Effect of Fuzheng Huayu prescription on hepatocyte extinction and regeneration in a mouse model of liver cirrhosis / 临床肝胆病杂志

ObjectiveTo investigate the effect of Fuzheng Huayu prescription on hepatocyte extinction and regeneration in fibrotic liver and its mechanism of action in promoting hepatocyte regeneration. MethodsMice were given intraperitoneal injection of CCl4 for 6 weeks to establish a model of liver cirrhosis， and there were 10 mice in the model group， 10 in the sorafenib group， 10 in the Fuzheng Huayu prescription group， and 9 in the normal control group. Since week 4 of modeling， the mice in the Fuzheng Huayu prescription group and the sorafenib group were given the corresponding drug by gavage at a dose of 4.8 g/kg and 4 mg/kg， respectively， for three consecutive weeks， and those in the normal group and the model group were given an equal volume of sodium carboxymethyl cellulose. Serum liver function parameters were measured； the METAVIR scoring system was used to evaluate liver inflammation and fibrosis stage； Sirius Red staining and hydroxyproline （Hyp） content in liver tissue were used to evaluate collagen deposition； immunohistochemistry was used to measure the protein expression levels of type IV collagen， CD31， CD32b， Ki67， CyclinD1， glutamine synthetase， Wnt2， and HGF， and Western blot was used to measure the expression levels of Wnt2， LRP6， β-catenin， p-β-catenin， and CyclinD1 in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the model group， the Fuzheng Huayu prescription group and the sorafenib group showed the following changes： significant reductions in the serum levels of alanine aminotransferase and aspartate aminotransferase and the content of Hyp in liver tissue （all P<0.01）； a significant reduction in METAVIR score； significant reductions in the expression levels of type Ⅳ collagen and CD31 （all P<0.05） and a significant increase in the expression level of CD32b （P<0.01）； significant reductions in the number of parenchymal extinction lesions and significant increases in the expression levels of Ki67 and CyclinD1 in liver tissue （all P<0.01）； significant increases in the protein expression levels of Wnt2， LRP6， β-catenin， and CyclinD1 and a significant reduction in the protein expression level of p-β-catenin （all P<0.05）； significant increases in the number of cells stained positive for both CD32b and Wnt2. ConclusionFuzheng Huayu prescription can inhibit hepatic sinusoidal capillarization， improve the Wnt2 exocrine function of liver sinusoidal endothelial cells， activate the Wnt/β-catenin signaling pathway associated with hepatocyte regeneration， and finally reverse liver cirrhosis.

Effect and mechanism of long-term indwelling needle at Baihui acupoint on improving neurological function in ischemic stroke mice / 中华老年心脑血管病杂志

Objective To investigate the effect and mechanism of long-term indwelling needle of Baihui acupoint during acupuncture on improving neurological function in ischemic stroke mice through brain-derived neurotrophic factor(BDNF)/tyrosine receptor kinase B(TrkB)pathway.Methods A total of 48 male C57BL/6J mice were randomly divided into sham group 1,model group 1,long-term indwelling needle group 1 and conventional indwelling needle group,with 12 mice in each group.A mouse model of ischemic stroke was established by thread occlusion in the latter 3 groups.From the first day after modeling,long-term and conventional indwelling needle at Baihui acupoint was given to the mice in the corresponding groups for 14 consecutive days.Anoth-er 40 male C57BL/6J mice were also subjected and randomly divided into sham group 2,model group 2,and long-term indwelling needle groups 2 and 3,with 10 mice in each group.After model-ing in the latter 3 groups,100 pl adeno-associated virus was injected by caudal vein before acu-puncture treatment.Modified neurological severity score(mNSS)and escape latency,residence time in the target quadrant,and times of crossing the original platform in water maze test were used to evaluate neural function.Results Decreased mNSS score,shorter residence time in the target quadrant,less times of crossing the original platform,and reduced expression levels of BDNF and TrkB in the ischemic brain tissue,and higher apoptotic rate and elevated level of cleaved Caspase-3 in the ischemic brain tissue were observed in the model group 1 when compared with the sham group 1(P＜0.05).While long-term and conventional indwelling needle could reverse above indicators,with long-term indwelling needle more significant than the conventional method(P＜0.05).The long-term indwelling needle group 3 obtained lower mNSS score,reduced residence time in the target quadrant,lower times of crossing the original platform and decreased levels of BDNF and TrkB in the ischemic brain tissue(P＜0.05),and higher apoptotic rate and elevated level of cleaved Caspase-3 in the ischemic brain tissue than the long-term indwelling nee-dle group 2[(16.41±2.25)％vs(7.59±1.09)％,1.46±0.16 vs 0.94±0.12,P＜0.05].Conclusion Long-term indwelling needle at Baihui acupoint more significantly improves the neurological func-tion in ischemic stroke mice than ordinary indwelling needle treatment.Its molecular mechanism is due to activating the BDNF/TrkB pathway.

