenses, drug proportion, human resource investments, adverse events, 30-day readmission rate, and 1-year mortality.Results:There were no significant difference in baseline indicators such as frailty index and ADL score between the two groups at admission.The ADL score(Barthel index)of the ACE group was significantly improved compared with the control group at discharge(81.71±14.23 vs.70.9±23.89, P<0.001)and at 30 days after discharge(85.84±15.25 vs.68.29±30.91, P<0.001). The hospital cost[(12 735.81±6 541.41)￥ vs.(16 391.54±12 962.34)￥, P=0.002], drug proportion(21.34% vs.28.93 %, P=0.036)and 30-day readmission rate(13.1% vs.23.4%, P=0.037)of the ACE group were significantly lower compared to the control group.The human resource input(32.97±6.72 vs.25.03±5.31, P=0.008)and patient satisfaction(98.23% vs.90.66%, P=0.031)in the ACE group were significantly higher than those of the control group.(4)The incidence of adverse events during hospitalization was significantly lower in the ACE group than in the control group in terms of aspiration(0.63% vs.20.8%, P<0.001), falls(0 vs.10.4%, P<0.001), incontinence dermatitis(0 vs.3.9%, P=0.033), and 1-year mortality(6.3% vs.24.7%, P<0.001). There was no significant difference in the average length of stay(8.98±4.25 vs.10.03±5.32, P=0.101), pressure sores(13.01±4.77 vs.13.27±4.89, P=0.364), DVT risk score(8.53±2.79 vs.8.89±2.76, P=0.340)and medical staff satisfaction(73% vs.80%, P=0.240)between the two groups. Conclusions:The ACE model helps to reduce the disability rate of elderly patients with frailty, adverse events during hospitalization, save drug costs, and improve patient satisfaction.It is worth promoting in geriatric practice, but its localization management details and processes still face many challenges.

Objective: To compare the diagnostic performance between panoramic radiography(PR)and cone beam computed tomography(CBCT)in the assessment of external root resorption(ERR)of mandibular second molars associated with impacted third molars. Methods: A total number of 832 patients with 1 074 mesially and horizontally impacted mandibular third molars treated at our institution from January 2019 to December 2020 were retrospectively analyzed. Presence of ERR on the adjacent second molar was investigated with PR and CBCT. Factors affecting the diagnostic accuracy of PR were determined. Results: The overall incidence of ERR in second molars was 33.15%(356/1 074)as detected by CBCT images. The accuracy of PR was 66.39%. Multivariate Logistic regression analyses further revealed that middle and Class Ⅲ impaction, crown contact or overlap with the root of adjacent tooth were risk factors for inaccurate diagnosis of PR(P<0.05). Conclusion The accuracy of detection on ERR of mandibular second molar associated with impacted third molar using panoramic radiography is lower. CBCT is recommended for this clinical scenario.

Objective:To seek any correlation between cortical activity and the swallowing of dysphagia patients with infratentorial stroke, and to observe any effect of three-needle acupuncture of the tongue on such activity.Methods:Thirty infratentorial stroke survivors with dysphagia were randomly divided into a tongue three-needle group and a sham acupuncture group, each of 15. Functional near-infrared spectroscopy was used to monitor changes in the concentration of oxygenated hemoglobin (ΔHbO 2) at rest, during acupuncture (or sham acupuncture), during real or sham electro-acupuncture, and at rest after the acupuncture or sham acupuncture treatment. The Modified Rankin Scale, a Penetration-Aspiration Scale (PAS), and the Functional Oral Intake Scale were employed to assess overall functional disability and the swallowing of both groups. Results:At rest the average ΔHbO 2 concentrations recorded in the left primary motor cortex, the left dorsolateral prefrontal cortex and the left premotor cortex in both groups were positively correlated with the PAS scores. During the acupuncture ΔHbO 2 concentration in the right inferior frontal gyrus and the left middle temporal gyrus increased significantly in the tongue three-needle group. It decreased significantly in the left somatosensory cortex and the left primary motor cortex. Conclusion:Three-needle acupuncture of the tongue induces changes in cortical activity in infratentorial stroke survivors with dysphagia, suggesting a potential technique for improving disordered swallowing.

Objective:To analyze the influence of work engagement and self-efficacy of nurses on clinical practice ability in burn intensive care unit (BICU), and to explore its potential pathways of action.Methods:A cross-sectional survey was conducted. From May to October 2020, a total of 30 hospitals with BICU in China were selected by stratified sampling method. Among BICU nurses who met the inclusion criteria, their clinical practice ability, work engagement, and self-efficacy were evaluated by self-evaluation scale of oriented problem-solving behavior in nursing practice (OPSN), Utrecht work engagement scale (UWES), and general self-efficacy scale (GSES), respectively. The total scale scores of each index and the average item scores were recorded. The self-designed general data questionnaire was used to investigate the nurses' gender, age, marital status, education background, working years, professional title, and the economic region of the hospital that they belonged to. The total scale scores of the above-mentioned three evaluation indexes were compared after the classification of nurses according to general data, and the data were statistically analyzed with independent sample t test or one-way analysis of variance. Pearson correlation analysis was used to analyze the correlation between the total scale scores of the three evaluation indexes. Based on the total scale scores of the above-mentioned three evaluation indexes, a structural equation model was established, the mediation analysis of the relationship among the three evaluation indexes and the pathway analysis of the structural model were conducted, and the Bootstrap method was used to verify the pathways of action. Results:A total of 401 questionnaires were distributed, and 337 valid questionnaires were returned, with a valid return rate of 84.04%. The total scale scores of clinical practice ability, work engagement, and self-efficacy of 337 nurses were 98.2±11.7, 67.7±18.6, and 26.6±5.6, respectively, and the average item scores were 3.9±0.5, 4.5±1.2, and 2.7±0.6, respectively. Among the 337 nurses, the majority were female, aged 40 or below, married, and had a bachelor's degree with work experience of ≤10 years; both nurses with professional nurse title and nurses from the Southeast region accounted for about 50%. There were statistically significant differences in the total scale score of clinical practice ability among nurses with different ages, education backgrounds, working years, and professional titles (with F values of 3.26, 4.36, 3.12, and 2.80, respectively, P<0.05). There was statistically significant difference in the total scale score of work engagement among nurses with different working years ( F=4.50, P<0.05). There were statistically significant differences in the total scale score of self-efficacy among nurses with different ages, working years, and professional titles (with F values of 4.91, 4.50, and 2.91, respectively, P<0.05). The total scale score of nurses' work engagement was significantly positively correlated with the total scale score of clinical practice ability and the total scale score of self-efficacy (with r values of 0.30 and 0.51, respectively, P<0.05). The total scale score of nurses' self-efficacy was significantly positively correlated with the total scale score of clinical practice ability ( r=0.37, P<0.05). The model had good adaptability, and the intermediary model was established. Nurses' work engagement had a significantly positive effect on both self-efficacy and clinical practice ability (with β values of 0.54 and 0.16, respectively, P<0.05), and nurses' self-efficacy had a significantly positive effect on clinical practice ability ( β=0.29, P<0.05). Work engagement had a direct effect on self-efficacy and clinical practice ability, and self-efficacy had a direct effect on clinical practice ability and played a mediating role between work engagement and clinical practice ability. Bootstrap validation showed that self-efficacy played a significantly mediating role in the influence of work engagement on clinical practice ability (with effect size of 0.16, with 95% confidence interval of 0.08-0.24, P<0.05), accounting for half of the total effect of work engagement on clinical practice ability (with effect size of 0.32). Conclusions:BICU nurses have an above-average level of clinical practice ability, a medium level of self-efficacy, and a high level of work engagement. Work engagement and self-efficacy are positively correlated with clinical practice ability. Work engagement can directly affect clinical practice ability or indirectly affect clinical practice ability through the mediating role of self-efficacy.

Objective:To establish a prediction model of acute upper gastrointestinal rebleeding (AUGIRB) for elderly patients by combining and applying multiple indicators.Methods:A retrospective observational study was conducted. The clinical data of 161 elderly patients (age ≥ 65 years old) who suffered from acute upper gastrointestinal bleeding (AUGIB) and who were hospitalized in Shanghai General Hospital from July 2018 to December 2020 were recorded. The patients were divided into the rebleeding group (31 cases) and the non-rebleeding group (130 cases) according to whether gastrointestinal rebleeding occurred. Univariate analysis was adopted to screen AUGIRB-related risk factors and Logistic regression analysis was used to screen independent predictors of AUGIRB so that a predictive model was constructed. Based on the area under the curve (AUC) of the receiver operator characteristic curve (ROC curve), the predictive ability of the prediction model for AUGIRB was evaluated, the optimal cut-off value was determined, and the odds ratio ( OR) and its 95% confidence interval (95% CI) were calculated. Bootstrap resampling technology was used to validate the predictive ability of the model. Results:Univariate Logistic analysis showed that oral anticoagulant drugs, oral antiplatelet drugs, albumin (ALB), platelet count (PLT), Glasgow-Blatchford bleeding score (GBS), D-dimer, fibrinogen (FIB), and international normalized ratio (INR) all had a significant effect on the occurrence of AUGIRB among elderly patients. Multivariate Logistic regression analysis showed that the oral antiplatelet drugs ( OR = 11.150, 95% CI was 1.888-65.852, P < 0.05) and GBS score ( OR = 2.503, 95% CI was 1.523-4.114, P < 0.05) were the independent risk factors of AUGIRB among elderly patients, while the ALB ( OR = 0.764, 95% CI was 0.626-0.932, P < 0.05) and FIB ( OR = 0.065, 95% CI was 0.011-0.370, P < 0.05) were the protective factors of AUGIRB among elderly patients. The AUC of the above four indexes joint prediction model was 0.979. The verification results of the model showed that the consistency index (C-index) of the model was 0.986. Conclusion:The prediction model fitted in this research has a high prediction accuracy and it also has a certain reference value for the judgment of elderly patients who suffer from AUGIRB.