Effect of propofol or different doses of remimazolam on median effective dose of sufentanil for suppressing tracheal intubation response in elderly patients / 中国现代医生

@#Objective To investigate the effect of propofol or different doses of remimazolam on effective dose(ED50)of sufentanil in elderly patients with tracheal intubation response by sequential method.Methods Elderly patients,American Society of Anesthesiologists(ASA)Ⅰ and Ⅱ,aged 65-80 years,undergoing elective surgery under general anesthesia with endotracheal intubation from October to December 2022 were selected and randomly divided into 4 groups:Group P(propofol 2mg/kg)and group R1,R2 and R3(remimazolam 0.2,0.3 and 0.4mg/kg)were administered intravenously.During anesthesia induction,sufentanil was given with the dose set by Dixon sequential method,followed by intravenous injection of propofol or corresponding dose of remimazolam and cisatracurium 0.15mg/kg.Tracheal intubation was performed when train of four(TOF)count was 0.If the tracheal intubation response is positive,the sufentanil dose of the next patient is increased by 1 concentration gradient,otherwise,the sufentanil dose is decreased by 1 concentration gradient,and the ratio between adjacent concentrations is 1∶1.1,until 7 turning points appear and the study is terminated.Probit regression analysis was used to calculate the median ED50 and 95%effective dose(ED95)of sufentanil for suppressing tracheal intubation response in elderly patients,and the corresponding 95%CI.The incidence of hypotension,bradycardia,injection pain and other adverse reactions were recorded.Results A total of 113 elderly patients were included in this study,including 24,28,30 and 31 patients in P,R1,R2 and R3 groups,respectively.The ED50 and ED95 and corresponding 95%CI of sufentanil for suppressing tracheal intubation response in elderly patients with propofol 2 mg/kg or remimazolam 0.2,0.3,0.4mg/kg were:The ED50 and ED95 of group P were 0.236μg/kg(95%CI:0.218-0.256)and 0.266μg/kg(95%CI:0.250-0.398),respectively.The ED50 and ED95 of group R1 were 0.284μg/kg(95%CI:0.265-0.309)and 0.329μg/kg(95%CI:0.306-0.478),respectively.The ED50 and ED95 of R2 group were 0.239μg/kg(95%CI:0.221-0.260)and 0.282μg/kg(95%CI:0.261-0.415),respectively.The ED50 and ED95 of R3 group were 0.198μg/kg(95%CI:0.182-0.211)and 0.231μg/kg(95%CI:0.216-0.303),respectively.The incidence of hypotension,bradycardia and injection pain in R1,R2 and R3 groups were lower than those in P group(P<0.05).The ED50 of sufentanil in group R2 was similar to that in group P,but the incidence of hypotension and injection pain in group R2 was lower than that in group P.Conclusion With the increase of the dose of remimazolam,the ED50 of sufentanil to inhibit tracheal intubation reaction in elderly patients gradually decreased,and in the case of similar ED50,the incidence of hypotension,bradycardia and injection pain induced by remimazolam was lower than that induced by propofol,so remimazolam induction was more advantageous in general anesthesia for tracheal intubation in elderly patients.

Predictive value of renal venous Doppler waveform pattern for 28-day renal dysfunction in critically ill patients / 中华急诊医学杂志

Objective:This study aimed to explore the performance of renal resistive index (RRI), semiquantitative power Doppler ultrasound (PDU) score, and renal venous Doppler waveform (RVDW) pattern in predicting 28-day renal dysfunction in critically ill patients and establish nomogram model.Methods:This was a prospective, observational study. Critically ill patients admitted to the emergency intensive care unit (ICU) of Cangzhou Central Hospital from January 2018 to October 2022 were included. Patients underwent renal ultrasound examination to obtain RRI, PDU score and RVDW pattern within 24 h after ICU admission. The following clinical variables were collected during the renal ultrasound examination session, including heart rate, mean arterial pressure, type and dose of vasoactive drugs, oxygen therapy parameters, and average urine volume per hour derived from a period of 6 h prior to the ultrasound examination. The data on duration of AKI and mortality were recorded on the 28th day of follow-up. Patients were divided into 28-day normal renal function group and 28-day renal dysfunction group according to 28-day renal dysfunction. 28-days of renal dysfunction was defined as failure to achieve renal function recovery within 28 days of ICU admission. The difference of each index between the two groups was compared. Associated factors for 28-day renal dysfunction were determined by univariate and multivariate COX regression analyses. A nomogram was developed based on the independently factors associated with 28-day renal dysfunction. Survival receiver operator characteristic (ROC) curves were plotted to assess diagnostic performance in predicting 28-day renal dysfunction. Delong’s test was used to compare area under the curves (AUC) between each predictor.Results:187 patients were enrolled for the final analysis: 97 with no AKI, 48 with AKI stage 1, 24 with AKI stage 2, and 18 with AKI stage 3 upon enrollment. At 28-day follow up, 16 patients had renal dysfunction and 2 required continuous renal replacement therapy (CRRT). The multivariate COX regression showed that RVDW and SCr upon enrollment were the independent risk predictors. Nomogram based on RVDW and SCr upon enrollment showed the best performance in predicting 14-day renal dysfunction (AUC = 0.918, 95% CI:0.871-0.964, P<0.05), and the AUC was statistically significantly higher than single index (all P<0.05). Nomogram also showed the best performance in predicting 28-day renal dysfunction (AUC = 0.924, 95% CI:0.865-0.983, P<0.05), and the AUC was statistically significantly higher than single index (all P<0.05) except for SCr upon enrollment. The optimal cutoff for nomogram in predicting 28-day renal dysfunction was ≤89.5 (sensitivity, 81.2%; specificity, 90.6%; Youden index, 0.719). Kaplan-Meier analysis showed that the median duration of renal dysfunction in the groups with total nomogram score >85.9 and ≤85.9 was 0 and 22 days (HR=0.220, 95% CI:0.129-0.376, P<0.001). Conclusions:SCr and RVDW pattern within 24 h from ICU admission were independent factors associated with 28-day renal dysfunction in critically ill patients. The value of the nomogram model based on these two factors in predicting 28-day renal dysfunction is superior to each single intrarenal Doppler spectrum indicator and clinical indicator.

A narrative review on the research history of renal fibrosis from 1836 to 2000 / 中华肾脏病杂志

Renal fibrosis (RF) is the key pathological feature for the progression of chronic kidney disease to end-stage renal failure. It has been an important scientific issue to understand its mechanism of RF in the field of kidney diseases in the past near two centuries. The progress of science and technology has not only provided a strong tool for RF research, but also given us many new ideas for RF prevention and treatment. The paper briefly reviews the key histories of RF research, with focuses on early studies of renal fibrosis, application of renal biopsy technology, establishment of RF animal models, advancements in cell and molecular biotechnology, and exploration into mechanisms underlying RF, to clarify future directions for chronic kidney disease prevention and treatment research.

Effects of long-time needle retaining at Baihui(GV20)on post-stroke cognitive impairment / 针灸推拿医学（英文版）

Objective:To observe the clinical efficacy of long-time needle retaining at Baihui(GV20)on post-stroke cognitive impairment(PSCI)and its effects on the cognitive ability and living ability of the patients.Methods:A total of 62 PSCI patients were divided into a control group and an observation group by the random number table method,with 31 cases in each group.The control group was treated with routine treatment for stroke in the recovery period plus cognitive training.The observation group received additional acupuncture at Baihui(GV20)with long-time needle retaining based on the same intervention in the control group.The Montreal cognitive assessment(MoCA)was used to evaluate the cognitive ability of patients.The activities of daily living(ADL)scale was used to evaluate the living ability of patients.And the mini-mental state examination(MMSE)scale was used to evaluate the mental state,concentration,language,and abstraction cognition of patients.After 4 weeks,the curative efficacy was observed,and the scores of cognitive level,living ability,mental state and concentration,language,and abstraction understanding ability were compared between the two groups.Results:During the trial,1 patient in each group dropped out due to personal reasons and was unable to continue the treatment.After 4 weeks of treatment,the total effective rate was 83.3%in the observation group and 66.7%in the control group,and the difference between the two groups was statistically significant(P<0.05);the scores of MoCA,ADL,and MMSE,and scores of concentration,language ability,and abstraction understanding ability were all increased,and were statistically different from those before treatment in each group(P<0.05);the scores in the observation group were all higher than those in the control group,and the differences between the groups were statistically significant(P<0.05).Conclusion:On the basis of routine treatment and cognitive training,the clinical efficacy of additional acupuncture at Baihui(GV20)with long-time needle retaining in the treatment of PSCI is better than that of routine treatment plus cognitive training;the treatment can better improve the cognitive function and mental state of patients,and improve their living ability.

Effects of intravenous thrombolysis with a recombinant tissue plasminogen activator at different time windows on acute ischemic stroke in patients / 中国基层医药

Objective:To investigate the clinical efficacy of intravenous thrombolysis with a recombinant tissue plasminogen activator at different time windows on acute ischemic stroke in patients.Methods:A total of 172 patients with acute ischemic stroke who received treatment in Lishui Municipal Central Hospital from January 2019 to December 2021 were included in this study. They were divided into observation (onset to admission < 3 hours, n = 86) and control (onset to admission = 3-4.5 hours, n = 86) groups according to the time from onset to admission. Clinical efficacy, coagulation indexes, the National Institutes of Health Stroke Scale score, and the modified Rankin Scale score were compared between the two groups. Results:Total response rate in the observation group was significantly higher than that in the control group [89.54% (77/86) vs. 75.58% (65/86), χ2 = 4.89, P < 0.05]. After treatment, fibrinogen, low whole blood viscosity, and plasma viscosity in the observation group were (2.55 ± 0.62) g/L, (9.68 ± 1.37) mPa·s, (1.45 ± 0.17) mPa·s, respectively, which were significantly higher than (1.53 ± 0.58) g/L, (9.19 ± 1.46) mPa·s, (1.32 ± 0.15) mPa·s in the control group ( t = -11.14, -2.27, -5.32, all P < 0.05). Antithrombin III level in the observation group was significantly lower than that in the control group [(91.65 ± 7.23)% vs. (97.74 ± 6.82)%, t = 5.68, P < 0.05]. At 2 hours, 1 day, and 2 weeks after thrombolysis, the National Institutes of Health Stroke Scale scores in the observation group were (2.49 ± 0.31) points, (1.98 ± 0.24) points, (1.79 ± 0.05) points, which were significantly lower than (3.32 ± 1.08) points, (2.69 ± 0.35) points, (2.18 ± 0.21) points in the control group ( t = 6.85, 15.52, 16.75, all P < 0.001). After treatment, the modified Rankin Scale score in the observation group was significantly lower than that in the control group [(2.01 ± 0.79) points vs. (2.88 ± 0.64) points, t = 7.94, P < 0.001]. Conclusion:Intravenous thrombolysis with a recombinant tissue plasminogen activator within 4.5 hours after onset exhibits good therapeutic efficacy in patients with acute ischemic stroke. Earlier thrombolysis leads to better therapeutic efficacy and prognosis.