OBJECTIVE: To explore the genetic basis for a child with Rothmund-Thomson syndrome (RTS). METHODS: The child has featured poikeloderma, short stature, cataract, sparse hair and skeletal malformation. Peripheral blood samples of the child and her family members were collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. RESULTS: The child was found to harbor compound heterozygous variants of the RECQL4 gene, namely c.1048_1049delAG and c.2886-1G>A, among which c.2886-1G>A was unreported previously. According to the ACMG guidelines, the c.1048_1049delAG was predicted to be pathogenic (PVS1+PM3_Strong+PM2), while the c.2886-1G>A was predicted to be likely pathogenic (PVS1+PM2). CONCLUSION The compound heterozygous variants of the RECQL4 gene probably underlay the pathogenesis of RTS in this patient. Above finding has enriched the mutational spectrum of the RECQL4 gene.
Child ; Family ; Female ; Humans ; Mutation ; RecQ Helicases/genetics* ; Rothmund-Thomson Syndrome/genetics* ; Whole Exome Sequencing

Antibody-drug conjugates(ADCs)are commonly heterogeneous and require extensive assessment of exposure-efficacy and exposure-safety relationships in preclinical and clinical studies.In this study,we report the generation of a monoclonal antibody against monomethyl auristatin E(MMAE)and the development,validation,and application of sensitive and high-throughput enzyme-linked immunosor-bent assays(ELISA)to measure the concentrations of MMAE-conjugated ADCs and total antibodies(tAb,antibodies in ADC plus unconjugated antibodies)in cynomolgus monkey sera.These assays were suc-cessfully applied to in vitro plasma stability and pharmacokinetic(PK)studies of SMADC001,an MMAE-conjugated ADC against trophoblast cell surface antigen 2(TROP-2).The plasma stability of SMADC001 was better than that of similar ADCs coupled with PEG4-Val-Cit,Lys(m-dPEG24)-Cit,and Val-Cit linkers.The developed ELISA methods for the calibration standards of ADC and tAb revealed a correlation be-tween serum concentrations and the OD450 values,with R2 at 1.000,and the dynamic range was 0.3-35.0 ng/mL and 0.2-22.0 ng/mL,respectively;the intra-and inter-assay accuracy bias％ranged from-12.2％to-5.2％,precision ranged from-12.4％to-1.4％,and the relative standard deviation(RSD)was less than 6.6％and 8.7％,respectively.The total error was less than 20.4％.The development and validation steps of these two assays met the acceptance criteria for all addressed validation parameters,which suggested that these can be applied to quantify MMAE-conjugated ADCs,as well as in PK studies.Furthermore,these assays can be easily adopted for development of other similar immunoassays.

Objective:To evaluate the efficacy of angioplasty on percutaneous superior vena cava occlusion in hemodialysis patients with tunnel-cuffed catheter (TCC) under digital subtraction angiography (DSA) guidance.Methods:A total of 62 hemodialysis patients with TCC in the First Affiliated Hospital of Sun Yat-sen University from December 2017 to June 2020 were enrolled retrospectively. According to the patency of the superior vena cava, the patients were divided into experiment group ( n=20) and control group ( n=42) in this study. Hemodialysis patients with superior vena cava occlusion in the experiment group received angioplasty, including balloon angioplasty, stenting and sharp recanalization, and catheterization with TCC under DSA guidance, while hemodialysis patients without superior vena cava occlusion in the control group only underwent catheterization with TCC under DSA guidance. The 1-year TCC patency rate, postoperative TCC blood flow and treatment-related complications between the two groups were compared. Results:In the experiment group, a total of 11 patients were treated only by percutaneous transluminal angioplasty, while 9 patients were treated combined percutaneous transluminal angioplasty with stent placement. In addition, 3 patients underwent sharp recanalization of superior vena cava occlusion. A total of 9 stents and 29 balloons were used. The course of dialysis in experiment group was longer than that in control group ( P<0.05). There were no significant differences in the 1-year TCC patency rate (85.0% vs 95.2%, P>0.05), postoperative TCC blood flow [(257.83±16.55) ml/min vs (251.90±18.79) ml/min, P>0.05] and incidence of treatment-related complications (grade 1-2, 30.0% vs 35.7%, P>0.05) between the two groups, respectively. Patients in the two groups had none of serious operation-related complications, and only some patients had mild clinical manifestations, such as postoperative pain and bleeding at the puncture point. Conclusions:For patients with longer duration of hemodialysis and superior vena cava stenosis and occlusion treated with angioplasty, the clinical effect of TCC within one year is equivalent to that of hemodialysis patients without angioplasty.