Regulatory effects of tenofovir disoproxil fumarate on oxidative stress and peripheral blood Th17/Treg balance in patients with hepatitis B cirrhosis / 中国基层医药

Objective:To investigate the regulatory effects of tenofovir disoproxil fumarate on oxidative stress and peripheral blood Th17/Treg balance in patients with hepatitis B cirrhosis.Methods:A total of 102 patients with hepatitis B cirrhosis who received treatment in the Marine Police Corps Hospital of Chinese People's Armed Police, China from March 2020 to June 2021 were included in this study. They were randomly assigned to undergo treatment with either tenofovir disoproxil fumarate ( n = 51, observation group) or entecavir ( n = 51, control group) for 42 weeks. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO), T helper 17 cells (Th17), regulatory T cells (Treg), Th17/Treg ratio, hyaluronic acid (HA), laminin (LN), type III procollagen (PC III), type IV collagen (IV-C), hepatitis B virus DNA negative rate, HBeAg negative rate, and alanine aminotransferase normalization rate pre- and post-treatment as well as the incidence of adverse reactions were compared between the two groups. Results:Before treatment, there were no significant differences in SOD, MDA, NO, Th17, Treg, Th17/Treg ratio, HA, LN, PC III, IV-C between the two groups (all P > 0.05). After treatment, SOD and Treg in the observation group were (121.52 ± 23.52) U/L and (3.51 ± 0.70)% in the observation group, respectively, which were significantly higher than (113.30 ± 20.05) U/L and (3.14 ± 0.49)%, respectively in the control group ( t = 1.90, -4.14, both P < 0.05). MDA, NO and Th17, Th17/Treg ratio, HA, LN, PC III, and IV-C in the observation group were (7.40 ± 1.35) mmol/L, (22.56 ± 4.25) μmol/L, (1.29 ± 0.46)%, (0.45 ± 0.11), (212.52 ± 16.62) μg/L, (135.52 ± 14.02) μg/L, (132.52 ± 15.62) μg/L,(96.52 ± 10.02) μg/L, respectively, which were significantly lower compared with the control group ( t = -6.81, 4.02, 3.10, -8.46, -13.27, -15.23, -13.67, -17.38, all P < 0.05). Hepatitis B virus DNA negative rate, HBeAg negative rate, and alanine aminotransferase normalization rate in the observation group were 76.47% (39/51), 68.63% (35/51) and 74.51% (38/51), respectively, which were higher than 56.86% (29/51), 41.18% (21/51), 54.90% (28/51) in the control group ( χ2 = 4.41, 7.76, 4.29, all P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Conclusion:Tenofovir disoproxil fumarate is highly effective on hepatitis B cirrhosis. It can reduce oxidative stress and regulate peripheral blood Th17/Treg balance.

Trans-ethnic Mendelian randomization study of systemic lupus erythematosus and common female hormone-dependent malignancies / 中华医学杂志(英文版)

BACKGROUND@#Observational research has reported that systemic lupus erythematosus (SLE) is related to common female hormone-dependent cancers, but the underlying causal effect remains undefined. This study aimed to explore the causal association of these conditions by Mendelian randomization (MR) analysis.@*METHODS@#We selected instrumental variables for SLE from genome-wide association studies (GWASs) conducted in European and East Asian populations. The genetic variants for female malignant neoplasms were obtained from corresponding ancestry GWASs. We utilized inverse variance weighted (IVW) as the primary analysis, followed by sensitivity analysis. Furthermore, we conducted multivariable MR (MVMR) to estimate direct effects by adjusting for the body mass index and estradiol. Finally, we implemented reverse direction MR analysis and gave a negative example to test the reliability of MR results.@*RESULTS@#We found SLE was significantly negatively associated with overall endometrial cancer risk (odds ratio [OR] = 0.961, 95% confidence interval [CI] = 0.935-0.987, P  = 3.57E-03) and moderately inversely related to endometrioid endometrial cancer (ENEC) (OR = 0.965, 95% CI = 0.936-0.995, P  = 0.024) risk in the European population by IVW. We replicated these results using other MR models and detected a direct effect by MVMR (overall endometrial cancer, OR = 0.962, 95% CI = 0.941-0.983, P  = 5.11E-04; ENEC, OR = 0.964, 95% CI = 0.940-0.989, P  = 0.005). Moreover, we revealed that SLE was correlated with decreased breast cancer risk (OR = 0.951, 95% CI = 0.918-0.986, P  = 0.006) in the East Asian population by IVW, and the effect was still significant in MVMR (OR = 0.934, 95% CI = 0.859-0.976, P  = 0.002). The statistical powers of positive MR results were all >0.9.@*CONCLUSION@#This finding suggests a possible causal effect of SLE on the risk of overall endometrial cancer and breast cancer in European and East Asian populations, respectively, by MR analysis, which compensates for inherent limitations of observational research.

Application of serum gastrin 17, pepsinogen I, pepsinogen II, and programmed cell death protein 5 protein in the identification of gastric precancerous state and diagnosis of early gastric cancer / 中国基层医药

Objective:To investigate the value of serum gastrin 17 (G-17), pepsinogen I (PG I), pepsinogen II (PG II), and programmed cell death protein 5 (PDCD5) in the identification of gastric precancerous state and the diagnosis of early gastric cancer.Methods:A total of 86 patients with early gastric cancer who received treatment at the Marine Police Corps Hospital of Chinese People's Armed Police Force from July 2018 to June 2022 were included in the gastric cancer group. Eighty patients with gastric precancerous states who concurrently received treatment in the same hospital were included in the precancerous state group. An additional 80 partiapants who concurrently received physical examination in the same hospital were included in the healthy group.The value of G-17, PG I, PG II, and PDCD5 in the diagnosis of early gastric cancer was analyzed.Results:The levels of G-17 and PG II in the precancerous state group [(10.87 ± 3.23) pmol/L, (15.78 ± 3.33) μg/L] and gastric cancer group [(18.78 ± 4.10) pmol/L, (21.25 ± 4.48) μg/L] were significantly higher compared with the healthy group [(5.56 ± 1.43) pmol/L, (13.52 ± 3.02) μg/L, F = 362.65, 94.12, all P < 0.05]. The levels of PG I and PDCD5 in the precancerous state group [(79.52 ± 16.62) μg/L, (1.35 ± 0.15) μg/L] and gastric cancer group [(50.06 ± 15.58) μg/L, (0.85 ± 0.13) μg/L] were significantly lower than those in the healthy group [(110.12 ± 30.23) μg/L, (1.60 ± 0.12) μg/L, F = 151.07, 650.56, all P < 0.05)].There were significant differences between the precancerous state and the gastric cancer groups in terms of family history of gastric cancer, consumption of high salt fried foods, alcohol consumption history, and Helicobacter pylori (Hp) infection ( χ2 = 10.39, 4.68, 11.47, 36.49, all P < 0.05). Family history of gastric cancer ( OR = 1.42, 95% CI = 1.03-1.96) and Hp infection ( OR = 3.76, 95% CI = 1.30-10.85) were identified as risk factors for gastric cancer ( P < 0.05). The combination of G-17, PG I, PG II, and PDCD5 had the highest predictive efficiency for early gastric cancer ( P < 0.05), with the area under the receiver operating characteristic curve being 0.982, sensitivity and specificity of 98.84% and 90.00%, respectively. Conclusion:Family history of gastric cancer and Hp infection are risk factors for gastric cancer. Patients with precancerous state and early gastric cancer have elevated serum levels of G-17 and PG II and reduced serum levels of PG I and PDCD5 protein. Combined detection of these four indicators has a high diagnostic value for early gastric cancer.

MiR-1294 suppresses ROS-dependent inflammatory response in atopic dermatitis via restraining STAT3/NF-κB pathway.

Atopic dermatitis (AD) is a common inflammatory skin disorder that affects children and adults. Despite the pathology of AD involves in immune dysfunction and epidermal barrier function destruction has been found, the mechanism of immune activation and barrier damage remain largely unknown. In the present study, The TNF-α/IFN-γ-stimulated HaCaTs, organotypic AD-like 3D skin equivalents and AD-like mouse model were constructed. The mRNA, histological morphology, protein levels, cytokines were detected by real-time quantitative polymerasechain reaction (RT-qPCR), hematoxylin and eosin (H & E) staining, Immunohistochemistry (IHC), immunoblotting, immunofluorescence (IF) staining, and enzyme linked immunosorbent assay (ELISA), respectively. Cell viability, cell cycle, and apoptosis were respectively calculated using a Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and flow cytometry. A dual-luciferase reporter gene system was used to investigate the relationship between miR-1294 and STAT3. Compared with the control group, the expression of miR-1294 decreased in TNF-α/IFN-γ-stimulated HaCaTs (P < 0.001), AD-like skin model, and AD-like mouse model (P < 0.001). Moreover, STAT3 was documented as a direct target of miR-1294. Inflammation (P < 0.05) and epidermal barrier function destruction (P < 0.05) in AD was suppressed by overexpression of miR-1294 but enhanced by STAT3 upregulation and its downstream NF-κB pathway. We also found miR-1294 upregulation inhibited inflammation and epidermal barrier function destruction via targeting STAT3 to suppress NF-κB pathway activation in AD.

Electromechanical Effects of Bone Remodeling Based on Edge Smoothed Finite Element Method / 医用生物力学

Objective Aiming at solving the problem of poor accuracy for numerical solution of traditional finite element method (FEM) in numerical analysis on piezoelectric effects of bone remodelling, a model with an edge-based smoothed FEM (ES-FEM) was proposed. Methods The bone model was discretized by triangular elements, and the smoothing domain was constructed based on edges of the existing mesh element. Based on gradient smoothing technique, the smoothed strain gradient and the smoothed electric field gradient were obtained, and the discrete equations of the system were constructed under the framework of smoothed Galerkin weakform. Results The changes of bone mineral density (BMD) and the distributions of electric potential under piezoelectric effects in the process of bone remodelling were reflected by using the above model. Compared with FEM, ES-FEM could improve the accuracy of simulation result for bone remodelling to a certain extent. Conclusions The proposed ES-FEM can simulate the process of bone remodelling more accurately. The accurate prediction for piezoelectric effect of bone reconstruction by this method provides an effective theoretical basis for clinical research of bone diseases.

Comparison of safety and efficacy of laparoscopy and laparotomy for 5-10 cm intermediate-risk primary gastric stromal tumors / 中华消化内镜杂志

Objective:To compare the safety and efficacy of laparoscopy and laparotomy for 5-10 cm intermediate-risk gastric stromal tumor, and to evaluate whether there was evident benefits of postoperative adjuvant treatment with imatinib.Methods:A retrospective study was conducted on 72 patients with moderate risk gastric stromal tumors (5-10 cm in diameter) who received operation in Nanjing Drum Tower Hospital from January 2010 to July 2020. There were 28 cases in the laparoscopy group and 44 cases in the laparotomy group. The clinical features, pathological data, perioperative results and hospitalization costs were compared between the two groups. The survival rates of postoperative adjuvant therapy with or without imatinib were analyzed and compared.Results:There was no significant difference in clinicopathological features between the two groups ( P>0.05). The incidences of postoperative complications in the laparoscopy group and the laparotomy group were 32.1% (9/28) and 52.3% (23/44) respectively, showing no significant difference ( P=0.094). Compared with the laparotomy group, both the hospital stay (12.5±3.2 days VS 15.0±3.5 days, P=0.004) and the median postoperative hospital stay (7.5 days VS 9.0 days, P=0.006) in the laparoscopy group were significantly shorter, and the first exhaust time was significantly shorter ( P=0.003). During the median follow-up period of 58 months (13-129 months), there was no tumor-related death. Two cases died of breast cancer and heart disease in the laparotomy group, and 1 case died irrelevant to gastric stromal tumor in the laparoscopy group. Of the 72 patients, 40 received postoperative imatinib adjuvant therapy, 22 cases (50.0%) in the laparotomy group and 18 cases (64.3%) in the laparoscopy group, with no significant difference in the proportion ( χ2=1.414, P=0.234). There was significant difference in the overall survival rate between the group treated with imatinib and the group without imatinib ( P=0.015). Conclusion:Laparoscopic resection is safe and effective for intermediate-risk gastric stromal tumor of 5-10 cm. Taking imatinib adjuvant treatment does not increase overall survival rate of patients with intermediate-risk gastric stromal tumors (5-10 cm), and there is no tumor-related death, recurrence or metastasis for those who did not accept imatinib adjuvant treatment after R0 resection.

Real-world evaluation of AI driven COVID-19 triage for emergency admissions: External validation & operational assessment of lab-free and high-throughput screening solutions

BackgroundUncertainty in patients COVID-19 status contributes to treatment delays, nosocomial transmission, and operational pressures in hospitals. However, typical turnaround times for batch-processed laboratory PCR tests remain 12-24h. Although rapid antigen lateral flow testing (LFD) has been widely adopted in UK emergency care settings, sensitivity is limited. We recently demonstrated that AI-driven triage (CURIAL-1.0) allows high-throughput COVID-19 screening using clinical data routinely available within 1h of arrival to hospital. Here we aimed to determine operational and safety improvements over standard-care, performing external/prospective evaluation across four NHS trusts with updated algorithms optimised for generalisability and speed, and deploying a novel lab-free screening pathway in a UK emergency department. MethodsWe rationalised predictors in CURIAL-1.0 to optimise separately for generalisability and speed, developing CURIAL-Lab with vital signs and routine laboratory blood predictors (FBC, U&E, LFT, CRP) and CURIAL-Rapide with vital signs and FBC alone. Models were calibrated during training to 90% sensitivity and validated externally for unscheduled admissions to Portsmouth University Hospitals, University Hospitals Birmingham and Bedfordshire Hospitals NHS trusts, and prospectively during the second-wave of the UK COVID-19 epidemic at Oxford University Hospitals (OUH). Predictions were generated using first-performed blood tests and vital signs and compared against confirmatory viral nucleic acid testing. Next, we retrospectively evaluated a novel clinical pathway triaging patients to COVID-19-suspected clinical areas where either model prediction or LFD results were positive, comparing sensitivity and NPV with LFD results alone. Lastly, we deployed CURIAL-Rapide alongside an approved point-of-care FBC analyser (OLO; SightDiagnostics, Israel) to provide lab-free COVID-19 screening in the John Radcliffe Hospitals Emergency Department (Oxford, UK), as trust-approved service improvement. Our primary improvement outcome was time-to-result availability; secondary outcomes were sensitivity, specificity, PPV, and NPV assessed against a PCR reference standard. We compared CURIAL-Rapides performance with clinician triage and LFD results within standard-care. Results72,223 patients met eligibility criteria across external and prospective validation sites. Model performance was consistent across trusts (CURIAL-Lab: AUROCs range 0.858-0.881; CURIAL-Rapide 0.836-0.854), with highest sensitivity achieved at Portsmouth University Hospitals (CURIAL-Lab:84.1% [95% Wilsons score CIs 82.5-85.7]; CURIAL-Rapide:83.5% [81.8 - 85.1]) at specificities of 71.3% (95% Wilsons score CIs: 70.9 - 71.8) and 63.6% (63.1 - 64.1). For 3,207 patients receiving LFD-triage within routine care for OUH admissions between December 23, 2021 and March 6, 2021, a combined clinical pathway increased sensitivity from 56.9% for LFDs alone (95% CI 51.7-62.0) to 88.2% with CURIAL-Rapide (84.4-91.1; AUROC 0.919) and 85.6% with CURIAL-Lab (81.6-88.9; AUROC 0.925). 520 patients were prospectively enrolled for point-of-care FBC analysis between February 18, 2021 and May 10, 2021, of whom 436 received confirmatory PCR testing within routine care and 10 (2.3%) tested positive. Median time from patient arrival to availability of CURIAL-Rapide result was 45:00 min (32-64), 16 minutes (26.3%) sooner than LFD results (61:00 min, 37-99; log-rank p<0.0001), and 6:52 h (90.2%) sooner than PCR results (7:37 h, 6:05-15:39; p<0.0001). Sensitivity and specificity of CURIAL-Rapide were 87.5% (52.9-97.8) and 85.4% (81.3-88.7), therefore achieving high NPV (99.7%, 98.2-99.9). CURIAL-Rapide correctly excluded COVID-19 for 58.5% of negative patients who were triaged by a clinician to COVID-19-suspected (amber) areas. ImpactCURIAL-Lab & CURIAL-Rapide are generalisable, high-throughput screening tests for COVID-19, rapidly excluding the illness with higher NPV than LFDs. CURIAL-Rapide can be used in combination with near-patient FBC analysis for rapid, lab-free screening, and may reduce the number of COVID-19-negative patients triaged to enhanced precautions ( amber) clinical areas.

Association of antinuclear antibody status with clinical features and malignancy risk in adult patients with dermatomyositis / 中华皮肤科杂志

Objective:To investigate the relationship of antinuclear antibody (ANA) status with clinical features and malignancy risk in adult patients with dermatomyositis.Methods:A retrospective analysis was performed to analyze clinical data from 101 inpatients with dermatomyositis in Department of Dermatology, the First Affiliated Hospital of Soochow University from April 2008 to April 2018. These patients were divided into ANA-positive group and ANA-negative group, and differences in myopathy and malignancy risks as well as other clinical features were analyzed between the 2 groups. A 2-year follow-up was undertaken among 92 patients. Chi-square test was used to analyze and compare clinical features between the 2 groups, and a multivariate regression model was used to analyze the relationship of ANA status with amyopathic dermatomyositis and malignancies.Results:Among the 101 patients with dermatomyositis, there were 42 males and 59 females, aged 55.13 ± 14.63 years; 14 patients had amyopathic dermatomyositis, 6 patients had hypomyopathic dermatomyositis, and 81 patients had myopathic dermatomyositis; 42 (41.58%) cases were positive for ANA, and 59 (58.41%) were negative for ANA. Compared with the ANA-negative group, the ANA-positive group showed significantly decreased incidence of cervical erythema (33.33% vs. 59.32%, P=0.010) and shawl sign (14.28% vs. 35.59%, P=0.017) . Twenty-eight (27.72%) patients with dermatomyositis were complicated by malignancies. Malignancies were found in 5 (11.9%) of ANA-positive patients, and in 23 (38.98%) of ANA-negative patients. Univariate analysis showed that ANA-negative patients with dermatomyositis had a higher risk of malignancies compared with ANA-positive patients with dermatomyositis, with an odds ratio of 7.52 (95% CI: 1.62-13.78, P=0.003) . In the multivariate regression model, the absence of ANA ( OR=4.34, 95% CI: 1.37-13.72, P=0.012) and cervical erythema ( OR=3.27, 95% CI: 1.20-8.91, P=0.020) were associated with high incidence of malignancies, while the absence of ANA was not significantly correlated with the occurrence of amyopathic dermatomyositis ( OR=0.99, 95% CI: 0.32-2.99, P=0.980) . Conclusions:ANA-negative adult dermatomyositis patients with cervical erythema had an increased risk of malignancies. Thus, close follow-up and regular tumor screening are necessary in these patients.

Expression and function of hypoxia-inducible factor 1 alpha signaling pathway in aortic calcification in rats with chronic kidney disease / 中华肾脏病杂志

Objective:To observe the expression of hypoxia-inducible factor 1 alpha (HIF-1α) signaling pathway in the aorta of chronic kidney disease (CKD) rats with vascular calcification and to explore the role of this pathway in aortic calcification of CKD.Methods:Forty 8-week-old male SD rats were randomly divided into control group (CON group, n=15) and CKD with aortic calcification group (CKD+AC group, n=25). The rats were sacrificed at the end of 4 th, 6 th and 8 th week respectively and urine, blood, aorta and kidney samples were collected. The level of serum HIF-1α was tested by ELISA. The pathology changes of kidney were observed by HE staining. The aortic calcification was evaluated by alizarin red staining and calcium content detection. Immunohistochemistry and real-time PCR were applied to detect the protein and mRNA expression of alpha-smooth muscle actin (α-SMA), Runt-related transcription factor 2 (Runx2), HIF-1α, vascular endothelial growth factor A (VEGFA) and Notch1 in the aorta. Results:Compared with CON group, serum urea, creatinine, cystatin C, phosphorus, calcium-phosphorus product and 24-h urine protein were significantly higher in CKD+AC group (all P<0.05). Serum HIF-1α levels were higher at 4 th and 8 th week in CKD+AC group than that in CON group (both P<0.05). There was no significant calcium deposit in the aorta of the CON group at all time points, and calcium deposits were seen in the aorta of the CKD+AC rats at each time point, which gradually increased with time. Compared with CON group, the expressions of aortic α-SMA protein and mRNA were significantly decreased in CKD+AC group at each time point, however the protein and mRNA expressions of Runx2, HIF-1α, VEGFA and Notch1 in the aorta of CKD+AC group rats were markedly increased at each time point (all P<0.05). Correlation analysis showed that the aortic calcium content was positively correlated with serum HIF-1α ( r=0.706, P<0.001) and the protein expressions of HIF-1α ( r=0.852, P<0.001), VEGFA ( r=0.747, P<0.001) and Notch1 ( r=0.813, P<0.001) in aorta. Conclusion:The HIF-1α-VEGFA-Notch1 signaling pathway is activated during aortic calcification in CKD rats, suggesting that this signaling pathway might be involved in the vascular calcification in CKD, and serum HIF-1α is expected to be one of serum markers for CKD vascular calcification.

Exploration of the production-education integration mode of higher diploma education for medical record information management professionals / 中华医院管理杂志

Medical record information is the core data source for diagnosis related groups(DRG)payment, and high-quality of medical record information is the foundation for DRG payment. The development of medical record management towards medical record information management, pushes up the demand for high-quality medical record information management professionals in hospitals. The conventional practice of professional training had resulted in such setbacks as professionals mismatch, long pre-employment training period, and large demand for continuing education. Based on the triple helix model theory, the study established a production-education integration training mode of university-government-hospital for medical record information management professionals. Capacity development was set as the goal and job demand as the guidance, for effectively integrating the educational resources, and promoting the model of " posts linked to training, employment following graduation" production-education integration training. The aim is to expand the quantity of talent team and improve the quality of talent training, thus effectively easing the shortage of medical record information management professionals.

Development and Validation of Early Warning Score Systems for COVID-19 Patients

COVID-19 is a major, urgent, and ongoing threat to global health. Globally more than 24 million have been infected and the disease has claimed more than a million lives as of October 2020. Predicting which patients will need respiratory support is important to guiding individual patient treatment and also to ensuring sufficient resources are available. We evaluated the ability of six common Early Warning Scores (EWS) to identify respiratory deterioration defined as the need for advanced respiratory support (high-flow nasal oxygen, continuous positive airways pressure, non-invasive ventilation, intubation) within a prediction window of 24 hours. We show these scores perform sub-optimally at this specific task. Therefore, we develop an alternative Early Warning Score based on a Gradient Boosting Trees (GBT) algorithm that is able to predict deterioration within the next 24 hours with high AUROC 94% and an accuracy, sensitivity and specificity of 70%, 96%, 70%, respectively. Our GBT model outperformed the best EWS (LDTEWS:NEWS), increasing the AUROC by 14%. Our GBT model makes the prediction based on the current and baseline measures of routinely available vital signs and blood tests.

Artificial intelligence driven assessment of routinely collected healthcare data is an effective screening test for COVID-19 in patients presenting to hospital

BackgroundRapid identification of COVID-19 is important for delivering care expediently and maintaining infection control. The early clinical course of SARS-CoV-2 infection can be difficult to distinguish from other undifferentiated medical presentations to hospital, however for operational reasons SARS-CoV-2 PCR testing can take up to 48 hours. Artificial Intelligence (AI) methods, trained using routinely collected clinical data, may allow front-door screening for COVID-19 within the first hour of presentation. MethodsDemographic, routine and prior clinical data were extracted for 170,510 sequential presentations to emergency and acute medical departments at a large UK teaching hospital group. We applied multivariate logistic regression, random forests and extreme gradient boosted trees to distinguish emergency department (ED) presentations and admissions due to COVID-19 from pre-pandemic controls. We performed stepwise addition of clinical feature sets and assessed performance using stratified 10-fold cross validation. Models were calibrated during training to achieve sensitivities of 70, 80 and 90% for identifying patients with COVID-19. To simulate real-world performance at different stages of an epidemic, we generated test sets with varying prevalences of COVID-19 and assessed predictive values. We prospectively validated our models for all patients presenting or admitted to our hospital group between 20th April and 6th May 2020, comparing model predictions to PCR test results. ResultsPresentation laboratory blood tests, point of care blood gas, and vital signs measurements for 115,394 emergency presentations and 72,310 admissions were analysed. Presentation laboratory tests and vital signs were most predictive of COVID-19 (maximum area under ROC curve [AUROC] 0.904 and 0.823, respectively). Sequential addition of informative variables improved model performance to AUROC 0.942. We developed two early-detection models to identify COVID-19, achieving sensitivities and specificities of 77.4% and 95.7% for our ED model amongst patients attending hospital, and 77.4% and 94.8% for our Admissions model amongst patients being admitted. Both models offer high negative predictive values (>99%) across a range of prevalences (<5%). In a two-week prospective validation period, our ED and Admissions models demonstrated 92.3% and 92.5% accuracy (AUROC 0.881 and 0.871 respectively) for all patients presenting or admitted to a large UK teaching hospital group. A sensitivity analysis to account for uncertainty in negative PCR results improves apparent accuracy (95.1% and 94.1%) and NPV (99.0% and 98.5%). Three laboratory blood markers, Eosinophils, Basophils, and C-Reactive Protein, alongside Calcium measured on blood-gas, and presentation Oxygen requirement were the most informative variables in our models. ConclusionArtificial intelligence techniques perform effectively as a screening test for COVID-19 in emergency departments and hospital admission units. Our models support rapid exclusion of the illness using routinely collected and readily available clinical measurements, guiding streaming of patients during the early phase of admission. BriefThe early clinical course of SARS-CoV-2 infection can be difficult to distinguish from other undifferentiated medical presentations to hospital, however viral specific real-time polymerase chain reaction (RT-PCR) testing has limited sensitivity and can take up to 48 hours for operational reasons. In this study, we develop two early-detection models to identify COVID-19 using routinely collected data typically available within one hour (laboratory tests, blood gas and vital signs) during 115,394 emergency presentations and 72,310 admissions to hospital. Our emergency department (ED) model achieved 77.4% sensitivity and 95.7% specificity (AUROC 0.939) for COVID-19 amongst all patients attending hospital, and Admissions model achieved 77.4% sensitivity and 94.8% specificity (AUROC 0.940) for the subset admitted to hospital. Both models achieve high negative predictive values (>99%) across a range of prevalences (<5%), facilitating rapid exclusion during triage to guide infection control. We prospectively validated our models across all patients presenting and admitted to a large UK teaching hospital group in a two-week test period, achieving 92.3% (n= 3,326, NPV: 97.6%, AUROC: 0.881) and 92.5% accuracy (n=1,715, NPV: 97.7%, AUROC: 0.871) in comparison to RT-PCR results. Sensitivity analyses to account for uncertainty in negative PCR results improves apparent accuracy (95.1% and 94.1%) and NPV (99.0% and 98.5%). Our artificial intelligence models perform effectively as a screening test for COVID-19 in emergency departments and hospital admission units, offering high impact in settings where rapid testing is unavailable.

Advances of Krüppel-like factors in hepatocellular carcinoma / 国际肿瘤学杂志

Krüppel-like factors (KLFs) play extremely important roles in genesis and development of tumors. Simultaneously, KLFs have been proven to affect the proliferation, differentiation and migration of hepatocellular carcinoma cells. Nine members in the KLFs family (KLF2, KLF4, KLF5, KLF6, KLF8, KLF9, KLF10, KLF14 and KLF17) are involved in the occurrence and development of hepatocellular carcinoma in various ways as an oncogene and tumor suppressor gene. Therefore, the KLFs family will hopefully become biological therapeutic targets for hepatocellular carcinoma.